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Sample records for hormone receptor-positive metastatic

  1. Palbociclib in Combination With Tamoxifen as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer

    Science.gov (United States)

    2017-08-23

    Hormone Receptor Positive Malignant Neoplasm of Breast; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Estrogen Receptor Positive Breast Cancer; Progesterone Receptor Positive Tumor; Metastatic Breast Cancer

  2. The role of histological subtype in hormone receptor positive metastatic breast cancer: similar survival but different therapeutic approaches.

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    Lobbezoo, Dorien; Truin, Wilfred; Voogd, Adri; Roumen, Rudi; Vreugdenhil, Gerard; Dercksen, Marcus Wouter; van den Berkmortel, Franchette; Smilde, Tineke; van de Wouw, Agnes; van Kampen, Roel; van Riel, Johanna; Peters, Natascha; Peer, Petronella; Tjan-Heijnen, Vivianne C G

    2016-05-17

    This study describes the differences between the two largest histological breast cancer subtypes (invasive ductal carcinoma (IDC) and invasive (mixed) lobular carcinoma (ILC) with respect to patient and tumor characteristics, treatment-choices and outcome in metastatic breast cancer. Patients with ILC were older at diagnosis of primary breast cancer and had more often initial bone metastasis (46.5% versus 34.8%, P = 0.01) and less often multiple metastatic sites compared to IDC (23.7% versus 30.9%, P = 0.11). Six months after diagnosis of metastatic breast cancer, 28.1% of patients with ILC and 39.8% of patients with IDC had received chemotherapy with a longer median time to first chemotherapy for those with ILC (P = 0.001). After six months 84.8% of patients with ILC had received endocrine therapy versus 72.5% of patients with IDC (P = 0.0001). Median overall survival was 29 months for ILC and 25 months for IDC (P = 0.53). We included 437 patients with hormone receptor-positive IDC and 131 patients with hormone receptor-positive ILC, all diagnosed with metastatic breast cancer between 2007-2009, irrespective of date of the primary diagnosis. Patient and tumor characteristics and data on treatment and outcome were collected. Survival curves were obtained using the Kaplan-Meier method. Treatment strategies of hormone receptor-positive metastatic breast cancer were remarkably different for patients with ILC and IDC. Further research is required to understand tumor behavior and treatment-choices in real-life.

  3. Analysis of Paired Primary-Metastatic Hormone-Receptor Positive Breast Tumors (HRPBC Uncovers Potential Novel Drivers of Hormonal Resistance.

    Directory of Open Access Journals (Sweden)

    Luis Manso

    Full Text Available We sought to identify genetic variants associated with disease relapse and failure to hormonal treatment in hormone-receptor positive breast cancer (HRPBC. We analyzed a series of HRPBC with distant relapse, by sequencing pairs (n = 11 of tumors (primary and metastases at >800X. Comparative genomic hybridization was performed as well. Top hits, based on the frequency of alteration and severity of the changes, were tested in the TCGA series. Genes determining the most parsimonious prognostic signature were studied for their functional role in vitro, by performing cell growth assays in hormonal-deprivation conditions, a setting that mimics treatment with aromatase inhibitors. Severe alterations were recurrently found in 18 genes in the pairs. However, only MYC, DNAH5, CSFR1, EPHA7, ARID1B, and KMT2C preserved an independent prognosis impact and/or showed a significantly different incidence of alterations between relapsed and non-relapsed cases in the TCGA series. The signature composed of MYC, KMT2C, and EPHA7 best discriminated the clinical course, (overall survival 90,7 vs. 144,5 months; p = 0.0001. Having an alteration in any of the genes of the signature implied a hazard ratio of death of 3.25 (p<0.0001, and early relapse during the adjuvant hormonal treatment. The presence of the D348N mutation in KMT2C and/or the T666I mutation in the kinase domain of EPHA7 conferred hormonal resistance in vitro. Novel inactivating mutations in KMT2C and EPHA7, which confer hormonal resistance, are linked to adverse clinical course in HRPBC.

  4. In real life, one-quarter of patients with hormone receptor-positive metastatic breast cancer receive chemotherapy as initial palliative therapy: a study of the Southeast Netherlands Breast Cancer Consortium

    NARCIS (Netherlands)

    Lobbezoo, D.J.; Kampen, R.J. van; Voogd, A.C.; Dercksen, M.W.; Berkmortel, F. van den; Smilde, T.J.; Wouw, A.J. van de; Peters, F.P.; Riel, J.M. van; Peters, N.A.; Boer, M. de; Peer, P.G.; Tjan-Heijnen, V.C.

    2016-01-01

    BACKGROUND: The objective of this study was to present initial systemic treatment choices and the outcome of hormone receptor-positive (HR+) metastatic breast cancer. PATIENTS AND METHODS: All the 815 consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight participating

  5. Use of Palliative Endocrine Therapy in Patients with Hormone Receptor-Positive Distant Metastatic Breast Cancer: How Often, How Effective, How Long?

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    Güth, Uwe; Huang, Dorothy Jane; Schötzau, Andreas; Schmid, Seraina Margaretha

    2016-01-01

    This study provides real-world clinical evidence regarding palliative endocrine therapy (ET) in breast cancer (BC). The main questions to be answered were: how often and how long did patients receive ET? A particular aspect was the analysis of compliance and persistence with ET. An analysis of a nonselected/consecutive cohort of women with distant metastatic hormone receptor-positive BC (n = 205) was conducted. In all, 165 patients (80.5%) received ET during the palliative disease course. The noncompliance rate was 1.5%. Sixty-seven patients (40.6%) had ET as the only antineoplastic therapy. The median number of therapy lines was 2, and the median duration was 18 months. The median metastatic disease survival (MDS) was 34 months. In patients who had an MDS of ≥9 months (n = 145; 87.9%), during 70.6% of the MDS time only ET had been administered. Patients who were naïve to ET more often had a good response to and a longer duration of palliative ET than those who were not. The nonpersistence rate was 4.3%. Excluding the few patients who had a rapidly progressive course, the disease was controlled for about 70% of the entire palliative disease course with ET alone. Only very few patients were nonpersistent with ET and consciously stopped a still effective, ongoing ET. © 2015 S. Karger AG, Basel.

  6. Challenges in the treatment of hormone receptor-positive, HER2-negative metastatic breast cancer with brain metastases.

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    Liu, Minetta C; Cortés, Javier; O'Shaughnessy, Joyce

    2016-06-01

    Brain metastases are a major cause of morbidity and mortality for women with hormone receptor (HR)-positive breast cancer, yet little is known about the optimal treatment of brain disease in this group of patients. Although these patients are at lower risk for brain metastases relative to those with HER2-positive and triple-negative disease, they comprise the majority of women diagnosed with breast cancer. Surgery and radiation continue to have a role in the treatment of brain metastases, but there is a dearth of effective systemic therapies due to the poor penetrability of many systemic drugs across the blood-brain barrier (BBB). Additionally, patients with brain metastases have long been excluded from clinical trials, and few studies have been conducted to evaluate the safety and effectiveness of systemic therapies specifically for the treatment of HER2-negative breast cancer brain metastases. New approaches are on the horizon, such as nanoparticle-based cytotoxic drugs that have the potential to cross the BBB and provide clinically meaningful benefits to patients with this life-threatening consequence of HR-positive breast cancer.

  7. FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

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    Walker, Amanda J; Wedam, Suparna; Amiri-Kordestani, Laleh; Bloomquist, Erik; Tang, Shengui; Sridhara, Rajeshwari; Chen, Wei; Palmby, Todd R; Fourie Zirkelbach, Jeanne; Fu, Wentao; Liu, Qi; Tilley, Amy; Kim, Geoffrey; Kluetz, Paul G; McKee, Amy E; Pazdur, Richard

    2016-10-15

    On February 19, 2016, the FDA approved palbociclib (Ibrance, Pfizer) for use in combination with fulvestrant (Faslodex, AstraZeneca) for the treatment of women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer (MBC) with disease progression following endocrine therapy. The approval was based on the results of a randomized, double-blind, placebo-controlled trial conducted in 521 pre- and postmenopausal women with HR-positive, HER2-negative advanced or MBC. Patients were randomized (2:1) to receive palbociclib plus fulvestrant (n = 347) or placebo plus fulvestrant (n = 174). The primary endpoint was investigator-assessed progression-free survival (PFS). A statistically significant and clinically meaningful improvement in PFS (9.5 months vs. 4.6 months) was observed in patients receiving palbociclib plus fulvestrant [HR 0.46; 95% confidence interval (CI), 0.36-0.59; P palbociclib. The most common adverse reactions (>20%) in patients treated with palbociclib were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, and thrombocytopenia. This approval was granted in the context of a prior accelerated approval for palbociclib in combination with letrozole in patients with HR-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy. Clin Cancer Res; 22(20); 4968-72. ©2016 AACR. ©2016 American Association for Cancer Research.

  8. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer.

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    Turner, Nicholas C; Ro, Jungsil; André, Fabrice; Loi, Sherene; Verma, Sunil; Iwata, Hiroji; Harbeck, Nadia; Loibl, Sibylle; Huang Bartlett, Cynthia; Zhang, Ke; Giorgetti, Carla; Randolph, Sophia; Koehler, Maria; Cristofanilli, Massimo

    2015-07-16

    Growth of hormone-receptor-positive breast cancer is dependent on cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), which promote progression from the G1 phase to the S phase of the cell cycle. We assessed the efficacy of palbociclib (an inhibitor of CDK4 and CDK6) and fulvestrant in advanced breast cancer. This phase 3 study involved 521 patients with advanced hormone-receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that had relapsed or progressed during prior endocrine therapy. We randomly assigned patients in a 2:1 ratio to receive palbociclib and fulvestrant or placebo and fulvestrant. Premenopausal or perimenopausal women also received goserelin. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, objective response, rate of clinical benefit, patient-reported outcomes, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee after 195 events of disease progression or death had occurred. The median progression-free survival was 9.2 months (95% confidence interval [CI], 7.5 to not estimable) with palbociclib-fulvestrant and 3.8 months (95% CI, 3.5 to 5.5) with placebo-fulvestrant (hazard ratio for disease progression or death, 0.42; 95% CI, 0.32 to 0.56; Ppalbociclib-fulvestrant group were neutropenia (62.0%, vs. 0.6% in the placebo-fulvestrant group), leukopenia (25.2% vs. 0.6%), anemia (2.6% vs. 1.7%), thrombocytopenia (2.3% vs. 0%), and fatigue (2.0% vs. 1.2%). Febrile neutropenia was reported in 0.6% of palbociclib-treated patients and 0.6% of placebo-treated patients. The rate of discontinuation due to adverse events was 2.6% with palbociclib and 1.7% with placebo. Among patients with hormone-receptor-positive metastatic breast cancer who had progression of disease during prior endocrine therapy, palbociclib combined with fulvestrant resulted in longer progression-free survival than fulvestrant alone

  9. In real life, one-quarter of patients with hormone receptor-positive metastatic breast cancer receive chemotherapy as initial palliative therapy: a study of the Southeast Netherlands Breast Cancer Consortium.

    Science.gov (United States)

    Lobbezoo, D J A; van Kampen, R J W; Voogd, A C; Dercksen, M W; van den Berkmortel, F; Smilde, T J; van de Wouw, A J; Peters, F P J; van Riel, J M G H; Peters, N A J B; de Boer, M; Peer, P G M; Tjan-Heijnen, V C G

    2016-02-01

    The objective of this study was to present initial systemic treatment choices and the outcome of hormone receptor-positive (HR+) metastatic breast cancer. All the 815 consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight participating hospitals were identified. From the 611 patients with HR+ disease, a total of 520 patients with HER2-negative (HER2-) breast cancer were included. Initial palliative systemic treatment was registered. Progression-free survival (PFS) and overall survival (OS) per initial palliative systemic therapy were obtained using the Kaplan-Meier method and compared using the log-rank test. From the total of 520 patients with HR+/HER2- metastatic breast cancer, 482 patients (93%) received any palliative systemic therapy. Patients that received initial chemotherapy (n = 116) were significantly younger, had less comorbidity, had received more prior adjuvant systemic therapy and were less likely to have bone metastasis only compared with patients that received initial endocrine therapy (n = 366). Median PFS of initial palliative chemotherapy was 5.3 months [95% confidence interval (CI) 4.2-6.2] and of initial endocrine therapy 13.3 months (95% CI 11.3-15.5), with a median OS of 16.1 and 36.9 months, respectively. Initial chemotherapy was also associated with worse outcome in terms of PFS and OS after adjustment for prognostic factors. A high percentage of patients with HR+ disease received initial palliative chemotherapy, which was associated with worse outcome, even after adjustment of relevant prognostic factors. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. Bosutinib in combination with the aromatase inhibitor letrozole: a phase II trial in postmenopausal women evaluating first-line endocrine therapy in locally advanced or metastatic hormone receptor-positive/HER2-negative breast cancer.

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    Moy, Beverly; Neven, Patrick; Lebrun, Fabienne; Bellet, Meritxell; Xu, Binghe; Sarosiek, Tomasz; Chow, Louis; Goss, Paul; Zacharchuk, Charles; Leip, Eric; Turnbull, Kathleen; Bardy-Bouxin, Nathalie; Duvillié, Ladan; Láng, István

    2014-04-01

    Endocrine therapy resistance in hormone receptor-positive (HR+) breast cancer (BC) may involve crosstalk between HRs and growth factor signaling pathways. We evaluated bosutinib, a dual Src/Abl tyrosine kinase inhibitor that has previously demonstrated some antitumor activity in BC, plus letrozole as first-line endocrine therapy in locally advanced or metastatic HR+/HER2- BC. METHODS; Sixteen postmenopausal women were enrolled in a phase II study evaluating the safety/efficacy of bosutinib plus letrozole. In the single-arm safety/dose-confirming lead-in (part 1), patients received oral bosutinib at 400 mg/day plus letrozole at 2.5 mg/day; adverse events (AEs) and dose-limiting toxicities (DLTs) were monitored, and initial efficacy was assessed. A randomized efficacy/safety phase (part 2) was planned to evaluate the combination versus letrozole monotherapy. Fifteen of 16 subjects experienced treatment-related AEs, most commonly diarrhea (69%). Treatment-related hepatotoxicity AEs (primarily alanine aminotransferase [ALT] or aspartate aminotransferase [AST] elevations) occurred in 6 of 16 patients (38%). Four of 15 evaluable patients (27%) experienced a DLT (grade 3/4 ALT/AST elevations, n = 2; grade 3 rash, n = 1; grade 3 diarrhea or vomiting, n = 1), including 1 Hy's law hepatotoxicity case. All DLTs resolved following treatment discontinuation. One patient achieved confirmed partial response; one had stable disease for >24 weeks. Study termination occurred before part 2. The unfavorable risk-benefit ratio did not warrant further investigation of bosutinib plus letrozole.

  11. Bosutinib in combination with the aromatase inhibitor exemestane: a phase II trial in postmenopausal women with previously treated locally advanced or metastatic hormone receptor-positive/HER2-negative breast cancer.

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    Moy, Beverly; Neven, Patrick; Lebrun, Fabienne; Bellet, Meritxell; Xu, Binghe; Sarosiek, Tomasz; Chow, Louis; Goss, Paul; Zacharchuk, Charles; Leip, Eric; Turnbull, Kathleen; Bardy-Bouxin, Nathalie; Duvillié, Ladan; Láng, István

    2014-04-01

    Bosutinib is an oral, selective Src/Abl tyrosine kinase inhibitor with activity in breast cancer (BC). We evaluated bosutinib plus exemestane as second-line therapy in previously treated hormone receptor-positive (HR+) locally advanced or metastatic BC. This was a phase II study with patients enrolled in a single-arm safety lead-in phase. Patients receiving bosutinib at 400 mg or 300 mg/day (based on toxicity) plus exemestane at 25 mg/day were monitored for adverse events (AEs) and dose-limiting toxicities for 28 days, and initial efficacy was assessed. After the lead-in and dose-determination phase, randomized evaluation of combination therapy versus exemestane was planned. Thirty-nine of 42 patients (93%) experienced treatment-related AEs including diarrhea in 28 (67%) and hepatotoxicity in 11 (26%); overall serious treatment-related AEs were recorded in 4 (10%). No liver toxicity met Hy's law criteria. Dose-limiting toxicities occurred in 5 of 13 patients receiving 400 mg (38%) and 3 of 26 patients receiving 300 mg (12%) of bosutinib; all resolved on treatment discontinuation. One patient (300 mg/day) achieved confirmed partial response; three (400 mg/day, n = 2; 300 mg/day, n = 1) maintained stable disease for >24 weeks; a best response of progressive disease occurred in 15 of 42 patients (36%). Median progression-free survival was 12.3 weeks (80% confidence interval: 11.0-15.6). The risk-benefit profile of bosutinib at 300 mg/day plus exemestane resulted in early study termination before the randomized portion. Alternative bosutinib regimens merit investigation in BC.

  12. Prevention of everolimus-related stomatitis in women with hormone receptor-positive, HER2-negative metastatic breast cancer using dexamethasone mouthwash (SWISH): a single-arm, phase 2 trial.

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    Rugo, Hope S; Seneviratne, Lasika; Beck, J Thaddeus; Glaspy, John A; Peguero, Julio A; Pluard, Timothy J; Dhillon, Navneet; Hwang, Leon Christopher; Nangia, Chaitali; Mayer, Ingrid A; Meiller, Timothy F; Chambers, Mark S; Sweetman, Robert W; Sabo, J Randy; Litton, Jennifer K

    2017-05-01

    Stomatitis is a class effect associated with the inhibition of mTOR and is associated with everolimus therapy for breast cancer. Topical steroids might reduce stomatitis incidence and severity, and the need for dose reductions and interruptions of everolimus. Anecdotal use of topical steroid oral prophylaxis has been reported in patients with breast cancer. We aimed to assess dexamethasone-based mouthwash for prevention of stomatitis in patients with breast cancer. This US-based, multicentre, single-arm, phase 2 prevention study enrolled women aged 18 years and older with postmenopausal status who had histologically or cytologically confirmed metastatic hormone receptor-positive, HER2-negative breast cancer. Beginning on day 1 of cycle 1, patients received everolimus 10 mg plus exemestane 25 mg daily, with 10 mL of alcohol-free dexamethasone 0·5 mg per 5 mL oral solution (swish for 2 min and spit, four times daily for 8 weeks). After 8 weeks, dexamethasone mouthwash could be continued for up to eight additional weeks at the discretion of the clinician and patient. The primary endpoint was incidence of grade 2 or worse stomatitis by 8 weeks assessed in the full analysis set (patients who received at least one dose of everolimus and exemestane and at least one confirmed dose of dexamethasone mouthwash) versus historical controls from the BOLERO-2 trial (everolimus and exemestane treatment in patients with hormone receptor-positive advanced breast cancer who were not given dexamethasone mouthwash for prevention of stomatitis). This trial is registered at ClinicalTrials.gov, number NCT02069093. Between May 28, 2014, and Oct 8, 2015, we enrolled 92 women; 85 were evaluable for efficacy. By 8 weeks, the incidence of grade 2 or worse stomatitis was two (2%) of 85 patients (95% CI 0·29-8·24), versus 159 (33%) of 482 patients (95% CI 28·8-37·4) for the duration of the BOLERO-2 study. Overall, 83 (90%) of 92 patients had at least one adverse event. The most frequently

  13. Quality of life with palbociclib plus fulvestrant in previously treated hormone receptor-positive, HER2-negative metastatic breast cancer: patient-reported outcomes from the PALOMA-3 trial.

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    Harbeck, N; Iyer, S; Turner, N; Cristofanilli, M; Ro, J; André, F; Loi, S; Verma, S; Iwata, H; Bhattacharyya, H; Puyana Theall, K; Bartlett, C H; Loibl, S

    2016-06-01

    In the PALOMA-3 study, palbociclib plus fulvestrant demonstrated improved progression-free survival compared with fulvestrant plus placebo in hormone receptor-positive, HER2- endocrine-resistant metastatic breast cancer (MBC). This analysis compared patient-reported outcomes (PROs) between the two treatment groups. Patients were randomized 2 : 1 to receive palbociclib 125 mg/day orally for 3 weeks followed by 1 week off (n = 347) plus fulvestrant (500 mg i.m. per standard of care) or placebo plus fulvestrant (n = 174). PROs were assessed on day 1 of cycles 1-4 and of every other subsequent cycle starting with cycle 6 using the EORTC QLQ-C30 and its breast cancer module, QLQ-BR23. High scores (range 0-100) could indicate better functioning/quality of life (QoL) or worse symptom severity. Repeated-measures mixed-effect analyses were carried out to compare on-treatment overall scores and changes from baseline between treatment groups while controlling for baseline. Between-group comparisons of time to deterioration in global QoL and pain were made using an unstratified log-rank test and Cox proportional hazards model. Questionnaire completion rates were high at baseline and during treatment (from baseline to cycle 14, ≥95.8% in each group completed ≥1 question on the EORTC QLQ-C30). On treatment, estimated overall global QoL scores significantly favored the palbociclib plus fulvestrant group [66.1, 95% confidence interval (CI) 64.5-67.7 versus 63.0, 95% CI 60.6-65.3; P = 0.0313]. Significantly greater improvement from baseline in pain was also observed in this group (-3.3, 95% CI -5.1 to -1.5 versus 2.0, 95% CI -0.6 to 4.6; P = 0.0011). No significant differences were observed for other QLQ-BR23 functioning domains, breast or arm symptoms. Treatment with palbociclib plus fulvestrant significantly delayed deterioration in global QoL (P Palbociclib plus fulvestrant allowed patients to maintain good QoL in the endocrine resistance setting while experiencing

  14. Palbociclib for the Treatment of Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

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    Morikawa, Aki; Henry, N Lynn

    2015-08-15

    Palbociclib is a selective inhibitor of cyclin-dependent kinases 4 and 6 that acts by reducing phosphorylation of the tumor suppressor gene retinoblastoma. When added to the aromatase inhibitor letrozole in a randomized phase II trial for first-line therapy of estrogen receptor-positive, HER2-negative metastatic breast cancer, palbociclib significantly increased progression-free survival compared with letrozole alone [palbociclib + letrozole: 20.2 months; 95% confidence interval (CI), 13.8-27.5; letrozole: 10.2 months; 95% CI, 5.7-12.6; HR, 0.49; 95% CI, 0.32-0.75; P = 0.0004]. On the basis of these results, the drug was recently granted accelerated approval by the FDA, and confirmatory studies are ongoing. Because this drug has a rational target in an oncologic pathway, concurrent biomarker development is of interest. In breast cancer, the most useful predictive biomarkers identified thus far are estrogen receptor and HER2 receptor status, although additional studies are ongoing. In this article, we review the development of palbociclib and its use in treatment of hormone receptor-positive metastatic breast cancer in the context of other FDA-approved agents in this setting. ©2015 American Association for Cancer Research.

  15. Palbociclib in Combination With Fulvestrant in Women With Hormone Receptor-Positive/HER2-Negative Advanced Metastatic Breast Cancer: Detailed Safety Analysis From a Multicenter, Randomized, Placebo-Controlled, Phase III Study (PALOMA-3).

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    Verma, Sunil; Bartlett, Cynthia Huang; Schnell, Patrick; DeMichele, Angela M; Loi, Sherene; Ro, Jungsil; Colleoni, Marco; Iwata, Hiroji; Harbeck, Nadia; Cristofanilli, Massimo; Zhang, Ke; Thiele, Alexandra; Turner, Nicholas C; Rugo, Hope S

    2016-10-01

    Palbociclib enhances endocrine therapy and improves clinical outcomes in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Because this is a new target, it is clinically important to understand palbociclib's safety profile to effectively manage toxicity and optimize clinical benefit. Patients with endocrine-resistant, HR-positive/HER2-negative MBC (n = 521) were randomly assigned 2:1 to receive fulvestrant (500 mg intramuscular injection) with or without goserelin with oral palbociclib (125 mg daily; 3 weeks on/1 week off) or placebo. Safety assessments at baseline and day 1 of each cycle included blood counts on day 15 for the first 2 cycles. Hematologic toxicity was assessed by using laboratory data. A total of 517 patients were treated (palbociclib, n = 345; placebo, n = 172); median follow-up was 8.9 months. With palbociclib, neutropenia was the most common grade 3 (55%) and 4 (10%) adverse event; median times to onset and duration of grade ≥3 episodes were 16 and 7 days, respectively. Asian ethnicity and below-median neutrophil counts at baseline were significantly associated with an increased chance of developing grade 3-4 neutropenia with palbociclib. Dose modifications for grade 3-4 neutropenia had no adverse effect on progression-free survival. In the palbociclib arm, febrile neutropenia occurred in 3 (Palbociclib plus fulvestrant treatment was well-tolerated, and the primary toxicity of asymptomatic neutropenia was effectively managed by dose modification without apparent loss of efficacy. This study appears at ClinicalTrials.gov, NCT01942135. Treatment with palbociclib in combination with fulvestrant was generally safe and well-tolerated in patients with hormone receptor (HR)-positive metastatic breast cancer. Consistent with the drug's proposed mechanism of action, palbociclib-related neutropenia differs in its clinical time course, patterns, and consequences from those seen with

  16. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial.

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    Cristofanilli, Massimo; Turner, Nicholas C; Bondarenko, Igor; Ro, Jungsil; Im, Seock-Ah; Masuda, Norikazu; Colleoni, Marco; DeMichele, Angela; Loi, Sherene; Verma, Sunil; Iwata, Hiroji; Harbeck, Nadia; Zhang, Ke; Theall, Kathy Puyana; Jiang, Yuqiu; Bartlett, Cynthia Huang; Koehler, Maria; Slamon, Dennis

    2016-04-01

    In the PALOMA-3 study, the combination of the CDK4 and CDK6 inhibitor palbociclib and fulvestrant was associated with significant improvements in progression-free survival compared with fulvestrant plus placebo in patients with metastatic breast cancer. Identification of patients most suitable for the addition of palbociclib to endocrine therapy after tumour recurrence is crucial for treatment optimisation in metastatic breast cancer. We aimed to confirm our earlier findings with this extended follow-up and show our results for subgroup and biomarker analyses. In this multicentre, double-blind, randomised phase 3 study, women aged 18 years or older with hormone-receptor-positive, HER2-negative metastatic breast cancer that had progressed on previous endocrine therapy were stratified by sensitivity to previous hormonal therapy, menopausal status, and presence of visceral metastasis at 144 centres in 17 countries. Eligible patients-ie, any menopausal status, Eastern Cooperative Oncology Group performance status 0-1, measurable disease or bone disease only, and disease relapse or progression after previous endocrine therapy for advanced disease during treatment or within 12 months of completion of adjuvant therapy-were randomly assigned (2:1) via a centralised interactive web-based and voice-based randomisation system to receive oral palbociclib (125 mg daily for 3 weeks followed by a week off over 28-day cycles) plus 500 mg fulvestrant (intramuscular injection on days 1 and 15 of cycle 1; then on day 1 of subsequent 28-day cycles) or placebo plus fulvestrant. The primary endpoint was investigator-assessed progression-free survival. Analysis was by intention to treat. We also assessed endocrine therapy resistance by clinical parameters, quantitative hormone-receptor expression, and tumour PIK3CA mutational status in circulating DNA at baseline. This study is registered with ClinicalTrials.gov, NCT01942135. Between Oct 7, 2013, and Aug 26, 2014, 521 patients were

  17. PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy-Safety and Efficacy in Asian Patients.

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    Iwata, Hiroji; Im, Seock-Ah; Masuda, Norikazu; Im, Young-Hyuck; Inoue, Kenichi; Rai, Yoshiaki; Nakamura, Rikiya; Kim, Jee Hyun; Hoffman, Justin T; Zhang, Ke; Giorgetti, Carla; Iyer, Shrividya; Schnell, Patrick T; Bartlett, Cynthia Huang; Ro, Jungsil

    2017-08-01

    To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy-resistant metastatic breast cancer. The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3) trial, a double-blind phase III study, included 521 patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs) were assessed on study treatment and at the end of treatment. This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71) or placebo plus fulvestrant (n = 31). Palbociclib plus fulvestrant improved progression-free survival (PFS) compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached) but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065). The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92%) and leukopenia (29%); febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study.

  18. [Advanced luminal breast cancer (hormone receptor-positive, HER2 negative): New therapeutic options in 2015].

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    Vanacker, Hélène; Bally, Olivia; Kassem, Loay; Tredan, Olivier; Heudel, Pierre; Bachelot, Thomas

    2015-06-01

    Despite improvements in early detection, surgery and systemic therapy, metastatic breast cancer remains a major cause of death. Luminal type breast cancers expressing hormone estrogen receptor (ER) or progesterone (PR) and without HER2 overexpression are generally sensitive to endocrine therapy, but raise the issue of the occurrence of resistance to treatment, particularly at metastatic stage. A better understanding of hormone resistance may guide the development of new therapeutics. New strategies aim at enhancing and prolonging of endocrine sensitivity, by optimizing existing schemes, or by combining an endocrine therapy with a targeted therapies specific to hormone resistance pathways: ER signaling, PI3K/AKT/mTOR and Cyclin Dependent Kinase (CDK). Key corners of 2014 include confirmation of benefit of high dose fulvestrant, and commercialization of everolimus as the first mTOR inhibitor in this indication. Other strategies are being tested dealing with new endocrine therapies or new molecular targets such as PI3K inhibitors, insulin-like growth factor receptor (IGF-R) and histone deacetylase (HDAC) inhibitors. Coming years may be fruitful and might radically change our way to treat these patients. Copyright © 2015 Société Françise du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés. Published by Elsevier Masson SAS. All rights reserved.

  19. Pharmacologic management of bone-related complications and bone metastases in postmenopausal women with hormone receptor-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Yardley DA

    2016-05-01

    Full Text Available Denise A Yardley1,2 1Sarah Cannon Research Institute, Nashville, TN, USA; 2Tennessee Oncology, Nashville, TN, USA Abstract: There is a high risk for bone loss and skeletal-related events, including bone metastases, in postmenopausal women with hormone receptor-positive breast cancer. Both the disease itself and its therapeutic treatments can negatively impact bone, resulting in decreases in bone mineral density and increases in bone loss. These negative effects on the bone can significantly impact morbidity and mortality. Effective management and minimization of bone-related complications in postmenopausal women with hormone receptor-positive breast cancer remain essential. This review discusses the current understanding of molecular and biological mechanisms involved in bone turnover and metastases, increased risk for bone-related complications from breast cancer and breast cancer therapy, and current and emerging treatment strategies for managing bone metastases and bone turnover in postmenopausal women with hormone receptor-positive breast cancer. Keywords: breast cancer, bone metastases, hormone receptor-positive, bone-related complications, interventions, management and management strategies, estrogen receptor-positive

  20. Palbociclib in hormone receptor positive advanced breast cancer: A cost-utility analysis.

    Science.gov (United States)

    Raphael, J; Helou, J; Pritchard, K I; Naimark, D M

    2017-11-01

    The addition of palbociclib to letrozole improves progression-free survival in the first-line treatment of hormone receptor positive advanced breast cancer (ABC). This study assesses the cost-utility of palbociclib from the Canadian healthcare payer perspective. A probabilistic discrete event simulation (DES) model was developed and parameterised with data from the PALOMA 1 and 2 trials and other sources. The incremental cost per quality-adjusted life-month (QALM) gained for palbociclib was calculated. A time horizon of 15 years was used in the base case with costs and effectiveness discounted at 5% annually. Time-to- progression and time-to-death were derived from a Weibull and exponential distribution. Expected costs were based on Ontario fees and other sources. Probabilistic sensitivity analyses were conducted to account for parameter uncertainty. Compared to letrozole, the addition of palbociclib provided an additional 14.7 QALM at an incremental cost of $161,508. The resulting incremental cost-effectiveness ratio was $10,999/QALM gained. Assuming a willingness-to-pay (WTP) of $4167/QALM, the probability of palbociclib to be cost-effective was 0%. Cost-effectiveness acceptability curves derived from a probabilistic sensitivity analysis showed that at a WTP of $11,000/QALM gained, the probability of palbociclib to be cost-effective was 50%. The addition of palbociclib to letrozole is unlikely to be cost-effective for the treatment of ABC from a Canadian healthcare perspective with its current price. While ABC patients derive a meaningful clinical benefit from palbociclib, considerations should be given to increase the WTP threshold and reduce the drug pricing, to render this strategy more affordable. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Chemotherapy-induced amenorrhea and the resumption of menstruation in premenopausal women with hormone receptor-positive early breast cancer.

    Science.gov (United States)

    Koga, Chinami; Akiyoshi, Sayuri; Ishida, Mayumi; Nakamura, Yoshiaki; Ohno, Shinji; Tokunaga, Eriko

    2017-09-01

    For premenopausal women with breast cancer, information on the effects of chemotherapy and the risk of infertility is important. In this study, the effect of chemotherapy on the ovarian function in premenopausal women with hormone receptor-positive breast cancer was investigated, with an age-stratified analysis of the appearance of amenorrhea and the resumption of menstruation after the use of chemotherapy with anthracyclines or taxanes. Premenopausal women diagnosed with operable Stage I-III hormone receptor-positive breast cancer and underwent neoadjuvant or adjuvant chemotherapy with the standard regimen of anthracyclines and/or taxanes were included. The patients were classified into age groups in 5-year increments, and the rates of chemotherapy-induced amenorrhea (CIA), resumption of menstruation, and duration of CIA after chemotherapy were analyzed. The subjects consisted of 101 patients (median age 45 years). CIA occurred in 97 (96%) patients and 40 patients resumed menstruation. In all patients aged ≤39 years menstruation restarted, whereas in all patients aged ≥50 years, menstruation did not restart. For the patients who resumed menstruation, the younger the patients, the sooner menstruation tended to restart. The resumption of menstruation occurred within 1 year for younger patients aged around 30 years, but for those aged ≥35 years, 60% of cases took around 2-3 years for resumption. The incidence of CIA, the resumption of menstruation and duration of CIA after chemotherapy depend greatly on the patient's age.

  2. Biological response to hormonal manipulation in oestrogen receptor positive ductal carcinoma in situ of the breast

    National Research Council Canada - National Science Library

    Boland, G P; McKeown, A; Chan, K C; Prasad, R; Knox, W F; Bundred, N J

    2003-01-01

    ...) to reduce local recurrence, despite 50% of lesions being oestrogen receptor (OR) negative. We have investigated the response to hormone manipulation in DCIS by studying changes in epithelial proliferation and progesterone receptor...

  3. Prostate-Derived Ets Transcription Factor Overexpression is Associated with Nodal Metastasis, Hormone Receptor Positivity in Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Simon Turcotte

    2007-10-01

    Full Text Available Prostate-derived Ets transcription factor (PDEF has recently been associated with invasive breast cancer, but no expression profile has been defined in clinical specimens. We undertook a comprehensive PDEF transcriptional expression study of 86 breast cancer clinical specimens, several cell lines, normal tissues. PDEF expression profile was analyzed according to standard clinicopathologic parameters, compared with hormonal receptor, HER-2/neu status, to the expression of the new tumor biomarker Dikkopf-1 (DKK1. Wide ranging PDEF overexpression was observed in 74% of tested tumors, at higher levels than the average expression found in normal breasts. High PDEF expression was associated with hormone receptor positivity (P < .001, moderate to good differentiation (less than grade III, P = .01, dissemination to axillary lymph nodes (P = .002. PDEF was an independent risk factor for nodal involvement (multivariate analysis, odds ratio 1.250, P = .002. It was expressed in a different subgroup compared to DKK1-expressing tumors (P < .001. Our data imply that PDEF mRNA expression could be useful in breast cancer molecular staging. Further insights into PDEF functions at the protein level, possible links with hormone receptors biology, bear great potential for new therapeutic avenues.

  4. Determination of HER2 phosphorylation at tyrosine 1221/1222 improves prediction of poor survival for breast cancer patients with hormone receptor-positive tumors

    DEFF Research Database (Denmark)

    Frogne, Thomas; Laenkholm, Anne-Vibeke; Lyng, Maria B

    2009-01-01

    INTRODUCTION: High expression of total HER2 protein confers poor prognosis for breast cancer patients. HER2 is a member of the HER family consisting of four receptors, HER1 to HER4. HER receptor activity is regulated by a variety of mechanisms, and phosphorylation of the C-terminal part of the HER...... metastases, by evaluating the expression of phosphorylated HER1, HER2, HER3, Erk, Akt and the total level of HER4 and HER2. METHODS: Immunohistochemical analysis was performed on 268 primary breast tumors and 30 paired metastatic lesions from postmenopausal women with hormone receptor-positive breast tumors...... in primary tumors versus metastasis was evaluated. RESULTS: In the primary tumors, 8%, 18%, 14% and 15% of cases were scored positive for total HER2, pHER1, pHER2 and pHER3 expression, respectively. HER4 was expressed with strong intensity in 68% and at moderate intensity in 29% of cases. The activated forms...

  5. Cost-effectiveness of palbociclib in hormone receptor-positive advanced breast cancer.

    Science.gov (United States)

    Mamiya, H; Tahara, R K; Tolaney, S M; Choudhry, N K; Najafzadeh, M

    2017-08-01

    Palbociclib (PAL), a novel small-molecule inhibitor of cyclin-dependent kinases 4 and 6 for the treatment of advanced breast cancer, has demonstrated significant efficacy in prolonging progression-free survival when added to existing therapies. Considering the high cost of PAL, we assessed cost-effectiveness of adding PAL to usual care in treatment of advanced breast cancer. We developed a discrete event simulation model to simulate time to cancer progression and to compare life time clinical benefit and cost of alternative treatment strategies for patients with metastatic disease from societal perspective. Per approved indication, endocrine treatment naive patients were assigned to PAL plus letrozole (PAL + LET) or letrozole alone (LET). Patients with prior endocrine therapy were assigned to PAL plus fulvestrant (FUL) (PAL + FUL) or FUL alone. The model assumptions were informed based on published clinical trial data and other peer reviewed studies. We carried out one-way and probabilistic sensitivity analyses to assess the robustness of our results to the changes in model assumptions. In treatment-naive patients, the addition of PAL to LET cost an estimated $768 498 per additional quality-adjusted life-year (QALY) gained. The addition of PAL to FUL in patients with prior endocrine therapy cost an estimated $918 166 per QALY gained. Sensitivity analyses demonstrated adding PAL has a 0% chance of being cost-effectiveness in either patient groups at a willingness-to-pay threshold of $100 000 per QALY. From a societal perspective, PAL treatment of both patient groups (with and without prior endocrine therapy) is highly unlikely to be cost-effective compared with the usual care in the USA.

  6. Palbociclib: a first-in-class CDK4/CDK6 inhibitor for the treatment of hormone-receptor positive advanced breast cancer.

    Science.gov (United States)

    Lu, Janice

    2015-08-13

    Palbociclib was approved by the FDA for use in combination with letrozole for the treatment of postmenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy. In addition, the combination of palbociclib with fulvestrant resulted in superior outcome than fulvestrant alone in those who had progressed during prior endocrine therapy. This research highlight summarized the current development of CDK4/CDK6 inhibitors and future directions in the treatment of advanced hormone-receptor-positive breast cancer.

  7. Palbociclib: A Novel Cyclin-Dependent Kinase Inhibitor for Hormone Receptor-Positive Advanced Breast Cancer.

    Science.gov (United States)

    Mangini, Neha S; Wesolowski, Robert; Ramaswamy, Bhuvaneswari; Lustberg, Maryam B; Berger, Michael J

    2015-11-01

    To review palbociclib, a novel small-molecule inhibitor of cyclin-dependent kinases 4 and 6, and its current place in therapy for the treatment of hormone receptor (HMR)-positive, human epidermal growth factor receptor 2 (Her2)-negative advanced breast cancer. Four phase I trials, 2 phase II trials, and 1 phase III trial were identified from May 2004 to May 2015 using PubMed, American Society of Clinical Oncology (ASCO) abstracts, and European Society of Medical Oncology (ESMO) abstracts. In the first-line setting, the phase II PALbociclib: Ongoing trials in the Management of breast cAncer (PALOMA)-1 trial randomized patients to receive letrozole alone or letrozole plus palbociclib 125 mg daily for 3 weeks, followed by 1 week off, as initial therapy for advanced breast cancer. The investigator-assessed median progression-free survival (PFS) was 20. 2 months for the combination versus 10.2 months for letrozole alone (hazard ratio [HR] = 0.488; 95% CI = 0.319-0.748; 1-sided P = 0.0004). The ensuing Food and Drug Administration approval of palbociclib was given a "breakthrough therapy" designation, where preliminary evidence suggests substantial improvement over existing therapies for a serious or life-threatening disease. A confirmatory phase III trial, PALOMA-2, is under way. In patients who were previously treated with endocrine therapy for advanced breast cancer, the phase III PALOMA-3 trial randomized patients to fulvestrant plus palbociclib versus fulvestrant plus placebo. The investigator-assessed median PFS at the time of a preplanned analysis was 9.2 months with palbociclib-fulvestrant compared with 3.8 months with placebo-fulvestrant (HR = 0.42; 95% CI = 0.32-0.56; P Palbociclib, the first-in-class CDK4/6 inhibitor, significantly extended PFS in combination with endocrine therapy in the first and subsequent lines of treatment for HMR-positive, Her2-negative advanced breast cancer. © The Author(s) 2015.

  8. The ability of PAM50 risk of recurrence score to predict 10-year distant recurrence in hormone receptor-positive postmenopausal women with special histological subtypes

    DEFF Research Database (Denmark)

    Laenkholm, Anne-Vibeke; Jensen, Maj-Britt; Eriksen, Jens Ole

    2017-01-01

    INTRODUCTION: The Prosigna-PAM50 risk of recurrence (ROR) score has been validated in randomized clinical trials to predict 10-year distant recurrence (DR) in hormone receptor-positive breast cancer. Here, we examine the ability of Prosigna for predicting DR at 10 years in a subgroup of postmenop...

  9. Surgery Should Complement Endocrine Therapy for Elderly Postmenopausal Women with Hormone Receptor-Positive Early-Stage Breast Cancer

    Directory of Open Access Journals (Sweden)

    Olivier Nguyen

    2012-01-01

    Full Text Available Introduction. Endocrine therapy (ET is an integral part of breast cancer (BC treatment with surgical resection remaining the cornerstone of curative treatment. The objective of this study is to compare the survival of elderly postmenopausal women with hormone receptor-positive early-stage BC treated with ET alone, without radiation or chemotherapy, versus ET plus surgery. Materials and Methods. This is a retrospective study based on a prospective database. The medical records of postmenopausal BC patients referred to the surgical oncology service of two hospitals during an 8-year period were reviewed. All patients were to receive ET for a minimum of four months before undergoing any surgery. Results. Fifty-one patients were included and divided in two groups, ET alone and ET plus surgery. At last follow-up in exclusive ET patients (n=28, 39% had stable disease or complete response, 22% had progressive disease, of which 18% died of breast cancer, and 39% died of other causes. In surgical patients (n=23, 78% were disease-free, 9% died of recurrent breast cancer, and 13% died of other causes. Conclusions. These results suggest that surgical resection is beneficial in this group and should be considered, even for patients previously deemed ineligible for surgery.

  10. Metastatic Breast Cancer and Hormonal Receptor Status among a ...

    African Journals Online (AJOL)

    hormone receptor status correlates with site of metastatic lesions and survival among breast cancer patients. Objective: To determine the sites of metastatic breast lesions and how they relate to the hormonal receptor status. Methods: In this cross sectional descriptive study, 71 women with histologically confirmed incident ...

  11. Treatment challenges for community oncologists treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Abdel-Razeq H

    2016-10-01

    Full Text Available Hikmat Abdel-RazeqDepartment of Internal Medicine, King Hussein Cancer Center, Amman, JordanI read with great interest the review written elegantly by Gradishar addressing the challenges that community oncologists face in treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor-2 (HER2-negative advanced breast cancer in your journal.1As the author correctly stated, resistance to endocrine therapy in women with hormone receptor-positive disease is very frequent and almost inevitable.Understanding the multiple known mechanisms for endocrine resistance has helped physicians and researchers target these pathways.2 Many of the recently introduced drugs, such as the mTOR inhibitor everolimus3 and the cyclin-dependent kinase (CDK 4/6 inhibitor palbociclib,4 are in clinical practice and have been already incorporated in international guidelines.5View original paper by Gradishar.

  12. Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial

    OpenAIRE

    Mauriac, L.; Keshaviah, A; Debled, M; Mouridsen, H; Forbes, Jf; Thürlimann, B; Paridaens, R; Monnier, A.; Láng, I.; Wardley, A; Nogaret, J-M; Gelber, RD; Castiglione-Gertsch, M.; Price, KN; Coates, AS

    2017-01-01

    Background: Aromatase inhibitors are considered standard adjuvant endocrine treatment of postmenopausal women with hormone receptor-positive breast cancer, but it remains uncertain whether aromatase inhibitors should be given upfront or sequentially with tamoxifen. Awaiting results from ongoing randomized trials, we examined prognostic factors of an early relapse among patients in the BIG 1-98 trial to aid in treatment choices. Patients and methods: Analyses included all 7707 eligible patient...

  13. Real-World Treatment Patterns for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer in Europe and the United States.

    Science.gov (United States)

    Caldeira, Rita; Scazafave, Mark

    2016-01-01

    Clinical guidelines generally recommend endocrine therapy over chemotherapy for hormone receptor-positive advanced breast cancer (unless life-threatening metastases are present). This study aimed to assess the real-world treatment patterns of patients with hormone receptor-positive advanced breast cancer in Europe and the United States. Treatment patterns in Europe (France, Germany, Italy, Spain, and the UK) and the United States from January 2012 to December 2014 were investigated using a patient record database (Global Oncology Monitor©). Sample data were projected to the wider clinical population to provide running annual estimates every 3 months. Sample sizes ranged from 1272 to 1640 patients in Europe and from 2225 to 2760 patients in the United States. Across all lines of therapy, 37-43% (Europe) and 45-50% (United States) of patients received chemotherapy. More patients received endocrine therapy than chemotherapy as first-line treatment for advanced breast cancer (Europe: 51-54% vs. 33-35%; United States: 53-60% vs. 34-42%). In contrast, endocrine therapy-only regimens were given less commonly than chemotherapy-only regimens in the third-line setting in both Europe and the United States. Chemotherapy is used extensively in routine clinical practice for hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The results also suggest that the treatment patternsin Europe and the United States are qualitatively different. Funding : Ipsos Healthcare and AstraZeneca.

  14. Interest in Integrative Medicine Among Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study.

    Science.gov (United States)

    Hack, Carolin C; Fasching, Peter A; Fehm, Tanja; de Waal, Johann; Rezai, Mahdi; Baier, Bernd; Baake, Gerold; Kolberg, Hans-Christian; Guggenberger, Martin; Warm, Mathias; Harbeck, Nadia; Wuerstlein, Rachel; Deuker, Jörg-Uwe; Dall, Peter; Richter, Barbara; Wachsmann, Grischa; Brucker, Cosima; Siebers, Jan W; Fersis, Nikos; Kuhn, Thomas; Wolf, Christopher; Vollert, Hans-Walter; Breitbach, Georg-Peter; Janni, Wolfgang; Landthaler, Robert; Kohls, Andreas; Rezek, Daniela; Noesslet, Thomas; Fischer, Gunnar; Henschen, Stefan; Praetz, Thomas; Heyl, Volker; Kühn, Thorsten; Krauss, Thomas; Thomssen, Christoph; Hohn, Andre; Tesch, Hans; Mundhenke, Christoph; Hein, Alexander; Rauh, Claudia; Bayer, Christian M; Jacob, Adib; Schmidt, Katja; Belleville, Erik; Hadji, Peyman; Brucker, Sara Y; Wallwiener, Diethelm; Kümmel, Sherko; Beckmann, Matthias W; Paepke, Daniela

    2017-06-01

    Breast cancer patients often use complementary and alternative medicine, but few prospectively collected data on the topic are available specifically for postmenopausal breast cancer patients. A large prospective study was therefore conducted within a noninterventional study in order to identify the characteristics of patients interested in integrative medicine. The EvAluate-TM study is a prospective, multicenter noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive primary breast cancer. Between 2008 and 2009, 5045 postmenopausal patients were enrolled at 339 certified breast centers in Germany. As part of the data collection process, patients were asked at the baseline about their interest in and information needs relating to integrative medicine. Of the 5045 patients recruited, 3411 responded to the questionnaire on integrative medicine and took part in the analysis, 1583 patients expressed an interest in integrative medicine, and 1828 patients declared no interest. Relevant predictors of interest in integrative medicine were age, body mass index, tumor size, previous chemotherapy, and use of concomitant medications for other medical conditions. Interest in integrative medicine declined highly significantly ( P 65 years, 38.0%). Patients in favor of integrative medicine were significantly less satisfied with the information received about individual treatments and antihormonal therapy. Patients with interest in integrative medicine were more often interested in rehabilitation and fitness, nutritional counseling, and additional support from self-help organizations. These women were mostly interested in receiving information about their disease and integrative medicine from a physician, rather than from other sources. This study shows that a considerable proportion of postmenopausal breast cancer patients are interested in integrative medicine. Information about

  15. A phase 1 trial of BKM120 (Buparlisib) in combination with fulvestrant in postmenopausal women with estrogen receptor positive metastatic breast cancer

    Science.gov (United States)

    Ma, Cynthia X.; Luo, Jingqin; Naughton, Michael; Ademuyiwa, Foluso; Suresh, Rama; Griffith, Malachi; Griffith, Obi L.; Skidmore, Zachary L.; Spies, Nicholas C.; Ramu, Avinash; Trani, Lee; Pluard, Timothy; Nagaraj, Gayathri; Thomas, Shana; Guo, Zhanfang; Hoog, Jeremy; Han, Jing; Mardis, Elaine; Lockhart, Craig; Ellis, Matthew J.

    2016-01-01

    Purpose This trial was conducted to determine the maximum tolerated dose (MTD) and preliminary efficacy of buparlisib, an oral pan-class I PI3K inhibitor, plus fulvestrant in postmenopausal women with metastatic estrogen receptor positive breast cancer (ER+BC). Experimental Design Phase IA employed a 3+3 design to determine the MTD of buparlisib daily plus fulvestrant. Subsequent cohorts evaluated intermittent (5 of 7 day dosing) and continuous buparlisib (100mg daily). No more than 3 prior systemic treatments in the metastatic setting were allowed in Phase IB and Cohort C. Results Thirty one patients were enrolled. MTD was defined as buparlisib 100mg daily plus fulvestrant. Common adverse events (AEs) included fatigue (38.7 %), transaminases elevation (35.5 %), rash (29%), and diarrhea (19.4%). C-peptide was significantly increased during treatment, consistent with on-target effect of buparlisib. Compared to intermittent dosing, daily buparlisib was associated with more frequent early onset AEs and higher buparlisib plasma concentrations. Among the 29 evaluable patients, the clinical benefit rate was 58.6% (95% CI 40.7–74.5%). Response was not associated with PIK3CA mutation or treatment cohort, however loss of PTEN, progesterone receptor (PgR) expression, or mutation in TP53 was commoner in resistant cases and mutations in AKT1 and ESR1 did not exclude treatment response. Conclusion Buparlisib plus fulvestrant is clinically active with manageable AEs in patients with metastatic ER+BC. Weekend breaks in buparlisib dosing reduced toxicity. Patients with PgR negative and TP53 mutation did poorly, suggesting buparlisib plus fulvestrant may not be adequately effective against tumors with these poor prognostic molecular features. PMID:26563128

  16. FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

    Science.gov (United States)

    Beaver, Julia A; Amiri-Kordestani, Laleh; Charlab, Rosane; Chen, Wei; Palmby, Todd; Tilley, Amy; Zirkelbach, Jeanne Fourie; Yu, Jingyu; Liu, Qi; Zhao, Liang; Crich, Joyce; Chen, Xiao Hong; Hughes, Minerva; Bloomquist, Erik; Tang, Shenghui; Sridhara, Rajeshwari; Kluetz, Paul G; Kim, Geoffrey; Ibrahim, Amna; Pazdur, Richard; Cortazar, Patricia

    2015-11-01

    On February 3, 2015, the FDA granted accelerated approval to palbociclib (IBRANCE, Pfizer Inc.), an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The approval is based on a randomized, multicenter, open-label phase I/II trial (PALOMA-1) in 165 patients randomized to palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg orally daily) or letrozole alone. The phase II portion of the trial was divided into two cohorts: cohort 1 enrolled 66 biomarker-unselected patients and cohort 2 enrolled 99 biomarker-positive patients. The major efficacy outcome measure was investigator-assessed progression-free survival (PFS). A large magnitude of improvement in PFS was observed in patients receiving palbociclib plus letrozole compared with patients receiving letrozole alone (HR, 0.488; 95% confidence interval, 0.319-0.748). Multiple sensitivity analyses were supportive of clinical benefit. The most common adverse reaction in patients receiving palbociclib plus letrozole was neutropenia. This article summarizes the FDA thought process and data supporting accelerated approval based on PALOMA-1 that may be contingent upon verification and description of clinical benefit in the ongoing and fully accrued confirmatory trial PALOMA-2. ©2015 American Association for Cancer Research.

  17. Metastatic Breast Cancer and Hormonal Receptor Status among a ...

    African Journals Online (AJOL)

    Background: Breast cancer is the third commonest cancer in women in Uganda. The majority of breast cancer patients in Uganda present with advanced disease. Many studies show that metastatic lesions frequently lodge in bones, lung and liver. Tumour hormone receptor status correlates with site of metastatic lesions and ...

  18. Management of adverse events in patients with hormone receptor-positive breast cancer treated with everolimus: observations from a phase III clinical trial.

    Science.gov (United States)

    Peterson, Mary E

    2013-08-01

    Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of advanced renal cell carcinoma, pancreatic neuroendocrine tumors, subependymal giant cell astrocytoma associated with tuberous sclerosis complex, renal angiomyolipoma and tuberous sclerosis complex, and, in combination with exemestane, for hormone receptor-positive HER2-negative advanced breast cancer after failure of treatment with letrozole or anastrozole. Results from the phase III BOLERO-2 trial demonstrated that everolimus in combination with exemestane provided significant clinical benefit to patients with advanced hormone receptor-positive breast cancer. Although everolimus is generally well tolerated, as with most therapies administered in an advanced cancer setting, drug-related adverse events (AEs) inevitably occur. Most common AEs observed in the everolimus studies include stomatitis, rash, infection, noninfectious pneumonitis, and hyperglycemia. Clinical awareness and early identification of such AEs by oncology nurses are essential to dosing (interruptions, reduction, and treatment discontinuation); quality of life; and, ultimately, patient outcomes. Because everolimus has already been shown to significantly improve clinical efficacy in patients with advanced breast cancer, a proactive approach to the practical management of AEs associated with this mTOR inhibitor as well as other most common AEs observed in this patient population has been reviewed and outlined here.

  19. Height, age at menarche and risk of hormone receptor-positive and -negative breast cancer: A cohort study

    NARCIS (Netherlands)

    Ritte, R.; Lukanova, A.; Tjonneland, A.; Olsen, A.; Overvad, K.; Mesrine, S.; Fagherazzi, G.; Dossus, L.; Teucher, B.; Duijnhoven, van F.J.B.

    2013-01-01

    Associations of breast cancer overall with indicators of exposures during puberty are reasonably well characterized; however, uncertainty remains regarding the associations of height, leg length, sitting height and menarcheal age with hormone receptor-defined malignancies. Within the European

  20. Genetic Analysis in Blood and Tumor Samples From Patients With Advanced or Metastatic Estrogen Receptor Positive and HER2 Negative Breast Cancer Receiving Palbociclib and Endocrine Therapy

    Science.gov (United States)

    2017-11-16

    Estrogen Receptor Positive; HER2/Neu Negative; Recurrent Breast Carcinoma; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  1. Efficacy of chemotherapy after hormone therapy for hormone receptor–positive metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Ryutaro Mori

    2014-11-01

    Full Text Available Objective: According to the guidelines for metastatic breast cancer, hormone therapy for hormone receptor–positive metastatic breast cancer without life-threatening metastasis should be received prior to chemotherapy. Previous trials have investigated the sensitivity of chemotherapy for preoperative breast cancer based on the efficacy of neoadjuvant hormone therapy. In this retrospective study, we investigated the efficacy of chemotherapy for metastatic breast cancer in hormone therapy–effective and hormone therapy–ineffective cases. Methods: Patients who received chemotherapy after hormone therapy for metastatic breast cancer between 2006 and 2013 at our institution were investigated. Results: A total of 32 patients received chemotherapy after hormone therapy for metastatic breast cancer. The median patient age was 59 years, and most of the primary tumors exhibited a T2 status. A total of 26 patients had an N(+ status, while 7 patients had human epidermal growth factor receptor 2–positive tumors. A total of 13 patients received clinical benefits from hormone therapy, with a rate of clinical benefit of subsequent chemotherapy of 30.8%, which was not significantly different from that observed in the hormone therapy–ineffective patients (52.6%. A total of 13 patients were able to continue the hormone therapy for more than 1 year, with a rate of clinical benefit of chemotherapy of 38.5%, which was not significantly different from that observed in the short-term hormone therapy patients (47.4%. The luminal A patients were able to continue hormone therapy for a significantly longer period than the non-luminal A patients (median survival time: 17.8 months vs 6.35 months, p = 0.0085. However, there were no significant differences in the response to or duration of chemotherapy. Conclusion: The efficacy of chemotherapy for metastatic breast cancer cannot be predicted based on the efficacy of prior hormone therapy or tumor subtype

  2. CYP19A1 polymorphisms and clinical outcomes in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial

    DEFF Research Database (Denmark)

    Leyland-Jones, Brian; Gray, Kathryn P; Abramovitz, Mark

    2015-01-01

    To determine whether CYP19A1 polymorphisms are associated with abnormal activity of aromatase and with musculoskeletal and bone side effects of aromatase inhibitors. DNA was isolated from tumor specimens of 4861 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1......-98 trial to receive tamoxifen and/or letrozole for 5 years. Tumors were genotyped for six CYP19A1 polymorphisms using PCR-based methods. Associations with breast cancer-free interval (BCFI), distant recurrence-free interval (DRFI), musculoskeletal and bone adverse events (AEs) were assessed using Cox...... proportional hazards models. All statistical tests were two-sided. No association between the CYP19A1 genotypes and BCFI or DRFI was observed overall. A reduced risk of a breast cancer event for tamoxifen-treated patients with rs700518 variants was observed (BCFI CC/TC vs. TT: HR 0.53, 95 % CI 0...

  3. Height, age at menarche and risk of hormone receptor-positive and -negative breast cancer: a cohort study.

    Science.gov (United States)

    Ritte, Rebecca; Lukanova, Annekatrin; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Mesrine, Sylvie; Fagherazzi, Guy; Dossus, Laure; Teucher, Birgit; Steindorf, Karen; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Grioni, Sara; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Quirós, José Ramón; Buckland, Genevieve; Molina-Montes, Esther; Chirlaque, María-Dolores; Ardanaz, Eva; Amiano, Pilar; Bueno-de-Mesquita, Bas; van Duijnhoven, Franzel; van Gils, Carla H; Peeters, Petra Hm; Wareham, Nick; Khaw, Kay-Tee; Key, Timothy J; Travis, Ruth C; Krum-Hansen, Sanda; Gram, Inger Torhild; Lund, Eiliv; Sund, Malin; Andersson, Anne; Romieu, Isabelle; Rinaldi, Sabina; McCormack, Valerie; Riboli, Elio; Kaaks, Rudolf

    2013-06-01

    Associations of breast cancer overall with indicators of exposures during puberty are reasonably well characterized; however, uncertainty remains regarding the associations of height, leg length, sitting height and menarcheal age with hormone receptor-defined malignancies. Within the European Prospective Investigation into Cancer and Nutrition cohort, Cox proportional hazards models were used to describe the relationships of adult height, leg length and sitting height and age at menarche with risk of estrogen and progesterone receptor negative (ER-PR-) (n = 990) and ER+PR+ (n = 3,524) breast tumors. Height as a single risk factor was compared to a model combining leg length and sitting height. The possible interactions of height, leg length and sitting height with menarche were also analyzed. Risk of both ER-PR- and ER+PR+ malignancies was positively associated with standing height, leg length and sitting height and inversely associated with increasing age at menarche. For ER+PR+ disease, sitting height (hazard ratios: 1.14[95% confidence interval: 1.08-1.20]) had a stronger risk association than leg length (1.05[1.00-1.11]). In comparison, for ER-PR- disease, no distinct differences were observed between leg length and sitting height. Women who were tall and had an early menarche (≤13 years) showed an almost twofold increase in risk of ER+PR+ tumors but no such increase in risk was observed for ER-PR- disease. Indicators of exposures during rapid growth periods were associated with risks of both HR-defined breast cancers. Exposures during childhood promoting faster development may establish risk associations for both HR-positive and -negative malignancies. The stronger associations of the components of height with ER+PR+ tumors among older women suggest possible hormonal links that could be specific for postmenopausal women. Copyright © 2012 UICC.

  4. Hormone therapy in metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Jebelameli P

    1997-09-01

    Full Text Available Only orchiectomy is still commonly used today either as a single therapy or in combination regimens. Hypophysectomy & adrenalectomy showed such devastating effects on the endocrine equilibrium as to be inconsistent with an acceptable quality of life or even with survival. Chemical adrenalectomy was also tried with drugs (eg. aminoglutethmide, spironolactone leading to consequences superimposable to those of surgical adrenalectomy. Along with orchiectomy, three groups of substances are commonly used today for the hormonal therapy of prostate cancer: estrogens, LHRH agonists & anti androgens. Bilateral orchiectomy removes 90-95% of circulating testosterone. Clinical studies document 60-80% of positive responders to castration, on continued evaluation, relapse occurs usually within 6-24 months in responders, with a death rate of 50% within 6 months. The androgenic activity still remaining after castration may explain the partial & progressively decreasing effectiveness of this & other testosterone reducing therapies. Antiandrogens define substances that act directly at the target site, where interacting with steroid hormone receptors, they impede the binding of androgens. A trend towards the combination of testosterone-reducing & androgen-blocking treatment is developing in modern therapy of prostate cancer. This is due to the complementary characteristics of the two different pharmacological mechanisms that are involved. In this study castration+antiandrogen is compared to castration alone. The results demonstrate a significantly greater percentage of positive objective & subjective responses with antiandrogen than with placebo. In addition survival time was increased in patients treated with castration+antiandrogen than castration+placebo.

  5. Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial.

    Science.gov (United States)

    Zdenkowski, N; Forbes, J F; Boyle, F M; Kannourakis, G; Gill, P G; Bayliss, E; Saunders, C; Della-Fiorentina, S; Kling, N; Campbell, I; Mann, G B; Coates, A S; Gebski, V; Davies, L; Thornton, R; Reaby, L; Cuzick, J; Green, M

    2016-05-01

    Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy. This randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed ≥4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] ≥1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety. Between 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1-4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole. These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy. Australian New

  6. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up

    DEFF Research Database (Denmark)

    Regan, Meredith M; Neven, Patrick; Giobbie-Hurder, Anita

    2011-01-01

    Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast-cancer recurrence and death. Therefore, trials assessing endocrine therapies for this patient population need extended follow-up. We present an update of efficacy outcomes in the Brea...

  7. The prognostic and predictive value of Tregs and tumor immune subtypes in postmenopausal, hormone receptor-positive breast cancer patients treated with adjuvant endocrine therapy: a Dutch TEAM study analysis

    NARCIS (Netherlands)

    C.C. Engels (Charla C.); A. Charehbili; C.J.H. van de Velde; E. Bastiaannet (Esther); A. Sajet (Anita); H. Putter (Hein); E.A. van Vliet; R.L.P. van Vlierberghe (Ronald L.); V.T.H.B.M. Smit (Vincent); J.M.S. Bartlett (John); C.M. Seynaeve (Caroline); G.-J. Liefers (Gerrit-Jan); P.J.K. Kuppen (P. J K)

    2015-01-01

    textabstractEvidence exists for an immunomodulatory effect of endocrine therapy in hormone receptor-positive (HR+ve) breast cancer (BC). Therefore, the aim of this study was to define the prognostic and predictive value of tumor immune markers and the tumor immune profile in HR+ve BC, treated with

  8. Low Ki67/high ATM protein expression in malignant tumors predicts favorable prognosis in a retrospective study of early stage hormone receptor positive breast cancer.

    Science.gov (United States)

    Feng, Xiaolan; Li, Haocheng; Kornaga, Elizabeth N; Dean, Michelle; Lees-Miller, Susan P; Riabowol, Karl; Magliocco, Anthony M; Morris, Don; Watson, Peter H; Enwere, Emeka K; Bebb, Gwyn; Paterson, Alexander

    2016-12-27

    This study was designed to investigate the combined influence of ATM and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (ATM and Ki67 proteins using fluorescence and brightfield immunohistochemistry respectively, and quantified their expression with digital image analysis. Data on expression levels were subsequently correlated with clinical outcome. Remarkably, ATM expression was useful to stratify the low Ki67 group into subgroups with better or poorer prognosis. Specifically, in the low Ki67 subgroup defined as having smaller tumors and no positive nodes, patients with high ATM expression showed better outcome than those with low ATM, with estimated survival rates of 96% and 89% respectively at 15 years follow up (p = 0.04). Similarly, low-Ki67 patients with smaller tumors, 1-3 positive nodes and high ATM also had significantly better outcomes than their low ATM counterparts, with estimated survival rates of 88% and 46% respectively (p = 0.03) at 15 years follow up. Multivariable analysis indicated that the combination of high ATM and low Ki67 is prognostic of improved survival, independent of tumor size, grade, and lymph node status (p = 0.02). These data suggest that the prognostic value of Ki67 can be improved by analyzing ATM expression in ES-HPBC.

  9. Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial.

    Science.gov (United States)

    Mauriac, L; Keshaviah, A; Debled, M; Mouridsen, H; Forbes, J F; Thürlimann, B; Paridaens, R; Monnier, A; Láng, I; Wardley, A; Nogaret, J-M; Gelber, R D; Castiglione-Gertsch, M; Price, K N; Coates, A S; Smith, I; Viale, G; Rabaglio, M; Zabaznyi, N; Goldhirsch, A

    2007-05-01

    Aromatase inhibitors are considered standard adjuvant endocrine treatment of postmenopausal women with hormone receptor-positive breast cancer, but it remains uncertain whether aromatase inhibitors should be given upfront or sequentially with tamoxifen. Awaiting results from ongoing randomized trials, we examined prognostic factors of an early relapse among patients in the BIG 1-98 trial to aid in treatment choices. Analyses included all 7707 eligible patients treated on BIG 1-98. The median follow-up was 2 years, and the primary end point was breast cancer relapse. Cox proportional hazards regression was used to identify prognostic factors. Two hundred and eighty-five patients (3.7%) had an early relapse (3.1% on letrozole, 4.4% on tamoxifen). Predictive factors for early relapse were node positivity (P < 0.001), absence of both receptors being positive (P < 0.001), high tumor grade (P < 0.001), HER-2 overexpression/amplification (P < 0.001), large tumor size (P = 0.001), treatment with tamoxifen (P = 0.002), and vascular invasion (P = 0.02). There were no significant interactions between treatment and the covariates, though letrozole appeared to provide a greater than average reduction in the risk of early relapse in patients with many involved lymph nodes, large tumors, and vascular invasion present. Upfront letrozole resulted in significantly fewer early relapses than tamoxifen, even after adjusting for significant prognostic factors.

  10. Disease management patterns for postmenopausal women in Europe with hormone-receptor-positive, human epidermal growth factor receptor-2 negative advanced breast cancer.

    Science.gov (United States)

    André, Fabrice; Neven, Patrick; Marinsek, Nina; Zhang, Jie; Baladi, Jean-Francois; Degun, Ravi; Benelli, Giancarlo; Saletan, Stephen; Jerusalem, Guy

    2014-06-01

    International guidelines for hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2 negative (HER2(-)) advanced breast cancer (BC) recommend sequential lines of hormonal therapy (HT), and only recommend chemotherapy for patients with extensive visceral involvement or rapidly progressive disease. This study evaluated actual physician-reported treatments for advanced BC in Europe. We conducted a retrospective chart review of 355 postmenopausal women with HR(+), HER2(-) advanced BC who progressed on ≥1 line of HT (adjuvant or advanced) and completed ≥1 line of chemotherapy (advanced). Treatment choice was evaluated for each line of therapy. Of 355 patients, 111 (31%) received first-line chemotherapy, whereas 218 (61%) and 26 (7%) switched from HT to chemotherapy in second and third line, respectively. More patients receiving first-line HT had bone metastases (73% vs 27% chemotherapy). Patients treated with first-line chemotherapy had more brain (12% vs 3% HT) or extensive liver (13% vs 6% HT) metastases. Subgroup analysis of 188 patients who received first-line HT and had de novo advanced BC or relapsed/recurrent disease more than 1 year after adjuvant therapy found that the majority (89%; n = 167) of these patients switched to chemotherapy in second line. However, among these 167 patients, 27% had no significant changes in metastases between first and second line. Among the 73% of patients who had significant changes in metastases, 20% had no brain metastases or extensive visceral disease. Our study suggests that the guideline-recommended use of multiple HT lines is open to interpretation and that optimal treatment for European postmenopausal women with HR(+), HER2(-) advanced BC who responded to HT may not be achieved.

  11. High CDK6 protects cells from fulvestrant-mediated apoptosis and is a predictor of resistance to fulvestrant in estrogen receptor-positive metastatic breast cancer

    DEFF Research Database (Denmark)

    Alves, Carla Maria Lourenco; Elias, Daniel; Lyng, Maria B

    2016-01-01

    expression impaired fulvestrant-resistant cell growth and induced apoptosis. Treatment with palbociclib re-sensitized fulvestrant-resistant cells to fulvestrant through alteration of retinoblastoma protein phosphorylation. High CDK6 levels in metastatic samples from two independent cohorts of breast cancer...

  12. Cost-effectiveness analysis of extended adjuvant endocrine therapy in the treatment of post-menopausal women with hormone receptor positive breast cancer.

    Science.gov (United States)

    Erman, Aysegul; Nugent, Arlene; Amir, Eitan; Coyte, Peter C

    2014-06-01

    Five years of Tamoxifen (Standard TAM) is a common treatment option for early-stage, hormone receptor positive (HR+) breast cancer (BC). Extending Standard TAM by 5 additional years (Extended TAM) can improve survival and BC recurrences. In postmenopausal women, the use of extended aromatase inhibitors (Extended AI) after Standard TAM is an alternative to Extended TAM. This study examines the cost-effectiveness (CE) of extending Standard TAM with Extended TAM vs. Extended AI in postmenopausal HR+ early-stage BC patients. Three treatments were assessed: (1) Standard TAM; (2) Extended TAM; (3) Extended AI through a Markov model using a Canadian health system perspective, lifetime time-horizon, quality adjusted life years (QALYs), and a 5 % discount rate for future costs and utilities. Incremental cost-effectiveness ratios (ICERs) were calculated, and the impact of parameter uncertainty was assessed through probabilistic sensitivity analyses (SA) using conventional CE thresholds. The estimated total per person costs in 2012 Canadian dollars [$1.00 CAD = $0.99 US 2012] were the least for Extended TAM ($8,623 CAD) and most for Extended AI ($9,432 CAD). Extended AI was the most effective regimen, while Standard TAM was the least. Extended AI was cost-effective at conventional thresholds vs. Extended TAM (ICER: $3,402 CAD/QALY) which was robust to the SA. This study suggests that Extended AI and Extended TAM result in improved QALYs and lower healthcare costs vs Standard TAM. Extended AI results in the greatest improvement in QALYs and is the most cost-effective treatment alternative despite its higher drug costs.

  13. Dissecting the Biological Heterogeneity within Hormone Receptor Positive HER2 Negative Breast Cancer by Gene Expression Markers Identifies Indolent Tumors within Late Stage Disease

    Directory of Open Access Journals (Sweden)

    Jyothi S Prabhu

    2017-08-01

    Full Text Available Hormone receptor positive (HR+ breast cancers are a heterogeneous class with differential prognosis. Although more than half of Indian women present with advanced disease, many such patients do well. We have attempted identification of biologically indolent tumors within HR+HER2- tumors based on gene expression using histological grade as a guide to tumor aggression. 144 HR+HER2- tumors were divided into subclasses based on scores derived by using transcript levels of multiple genes representing survival, proliferation, and apoptotic pathways and compared to classification by Ki-67 labeling index (LI. Clinical characters and disease free survival were compared between the subclasses. The findings were independently validated in the METABRIC data set. Using the previously established estrogen receptor (ER down stream activity equation, 20% of the tumors with greater than 10% HR positivity by immunohistochemistry (IHC were still found to have inadequate ER function. A tumor aggression probability score was used to segregate the remainder of tumors into indolent (22% and aggressive (58% classes. Significant difference in disease specific survival was seen between the groups (P = .02. Aggression probability based subclassification had a higher hazard ratio and also independent prognostic value (P < .05. Independent validation of the gene panel in the METABRIC data set showed all 3 classes; indolent (24%, aggressive (68%, and insufficient ER signaling (7% with differential survival (P = .01. In agreement with other recent reports, biologically indolent tumors can be identified with small sets of gene panels and these tumors exist in a population with predominantly late stage disease.

  14. Reverse phase protein array based tumor profiling identifies a biomarker signature for risk classification of hormone receptor-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Johanna Sonntag

    2014-03-01

    Full Text Available A robust subclassification of luminal breast cancer, the most common molecular subtype of human breast cancer, is crucial for therapy decisions. While a part of patients is at higher risk of recurrence and requires chemo-endocrine treatment, the other part is at lower risk and also poorly responds to chemotherapeutic regimens. To approximate the risk of cancer recurrence, clinical guidelines recommend determining histologic grading and abundance of a cell proliferation marker in tumor specimens. However, this approach assigns an intermediate risk to a substantial number of patients and in addition suffers from a high interobserver variability. Therefore, the aim of our study was to identify a quantitative protein biomarker signature to facilitate risk classification. Reverse phase protein arrays (RPPA were used to obtain quantitative expression data for 128 breast cancer relevant proteins in a set of hormone receptor-positive tumors (n = 109. Proteomic data for the subset of histologic G1 (n = 14 and G3 (n = 22 samples were used for biomarker discovery serving as surrogates of low and high recurrence risk, respectively. A novel biomarker selection workflow based on combining three different classification methods identified caveolin-1, NDKA, RPS6, and Ki-67 as top candidates. NDKA, RPS6, and Ki-67 were expressed at elevated levels in high risk tumors whereas caveolin-1 was observed as downregulated. The identified biomarker signature was subsequently analyzed using an independent test set (AUC = 0.78. Further evaluation of the identified biomarker panel by Western blot and mRNA profiling confirmed the proteomic signature obtained by RPPA. In conclusion, the biomarker signature introduced supports RPPA as a tool for cancer biomarker discovery.

  15. Budget impact analysis of everolimus for the treatment of hormone receptor positive, human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer in the United States.

    Science.gov (United States)

    Xie, Jipan; Diener, Melissa; De, Gourab; Yang, Hongbo; Wu, Eric Q; Namjoshi, Madhav

    2013-01-01

    To estimate the budget impact of everolimus as the first and second treatment option after letrozole or anastrozole (L/A) failure for post-menopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (ABC). Pharmacy and medical budget impacts (2011 USD) were estimated over the first year of everolimus use in HR+, HER2- ABC from a US payer perspective. Epidemiology data were used to estimate target population size. Pre-everolimus entry treatment options included exemestane, fulvestrant, and tamoxifen. Pre- and post-everolimus entry market shares were estimated based on market research and assumptions. Drug costs were based on wholesale acquisition cost. Patients were assumed to be on treatment until progression or death. Annual medical costs were calculated as the average of pre- and post-progression medical costs weighted by the time in each period, adjusted for survival. One-way and two-way sensitivity analyses were conducted to assess the model robustness. In a hypothetical 1,000,000 member plan, 72 and 159 patients were expected to be candidates for everolimus treatment as first and second treatment option, respectively, after L/A failure. The total budget impact for the first year post-everolimus entry was $0.044 per member per month [PMPM] (pharmacy budget: $0.058 PMPM; medical budget: -$0.014 PMPM), assuming 10% of the target population would receive everolimus. The total budget impacts for the first and second treatment options after L/A failure were $0.014 PMPM (pharmacy budget: $0.018; medical budget: -$0.004) and $0.030 PMPM (pharmacy budget: $0.040; medical budget: -$0.010), respectively. Results remained robust in sensitivity analyses. Assumptions about some model input parameters were necessary and may impact results. Increased pharmacy costs for HR+, HER2- ABC following everolimus entry are expected to be partially offset by reduced medical service costs. Pharmacy and total

  16. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial.

    Science.gov (United States)

    Baselga, José; Im, Seock-Ah; Iwata, Hiroji; Cortés, Javier; De Laurentiis, Michele; Jiang, Zefei; Arteaga, Carlos L; Jonat, Walter; Clemons, Mark; Ito, Yoshinori; Awada, Ahmad; Chia, Stephen; Jagiełło-Gruszfeld, Agnieszka; Pistilli, Barbara; Tseng, Ling-Ming; Hurvitz, Sara; Masuda, Norikazu; Takahashi, Masato; Vuylsteke, Peter; Hachemi, Soulef; Dharan, Bharani; Di Tomaso, Emmanuelle; Urban, Patrick; Massacesi, Cristian; Campone, Mario

    2017-07-01

    Phosphatidylinositol 3-kinase (PI3K) pathway activation is a hallmark of endocrine therapy-resistant, hormone receptor-positive breast cancer. This phase 3 study assessed the efficacy of the pan-PI3K inhibitor buparlisib plus fulvestrant in patients with advanced breast cancer, including an evaluation of the PI3K pathway activation status as a biomarker for clinical benefit. The BELLE-2 trial was a randomised, double-blind, placebo-controlled, multicentre study. Postmenopausal women aged 18 years or older with histologically confirmed, hormone receptor-positive and human epidermal growth factor (HER2)-negative inoperable locally advanced or metastatic breast cancer whose disease had progressed on or after aromatase inhibitor treatment and had received up to one previous line of chemotherapy for advanced disease were included. Eligible patients were randomly assigned (1:1) using interactive voice response technology (block size of 6) on day 15 of cycle 1 to receive oral buparlisib (100 mg/day) or matching placebo, starting on day 15 of cycle 1, plus intramuscular fulvestrant (500 mg) on days 1 and 15 of cycle 1, and on day 1 of subsequent 28-day cycles. Patients were assigned randomisation numbers with a validated interactive response technology; these numbers were linked to different treatment groups which in turn were linked to treatment numbers. PI3K status in tumour tissue was determined via central laboratory during a 14-day run-in phase. Randomisation was stratified by PI3K pathway activation status (activated vs non-activated vs and unknown) and visceral disease status (present vs absent). Patients, investigators, local radiologists, study team, and anyone involved in the study were masked to the identity of the treatment until unblinding. The primary endpoints were progression-free survival by local investigator assessment per Response Evaluation Criteria In Solid Tumors (version 1.1) in the total population, in patients with known (activated or non

  17. PALBOCICLIB IN COMBINATION WITH HORMONE THERAPY FOR LUMINAL HER2-NEGATIVE METASTATIC BREAST CANCER: NEW HIGHLY EFFECTIVE STRATEGY OF DRUG TREATMENT

    Directory of Open Access Journals (Sweden)

    E. V. Artamonova

    2017-01-01

    Full Text Available The review considers a new oral targeted drug palbociclib and its place in treatment of luminal (estrogen receptor-positive HER2– metastatic breast cancer. The results of randomized clinical trials have shown that inclusion of palbociclib in various hormone therapy regimens for treatment of HER2– metastatic breast cancer with expression of estrogen receptors allows to significantly improve clinical outcomes and increase survival, objective response rate and its duration, as well as clinical benefit rate (CBR. Addition of palbociclib to letrozole in the 1st line hormone therapy or to fulvestrant in patients with progression at/after previous endocrine therapy increased progression-free survival in all groups irrespective of clinical characteristics, tumor progression, or expression of molecular markers mediating development of hormone resistance. The main adverse events associated with palbociclib were neutropenia, leukopenia and thrombocytopenia, but overall hematological toxicity was manageable, and the therapy itself was safe. This strategy received a “breakthrough therapy designation” from the experts and combines proven effectiveness and satisfactory tolerability, allows to maintain high quality of life, and should be prescribed to patients with luminal HER2– metastatic breast cancer.

  18. Estrogen and progesterone receptor expression levels do not differ between lobular and ductal carcinoma in patients with hormone receptor-positive tumors

    NARCIS (Netherlands)

    Truin, Wilfred; Roumen, Rudi M.H.; Siesling, Sabine; van de Vijver, Koen K.; Tjan-Heijnen, Vivianne C.G.; Voogd, Adri C.

    Background Differences in estrogen (ER) and progesterone (PR) expression between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) could be an underlying reason for the difference in chemo-sensitivity and response to hormonal therapy between ILC and IDC. The aim of this study was

  19. Acupuncture versus venlafaxine for the management of vasomotor symptoms in patients with hormone receptor-positive breast cancer: a randomized controlled trial.

    Science.gov (United States)

    Walker, Eleanor M; Rodriguez, Alba I; Kohn, Beth; Ball, Ronald M; Pegg, Jan; Pocock, Jeffrey R; Nunez, Ramon; Peterson, Ed; Jakary, Susan; Levine, Robert A

    2010-02-01

    Vasomotor symptoms are common adverse effects of antiestrogen hormone treatment in conventional breast cancer care. Hormone replacement therapy is contraindicated in patients with breast cancer. Venlafaxine (Effexor), the therapy of choice for these symptoms, has numerous adverse effects. Recent studies suggest acupuncture may be effective in reducing vasomotor symptoms in menopausal women. This randomized controlled trial tested whether acupuncture reduces vasomotor symptoms and produces fewer adverse effects than venlafaxine. Fifty patients were randomly assigned to receive 12 weeks of acupuncture (n = 25) or venlafaxine (n = 25) treatment. Health outcomes were measured for up to 1 year post-treatment. Both groups exhibited significant decreases in hot flashes, depressive symptoms, and other quality-of-life symptoms, including significant improvements in mental health from pre- to post-treatment. These changes were similar in both groups, indicating that acupuncture was as effective as venlafaxine. By 2 weeks post-treatment, the venlafaxine group experienced significant increases in hot flashes, whereas hot flashes in the acupuncture group remained at low levels. The venlafaxine group experienced 18 incidences of adverse effects (eg, nausea, dry mouth, dizziness, anxiety), whereas the acupuncture group experienced no negative adverse effects. Acupuncture had the additional benefit of increased sex drive in some women, and most reported an improvement in their energy, clarity of thought, and sense of well-being. Acupuncture appears to be equivalent to drug therapy in these patients. It is a safe, effective and durable treatment for vasomotor symptoms secondary to long-term antiestrogen hormone use in patients with breast cancer.

  20. Prognostic factors of early distant recurrence in hormone receptor-positive, postmenopausal breast cancer patients receiving adjuvant tamoxifen therapy: results of a retrospective analysis.

    Science.gov (United States)

    Debled, Marc; MacGrogan, Gaëtan; Brouste, Véronique; Mathoulin-Pelissier, Simone; Durand, Michel; Mauriac, Louis

    2007-06-01

    Current adjuvant hormone therapy in postmenopausal women with breast cancer is debatable between upfront aromatase inhibitors (AIs) and sequential treatment with tamoxifen. A major concern is the higher rate of early recurrences observed with sequential treatment. The authors conducted a retrospective analysis to identify risk factors of early recurrences in hormone receptor (HR)-positive, postmenopausal women within the first 3 years of adjuvant tamoxifen. Between 1986 and 2000, operable breast cancer patients who received exclusively adjuvant tamoxifen for at least 3 years were selected from the authors' institutional database. Age, histology, pathologic tumor size, modified Scarff-Bloom-Richardson (mSBR) grade, mitotic index, tumor necrosis, peritumoral vascular emboli (PVE), HR status, and the number of involved axillary lymph-node were considered as prognostic factors of recurrence. Among 715 patients who met the inclusion criteria, a distant recurrence occurred in 38 patients (5.3%) within the first 3 years of tamoxifen therapy. Significant prognostic factors of early recurrence were mSBR, axillary lymph node involvement, tumor necrosis, mitotic index, PVE, and pathologic tumor size. Grade 1 and/or lymph node-negative tumors were excluded from the multivariate analysis (1 recurrence in 208 patients). In this model, mSBR grade 3 was the only significant predictive factor of early recurrence (hazard ratio, 3.72; P<.001). In this study, a subset of patients was identified that was at low-risk of early recurrence (mSBR grade 1 and/or negative lymph node status). Women in that subset could be treated using sequential hormone therapy with tamoxifen and AIs. In women with mSBR grade 3 or lymph node-positive tumors, an upfront treatment with AIs seemed to be the current optimal strategy. (c) 2007 American Cancer Society.

  1. CYP19 Genetic Polymorphism Haplotype AASA Is Associated with a Poor Prognosis in Premenopausal Women with Lymph Node-Negative, Hormone Receptor-Positive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sung-Hsin Kuo

    2013-01-01

    Full Text Available Given the critical role of CYP19 in estrogen synthesis, we investigated the influence of CYP19 gene polymorphisms on the clinical outcome of lymph node- (LN- negative, hormone receptor- (HR- positive early breast cancers. Genotyping for the CYP19 polymorphisms rs4646 (A/C, rs1065779 (A/C, CYP19 (TTTAn (short allele/long (S/L allele using the 7 TTTA repeat polymorphism as the cut-off, and rs1870050 (A/C was performed on 296 patients with LN-negative, HR-positive breast cancers. All patients received adjuvant hormonal therapy. Associations were examined between these 4 genotypes and 6 common haplotypes of CYP19 and distant disease-free survival (DDFS, disease-free survival (DFS, and overall survival (OS. Patients were divided into the 6 subhaplotypes of CCLA (41.1%, AASA (17.1%, CASA (11.9%, CCLC (8.9%, CCSA (7.5%, AASC (8.9%, and others (4.6%. In premenopausal patients, haplotype AASA was significantly associated with a poor DDFS (adjusted hazard ratio (aHR, 3.3; P=0.001, DFS (aHR, 2.5; P=0.0008, and OS (aHR, 2.9; P=0.0004 after adjusting for age, tumor size, tumor grade, estrogen receptor status, progesterone receptor status, chemotherapy, pathology, adjuvant hormone therapy, menopausal status, and radiotherapy. Furthermore, haplotype AASA remained a negative prognostic factor for premenopausal patients receiving adjuvant chemotherapy in terms of DDFS (aHR, 4.5; P=0.0005, DFS (HR, 3.2; P=0.003, and OS (HR, 6.4; P=0.0009. However, in postmenopausal patients, haplotype AASA was not associated with a poor prognosis, whereas the AASC haplotype was significantly associated with a poor DFS (aHR, 3.1; P=0.03 and OS (aHR, 4.4; P=0.01. Our results indicate that, in patients with LN-negative, HR-positive breast cancers, genetic polymorphism haplotype AASA is associated with poor survival of premenopausal women but does not affect survival of postmenopausal women.

  2. Circulating oxysterol metabolites as potential new surrogate markers in patients with hormone receptor-positive breast cancer: Results of the OXYTAM study.

    Science.gov (United States)

    Dalenc, Florence; Iuliano, Luiggi; Filleron, Thomas; Zerbinati, Chiara; Voisin, Maud; Arellano, Cécile; Chatelut, Etienne; Marquet, Pierre; Samadi, Mohammad; Roché, Henri; Poirot, Marc; Silvente-Poirot, Sandrine

    2017-05-01

    Accumulating evidence indicates that cholesterol oxygenation products, also known as oxysterols (OS), are involved in breast cancer (BC) promotion. The impact of Tam, as well as aromatase inhibitors (AI), an alternative BC endocrine therapy (ET), on OS metabolism in patients is currently unknown. We conducted a prospective clinical study in BC patients receiving Tam (n=15) or AI (n=14) in adjuvant or in metastatic settings. The primary end point was the feasibility of detecting and quantifying 11 different OS in the circulation of patients before and after 28days of treatment with Tam or AI. Key secondary end points were the measurements of variations in the concentrations of OS according to differences between patients and treatments. OS profiling in the serum of patients was determined by gas chromatography coupled to mass spectrometry. OS profiling was conducted in all patients both at baseline and during treatment regimens. An important inter-individual variability was observed for each OS. Interestingly 5,6β-epoxycholesterol relative concentrations significantly increased in the entire population (p=0.0109), while no increase in Cholestane-triol (CT) levels was measured. Interestingly, we found that, in contrast to AI, Tam therapy significantly decreased blood levels of 24-hydroxycholesterol (24-HC), 7α-HC and 25-HC (a tumor promoter) (p=0.0007, p=0.0231 and p=0.0231, respectively), whereas 4β-HC levels increased (p=0.0010). Interestingly, levels of 27-HC (a tumor promoter) significantly increased in response to AI (p=0.0342), but not Tam treatment. According to these results, specific OS are promising candidate markers of Tam and AI efficacy. Thus, further clinical investigations are needed to confirm the use of oxysterols as biomarkers of both prognosis and/or the efficacy of ET. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Prognostic factors for survival in metastatic breast cancer by hormone receptor status

    NARCIS (Netherlands)

    Kwast, A.B.G.; Voogd, A.C.; Menke-Pluijmers, M.B.E.; Linn, S.C.; Sonke, G.S.; Kiemeney, L.A.; Siesling, Sabine

    2014-01-01

    Hormone receptor (HR) status is an important prognostic factor for patients with metastatic breast cancer (MBC) and is also correlated with other prognostic factors, such as initial lymph node status, HER2-Neu status and age. The prognostic value of these other factors, however, is unknown when

  4. Overcoming Endocrine Resistance in Hormone-Receptor Positive Advanced Breast Cancer-The Emerging Role of CDK4/6 Inhibitors.

    Science.gov (United States)

    O'Sullivan, Ciara C

    Dysregulation of the cyclin D and cyclin-dependent kinase (CDK) pathway in cancer cells may inhibit senescence and promote cellular proliferation. By using various different mechanisms, malignant cells may increase cyclin D-dependent activity. The cyclin D-cyclin-dependent kinases 4 and 6 (CDK4/6)-retinoblastoma (Rb) pathway controls the cell cycle restriction point, and is commonly dysregulated in breast cancer; making it a rational target for anticancer therapy. To date, three oral highly selective cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are in various stages of clinical development: PD0332991 (palbociclib), LEE011 (ribociclib) and LY2835219 (abemaciclib). Results from phase I, II and III trials in hormone-receptor (HR)-positive breast cancer have been encouraging, demonstrating convincing efficacy and a tolerable side-effect profile (mainly uncomplicated neutropenia). This article will review the preclinical and clinical development of the CDK4/6i, as well as reviewing the existing preclinical evidence regarding combination of these agents with chemotherapy and other targeted therapies. Future and ongoing clinical trials, which may expand the potential application of these agents, will also be discussed. In summary, CDK4/6i are exciting compounds which may change the therapeutic landscape of HR-positive breast cancer.

  5. Comparative Efficacy and Safety of Adjuvant Letrozole Versus Anastrozole in Postmenopausal Patients With Hormone Receptor-Positive, Node-Positive Early Breast Cancer

    DEFF Research Database (Denmark)

    Smith, Ian; Yardley, Denise; Burris, Howard

    2017-01-01

    Purpose The Letrozole (Femara) Versus Anastrozole Clinical Evaluation (FACE) study compared the efficacy and safety of adjuvant letrozole versus anastrozole in postmenopausal patients with hormone receptor (HR) -positive and node-positive early breast cancer (eBC). Methods Postmenopausal women...... receptor 2 status. The primary end point was 5-year disease-free survival (DFS), and the key secondary end points were overall survival and safety. Results A total of 4,136 patients were randomly assigned to receive either letrozole (n = 2,061) or anastrozole (n = 2,075). The final analysis was done at 709.......9% for all adverse events), hypertension (1.2% v 1.0%), hot flushes (0.8% v 0.4%), myalgia (0.8% v 0.7%), dyspnea (0.8% v 0.5%), and depression (0.8% v 0.6%). Conclusion Letrozole did not demonstrate significantly superior efficacy or safety compared with anastrozole in postmenopausal patients with HR...

  6. Use of Geriatric Assessment Tools in Selecting Therapies in Women Aged ≥70 Years With Hormone Receptor-Positive Early-Stage Breast Cancer: Preliminary Experience With a Quality Improvement Initiative.

    Science.gov (United States)

    Wright, Jean L; Parekh, Arti; Pollock, Yao Yao; Schoenborn, Nancy; Smith, Karen L; Magnant, Colette; Stearns, Vered

    2017-07-15

    To develop a multidisciplinary algorithmic approach to management of women aged ≥70 years with clinically staged T1N0 hormone receptor-positive breast cancer, including geriatric assessments predicting life expectancy and the likelihood of functional decline in the near future, in the context of a program-wide quality improvement initiative, to better select patients for therapeutic interventions. Two geriatric assessment tools, the Combined Lee-Schonberg Index and the Vulnerable Elderly Scale, were introduced into our clinical workflow to predict long-term mortality and likelihood of functional decline. Scores from these tools, along with patient preferences and clinical features, were incorporated into a preoperative algorithm addressing the use of sentinel lymph node biopsy (SLNB), and a postoperative algorithm addressing the use of adjuvant radiation therapy (RT). The algorithms were approved for use in August 2015. Twenty-four patients were identified by in-clinic screening and have been managed using the algorithms as a guide. Mean patient age was 80 years (range, 71-89 years). Per the preoperative algorithm, consideration of omission of SLNB was an option in 11 of 24 patients (46%), and in total 18 of 24 (75%) opted against SLNB. Per the postsurgical algorithm, consideration of omission of adjuvant RT was an option for 19 of 24 patients (79%), and in total 17 of 24 (71%) opted to forego RT. Incorporation of simple geriatric assessments seems to have had a marked impact on decision making regarding both surgical and adjuvant therapies for women aged ≥70 years with early-stage hormone-positive breast cancer compared with historical patterns, with ≥71% omission of both SLNB and adjuvant RT in patients managed according to an institutional quality improvement initiative. Copyright © 2017. Published by Elsevier Inc.

  7. Continuation of bevacizumab and addition of hormone therapy following weekly paclitaxel therapy in HER2-negative metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Redondo A

    2014-11-01

    Full Text Available Andrés Redondo,1,* Virginia Martínez,1,* Pilar Zamora,1 Beatriz Castelo,1 Alvaro Pinto,1 Patricia Cruz,1 Oliver Higuera,1 Marta Mendiola,2 David Hardisson,3 Enrique Espinosa11Medical Oncology Department, 2Translational Oncology and Molecular Pathology Laboratory, 3Pathology Department, University Hospital La Paz (IdiPAZ, Madrid, Spain*These authors contributed equally to this workBackground: Bevacizumab plus taxane chemotherapy improves progression-free survival (PFS versus taxane monotherapy in the first-line treatment of HER2-negative metastatic breast cancer (MBC and appears promising in the second-line setting. This retrospective analysis evaluated the efficacy and safety of this combination in a real-world setting.Patients and methods: Eligible patients received bevacizumab (10 mg/kg days 1 and 15, every 28 days plus paclitaxel (80 mg/m2 days 1, 8, and 15, every 28 days as first-line therapy for MBC, or as subsequent lines, including bevacizumab continuation therapy, at La Paz University Hospital between August 2007 and October 2012. End points included objective response rate (ORR, PFS, overall survival (OS, and safety.Results: Seventy-eight patients were included. Median PFS was 12.8 months for patients receiving first-line treatment and 9.3 months for subsequent lines. Forty-five patients (57.7% continued bevacizumab after stopping paclitaxel, and had significantly longer PFS and OS than those who did not (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.248–0.653, P<0.001; HR 0.39, 95% CI 0.218–0.710, P=0.002; respectively. In the continuation phase, estrogen receptor-positive patients had longer PFS and OS when receiving hormone therapy plus bevacizumab versus patients receiving only bevacizumab (HR 0.50, 95% CI 0.24–1.04, P=0.06; HR 0.43, 95% CI 0.16–1.16, P=0.09; respectively. Thirty-five patients (44.9% reported grade 3–4 adverse events.Conclusion: Bevacizumab plus paclitaxel was effective in HER2-negative MBC

  8. Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT.

    Science.gov (United States)

    Chia, Stephen; Gradishar, William; Mauriac, Louis; Bines, Jose; Amant, Frederic; Federico, Miriam; Fein, Luis; Romieu, Gilles; Buzdar, Aman; Robertson, John F R; Brufsky, Adam; Possinger, Kurt; Rennie, Pamela; Sapunar, Francisco; Lowe, Elizabeth; Piccart, Martine

    2008-04-01

    The third-generation nonsteroidal aromatase inhibitors (AIs) are increasingly used as adjuvant and first-line advanced therapy for postmenopausal, hormone receptor-positive (HR+) breast cancer. Because many patients subsequently experience progression or relapse, it is important to identify agents with efficacy after AI failure. Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) is a randomized, double-blind, placebo controlled, multicenter phase III trial of fulvestrant versus exemestane in postmenopausal women with HR+ advanced breast cancer (ABC) progressing or recurring after nonsteroidal AI. The primary end point was time to progression (TTP). A fulvestrant loading-dose (LD) regimen was used: 500 mg intramuscularly on day 0, 250 mg on days 14, 28, and 250 mg every 28 days thereafter. Exemestane 25 mg orally was administered once daily. A total of 693 women were randomly assigned to fulvestrant (n = 351) or exemestane (n = 342). Approximately 60% of patients had received at least two prior endocrine therapies. Median TTP was 3.7 months in both groups (hazard ratio = 0.963; 95% CI, 0.819 to 1.133; P = .6531). The overall response rate (7.4% v 6.7%; P = .736) and clinical benefit rate (32.2% v 31.5%; P = .853) were similar between fulvestrant and exemestane respectively. Median duration of clinical benefit was 9.3 and 8.3 months, respectively. Both treatments were well tolerated, with no significant differences in the incidence of adverse events or quality of life. Pharmacokinetic data confirm that steady-state was reached within 1 month with the LD schedule of fulvestrant. Fulvestrant LD and exemestane are equally active and well-tolerated in a meaningful proportion of postmenopausal women with ABC who have experienced progression or recurrence during treatment with a nonsteroidal AI.

  9. The prognostic and predictive value of Tregs and tumor immune subtypes in postmenopausal, hormone receptor-positive breast cancer patients treated with adjuvant endocrine therapy: a Dutch TEAM study analysis.

    Science.gov (United States)

    Engels, C C; Charehbili, A; van de Velde, C J H; Bastiaannet, E; Sajet, A; Putter, H; van Vliet, E A; van Vlierberghe, R L P; Smit, V T H B M; Bartlett, J M S; Seynaeve, C; Liefers, G J; Kuppen, P J K

    2015-02-01

    Evidence exists for an immunomodulatory effect of endocrine therapy in hormone receptor-positive (HR+ve) breast cancer (BC). Therefore, the aim of this study was to define the prognostic and predictive value of tumor immune markers and the tumor immune profile in HR+ve BC, treated with different endocrine treatment regimens. 2,596 Dutch TEAM patients were treated with 5 years of adjuvant hormonal treatment, randomly assigned to different regimens: 5 years of exemestane or sequential treatment (2.5 years of tamoxifen-2.5 years of exemestane). Immunohistochemistry was performed for HLA class I, HLA-E, HLA-G, and FoxP3. Tumor immune subtypes (IS) (low, intermediate & high immune susceptible) were determined by the effect size of mono-immune markers on relapse rate. Patients on sequential treatment with high level of tumor-infiltrating FoxP3+ cells had significant (p = 0.019, HR 0.729, 95% CI 0.560-0.949) better OS. Significant interaction for endocrine treatment and FoxP3+ presence was seen (OS p Tumor IS were only of prognostic value for the sequentially endocrine-treated patients (RFP: p = 0.035, HR intermediate IS 1.420, 95% CI 0.878-2.297; HR low IS 1.657, 95% CI 1.131-2.428; BCSS: p = 0.002, HR intermediate IS 2.486, 95% CI 1.375-4.495; HR low IS 2.422, 95% CI 1.439-4.076; and OS: p = 0.005, HR intermediate IS 1.509, 95% CI 0.950-2.395; HR low IS 1.848, 95% CI 1.277-2.675). Tregs and the tumor IS presented in this study harbor prognostic value for sequentially endocrine-treated HR+ve postmenopausal BC patients, but not for solely exemestane-treated patients. Therefore, these markers could be used as a clinical risk stratification tool to guide adjuvant treatment in this BC population.

  10. Cost-Effectiveness of Lapatinib plus Letrozole in Post-Menopausal Women with Hormone Receptor-and HER2-Positive Metastatic Breast Cancer.

    Science.gov (United States)

    Delea, Thomas E; Hawkes, Carol; Amonkar, Mayur M; Lykopoulos, Konstantinos; Johnston, Stephen R D

    2013-12-01

    In the EGF30008 and TAnDEM (TrAstuzumab in Dual HER2 ER-positive Metastatic breast cancer) trials, anti-HER2 therapy plus an aromatase inhibitor (lapatinib + letrozole (LAP + LET) and trastuzumb + anastrozole (TZ + ANA), respectively) improved time to progression versus aromatase inhibitor monotherapy (LET and ANA, respectively) in post-menopausal women with previously untreated hormone receptor-positive (HR+) and HER2-positive (HER2+) metastatic breast cancer. A partitionedsurvival analysis model using data from EGF30008 and published results of TAnDEM and other literature was used to evaluate the incremental direct medical cost per quality-adjusted life year (QALY) gained with LAP + LET versus LET, ANA, and TZ + ANA in post-menopausal women with previously untreated HR+ and HER2+ metastatic breast cancer from the UK National Health Service (NHS) perspective. Incremental costs for LAP + LET are £ 34,737 versus LET, £ 35,995 versus ANA, and £ 5,513 versus TZ + ANA. Corresponding QALYs gained are 0.467, 0.601, and 0.252 years. Cost/QALY gained with LAP + LET is £ 74,448 versus LET, £ 59,895 versus ANA, and £ 21,836 versus TZ + ANA. Given a threshold of £ 30,000/QALY, the estimated probability that LAP + LET is cost-effective is 1.4% versus LET, 9.2% versus ANA, and 51% versus TZ + ANA. Based on criteria for the evaluation of health technologies in the UK (£ 30,000/QALY), LAP + LET is not likely to be cost-effective versus aromatase inhibitor monotherapy but may be cost-effective versus TZ + ANA, although the latter comparison is associated with substantial uncertainty.

  11. Cabazitaxel: a guide to its use in hormone-refractory metastatic prostate cancer.

    Science.gov (United States)

    Keating, Gillian M

    2013-05-01

    The taxane derivative cabazitaxel (Jevtana(®)) is approved in the USA and the EU for use in combination with prednisone for the treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen. In the pivotal TROPIC trial, overall survival was significantly prolonged with cabazitaxel plus prednisone versus mitoxantrone plus prednisone in patients with metastatic castration-resistant prostate cancer who had progressed during or after docetaxel therapy. In addition, progression-free survival, the times to tumour progression and prostate specific antigen (PSA) progression, and tumour and PSA response rates were improved with cabazitaxel plus prednisone. Intravenous cabazitaxel had an acceptable tolerability profile, with haematological adverse events occurring most commonly, and diarrhoea being the most common nonhaematological adverse event.

  12. Clinical and genomic analysis of a randomised phase II study evaluating anastrozole and fulvestrant in postmenopausal patients treated for large operable or locally advanced hormone-receptor-positive breast cancer.

    Science.gov (United States)

    Quenel-Tueux, Nathalie; Debled, Marc; Rudewicz, Justine; MacGrogan, Gaetan; Pulido, Marina; Mauriac, Louis; Dalenc, Florence; Bachelot, Thomas; Lortal, Barbara; Breton-Callu, Christelle; Madranges, Nicolas; de Lara, Christine Tunon; Fournier, Marion; Bonnefoi, Hervé; Soueidan, Hayssam; Nikolski, Macha; Gros, Audrey; Daly, Catherine; Wood, Henry; Rabbitts, Pamela; Iggo, Richard

    2015-08-11

    The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment. One hundred and twenty post-menopausal patients were randomised to receive 1 mg anastrozole (61 patients) or 500 mg fulvestrant (59 patients) for 6 months. Genomic DNA copy number profiles were generated for a subgroup of 20 patients before and after treatment. A total of 108 patients were evaluable for efficacy and 118 for toxicity. The objective response rate determined by clinical palpation was 58.9% (95% CI=45.0-71.9) in the anastrozole arm and 53.8% (95% CI=39.5-67.8) in the fulvestrant arm. The breast-conserving surgery rate was 58.9% (95% CI=45.0-71.9) in the anastrozole arm and 50.0% (95% CI=35.8-64.2) in the fulvestrant arm. Pathological responses >50% occurred in 24 patients (42.9%) in the anastrozole arm and 13 (25.0%) in the fulvestrant arm. The Ki-67 score fell after treatment but there was no significant difference between the reduction in the two arms (anastrozole 16.7% (95% CI=13.3-21.0) before, 3.2% (95% CI=1.9-5.5) after, n=43; fulvestrant 17.1% (95%CI=13.1-22.5) before, 3.2% (95% CI=1.8-5.7) after, n=38) or between the reduction in Ki-67 in clinical responders and non-responders. Genomic analysis appeared to show a reduction of clonal diversity following treatment with selection of some clones with simpler copy number profiles. Both anastrozole and fulvestrant were effective and well-tolerated, enabling breast-conserving surgery in over 50% of patients. Clonal changes consistent with clonal selection by the treatment were seen in a subgroup of patients.

  13. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up.

    Science.gov (United States)

    Regan, Meredith M; Neven, Patrick; Giobbie-Hurder, Anita; Goldhirsch, Aron; Ejlertsen, Bent; Mauriac, Louis; Forbes, John F; Smith, Ian; Láng, István; Wardley, Andrew; Rabaglio, Manuela; Price, Karen N; Gelber, Richard D; Coates, Alan S; Thürlimann, Beat

    2011-11-01

    Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast-cancer recurrence and death. Therefore, trials assessing endocrine therapies for this patient population need extended follow-up. We present an update of efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8·1 years median follow-up. BIG 1-98 is a randomised, phase 3, double-blind trial of postmenopausal women with hormone receptor-positive early breast cancer that compares 5 years of tamoxifen or letrozole monotherapy, or sequential treatment with 2 years of one of these drugs followed by 3 years of the other. Randomisation was done with permuted blocks, and stratified according to the two-arm or four-arm randomisation option, participating institution, and chemotherapy use. Patients, investigators, data managers, and medical reviewers were masked. The primary efficacy endpoint was disease-free survival (events were invasive breast cancer relapse, second primaries [contralateral breast and non-breast], or death without previous cancer event). Secondary endpoints were overall survival, distant recurrence-free interval (DRFI), and breast cancer-free interval (BCFI). The monotherapy comparison included patients randomly assigned to tamoxifen or letrozole for 5 years. In 2005, after a significant disease-free survival benefit was reported for letrozole as compared with tamoxifen, a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting (IPCW) are used to account for selective crossover to letrozole of patients (n=619) in the tamoxifen arm. Comparison of sequential treatments to letrozole monotherapy included patients enrolled and randomly assigned to letrozole for 5 years, letrozole for 2 years followed by tamoxifen for 3 years, or tamoxifen for 2 years followed by letrozole for 3 years

  14. Evaluating Letrozole and Tamoxifen Alone and in Sequence for Postmenopausal Women with Steroid Hormone Receptor-Positive Breast Cancer: the BIG 1-98 Randomized Clinical Trial at 8.1 years Median Follow-Up

    Science.gov (United States)

    Regan, Meredith M.; Neven, Patrick; Giobbie-Hurder, Anita; Goldhirsch, Aron; Ejlertsen, Bent; Mauriac, Louis; Forbes, John F.; Smith, Ian; Láng, István; Wardley, Andrew; Rabaglio, Manuela; Price, Karen N.; Gelber, Richard D.; Coates, Alan S.; Thürlimann, Beat

    2011-01-01

    Background Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast cancer recurrence and death. Therefore, trials evaluating endocrine therapies for this patient population require extended follow-up. We present an update of efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8.1 years median follow-up. Methods BIG 1-98 is a randomized, phase III, double-blind trial of 8010 postmenopausal women with hormone receptor-positive early breast cancer that compares five years of tamoxifen or letrozole monotherapy or sequential treatment with two years of one of these agents followed by three years of the other. The primary efficacy endpoint is disease-free survival (DFS: events comprise invasive breast cancer relapse, second primaries [contralateral breast and non-breast], or death without prior cancer event), and secondary endpoints are overall survival (OS), distant recurrence-free interval (DRFI) and breast cancer-free interval (BCFI). The monotherapy comparison includes patients randomized to tamoxifen × 5 years (n=2459) or letrozole × 5 years (n=2463). In 2005, after significant DFS benefit was reported for letrozole as compared with tamoxifen, a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting (IPCW) are used to account for selective crossover to letrozole of 619 patients in the tamoxifen arm. The comparison of sequential treatments to letrozole monotherapy includes patients enrolled in the four-arm option of the trial and randomized to letrozole × 5 years (n=1546), letrozole × 2 years followed by tamoxifen × 3 years (n=1540), or tamoxifen × 2 years followed by letrozole × 3 years (n=1548). All patients have completed study treatment; follow up is continuing for those enrolled in the four-arm option. BIG 1-98 is registered at

  15. Metastatic Follicular Thyroid Carcinoma Secreting Thyroid Hormone and Radioiodine Avid without Stimulation: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Syed A. Abid

    2014-01-01

    Full Text Available Introduction. This is an extremely rare case of a patient with metastatic follicular thyroid cancer who continued to produce thyroid hormone and was iodine scan positive without stimulation after thyroidectomy and radioiodine (I-131 therapy. Patient Findings. A 76-year-old Caucasian male was diagnosed with metastatic follicular thyroid carcinoma on lung nodule biopsy. Total thyroidectomy was performed and he was ablated with 160 mCi of I-131 after recombinant human thyrotropin (rhTSH stimulation. Whole body scan (WBS after treatment showed uptake in bilateral lungs, right sacrum, and pelvis. The thyroglobulin decreased from 2,063 to 965 four months after treatment but rapidly increased to 2,506 eleven months after I-131. Thyroid stimulating hormone (TSH remained suppressed and free T4 remained elevated after I-131 therapy without thyroid hormone supplementation. He was treated with an additional 209 mCi with WBS findings positive in lung and pelvis. Despite I-131, new metastatic lesions were noted in the left thyroid bed and large destructive lesion to the first cervical vertebrae four months after the second I-131 dose. Conclusions. This case is exceptional because of its rarity and also due to the dissociation between tumor differentiation and aggressiveness. The metastatic lesions continued to secrete thyroid hormone and remained radioiodine avid with rapid progression after I-131 therapy.

  16. Impact of palbociclib combinations on treatment of advanced estrogen receptor-positive/human epidermal growth factor 2-negative breast cancer.

    Science.gov (United States)

    Boér, Katalin

    2016-01-01

    Breast cancer is a heterogeneous disease with multiple subgroups based on clinical and molecular characteristics. For the largest subgroup of breast cancers, hormone receptor-positive/human epidermal growth factor 2 (HER2)-negative tumors, hormone treatment is the mainstay of therapy and is likely to result in significant improvement in disease outcomes. However, some of these cancers demonstrate de novo or acquired resistance to endocrine therapy. Despite intensive research to develop new strategies to enhance the efficacy of currently available treatment options for hormone receptor-positive breast cancer, progress has been slow, and there were few advances for a period of 10 years. In 2012, a new molecularly targeted therapeutic strategy, inhibition of mammalian target of rapamycin with everolimus, was introduced into clinical practice. Everolimus, in combination with a steroidal aromatase inhibitor, exemestane, resulted in an increase in progression-free survival, but not overall survival in patients with estrogen receptor (ER)+ve advanced disease who had progressed on hormone therapy. In 2015, the first cyclin-dependent kinases 4/6 (CDK4/6) inhibitor, palbociclib, received accelerated US Food and Drug Administration approval for use in combination with letrozole for the treatment of postmenopausal ER+ve/HER2-ve advanced breast cancer as initial, endocrine-based therapy. The addition of palbociclib to endocrine therapy resulted in longer progression-free survival than letrozole alone. One year later, palbociclib received a new indication, use in combination with fulvestrant, in both premenopausal and postmenopausal females with advanced breast cancer of the same subtype with disease progression following endocrine therapy. Adding palbociclib to fulvestrant resulted in a significantly increased median progression-free survival compared to fulvestrant monotherapy. These new combination regimens of palbociclib with endocrine agents represent an important addition

  17. Bone Scan Index predicts outcome in patients with metastatic hormone-sensitive prostate cancer.

    Science.gov (United States)

    Poulsen, Mads H; Rasmussen, Janne; Edenbrandt, Lars; Høilund-Carlsen, Poul F; Gerke, Oke; Johansen, Allan; Lund, Lars

    2016-05-01

    To evaluate the Bone Scan Index (BSI) for prediction of castration resistance and prostate cancer-specific survival (PCSS). In this retrospective study, we used novel computer-assisted software for automated detection/quantification of bone metastases by BSI. Patients with prostate cancer are M-staged by whole-body bone scintigraphy (WBS) and categorised as M0 or M1. Within the M1 group, there is a wide range of clinical outcomes. The BSI was introduced a decade ago providing quantification of bone metastases by estimating the percentage of bone involvement. Being too time consuming, it never gained widespread clinical use. In all, 88 patients with prostate cancer awaiting initiation of androgen-deprivation therapy due to metastases were included. WBS was performed using a two-headed γ-camera. BSI was obtained using the automated platform EXINI bone (EXINI Diagnostics AB, Lund, Sweden). In Cox proportional hazard models, time to castration-resistant prostate cancer (CRPC) and PCSS were modelled as the dependent variables, whereas prostate-specific antigen (PSA) level, Gleason score and BSI were used as explanatory factors. For Kaplan-Meier estimates, BSI groups were dichotomously split into: BSI Gleason score was 7.7 (2-10), and the mean (range) BSI was 1.0 (0-9.2). During a mean (range) follow-up of 26 (8-49) months, 48 patients became castration resistant and 15 had died; most (13) from prostate cancer. In multivariate analysis including PSA level, Gleason score and BSI, only prediction by BSI was statistically significant. This was true both for time to CRPC (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.22-1.74; C-index increase from 0.49 to 0.69) and for PCSS (HR 1.34, 95% CI 1.07-1.67; C-index increase from 0.76 to 0.95). BSI obtained using a novel automated computer-assisted algorithm appears to be a useful predictor of outcome for time to CRPC and PCSS in patients with hormone-sensitive metastatic prostate cancer. © 2015 The Authors BJU

  18. Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

    DEFF Research Database (Denmark)

    Sustarsic, Elahu G; Junnila, Riia K; Kopchick, John J.

    2013-01-01

    Cancer Institute's NCI60 panel includes 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real......Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National......-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human...

  19. Treatment of Hormone Resistance with Docetaxel in Metastatic Prostate Cancer Patients: Results of a Clinical Experience at Omid Hospital, Isfahan, Iran

    Directory of Open Access Journals (Sweden)

    Mina Tajvidi

    2017-01-01

    Full Text Available Background: Metastatic prostate cancer is one of the most important cancers among men worldwide. Androgen ablation therapy can be used in treatment of these patients; however, most will progress to metastatic hormone-refractory prostate cancer. In this regard, docetaxel has been approved to treat metastatic hormone-refractory prostate cancer in the United States. In this study, we aimed to investigate the results of this treatment modality in metastatic prostate cancer patients from Iran. Methods:We evaluated PSA response and bone pain relief in 18 metastatic prostate cancer patients who underwent treatment with docetaxel at a dose of 75 mg/m2 intravenously on the first day of treatment. The treatment was repeated every three weeks (6 cycles along with 10 mg of prednisolone. Results: Of 18 patients, 39% had >50% decline in PSA levels.There were 16% of the patients with a PSA decline of approximately 30% to 50% of the pre-treatment levels. In addition, 29% of the patients had progressive PSA levels during chemotherapy. Among them, 55% had significant pain relief. Conclusion: This research showed the effectiveness of docetaxel to decrease PSA levels in metastatic hormone-refractory prostate cancer patients from Iran. Docetaxel was also valuable in alleviation of pain in these patients. However, prospective studies should validate this approach.

  20. Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

    Energy Technology Data Exchange (ETDEWEB)

    Sustarsic, Elahu G. [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States); Department of Biological Sciences, Ohio University, Athens, OH (United States); Junnila, Riia K. [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States); Kopchick, John J., E-mail: kopchick@ohio.edu [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States); Department of Biological Sciences, Ohio University, Athens, OH (United States); Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH (United States)

    2013-11-08

    Highlights: •Most cancer types of the NCI60 have sub-sets of cell lines with high GHR expression. •GHR is highly expressed in melanoma cell lines. •GHR is elevated in advanced stage IV metastatic tumors vs. stage III. •GH treatment of metastatic melanoma cell lines alters growth and cell signaling. -- Abstract: Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National Cancer Institute’s NCI60 panel includes 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human biopsies, the level of GHR mRNA is elevated in advanced stage IV tumor samples compared to stage III. Due to the novel finding of high GHR in melanoma, we examined the effect of GH treatment on three NCI60 melanoma lines (MDA-MB-435, UACC-62 and SK-MEL-5). GH increased proliferation in two out of three cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found that human metastatic melanoma tumors express GHR and cell lines possess active GHRs that can modulate multiple signaling pathways and alter cell proliferation. Based on

  1. Changes of biochemical markers of bone turnover and YKL-40 following hormonal treatment for metastatic prostate cancer are related to survival

    DEFF Research Database (Denmark)

    Johansen, Julia S; Brasso, Klaus; Iversen, Peter

    2007-01-01

    Elevated serum levels of biochemical markers of bone turnover and YKL-40 in patients with metastatic prostate cancer (PC) at the time of diagnosis are associated to poor prognosis. In this study, we evaluated the value of these biomarkers in monitoring the patients during hormonal treatment....

  2. A Phase II Study Evaluating the Role of Androgen Receptors as Targets for Therapy of Pre-treated Post-menopausal Patients With ER/PgR-negative/AR-positive or ER and/or PgRpositive/ AR-positive Metastatic Breast Cancer (ARTT)

    Science.gov (United States)

    2016-09-28

    Metastatic Breastcancer; Estrogen Receptor Positive Breast Cancer; Estrogen Receptor Negative Neoplasm; Progesterone Receptor Positive Tumor; Progesterone Receptor Negative Neoplasm; Androgen Receptor Gene Overexpression

  3. Impact of palbociclib combinations on treatment of advanced estrogen receptor-positive/human epidermal growth factor 2-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Boér K

    2016-10-01

    Full Text Available Katalin Boér Department of Medical Oncology, Szent Margit Hospital, Budapest, Hungary Abstract: Breast cancer is a heterogeneous disease with multiple subgroups based on clinical and molecular characteristics. For the largest subgroup of breast cancers, hormone receptor-positive/human epidermal growth factor 2 (HER2-negative tumors, hormone treatment is the mainstay of therapy and is likely to result in significant improvement in disease outcomes. However, some of these cancers demonstrate de novo or acquired resistance to endocrine therapy. Despite intensive research to develop new strategies to enhance the efficacy of currently available treatment options for hormone receptor-positive breast cancer, progress has been slow, and there were few advances for a period of 10 years. In 2012, a new molecularly targeted therapeutic strategy, inhibition of mammalian target of rapamycin with everolimus, was introduced into clinical practice. Everolimus, in combination with a steroidal aromatase inhibitor, exemestane, resulted in an increase in progression-free survival, but not overall survival in patients with estrogen receptor (ER+ve advanced disease who had progressed on hormone therapy. In 2015, the first cyclin-dependent kinases 4/6 (CDK4/6 inhibitor, palbociclib, received accelerated US Food and Drug Administration approval for use in combination with letrozole for the treatment of postmenopausal ER+ve/HER2-ve advanced breast cancer as initial, endocrine-based therapy. The addition of palbociclib to endocrine therapy resulted in longer progression-free survival than letrozole alone. One year later, palbociclib received a new indication, use in combination with fulvestrant, in both premenopausal and postmenopausal females with advanced breast cancer of the same subtype with disease progression following endocrine therapy. Adding palbociclib to fulvestrant resulted in a significantly increased median progression-free survival compared to fulvestrant

  4. A multigene predictor of metastatic outcome in early stage hormone receptor-negative and triple-negative breast cancer.

    Science.gov (United States)

    Yau, Christina; Esserman, Laura; Moore, Dan H; Waldman, Fred; Sninsky, John; Benz, Christopher C

    2010-01-01

    Various multigene predictors of breast cancer clinical outcome have been commercialized, but proved to be prognostic only for hormone receptor (HR) subsets overexpressing estrogen or progesterone receptors. Hormone receptor negative (HRneg) breast cancers, particularly those lacking HER2/ErbB2 overexpression and known as triple-negative (Tneg) cases, are heterogeneous and generally aggressive breast cancer subsets in need of prognostic subclassification, since most early stage HRneg and Tneg breast cancer patients are cured with conservative treatment yet invariably receive aggressive adjuvant chemotherapy. An unbiased search for genes predictive of distant metastatic relapse was undertaken using a training cohort of 199 node-negative, adjuvant treatment naive HRneg (including 154 Tneg) breast cancer cases curated from three public microarray datasets. Prognostic gene candidates were subsequently validated using a different cohort of 75 node-negative, adjuvant naive HRneg cases curated from three additional datasets. The HRneg/Tneg gene signature was prognostically compared with eight other previously reported gene signatures, and evaluated for cancer network associations by two commercial pathway analysis programs. A novel set of 14 prognostic gene candidates were identified as outcome predictors: CXCL13, CLIC5, RGS4, RPS28, RFX7, EXOC7, HAPLN1, ZNF3, SSX3, HRBL, PRRG3, ABO, PRTN3, MATN1. A composite HRneg/Tneg gene signature index proved more accurate than any individual candidate gene or other reported multigene predictors in identifying cases likely to remain free of metastatic relapse. Significant positive correlations between the HRneg/Tneg index and three independent immune-related signatures (STAT1, IFN, and IR) were observed, as were consistent negative associations between the three immune-related signatures and five other proliferation module-containing signatures (MS-14, ONCO-RS, GGI, CSR/wound and NKI-70). Network analysis identified 8 genes within the

  5. Irofulven demonstrates clinical activity against metastatic hormone-refractory prostate cancer in a phase 2 single-agent trial.

    Science.gov (United States)

    Senzer, Neil; Arsenau, James; Richards, Donald; Berman, Barry; MacDonald, John R; Smith, Sheri

    2005-02-01

    The primary objective of this study was to assess the antitumor activity of irofulven in patients with hormone-refractory prostate cancer by measuring a sustained decrease of 50% or greater in serum prostate-specific antigen (PSA) levels. Forty-two patients (median age, 73 years) received at least 1 dose of 10.6 mg/m2 irofulven per day on days 1-5 of a 28-day course. Eligible patients had pathologically confirmed metastatic hormone-refractory adenocarcinoma of the prostate and had not received prior cytotoxic chemotherapy. Forty-two patients received a median of 3 courses of irofulven. Thirty-two patients received at least 2 courses of therapy and were evaluable for efficacy. Four patients (13%) achieved partial response, with a median duration of 2.9 months (range, 2.6-5.8 months). Twenty-seven patients (84%) had disease stabilization and 1 patient (3%) progressed on study. Median progression-free survival was 3.2 months (95% confidence interval, 2.3-4.2 months), with a median progression-free survival of 4.2 months (range, 3.5-6.9 months) for responders. Grade 4 toxicities consisted of thrombocytopenia, anemia, and neutropenia, occurring in 1 patient each. The most common treatment-related grade 3 nonhematologic toxicities included asthenia (19% of patients), vomiting (14%), nausea (12%), and infection without grade 3/4 neutropenia (10%). Irofulven shows activity in hormone-refractory prostate cancer and has an acceptable safety profile, warranting further investigation of this drug, particularly in combination therapies.

  6. Impact of new generation hormone-therapy on cognitive function in elderly patients treated for a metastatic prostate cancer: Cog-Pro trial protocol

    OpenAIRE

    Lange, Marie; Laviec, Heidi; Castel, Hélène; Heutte, Natacha; Leconte, Alexandra; Léger, Isabelle; Giffard, Bénédicte; Capel, Aurélie; Dubois, Martine; Clarisse, Bénédicte; Coquan, Elodie; Di Fiore, Frédéric; Gouérant, Sophie; Bartélémy, Philippe; Pierard, Laure

    2017-01-01

    Background New generation hormone-therapies (NGHT) targeting the androgen signalling pathway are nowadays proposed to elderly patients with metastatic castration-resistant prostate cancer (CRPCa). The impact of these treatments on cognitive function has never been evaluated whereas cognitive impairment may have an impact on the autonomy and the treatment adherence. The aim of this study is to prospectively assess the incidence of cognitive impairment in elderly men after treatment by NGHT for...

  7. Neoadjuvant tamoxifen for hormone-sensitive non-metastatic breast carcinomas in early postmenopausal women.

    Science.gov (United States)

    Mauriac, L; Debled, M; Durand, M; Floquet, A; Boulanger, V; Dagada, C; Trufflandier, N; MacGrogan, G

    2002-02-01

    From 1984 to 1996, 1581 postmenopausal women aged 50-70 years old were treated at Institut Bergonié for an infiltrative non-metastatic breast carcinoma with a positive estrogen and/or progesterone receptor determination. Among them, 199 were treated with first line tamoxifen. Ninety-seven had operable disease (T2 >30 mm, T3, N0/1) and 102 had T4 tumours. After a mean treatment duration of 5.3 months, 89 T2 and T3 (92%) and 93 T4 (91%) were treated by surgery (conservative or not) with or without irradiation, or by irradiation alone. Conserving treatment levels were 53.6% and 44%, respectively. The other women were treated with either second-line chemotherapy or another hormonotherapy; the remaining patients continued regularly with tamoxifen. Overall survival is analysed with a 83 month median follow-up. A comparison between neoadjuvant endocrine therapy and surgery seems feasible to assess the concept of neoadjuvant hormonotherapy.

  8. Activating ESR1 mutations in hormone-resistant metastatic breast cancer.

    Science.gov (United States)

    Robinson, Dan R; Wu, Yi-Mi; Vats, Pankaj; Su, Fengyun; Lonigro, Robert J; Cao, Xuhong; Kalyana-Sundaram, Shanker; Wang, Rui; Ning, Yu; Hodges, Lynda; Gursky, Amy; Siddiqui, Javed; Tomlins, Scott A; Roychowdhury, Sameek; Pienta, Kenneth J; Kim, Scott Y; Roberts, J Scott; Rae, James M; Van Poznak, Catherine H; Hayes, Daniel F; Chugh, Rashmi; Kunju, Lakshmi P; Talpaz, Moshe; Schott, Anne F; Chinnaiyan, Arul M

    2013-12-01

    Breast cancer is the most prevalent cancer in women, and over two-thirds of cases express estrogen receptor-α (ER-α, encoded by ESR1). Through a prospective clinical sequencing program for advanced cancers, we enrolled 11 patients with ER-positive metastatic breast cancer. Whole-exome and transcriptome analysis showed that six cases harbored mutations of ESR1 affecting its ligand-binding domain (LBD), all of whom had been treated with anti-estrogens and estrogen deprivation therapies. A survey of The Cancer Genome Atlas (TCGA) identified four endometrial cancers with similar mutations of ESR1. The five new LBD-localized ESR1 mutations identified here (encoding p.Leu536Gln, p.Tyr537Ser, p.Tyr537Cys, p.Tyr537Asn and p.Asp538Gly) were shown to result in constitutive activity and continued responsiveness to anti-estrogen therapies in vitro. Taken together, these studies suggest that activating mutations in ESR1 are a key mechanism in acquired endocrine resistance in breast cancer therapy.

  9. Prior administration of a non-steroidal anti-androgen failed to prevent the flare-up caused by a luteinizing hormone-releasing hormone agonist in a patient with metastatic prostate cancer.

    Science.gov (United States)

    Uehara, Sho; Yuasa, Takeshi; Fujii, Yasuhisa; Yano, Akihiro; Yamamoto, Shinya; Masuda, Hitoshi; Fukui, Iwao; Yonese, Junji

    2015-08-05

    'Flare phenomenon' after initial luteinizing hormone-releasing hormone agonist administration is a widely approved concept in the treatment of prostate cancer. In most guidelines, concomitant therapy with anti-androgens is recommended to prevent this flare phenomenon. However, there are few reports describing serum prostate-specific antigen transitions after hormonal therapy. Here, we present a case of a man who experienced the biochemical and clinical flare phenomenon despite prior anti-androgen use and who has detailed data. A 70-year-old Asian man with metastatic prostate cancer (multiple bone) was referred to our hospital. He was treated with prior anti-androgens and luteinizing hormone-releasing hormone agonist. Regardless of prior use of anti-androgens, his low back pain caused by bone metastases was deteriorated and serum prostate-specific antigen level was raised from 974.8 ng/mL to 2,555.5 ng/mL within 3 weeks. Then, his serum prostate specific antigen level started to decrease along with the pain. The nadir reached 1.0 ng/mL and remained for 6 months. Because the serum level of prostate-specific antigen then began to increase again, anti-androgen was discontinued for anti-androgen withdrawal syndrome. Then the serum level decreased again to less than 0.1 ng/mL. Until now, his serum prostate-specific antigen level has been maintained at less than 0.1 ng/mL for more than 30 months without any clinical progressions. We present the case of a patient in whom a clinical flare caused by an leuteinizing hormone-releasing hormone agonist was not prevented by prior anti-androgen administration. In addition, the nadir level of prostate-specific antigen when he received leuteinizing hormone-releasing hormone monotherapy was ten times lower than when he received concomitant therapy, and period of anti-androgen withdrawal syndrome was longer than usual. In this case, anti-androgen was probably not effective from the initial administration. Awareness of the possibility

  10. Phase II study of paclitaxel and vinorelbine (Pacl-Vin) in hormone-refractory metastatic prostate cancer: double tubulin targeting.

    Science.gov (United States)

    Sewak, S; Kosmider, S; Ganju, V; Woollett, A; Yeow, E G; Le, B; Henry, M; Debrincat, M A; Bell, R

    2010-03-01

    Androgen ablation is the standard treatment for advanced prostate cancer. However, most patients will eventually develop progressive hormone-refractory prostate cancer (HRPC). The aim of the Pacl-Vin study was to determine the efficacy and safety of paclitaxel in combination with vinorelbine in patients with HRPC, following from a phase I trial. Thirty castrate patients with progressive, metastatic prostate cancer were enrolled. Patients were treated with paclitaxel 40 mg/m2, vinorelbine 20 mg/m2 intravenously on day 1 and day 8 of a 21-day cycle. Two patients demonstrated a partial response and seven patients had stable disease from a cohort of 10 patients with measurable disease. Of 30 patients assessable for prostate-specific antigen (PSA) response, 19 showed stable disease, which was maintained for at least 4 weeks, while six (20%) experienced>or=50% decline in PSA levels. Median overall survival was 7.3 months (interquartile range (IQR): 4.7-9.9 months). Median progression-free survival was 3.3 months (IQR: 2.5-7.0 months). Improvement in quality of life measures was noted after three cycles of therapy. Grade 3 and 4 toxicities were: neutropenia 8%, febrile neutropenia 4%, infection 2%, anaemia 3%, lethargy 1% and somnolescence 1%. One patient died as a result of neutropenic sepsis. In a poor prognostic cohort of patients paclitaxel and vinorelbine is a tolerable regimen, with a 20% PSA and objective response rate. The majority of patients achieved PSA stability. Furthermore, quality of life parameters, such as pain, were improved. However, the low level of activity of this regimen precludes its further testing.

  11. Examining recombinant human TSH primed {sup 131}I therapy protocol in patients with metastatic differentiated thyroid carcinoma: comparison with the traditional thyroid hormone withdrawal protocol

    Energy Technology Data Exchange (ETDEWEB)

    Rani, Deepa; Kaisar, Sushma; Awasare, Sushma; Kamaldeep; Abhyankar, Amit; Basu, Sandip [Bhabha Atomic Research Centre (BARC), Radiation Medicine Centre, Mumbai (India)

    2014-09-15

    Recombinant human thyroid-stimulating hormone (rhTSH)-based protocol is a promising recent development in the management of differentiated thyroid carcinoma (DTC). The objectives of this prospective study were: (1) to assess the feasibility and efficacy of the rhTSH primed {sup 131}I therapy protocol in patients with DTC with distant metastatic disease, (2) to perform lesional dosimetry in this group of patients compared to the traditional protocol, (3) to document the practical advantages (patient symptoms and hospital stay) of the rhTSH protocol compared to the traditional thyroid hormone withdrawal protocol, (4) to document and record any adverse effect of this strategy, (5) to compare the renal function parameters, and (6) to compare the serum TSH values achieved in either of the protocols in this group of patients. The study included 37 patients with metastatic DTC having lung or skeletal metastases or both. A comparison of lesional radiation absorbed dose, hospital stay, renal function tests, and symptom profile was undertaken between the traditional thyroid hormone withdrawal protocol and rhTSH-based therapy protocol. Dosimetric calculations of metastatic lesions were performed using lesion uptake and survey meter readings for calculation of effective half-life. Non-contrast-enhanced CT was used for assessment of tumor volume. Quality of life was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QOL forms. A comparison of pretreatment withdrawal thyroglobulin (TG) was done with the withdrawal TG level 3 months after treatment. The mean effective half-life of {sup 131}I in metastatic lesions was less during the rhTSH protocol (29.49 h) compared to the thyroid hormone withdrawal protocol (35.48 h), but the difference was not statistically significant (p = 0.056). The mean 24-h % uptake of the lesions during the traditional protocol (4.84 %) was slightly higher than the 24-h % uptake during the rhTSH protocol (3.56 %), but

  12. Possible anti-tumor activity of initial treatment with zoledronic acid with hormonal therapy for bone-metastatic prostate cancer in multicenter clinical trial.

    Science.gov (United States)

    Uemura, Hiroji; Yanagisawa, Masahiro; Ikeda, Ichirou; Fujinami, Kiyoshi; Iwasaki, Akira; Noguchi, Sumio; Noguchi, Kazumi; Kubota, Yoshinobu

    2013-06-01

    To ascertain the anti-tumor effect of zoledronic acid (ZOL) treatment on clinical outcomes in patients with bone metastatic prostate cancer, we examined the effect of ZOL started simultaneously with hormonal therapy as initial treatment in these patients. Forty-seven patients with bone-metastatic prostate cancer who received a luteinizing hormone releasing-hormone (LHRH) analogue and an anti-androgen [maximal androgen blockade (MAB)] were assigned to receive ZOL (4 mg intravenous administration every month for 2 years). The time to progression (TTP) of the prostate-specific antigen (PSA), the overall survival (OS), and the rate of PSA decrease in patients with MAB and ZOL treatment (ZOL group) were compared with these parameters in patients who received only MAB at one institute as a control group (non-ZOL group). Although the nadir PSA level and the rate of PSA normalization showed no significant differences between the ZOL and non-ZOL groups, the time to nadir PSA in the ZOL group was significantly shorter than that in the non-ZOL group (P prostate cancer patients. Initial treatment with ZOL has the possibility of anti-tumor activity to delay disease progression.

  13. Prognosis of metastatic breast cancer subtypes: the hormone receptor/HER2-positive subtype is associated with the most favorable outcome.

    Science.gov (United States)

    Lobbezoo, Dorien J A; van Kampen, Roel J W; Voogd, Adri C; Dercksen, M Wouter; van den Berkmortel, Franchette; Smilde, Tineke J; van de Wouw, Agnes J; Peters, Frank P J; van Riel, Johanna M G H; Peters, Natascha A J B; de Boer, Maaike; Borm, George F; Tjan-Heijnen, Vivianne C G

    2013-10-01

    Contrary to the situation in early breast cancer, little is known about the prognostic relevance of the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) in metastatic breast cancer. The objectives of this study were to present survival estimates and to determine the prognostic impact of breast cancer subtypes based on HR and HER2 status in a recent cohort of metastatic breast cancer patients, which is representative of current clinical practice. Patients diagnosed with metastatic breast cancer between 2007 and 2009 were included. Information regarding patient and tumor characteristics and treatment was collected. Patients were categorized in four subtypes based on the HR and HER2 status of the primary tumor: HR positive (+)/HER2 negative (-), HR+/HER2+, HR-/HER2+ and triple negative (TN). Survival was estimated using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic impact of breast cancer subtype, adjusted for possible confounders. Median follow-up was 21.8 months for the 815 metastatic breast cancer patients included; 66 % of patients had the HR+/HER2- subtype, 8 % the HR-/HER2+ subtype, 15 % the TN subtype and 11 % the HR+/HER2+ subtype. The longest survival was observed for the HR+/HER2+ subtype (median 34.4 months), compared to 24.8 months for the HR+/HER2- subtype, 19.8 months for the HR-/HER2+ subtype and 8.8 months for the TN subtype (P < 0.0001). In the multivariate analysis, subtype was an independent prognostic factor, as were initial site of metastases and metastatic-free interval. The HR+/HER2+ subtype was associated with the longest survival after diagnosis of distant metastases.

  14. Impact of palbociclib combinations on treatment of advanced estrogen receptor-positive/human epidermal growth factor 2-negative breast cancer

    OpenAIRE

    Boér K

    2016-01-01

    Katalin Boér Department of Medical Oncology, Szent Margit Hospital, Budapest, Hungary Abstract: Breast cancer is a heterogeneous disease with multiple subgroups based on clinical and molecular characteristics. For the largest subgroup of breast cancers, hormone receptor-positive/human epidermal growth factor 2 (HER2)-negative tumors, hormone treatment is the mainstay of therapy and is likely to result in significant improvement in disease outcomes. However, some of these cancers ...

  15. Targeted Radiotherapy of Estrogen Receptor Positive Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Raghavan Rajagopalan

    2006-08-31

    The overall objectives of the proposal were to develop estrogen receptor (ER) binding small molecule radiopharmaceuticals for targeted radiotherapy of ER positive (ER+) tumors. In particular, this proposal focused on embedding a {sup 186,188}Re or a {sup 32}P radionuclide into an estrogen steroidal framework by isosteric substitution such that the resulting structure is topologically similar to the estrogen (estrogen mimic). The estrogen mimic molecules expected to bind to the ER and exhibit biodistribution akin to that of native estrogen due to structural mimicry. It is anticipated that the {sup 186,188}Re- or a {sup 32}P-containing estrogen mimics will be useful for targeted molecular radiotherapy of ER+ tumors. It is well established that the in vivo target tissue uptake of estrogen like steroidal molecules is related to the binding of the steroids to sex hormone binding globulin (SHBG). SHBG is important in the uptake of estrogens and testosterone in target tissues by SHBG receptors on the cell surface. However, hitherto the design of estrogen like small molecule radiopharmaceuticals was focused on optimizing ER binding characteristics without emphasis on SHBG binding properties. Consequently, even the molecules with good ER affinity in vitro, performed poorly in biodistribution studies. Based on molecular modeling studies the proposal focused on developing estrogen mimics 1-3 which were topologically similar to native estrogens, and form hydrogen bonds in ER and SHBG in the same manner as those of native estrogens. To this end the technical objectives of the proposal focused on synthesizing the rhenium-estrone and estradiol mimics 1 and 2 respectively, and phosphorous estradiol mimic 3 and to assess their stability and in vitro binding characteristics to ER and SHBG.

  16. Cabazitaxel for the second-line treatment of metastatic hormone-refractory prostate cancer: a NICE single technology appraisal.

    Science.gov (United States)

    Kearns, Ben; Lloyd Jones, Myfanwy; Stevenson, Matt; Littlewood, Chris

    2013-06-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of cabazitaxel (Jevtana®, sanofi-aventis, UK) to submit evidence of its clinical and cost effectiveness for the second-line treatment of metastatic hormone-refractory prostate cancer (mHRPC). The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. Clinical evidence was derived from a multinational randomized open-label phase III trial of cabazitaxel plus prednisone or prednisolone in men with mHRPC that had progressed during or following treatment with docetaxel. The comparator was mitoxantrone plus prednisone or prednisolone. Use of cabazitaxel was associated with a statistically significant improvement in overall survival, median progression-free survival and time to tumour progression. However, it was also associated with an increased incidence of adverse events such as neutropenia. Utility data were based on interim results from the early access programme for cabazitaxel. Data were only available for a small number of patients with stable disease, resulting in great uncertainty as to the effect of cabazitaxel on quality of life. For their economic evaluation, the manufacturer estimated that the use of cabazitaxel was associated with an incremental cost of £74,908 per QALY gained. However, the ERG disagreed with the manufacturer over two key methodological points. The first concerned modelling and extrapolating survival; the second point was concerned with the choice of patient population. The ERG altered the manufacturer's evaluation to take into account these two points of disagreement. The resulting cost per QALY gained was £82,950. The NICE Appraisal Committee believed the analysis

  17. Hormones

    Science.gov (United States)

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  18. Impact of new generation hormone-therapy on cognitive function in elderly patients treated for a metastatic prostate cancer: Cog-Pro trial protocol.

    Science.gov (United States)

    Lange, Marie; Laviec, Heidi; Castel, Hélène; Heutte, Natacha; Leconte, Alexandra; Léger, Isabelle; Giffard, Bénédicte; Capel, Aurélie; Dubois, Martine; Clarisse, Bénédicte; Coquan, Elodie; Di Fiore, Frédéric; Gouérant, Sophie; Bartélémy, Philippe; Pierard, Laure; Fizazi, Karim; Joly, Florence

    2017-08-16

    New generation hormone-therapies (NGHT) targeting the androgen signalling pathway are nowadays proposed to elderly patients with metastatic castration-resistant prostate cancer (CRPCa). The impact of these treatments on cognitive function has never been evaluated whereas cognitive impairment may have an impact on the autonomy and the treatment adherence. The aim of this study is to prospectively assess the incidence of cognitive impairment in elderly men after treatment by NGHT for a metastatic CRPCa. The Cog-Pro study is a multicentre longitudinal study including CRPCa patients ≥70 years old treated with NGHT (n = 134), control metastatic prostate cancer patients without castration resistance treated with first generation androgen deprivation therapy (n = 55), and healthy participants (n = 33), matched on age and education. Cognitive, geriatric and quality of life assessment and biological tests will be performed at baseline, 3, 6 and 12 months after start of the treatment (inclusion time). The primary endpoint is the proportion of elderly patients receiving a NGHT who will experience a decline in cognitive performances within 3 months after study enrollment. Secondary endpoints concern: autonomy, quality of life, anxiety, depression, cognitive reserve, adherence to hormone-therapy, comparison of the cognitive impact of 2 different NGHT (abiraterone acetate and enzalutamide), impact of co-morbidities and biological assessments. Evaluating, understanding and analyzing the incidence, severity of cognitive impairments and their impact on quality of life, autonomy and adherence in this group of patients with advanced disease is a challenge. This study should help to improve cancer care of elderly patients and secure the use of oral treatments as the risk of non-observance does exist. Our results will provide up-to date information for patients and caregivers on impact of these treatments on cognitive function in order to help the physicians in the choice of

  19. Prostate-specific antigen doubling time and response to cabazitaxel in a hormone-resistant metastatic prostate cancer patient

    OpenAIRE

    Ghosn, Marwan; Dagher, Alain; El-Karak, Fadi

    2014-01-01

    Abstract We report a case of metastatic castration-resistant prostate cancer, who received prior treatment with docetaxel and was then given cabazitaxel as salvage therapy. The patient was monitored by prostate-specific antigen doubling time and prostate-specific antigen absolute value. The prostate-specific antigen doubling time was found to be a good response predictor in the patient.

  20. Prostate-specific antigen doubling time and response to cabazitaxel in a hormone-resistant metastatic prostate cancer patient.

    Science.gov (United States)

    Ghosn, Marwan; Dagher, Alain; El-Karak, Fadi

    2015-09-01

    We report a case of metastatic castration-resistant prostate cancer, who received prior treatment with docetaxel and was then given cabazitaxel as salvage therapy. The patient was monitored by prostate-specific antigen doubling time and prostate-specific antigen absolute value. The prostate-specific antigen doubling time was found to be a good response predictor in the patient.

  1. Identification and clinical implications of circulating microRNAs for estrogen receptor-positive breast cancer.

    Science.gov (United States)

    Park, In Hae; Kang, Joo Hyun; Lee, Keun Seok; Nam, Seungyoon; Ro, Jungsil; Kim, Joo-Hang

    2014-12-01

    Cancer-associated microRNAs have been stably detected in blood. The objective of this study was to identify a panel of circulating microRNAs with the potential to serve as biomarkers for estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2 (HER2)- breast cancer. We used microarray-based expression profiling to compare the levels of circulating microRNAs in blood samples from 11 ER+/HER2- advanced breast cancer patients plus 5 age-matched controls. MicroRNA levels were validated by reverse transcription quantitative polymerase chain reaction in 40 control subjects, 187 early breast cancer patients, and 45 metastatic breast cancer patients. Then, we assessed the association between the levels of microRNA and clinical outcomes of ER+/HER2- metastatic breast cancer. Initially, we found that miR-1280, miR-1260, and miR-720 were up-regulated in blood from breast cancer patients (P breast cancer patients and reflected tumor status (controlcancercancer). Among 37 metastatic breast cancer patients, miR-1280 levels significantly decreased after treatment in patients who responded to systemic treatment (P breast cancer patients and may serve as a biomarker for ER-positive breast cancer.

  2. Strontium-89 (Metastron) and the bisphosphonate olpadronate reduce the incidence of spinal cord compression in patients with hormone-refractory prostate cancer metastatic to the skeleton

    Energy Technology Data Exchange (ETDEWEB)

    Soerdjbalie-Maikoe, Vidya; Pelger, Rob C.M.; Lycklama a Nijeholt, G.A.B. [Department of Urology, Leiden University Medical Center (Netherlands); Arndt, Jan-Willem [Department of Nuclear Medicine, Leiden University Medical Center (Netherlands); Zwinderman, Aeilko H. [Department of Medical Statistics, Leiden University Medical Center (Netherlands); Papapoulos, Socrates E.; Hamdy, Neveen A.T. [Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center (Netherlands)

    2002-04-01

    Spinal cord compression (SCC) is a devastating complication of metastatic cancer. We investigated the potential beneficial effect of two palliative therapies - strontium-89 (Metastron) and the nitrogen-containing bisphosphonate olpadronate - on the incidence of SCC in hormone-refractory prostate cancer (HRPC) metastatic to the skeleton. We retrospectively studied 415 patients with histologically proven prostate cancer who underwent bone scintigraphy at the time of diagnosis and were followed up at the Leiden University Medical Center between 1990 and 1999. Medical or surgical castration was undertaken in 172 patients with evidence for skeletal metastases. Within 2 years, 147 of these patients (85%) developed HRPC associated with severe progressive bone pain. Palliative treatment was given to 131 patients in the form of local radiotherapy (n=10), {sup 89}Sr (n=46) or intravenous olpadronate (n=66), with (n=57) or without (n=9) maintenance oral olpadronate. Nine patients received both {sup 89}Sr and olpadronate at various intervals. Sixteen patients who did not receive any of these treatments were used as historical controls. There was no significant difference in baseline characteristics between treatment modalities. The incidence of SCC was 17% in the whole group, and highest in controls receiving no palliation (50%). None of the patients treated with local radiotherapy, only 4% of patients receiving {sup 89}Sr and 21% of patients given olpadronate developed this complication. Our findings suggest a significant reduction in SCC in patients with symptomatic HRPC metastatic to the skeleton who receive palliative therapies. Local radiotherapy completely prevents the incidence of SCC, {sup 89}Sr leads to an important decrease in this complication and olpadronate induces a significant, albeit smaller decrease in the incidence of SCC. The use of these agents opens new avenues in the difficult management of patients with advanced prostate cancer who are most at risk of

  3. Phase I/IIa clinical trial of a novel hTERT peptide vaccine in men with metastatic hormone-naive prostate cancer.

    Science.gov (United States)

    Lilleby, Wolfgang; Gaudernack, Gustav; Brunsvig, Paal F; Vlatkovic, Ljiljana; Schulz, Melanie; Mills, Kate; Hole, Knut Håkon; Inderberg, Else Marit

    2017-07-01

    In newly diagnosed metastatic hormone-naive prostate cancer (mPC), telomerase-based immunotherapy with the novel hTERT peptide vaccine UV1 can induce immune responses with potential clinical benefit. This phase I dose escalation study of UV1 evaluated safety, immune response, effects on prostate-specific antigen (PSA) levels, and preliminary clinical outcome. Twenty-two patients with newly diagnosed metastatic hormone-naïve PC (mPC) were enrolled; all had started androgen deprivation therapy and had no visceral metastases. Bone metastases were present in 17 (77%) patients and 16 (73%) patients had affected lymph nodes. Three dose levels of UV1 were given as intradermal injections combined with GM-CSF (Leukine®). Twenty-one patients in the intention-to-treat population (95%) received conformal radiotherapy. Adverse events reported were predominantly grade 1, most frequently injection site pruritus (86.4%). Serious adverse events considered possibly related to UV1 and/or GM-CSF included anaphylactic reaction in two patients and thrombocytopenia in one patient. Immune responses against UV1 peptides were confirmed in 18/21 evaluable patients (85.7%), PSA declined to prostatic gland. At the end of the nine-month reporting period for the study, 17 patients had clinically stable disease. Treatment with UV1 and GM-CSF gave few adverse events and induced specific immune responses in a large proportion of patients unselected for HLA type. The intermediate dose of 0.3 mg UV1 resulted in the highest proportion of, and most rapid UV1-specific immune responses with an acceptable safety profile. These results warrant further clinical studies in mPC.

  4. Conversion to monotherapy with luteinizing-hormone releasing hormone agonist or orchiectomy after reaching PSA nadir following maximal androgen blockade is able to prolong progression-free survival in patients with metastatic prostate cancer: A propensity score matching analysis.

    Science.gov (United States)

    Min, Gyeong Eun; Ahn, Hanjong

    2017-06-01

    The present study evaluated androgen deprivation methods to determine the approach that most improves the progression-free survival (PFS) of patients with metastatic prostate cancer. Patients had received continuous maximal androgen blockade (MAB) or monotherapy [luteinizing-hormone releasing hormone (LHRH) agonist or orchiectomy] following the reaching of the prostate specific antigen (PSA) nadir. The medical records of 293 patients who received MAB following a diagnosis of metastatic prostate cancer were retrospectively reviewed. Following attainment of the PSA nadir and treatment with MAB, patients were maintained on continuous MAB (group CMAB) or converted to monotherapy (group MONO). Disease progression, defined as progression to castration-resistant prostate cancer, was evaluated and compared between the treatment modalities. PFS was compared between patients who received CMAB vs. MONO using 2:1 (102:53) propensity score matching; the basic clinicopathological characteristics (age, Gleason score, PSA and extent of bone metastasis) were similar between the groups. Disease progression was observed in 70.9% of all patients, with a median treatment period of 22.7 months. The median PFS time was 19.5 months in the CMAB group and 28.8 months in the MONO group (P=0.008). Kaplan-Meier analysis demonstrated that PFS was significantly associated with the type of maintenance androgen deprivation therapy (ADT; log rank bone metastasis were independent predictors of prolonged PFS. In this propensity score matched-analysis, conversion to monotherapy with a LHRH agonist or orchiectomy following attainment of the PSA nadir with initial MAB, prolonged the PFS, suggesting that monotherapy maintenance following initial MAB may benefit patients by reducing side effects without decreasing treatment efficacy.

  5. The HIF1A functional genetic polymorphism at locus +1772 associates with progression to metastatic prostate cancer and refractoriness to hormonal castration.

    Science.gov (United States)

    Fraga, Avelino; Ribeiro, Ricardo; Príncipe, Paulo; Lobato, Carlos; Pina, Francisco; Maurício, Joaquina; Monteiro, Cátia; Sousa, Hugo; Calais da Silva, F; Lopes, Carlos; Medeiros, Rui

    2014-01-01

    The hypoxia inducible factor 1 alpha (HIF1a) is a key regulator of tumour cell response to hypoxia, orchestrating mechanisms known to be involved in cancer aggressiveness and metastatic behaviour. In this study we sought to evaluate the association of a functional genetic polymorphism in HIF1A with overall and metastatic prostate cancer (PCa) risk and with response to androgen deprivation therapy (ADT). The HIF1A +1772 C>T (rs11549465) polymorphism was genotyped, using DNA isolated from peripheral blood, in 1490 male subjects (754 with prostate cancer and 736 controls cancer-free) through Real-Time PCR. A nested group of cancer patients who were eligible for androgen deprivation therapy was followed up. Univariate and multivariate models were used to analyse the response to hormonal treatment and the risk for developing distant metastasis. Age-adjusted odds ratios were calculated to evaluate prostate cancer risk. Our results showed that patients under ADT carrying the HIF1A +1772 T-allele have increased risk for developing distant metastasis (OR, 2.0; 95%CI, 1.1-3.9) and an independent 6-fold increased risk for resistance to ADT after multivariate analysis (OR, 6.0; 95%CI, 2.2-16.8). This polymorphism was not associated with increased risk for being diagnosed with prostate cancer (OR, 0.9; 95%CI, 0.7-1.2). The HIF1A +1772 genetic polymorphism predicts a more aggressive prostate cancer behaviour, supporting the involvement of HIF1a in prostate cancer biological progression and ADT resistance. Molecular profiles using hypoxia markers may help predict clinically relevant prostate cancer and response to ADT. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. [Direct and indirect costs of luteinising hormone-releasing hormone analogues in the treatment of locally advanced or metastatic prostate cancer in Italy].

    Science.gov (United States)

    Fadda, Valeria; Maratea, Dario

    2015-12-01

    When analyzing the use of luteinizing hormone-releasing hormone (LHRH) analogues for different clinical indications, current available evidence does not support a presumed drug class effect among the various LHRH in the treatment of prostate cancer. The following search key words were entered in the PubMed database and the NICE and FDA websites: “LHRH agonist AND prostatic cancer”, “androgen deprivation therapy”, “androgen suppression”, “buserelin”, “leuprorelin”, “goserelin”,“triptorelin”, “degarelix”. The direct costs included the following items: follow-up visits, diagnostic exams (e.g. prostate-specific antigen PSA) and drug costs. The indirect costs included working days lost by the patient. With intermittent therapy as a reference, leuprorelin injectable solution of 22,25 mg was associated with the lowest cost and degarelix with the highest cost. However, given the mandatory presence of a nurse for drug injection, the buserelin depot formulation was associated with the lowest cost. If the costs for hospital visits were added to drug costs, differences between the various therapeutic strategies were less remarkable. Our study showed how various factors (e.g. route of administration, frequency of administration, presence of a nurse for drug reconstitution and injection) should be taken into account by decision makers in addition to the price of drugs.

  7. Palbociclib for the Treatment of Estrogen Receptor–Positive, HER2-Negative Metastatic Breast Cancer

    Science.gov (United States)

    Morikawa, Aki; Henry, N. Lynn

    2015-01-01

    Palbociclib is a selective inhibitor of cyclin-dependent kinases 4 and 6 that acts by reducing phosphorylation of the tumor suppressor gene Retinoblastoma. When added to the aromatase inhibitor letrozole in a randomized phase II trial for first-line therapy of estrogen receptor-positive, HER2-negative metastatic breast cancer, palbociclib significantly increased progression-free survival compared to letrozole alone (palbociclib + letrozole: 20.2 months (95% CI 13.8-27.5), letrozole:10.2 months (95% CI 5.7-12.6); hazard ratio 0.49 (95% CI 0.32-0.75), p=0.0004). Based on these results the drug was recently granted accelerated approval by the FDA, and confirmatory studies are ongoing. Since this drug has a rational target in an oncologic pathway, concurrent biomarker development is of interest. In breast cancer, the most useful predictive biomarkers identified thus far are estrogen receptor and HER2 receptor status, although additional studies are ongoing. In this article, we review the development of palbociclib and its use in treatment of hormone receptor-positive metastatic breast cancer in the context of other FDA-approved agents in this setting. PMID:26100274

  8. Comparative effectiveness of early-line nab-paclitaxel vs. paclitaxel in patients with metastatic breast cancer: a US community-based real-world analysis

    Directory of Open Access Journals (Sweden)

    Mahtani RL

    2018-02-01

    Full Text Available Reshma L Mahtani,1 Monika Parisi,2 Stefan Glück,3 Quanhong Ni,2 Siyeon Park,4 Corey Pelletier,2 Claudio Faria,2 Fadi Braiteh5,6 1Division of Hematology/Oncology, University of Miami, Miami, FL, 2Health Economics and Outcomes Research, Celgene Corporation, Summit, NJ, 3Global Medical Affairs, Celgene Corporation, Summit, NJ, 4School of Pharmacy, The Ohio State University, Columbus, OH, 5Department of Hematology/Oncology, University of Nevada School of Medicine, Las Vegas, NV, 6Department of Hematology/Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA Background: Real-world analyses of treatments for patients with metastatic breast cancer are limited. We evaluated the comparative effectiveness of nab-paclitaxel vs. paclitaxel in patients with metastatic breast cancer using data from an electronic medical record database from community practices across the USA.Methods: We performed a retrospective cohort study using fully de-identified data from an independent US electronic medical record platform of patients with metastatic breast cancer initiating single-agent nab-paclitaxel or paclitaxel as a first- or second-line treatment from December 1, 2010 to October 6, 2014. The clinical efficacy objectives were time to treatment discontinuation (TTD and time to next treatment (TTNT. Subgroup analyses were performed in patients with 2 types of metastatic breast cancer as follows: 1 hormone receptor-positive and human epidermal growth factor receptor 2 negative, and 2 triple-negative disease. Results: This analysis included 925 patients. Patients receiving nab-paclitaxel vs. paclitaxel had significantly longer TTD (median 4.2 vs. 2.8 months, P<0.0001 and TTNT (median 6.0 vs. 4.2 months, P<0.0001; similar outcomes were observed for patients with hormone receptor-positive/human epidermal growth factor receptor 2 negative disease. Compared with paclitaxel, nab-paclitaxel was associated with significantly longer TTD in patients with triple

  9. Synchronization of cortisol circadian rhythm by the pineal hormone melatonin in untreatable metastatic solid tumor patients and its possible prognostic significance on tumor progression.

    Science.gov (United States)

    Brivio, Fernando; Fumagalli, Luca; Fumagalli, Gabriele; Pescia, Simonetta; Brivio, Rinaldo; Di Fede, Giuseppe; Rovelli, Franco; Lissoni, Paolo

    2010-01-01

    Cancer progression has been associated with neuroendocrine alterations involved in the control of the circadian rhythms, particularly those of cortisol. Moreover, the evidence of an altered cortisol rhythm may predict a poor prognosis in cancer patients. Finally, cancer progression has been proven to be associated with alterations in the pineal gland, which plays a fundamental role in the control of circadian biological rhythms. On this basis, a study was planned to evaluate the effects of a chronic treatment with the pineal hormone melatonin (MLT) in advanced cancer patients with altered cortisol circadian rhythm. The study included 14 untreatable metastatic cancer patients showing alterations of cortisol rhythm. They were treated by MLT at 20 mg/day orally, in the evening, for 3 consecutive months. a normalization of cortisol rhythm was achieved in 4/14 (29%) patients. Moreover, stable disease (SD) was obtained in 6/14 (43%) patients under MLT therapy, whereas the other 8 patients had progressive disease (PD). Finally, the percentage of cortisol rhythm normalization achieved in patients with SD was significantly higher than that observed in patients with PD. These results show that MLT may normalize cortisol rhythm in advanced cancer patients and this effect appears to be associated with SD, thus confirming the negative prognostic significance of cortisol rhythm alterations in cancer.

  10. Estrogen receptor-positive primary squamous cell carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Abby M. Pribish, BS

    2017-06-01

    Full Text Available Pure primary squamous cell carcinoma of the breast (SCCB represents around 0.1% of breast carcinomas. Diagnosis requires independence from adjacent skin without metastatic disease. SCCB is often large at presentation with nonspecific mammographic and ultrasound findings. It is typically hormone receptor negative and aggressive. Mastectomy and adjuvant chemotherapy is the most common treatment, although treatment guidelines are not well established. We present a case of pure primary SCCB detected by high risk screening mammogram and treated with breast conserving surgery, chemotherapy, and radiation. We discuss clinical, radiologic, and pathologic findings.

  11. Value of information and value of implementation: application of an analytic framework to inform resource allocation decisions in metastatic hormone-refractory prostate cancer.

    Science.gov (United States)

    Hoomans, Ties; Fenwick, Elisabeth A L; Palmer, Steve; Claxton, Karl

    2009-01-01

    In a budget-constrained health-care system, decisions about investing in strategies to promote implementation have to be made alongside decisions about health-care provision and research funding. Using a Bayesian decision-theoretic approach, an analytic framework has been developed to inform these separate but related decisions, establishing the expected value of both perfect information (EVPI) and perfect implementation (EVPIM). We applied this framework to inform decision-making about resource allocation to metastatic hormone-refractory prostate cancer (mHRPC) in the UK. Based on available evidence on the cost-effectiveness of all plausible treatments for mHRPC, we determined which treatment option(s) were cost-effective and explored the uncertainty surrounding this decision. Given the decision uncertainty and the variation in care provided by health-care professionals, we then determined the EVPI and EVPIM. Finally, we performed sensitivity analyses to explore the influence of alternative assumptions regarding various decision parameters on the efficiency of resource allocation. Depending on the cost-effectiveness threshold (lambda), we identified mitoxantrone plus prednisone/prednisolone and docetaxel plus prednisone/prednisolone (3 weekly) as the optimal treatments for mHRPC. Given current clinical practice, there appears to be considerable scope for improving the efficiency of health-care provision: the EVPI (estimated to be over pound13 million) indicates that acquiring further information could be cost-effective; and the EVPIM (estimated to be over pound4 million) suggests that investing in strategies to implement the treatments regimens being identified as optimal is potentially worthwhile. Through sensitivity analyses, we found that the EVPI and EVPIM are mainly driven by lambda, the number of treatment options being considered, the current level of implementation, and the size of the eligible patient population. The application demonstrates that the

  12. [Standards, Options and Recommendations for non metastatic breast cancer patients].

    Science.gov (United States)

    Mauriac, Louis

    2002-02-01

    The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Cancer Centers, and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. To develop clinical practice guidelines for non metastatic breast cancer patients according to the definitions of the Standards, Options and Recommendations project. Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 148 independent reviewers. This article is an update of the version published in 1996. The modified 2001 version of the standards, options and recommendations takes into account new information published. Important changes have been made in terms of clinical practice. They concern loco-regional and general therapy. Regarding loco-regional treatment, a increased dose to the tumor bed should be needs to be systematically delivered to the tumor bed for women under 50 years. The analysis of margin involvement is essential and constitutes an important factor for therapeutic decision. Regarding general therapy, hormone therapy with tamoxifen appeared, in 2001, as one of the standards in non-menopausal and oestrogen receptor-positive patients. Concerning patients with N- tumors, the standards and therapeutic options were refined with regard to the notion of metastatic relapse risk. Chemotherapy constitutes one of the standard treatments for non-menopausal women with one or more factor(s) predictive of metastatic relapse.

  13. Targeting the mammalian target of rapamycin pathway with everolimus: implications for the management of metastatic breast cancer.

    Science.gov (United States)

    Ng, Vin Cci; Johnson, Jeremy J; Cuellar, Sandra

    2015-12-01

    The inhibitors of mammalian target of rapamycin (mTOR) have documented antitumor activity via disruption of various signaling pathways leading to impaired cellular growth, proliferation, and survival. In preclinical studies, mTOR inhibitors use in combination with hormonal therapy has shown promising results in overcoming endocrine resistance in breast cancer cells. The role of everolimus in breast cancer was established in the Breast Cancer Trial of Oral Everolimus-2 (BOLERO-2) trial in combination with exemestane for patients with advanced metastatic hormone receptor-positive (HR+) breast cancer, who relapsed after initial hormonal manipulation. The study met its primary endpoint of significant improvement in progression free survival (PFS) with a median time to progression of 6.9 months in the combination group versus 2.8 months in exemestane group. Favorable improvements in PFS were reported across all patient subgroups regardless of age, Eastern Cooperative Oncology Group performance status, number of prior therapies, and presence of visceral metastases. Adverse events were mostly mild to moderate in severity and consistent with the known safety profile of everolimus. Major toxicities reported include stomatitis, non-infectious pneumonitis, and hyperglycemia. The purpose of this review is to discuss the role of everolimus as a valuable component in advanced metastatic breast cancer and delineate current strategies to prevent and manage the most common toxicities associated with this combination regimen. © The Author(s) 2014.

  14. 11q13 is a Susceptibility Locus for Hormone Receptor Positive Breast Cancer

    DEFF Research Database (Denmark)

    Lambrechts, Diether; Truong, Therese; Justenhoven, Christina

    2012-01-01

    A recent two-stage genome-wide association study (GWAS) identified five novel breast cancer susceptibility loci on chromosomes 9, 10 and 11. To provide more reliable estimates of the relative risk associated with these loci and investigate possible heterogeneity by subtype of breast cancer, we ge...

  15. Obesity is associated with a poorer prognosis in women with hormone receptor positive breast cancer.

    Science.gov (United States)

    Robinson, Penelope J; Bell, Robin J; Davis, Susan R

    2014-11-01

    Whether moderate to severe obesity (body mass index (BMI)≥30 to obesity on time to either local or distant recurrence or new breast cancer, or death due to breast cancer was determined by Cox regression. Women in the most extreme categories of BMI (age, 58.4±11.6 years, 53.8% had Stage 1 disease and 88.9% received oral adjuvant endocrine therapy (OAET) within 2 years of diagnosis. The likelihood of an event was significantly associated with moderate to severe obesity (HR=1.71, 95%CI, 1.12-2.62, p=0.014), disease beyond Stage 1 (HR=2.87, 95% CI 1.73-4.75, pobesity (HR 3.23, 95%CI 1.48-7.03, p=0.003) and OAET use (HR 0.41, 95%CI 0.17-0.98, p=0.046) were significantly associated with an event. Moderate to severe obesity is associated with a poorer invasive breast cancer prognosis; this is also true for women with Stage 1 disease, and is independent of age and treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Cabazitaxel for Hormone-Relapsed Metastatic Prostate Cancer Previously Treated With a Docetaxel-Containing Regimen: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    Science.gov (United States)

    Kearns, Benjamin; Pandor, Abdullah; Stevenson, Matt; Hamilton, Jean; Chambers, Duncan; Clowes, Mark; Graham, John; Kumar, M Satish

    2017-04-01

    As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures cabazitaxel (Jevtana®, Sanofi, UK) to submit evidence for the clinical and cost effectiveness of cabazitaxel for treatment of patients with metastatic hormone-relapsed prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the company's submission to NICE. Clinical evidence for cabazitaxel was derived from a multinational randomised open-label phase III trial (TROPIC) of cabazitaxel plus prednisone or prednisolone compared with mitoxantrone plus prednisone or prednisolone, which was assumed to represent best supportive care. The NICE final scope identified a further three comparators: abiraterone in combination with prednisone or prednisolone; enzalutamide; and radium-223 dichloride for the subgroup of people with bone metastasis only (no visceral metastasis). The company did not consider radium-223 dichloride to be a relevant comparator. Neither abiraterone nor enzalutamide has been directly compared in a trial with cabazitaxel. Instead, clinical evidence was synthesised within a network meta-analysis (NMA). Results from TROPIC showed that cabazitaxel was associated with a statistically significant improvement in both overall survival and progression-free survival compared with mitoxantrone. Results from a random-effects NMA, as conducted by the company and updated by the ERG, indicated that there was no statistically significant difference between the three active treatments for both overall survival and progression-free survival. Utility data were not collected as part of the TROPIC trial, and

  17. Adding abiraterone to androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis.

    Science.gov (United States)

    Rydzewska, Larysa H M; Burdett, Sarah; Vale, Claire L; Clarke, Noel W; Fizazi, Karim; Kheoh, Thian; Mason, Malcolm D; Miladinovic, Branko; James, Nicholas D; Parmar, Mahesh K B; Spears, Melissa R; Sweeney, Christopher J; Sydes, Matthew R; Tran, NamPhuong; Tierney, Jayne F

    2017-10-01

    There is a need to synthesise the results of numerous randomised controlled trials evaluating the addition of therapies to androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer (mHSPC). This systematic review aims to assess the effects of adding abiraterone acetate plus prednisone/prednisolone (AAP) to ADT. Using our framework for adaptive meta-analysis (FAME), we started the review process before trials had been reported and worked collaboratively with trial investigators to anticipate when eligible trial results would emerge. Thus, we could determine the earliest opportunity for reliable meta-analysis and take account of unavailable trials in interpreting results. We searched multiple sources for trials comparing AAP plus ADT versus ADT in men with mHSPC. We obtained results for the primary outcome of overall survival (OS), secondary outcomes of clinical/radiological progression-free survival (PFS) and grade III-IV and grade V toxicity direct from trial teams. Hazard ratios (HRs) for the effects of AAP plus ADT on OS and PFS, Peto Odds Ratios (Peto ORs) for the effects on acute toxicity and interaction HRs for the effects on OS by patient subgroups were combined across trials using fixed-effect meta-analysis. We identified three eligible trials, one of which was still recruiting (PEACE-1 (NCT01957436)). Results from the two remaining trials (LATITUDE (NCT01715285) and STAMPEDE (NCT00268476)), representing 82% of all men randomised to AAP plus ADT versus ADT (without docetaxel in either arm), showed a highly significant 38% reduction in the risk of death with AAP plus ADT (HR = 0.62, 95% confidence interval [CI] = 0.53-0.71, p = 0.55 × 10-10), that translates into a 14% absolute improvement in 3-year OS. Despite differences in PFS definitions across trials, we also observed a consistent and highly significant 55% reduction in the risk of clinical/radiological PFS (HR = 0.45, 95% CI = 0.40-0.51, p = 0.66

  18. HER2 protein and gene variation between primary and metastatic breast cancer: significance and impact on patient care.

    Science.gov (United States)

    Fabi, Alessandra; Di Benedetto, Anna; Metro, Giulio; Perracchio, Letizia; Nisticò, Cecilia; Di Filippo, Franco; Ercolani, Cristiana; Ferretti, Gianluigi; Melucci, Elisa; Buglioni, Simonetta; Sperduti, Isabella; Papaldo, Paola; Cognetti, Francesco; Mottolese, Marcella

    2011-04-01

    To analyze HER2 status in primary breast cancer (PBC) compared with correspondent metachronous metastases and to investigate whether BC phenotype may be predictive of change in HER2 expression. HER2 was investigated by immunohistochemistry, silver in situ hybridization (SISH), and FISH, in a series of 137 tumors, building up a tissue microarray to concurrently analyze each single PBC and metastatic (MBC) on the same slide. HER2 status was discordant in 14 cases (10%): 12 negative in PBC and positive in metastases and two positive in PBC and negative in metastases (P = 0.04). These findings were confirmed by a PCR based test termed Multiplex Ligation-dependent Probe Amplification (MLPA). HER2 status changed in hormone receptor-positive BC more frequently than in negative ones (P = 0.002). In addition, we evaluated HER2 gene and chromosome 17 copy number by SISH in the 123 cases with unchanged HER2 status during progression. We found consistent HER2 gene copy number stability in the 100 nonamplified cases. Conversely, of the 23 amplified PBC, 13 (57%) demonstrated a significant increase in the HER2 gene and chromosome 17 copy number in their paired metastases (P = 0.01), as defined by SISH (k = 0.54, P < 0.0001) and MLPA. Patients who changed HER2 status from negative to positive, presented significant longer time to progression when treated with trastuzumab compared to those who were untreated (P = 0.04). When feasible, HER2 reassessment in metastatic lesions should be carefully taken into account, especially for metastases coming from primary hormone receptor-positive BC.

  19. Establishment and characterization of a new human oestradiol- and progesterone-receptor-positive mammary carcinoma serially transplantable in nude mice.

    Science.gov (United States)

    Naundorf, H; Fichtner, I; Büttner, B; Frege, J

    1992-01-01

    A human mammary carcinoma originating from a postmenopausal patient was successfully transplanted into nude mice. According to the adopted criteria the tumour proved to be oestradiol- and progesterone-receptor-positive. Histological studies of the patient tumour revealed a ductal invasive mammary carcinoma with 80% tubular growth pattern. Following transplantation the adenoid structures decreased to 30%; the mitosis rate and grade of malignancy increased. Treatment of the nude mice with 20 micrograms oestradiol benzoate/mouse caused a loss of the oestradiol receptor of the mammary carcinoma. The mammary carcinoma 3366 can be used for testing of antineoplastic substances, antihormones and for studies in regard to down-regulation or blocking of hormone receptors and possible consequences for therapies.

  20. LYN-activating mutations mediate antiestrogen resistance in estrogen receptor-positive breast cancer.

    Science.gov (United States)

    Schwarz, Luis J; Fox, Emily M; Balko, Justin M; Garrett, Joan T; Kuba, María Gabriela; Estrada, Mónica Valeria; González-Angulo, Ana María; Mills, Gordon B; Red-Brewer, Monica; Mayer, Ingrid A; Abramson, Vandana; Rizzo, Monica; Kelley, Mark C; Meszoely, Ingrid M; Arteaga, Carlos L

    2014-12-01

    Estrogen receptor-positive (ER(+)) breast cancers adapt to hormone deprivation and become resistant to antiestrogen therapy. Here, we performed deep sequencing on ER(+) tumors that remained highly proliferative after treatment with the aromatase inhibitor letrozole and identified a D189Y mutation in the inhibitory SH2 domain of the SRC family kinase (SFK) LYN. Evaluation of 463 breast tumors in The Cancer Genome Atlas revealed four LYN mutations, two of which affected the SH2 domain. In addition, LYN was upregulated in multiple ER(+) breast cancer lines resistant to long-term estrogen deprivation (LTED). An RNAi-based kinome screen revealed that LYN is required for growth of ER(+) LTED breast cancer cells. Kinase assays and immunoblot analyses of SRC substrates in transfected cells indicated that LYN(D189Y) has higher catalytic activity than WT protein. Further, LYN(D189Y) exhibited reduced phosphorylation at the inhibitory Y507 site compared with LYN(WT). Other SH2 domain LYN mutants, E159K and K209N, also exhibited higher catalytic activity and reduced inhibitory site phosphorylation. LYN(D189Y) overexpression abrogated growth inhibition by fulvestrant and/or the PI3K inhibitor BKM120 in 3 ER(+) breast cancer cell lines. The SFK inhibitor dasatinib enhanced the antitumor effect of BKM120 and fulvestrant against estrogen-deprived ER(+) xenografts but not LYN(D189Y)-expressing xenografts. These results suggest that LYN mutations mediate escape from antiestrogens in a subset of ER(+) breast cancers.

  1. The potential therapeutic benefits of vitamin D in the treatment of estrogen receptor positive breast cancer.

    Science.gov (United States)

    Krishnan, Aruna V; Swami, Srilatha; Feldman, David

    2012-09-01

    Calcitriol (1,25-dihydroxyvitamin D(3)), the hormonally active form of vitamin D, inhibits the growth of many malignant cells including breast cancer (BCa) cells. The mechanisms of calcitriol anticancer actions include cell cycle arrest, stimulation of apoptosis and inhibition of invasion, metastasis and angiogenesis. In addition we have discovered new pathways of calcitriol action that are especially relevant in inhibiting the growth of estrogen receptor positive (ER+) BCa cells. Calcitriol suppresses COX-2 expression and increases that of 15-PGDH thereby reducing the levels of inflammatory prostaglandins (PGs). Our in vitro and in vivo studies show that calcitriol decreases the expression of aromatase, the enzyme that catalyzes estrogen synthesis selectively in BCa cells and in the mammary adipose tissue surrounding BCa, by a direct repression of aromatase transcription via promoter II as well as an indirect effect due to the reduction in the levels of PGs, which are major stimulator of aromatase transcription through promoter II. Calcitriol down-regulates the expression of ERα and thereby attenuates estrogen signaling in BCa cells including the proliferative stimulus provided by estrogens. Thus the inhibition of estrogen synthesis and signaling by calcitriol and its anti-inflammatory actions will play an important role in inhibiting ER+BCa. We hypothesize that dietary vitamin D would exhibit similar anticancer activity due to the presence of the enzyme 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) in breast cells ensuring conversion of circulating 25-hydroxyvitamin D to calcitriol locally within the breast micro-environment where it can act in a paracrine manner to inhibit BCa growth. Cell culture and in vivo data in mice strongly suggest that calcitriol and dietary vitamin D would play a beneficial role in the prevention and/or treatment of ER+BCa in women. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Metastatic Cancer

    Science.gov (United States)

    Metastatic cancer is cancer that spreads from its site of origin to another part of the body. Learn how cancer spreads, possible symptoms, common sites where cancer spreads, and how to find out about treatment options.

  3. Endocrine therapy use among elderly hormone receptor-pos...

    Data.gov (United States)

    U.S. Department of Health & Human Services — Clinical guidelines recommend that women with hormone-receptor positive breast cancer receive endocrine therapy (selective estrogen receptor modulators or aromatase...

  4. The impact of repeated cycles of radioligand therapy using [177Lu]Lu-PSMA-617 on renal function in patients with hormone refractory metastatic prostate cancer.

    Science.gov (United States)

    Yordanova, Anna; Becker, Anja; Eppard, Elisabeth; Kürpig, Stefan; Fisang, Christian; Feldmann, Georg; Essler, Markus; Ahmadzadehfar, Hojjat

    2017-08-01

    [177Lu]Lu-PSMA-617 is a well-tolerated therapy for the treatment of metastatic prostate cancer. However, because of the mainly renal excretion of the tracer, the kidneys are one of the most limiting organs. The purpose of this study was to examine the post-therapeutic changes in renal function over time and to identify risk factors for developing renal toxicity. We also tested the reliability of markers for renal function monitoring. Fifty-five patients with castrate-resistant metastatic prostate cancer treated with at least three cycles of [177Lu]Lu-PSMA-617 were investigated. Renal function was assessed through laboratory tests (creatinine, GFR, cystatin C) and Tc-99 m-MAG3 measurements. Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. To identify risk factors for renal toxicity, we used Pearson's correlation coefficient and the corresponding p values. None of the 55 patients experienced severe nephrotoxicity (grade 3/4). In 14 patients (25%), we observed increased creatinine levels of CTC 1° or 2°. There were 16 cases of increased GFR (grade 1/2). At the baseline, only 14 patients had elevated cystatin C. However, post-therapeutic cystatin C was elevated in 32 patients (58%). A significant effect on renal function was found for age (p = 0.049), hypertension (p = 0.001) and pre-existing kidney disease (p = 0.001). The most reliable predictive markers of nephrotoxicity were TER-MAG3 and cystatin C. Renal toxicity in patients treated with [177Lu]Lu-PSMA-617 was low. There was no (sub)acute grade 3 or 4 nephrotoxicity.

  5. The impact of repeated cycles of radioligand therapy using [{sup 177}Lu]Lu-PSMA-617 on renal function in patients with hormone refractory metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yordanova, Anna; Becker, Anja; Eppard, Elisabeth; Kuerpig, Stefan; Essler, Markus; Ahmadzadehfar, Hojjat [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Fisang, Christian [University Hospital Bonn, Department of Urology, Bonn (Germany); Feldmann, Georg [University Hospital Bonn, Department of Internal Medicine, MED3, Bonn (Germany)

    2017-08-15

    [{sup 177}Lu]Lu-PSMA-617 is a well-tolerated therapy for the treatment of metastatic prostate cancer. However, because of the mainly renal excretion of the tracer, the kidneys are one of the most limiting organs. The purpose of this study was to examine the post-therapeutic changes in renal function over time and to identify risk factors for developing renal toxicity. We also tested the reliability of markers for renal function monitoring. Fifty-five patients with castrate-resistant metastatic prostate cancer treated with at least three cycles of [{sup 177}Lu]Lu-PSMA-617 were investigated. Renal function was assessed through laboratory tests (creatinine, GFR, cystatin C) and Tc-99 m-MAG3 measurements. Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. To identify risk factors for renal toxicity, we used Pearson's correlation coefficient and the corresponding p values. None of the 55 patients experienced severe nephrotoxicity (grade 3/4). In 14 patients (25%), we observed increased creatinine levels of CTC 1 or 2 . There were 16 cases of increased GFR (grade 1/2). At the baseline, only 14 patients had elevated cystatin C. However, post-therapeutic cystatin C was elevated in 32 patients (58%). A significant effect on renal function was found for age (p = 0.049), hypertension (p = 0.001) and pre-existing kidney disease (p = 0.001). The most reliable predictive markers of nephrotoxicity were TER-MAG3 and cystatin C. Renal toxicity in patients treated with [{sup 177}Lu]Lu-PSMA-617 was low. There was no (sub)acute grade 3 or 4 nephrotoxicity. (orig.)

  6. A phase 2 study of high-activity {sup 186}Re-HEDP with autologous peripheral blood stem cell transplant in progressive hormone-refractory prostate cancer metastatic to bone

    Energy Technology Data Exchange (ETDEWEB)

    O' Sullivan, J.M. [Queen' s University Belfast/Belfast City Hospital, Department of Oncology, Belfast (United Kingdom); Norman, A.R. [Royal Marsden Foundation NHS Trust, Department of Computing, Sutton, Surrey (United Kingdom); McCready, V.R.; Flux, G.; Buffa, F.M. [Royal Marsden Foundation NHS Trust, Department of Physics, Sutton, Surrey (United Kingdom); Johnson, B. [Royal Marsden Foundation NHS Trust, Bob Champion Unit, Sutton, Surrey (United Kingdom); Coffey, J.; Horwich, A.; Huddart, R.A.; Parker, C.C.; Dearnaley, D.P. [Royal Marsden Foundation NHS Trust, Academic Unit of Urology, Sutton, Surrey (United Kingdom); Cook, G. [Royal Marsden Foundation NHS Trust, Department of Nuclear Medicine, Sutton, Surrey (United Kingdom); Treleaven, J. [Royal Marsden Foundation NHS Trust, Department of Haematology, Sutton, Surrey (United Kingdom)

    2006-09-15

    We investigated the potential for improvement in disease control by use of autologous peripheral blood stem cell transplant (PBSCT) to permit administration of high activities of {sup 186}Re-hydroxyethylidene diphosphonate (HEDP) in patients with progressive hormone-refractory prostate cancer (HRPC). Eligible patients had progressive HRPC metastatic to bone, good performance status and minimal soft tissue disease. Patients received 5,000 MBq of {sup 186}Re-HEDP i.v., followed 14 days later by PBSCT. Response was assessed using PSA, survival, pain scores and quality of life. Thirty-eight patients with a median age of 67 years (range 50-77) and a median PSA of 57 ng/ml (range 4-3,628) received a median activity of 4,978 MBq {sup 186}Re-HEDP (range 4,770-5,100 MBq). The most serious toxicity was short-lived grade 3 thrombocytopenia in 8 (21%) patients. The median survival of the group is 21 months (95%CI 18-24 months) with Kaplan-Meier estimated 1- and 2-year survival rates of 83% and 40% respectively. Thirty-one patients (81%, 95% CI 66-90%) had stable or reduced PSA levels 3 months post therapy while 11 (29%, 95% CI 15-49%) had PSA reductions of >50% lasting >4 weeks. Quality of life measures were stable or improved in 27 (66%) at 3 months. We have shown that it is feasible and safe to deliver high-activity radioisotope therapy with PBSCT to men with metastatic HRPC. Response rates and survival data are encouraging; however, further research is needed to define optimal role of this treatment approach. (orig.)

  7. PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery

    Science.gov (United States)

    2017-09-04

    Advanced Malignant Solid Neoplasm; Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Metastatic Malignant Solid Neoplasm; Progesterone Receptor Negative; PTEN Gene Mutation; Triple-Negative Breast Carcinoma; Unresectable Solid Neoplasm

  8. Phase II study of single-agent bosutinib, a Src/Abl tyrosine kinase inhibitor, in patients with locally advanced or metastatic breast cancer pretreated with chemotherapy.

    Science.gov (United States)

    Campone, M; Bondarenko, I; Brincat, S; Hotko, Y; Munster, P N; Chmielowska, E; Fumoleau, P; Ward, R; Bardy-Bouxin, N; Leip, E; Turnbull, K; Zacharchuk, C; Epstein, R J

    2012-03-01

    This phase II study evaluated single-agent bosutinib in pretreated patients with locally advanced or metastatic breast cancer. Patients received oral bosutinib 400 mg/day. The primary end point was the progression-free survival (PFS) rate at 16 weeks. Secondary end points included objective response rate, clinical benefit rate, 2-year overall survival rate, safety, and changes in levels of bone resorption/formation biomarkers. Seventy-three patients were enrolled and treated. Median time from diagnosis of metastatic disease to initiation of bosutinib treatment was 24.5 months. For the intent-to-treat population, the PFS rate at 16 weeks was 39.6%. Unexpectedly, all responding patients (n = 4) were hormone receptor positive. The clinical benefit rate was 27.4%. The 2-year overall survival rate was 26.4%. The main toxic effects were diarrhea (66%), nausea (55%), and vomiting (47%). Grade 3-4 laboratory aminotransferase elevations occurred in 14 (19%) patients. Myelosuppression was minimal. No consistent changes in the levels of bone resorption/formation biomarkers were seen. Bosutinib showed promising efficacy in prolonging time to progression in chemotherapy-pretreated patients with locally advanced or metastatic breast cancer. Bosutinib was generally well tolerated, with a safety profile different from that of the Src/Abl tyrosine kinase inhibitor dasatinib in a similar patient population.

  9. Androgen receptor expression on circulating tumor cells in metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    Takeo Fujii

    Full Text Available Androgen receptor (AR is frequently detected in breast cancers, and AR-targeted therapies are showing activity in AR-positive (AR+ breast cancer. However, the role of AR in breast cancers is still not fully elucidated and the biology of AR in breast cancer remains incompletely understood. Circulating tumor cells (CTCs can serve as prognostic and diagnostic tools, prompting us to measure AR protein expression and conduct genomic analyses on CTCs in patients with metastatic breast cancer.Blood samples from patients with metastatic breast cancer were deposited on glass slides, subjected to nuclear staining with DAPI, and reacted with fluorescent-labeled antibodies to detect CD45, cytokeratin (CK, and biomarkers of interest (AR, estrogen receptor [ER], and HER2 on all nucleated cells. The stained slides were scanned and enumerated by non-enrichment-based non-biased approach independent of cell surface epithelial cell adhesion molecule (EpCAM using the Epic Sciences CTC platform. Data were analyzed using established digital pathology algorithms.Of 68 patients, 51 (75% had at least 1 CTC, and 49 of these 51 (96% had hormone-receptor-positive (HR+/HER2-negative primary tumors. AR was expressed in CK+ CTCs in 10 patients. Of these 10 patients, 3 also had ER expression in CK+ CTCs. Single cell genomic analysis of 78 CTCs from 1 of these 3 patients identified three distinct copy number patterns. AR+ cells had a lower frequency of chromosomal changes than ER+ and HER2+ cells.CTC enumeration and analysis using no enrichment or selection provides a non-biased approach to detect AR expression and chromosomal aberrations in CTCs in patients with metastatic breast cancer. The heterogeneity of intrapatient AR expression in CTCs leads to the new hypothesis that patients with AR+ CTCs have heterogeneous disease with multiple drivers. Further studies are warranted to investigate the clinical applicability of AR+ CTCs and their heterogeneity.

  10. Androgen receptor expression on circulating tumor cells in metastatic breast cancer

    Science.gov (United States)

    Fujii, Takeo; Reuben, James M.; Huo, Lei; Espinosa Fernandez, Jose Rodrigo; Gong, Yun; Krupa, Rachel; Suraneni, Mahipal V.; Graf, Ryon P.; Lee, Jerry; Greene, Stephanie; Rodriguez, Angel; Dugan, Lyndsey; Louw, Jessica; Lim, Bora; Barcenas, Carlos H.; Marx, Angela N.; Tripathy, Debu; Wang, Yipeng; Landers, Mark; Dittamore, Ryan

    2017-01-01

    Purpose Androgen receptor (AR) is frequently detected in breast cancers, and AR-targeted therapies are showing activity in AR-positive (AR+) breast cancer. However, the role of AR in breast cancers is still not fully elucidated and the biology of AR in breast cancer remains incompletely understood. Circulating tumor cells (CTCs) can serve as prognostic and diagnostic tools, prompting us to measure AR protein expression and conduct genomic analyses on CTCs in patients with metastatic breast cancer. Methods Blood samples from patients with metastatic breast cancer were deposited on glass slides, subjected to nuclear staining with DAPI, and reacted with fluorescent-labeled antibodies to detect CD45, cytokeratin (CK), and biomarkers of interest (AR, estrogen receptor [ER], and HER2) on all nucleated cells. The stained slides were scanned and enumerated by non-enrichment-based non-biased approach independent of cell surface epithelial cell adhesion molecule (EpCAM) using the Epic Sciences CTC platform. Data were analyzed using established digital pathology algorithms. Results Of 68 patients, 51 (75%) had at least 1 CTC, and 49 of these 51 (96%) had hormone-receptor-positive (HR+)/HER2-negative primary tumors. AR was expressed in CK+ CTCs in 10 patients. Of these 10 patients, 3 also had ER expression in CK+ CTCs. Single cell genomic analysis of 78 CTCs from 1 of these 3 patients identified three distinct copy number patterns. AR+ cells had a lower frequency of chromosomal changes than ER+ and HER2+ cells. Conclusions CTC enumeration and analysis using no enrichment or selection provides a non-biased approach to detect AR expression and chromosomal aberrations in CTCs in patients with metastatic breast cancer. The heterogeneity of intrapatient AR expression in CTCs leads to the new hypothesis that patients with AR+ CTCs have heterogeneous disease with multiple drivers. Further studies are warranted to investigate the clinical applicability of AR+ CTCs and their

  11. The European Medicines Agency review of cabazitaxel (Jevtana®) for the treatment of hormone-refractory metastatic prostate cancer: summary of the scientific assessment of the committee for medicinal products for human use.

    Science.gov (United States)

    Pean, Elias; Demolis, Pierre; Moreau, Alexandre; Hemmings, Robert James; O'Connor, Daniel; Brown, David; Shepard, Terry; Abadie, Eric; Pignatti, Francesco

    2012-01-01

    On March 17, 2011 the European Commission issued a marketing authorization valid throughout the European Union for Jevtana® (Sanofi-Aventis, Paris, France) for the treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen. The active substance of Jevtana® is cabazitaxel acetone solvate, an antineoplastic agent that acts by disrupting the microtubular network in cells. The recommended dose of cabazitaxel is 25 mg/m2 administered as a 1-hour i.v. infusion every 3 weeks in combination with oral prednisone or prednisolone, 10 mg, administered daily throughout treatment. In the main study submitted for this application, a 2.4-month longer median overall survival time and a 30% lower risk for death were observed for cabazitaxel, compared with mitoxantrone. The most common side effects with cabazitaxel were anemia, leukopenia, neutropenia, thrombocytopenia, and diarrhea. This paper summarizes the scientific review of the application leading to approval in the European Union. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the European Medicines Agency Web site (http://www.ema.europa.eu).

  12. Positron emission tomography of tumour [{sup 18}F]fluoroestradiol uptake in patients with acquired hormone-resistant metastatic breast cancer prior to oestradiol therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kruchten, Michel van; Schroeder, Carolien P.; Vries, Elisabeth G.E. de; Hospers, Geke A.P. [University of Groningen, Department of Medical Oncology, University Medical Centre Groningen (Netherlands); Glaudemans, Andor W.J.M.; Vries, Erik F.J. de [University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen (Netherlands)

    2015-10-15

    Whereas anti-oestrogen therapy is widely applied to treat oestrogen receptor (ER) positive breast cancer, paradoxically, oestrogens can also induce tumour regression. Up-regulation of ER expression is a marker for oestrogen hypersensitivity. We, therefore, performed an exploratory study to evaluate positron emission tomography (PET) with the tracer 16α-[{sup 18}F]fluoro-17β-oestradiol ({sup 18}F-FES) as potential marker to select breast cancer patients for oestradiol therapy. Eligible patients had acquired endocrine-resistant metastatic breast cancer that progressed after ≥2 lines of endocrine therapy. All patients had prior ER-positive histology. Treatment consisted of oestradiol 2 mg, three times daily, orally. Patients underwent {sup 18}F-FES-PET/CT imaging at baseline. Tumour {sup 18}F-FES-uptake was quantified for a maximum of 20 lesions and expressed as maximum standardised uptake value (SUV{sub max}). CT-scan was repeated every 3 months to evaluate treatment response. Clinical benefit was defined as time to radiologic or clinical progression ≥24 weeks. {sup 18}F-FES uptake, quantified for 255 lesions in 19 patients, varied greatly between lesions (median 2.8; range 0.6-24.3) and between patients (median 2.5; range 1.1-15.5). Seven (37 %) patients experienced clinical benefit of oestrogen therapy, eight progressed (PD), and four were non-evaluable due to side effects. The positive and negative predictive value (PPV/NPV) of {sup 18}F-FES-PET for response to treatment were 60 % (95 % CI: 31-83 %) and 80 % (95 % CI: 38-96 %), respectively, using SUV{sub max} >1.5. {sup 18}F-FES-PET may aid identification of patients with acquired antihormone resistant breast cancer that are unlikely to benefit from oestradiol therapy. (orig.)

  13. Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor positive breast cancer

    Science.gov (United States)

    Meric-Bernstam, Funda; Gonzalez-Angulo, Ana Maria; Ferrer-Lozano, Jaime; Perez-Fidalgo, Jose A.; Cristofanilli, Massimo; Gómez, Henry; Arteaga, Carlos L.; Giltnane, Jennifer; Balko, Justin M.; Cronin, Maureen T; Jarosz, Mirna; Sun, James; Hawryluk, Matthew; Lipson, Doron; Otto, Geoff; Ross, Jeffrey S; Dvir, Addie; Soussan-Gutman, Lior; Wolf, Ido; Rubinek, Tamar; Gilmore, Lauren; Schnitt, Stuart; Come, Steven E.; Pusztai, Lajos; Stephens, Philip; Brown, Myles; Miller, Vincent A.

    2014-01-01

    Purpose We undertook this study to determine the prevalence of estrogen receptor (ER) α (ESR1) mutations throughout the natural history of hormone dependent breast cancer and to delineate the functional roles of the most commonly detected alterations. Experimental Design We studied a total of 249 tumor specimens from 208 patients. The specimens include 134 ER positive (ER+/HER2–) and, as controls, 115 ER negative (ER−) tumors. The ER+ samples consist of 58 primary breast cancers and 76 metastatic samples. All tumors were sequenced to high unique coverage using next generation sequencing targeting the coding sequence of the estrogen receptor and an additional 182 cancer-related genes. Results Recurring somatic mutations in codons 537 and 538 within the ligand-binding domain of ER were detected in ER+ metastatic disease. Overall, the frequency of these mutations was 12% (9/76, 95% CI 6%-21%) in metastatic tumors and in a subgroup of patients who received an average of 7 lines of treatment the frequency was 20% (5/25, 95% CI 7%-41%). These mutations were not detected in primary or treatment naïve ER+ cancer or in any stage of ER− disease. Functional studies in cell line models demonstrate that these mutations render estrogen receptor constitutive activity and confer partial resistance to currently available endocrine treatments. Conclusions In this study we show evidence for the temporal selection of functional ESR1 mutations as potential drivers of endocrine resistance during the progression of ER positive breast cancer. PMID:24398047

  14. Efficacy and Safety of Combined Androgen Deprivation Therapy (ADT and Docetaxel Compared with ADT Alone for Metastatic Hormone-Naive Prostate Cancer: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Tobias Engel Ayer Botrel

    Full Text Available Prostate cancer is the most common nonskin cancer and second most common cause of cancer mortality in older men in the United States (USA and Western Europe. Androgen-deprivation therapy alone (ADT remains the first line of treatment in most cases, for metastatic disease. We performed a systematic review and meta-analysis of all randomized controlled trials (RCT that compared the efficacy and adverse events profile of a chemohormonal therapy (ADT ± docetaxel for metastatic hormone-naive prostate cancer (mHNPC.Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoint was overall survival. Data extracted from the studies were combined by using the hazard ratio (HR or risk ratio (RR with their corresponding 95% confidence intervals (95% CI.The final analysis included 3 trials comprising 2,264 patients (mHNPC. Patients who received the chemohormonal therapy had a longer clinical progression-free survival interval (HR = 0.64; 95% CI: 0.55 to 0.75; p<0.00001, and no heterogeneity (Chi2 = 0.64; df = 1 [p = 0.42]; I2 = 0%. The biochemical progression-free survival (bPFS also was higher in patients treated with ADT plus docetaxel (HR = 0.63; 95% CI: 0.57 to 0.69; p<0.00001, also with no heterogeneity noted (Chi2 = 0.48; df = 2 [p = 0.79]; I2 = 0%. Finally, the combination of ADT with docetaxel showed a superior overall survival (OS compared with ADT alone (HR = 0.73; 95% CI: 0.64 to 0.84; p<0.0001, with moderate heterogeneity (Chi2 = 3.84; df = 2 [p = 0.15]; I2 = 48%. A random-effects model analysis was performed, and the results remained favorable to the use of ADT plus docetaxel (HR = 0.73; 95% CI: 0.60 to 0.89; p = 0.002. In the final combined analysis of the high-volume disease patients, the use of the combination therapy also favored an increased overall survival (HR = 0.67; 95% CI: 0.54 to 0.83; p = 0.0003. Regarding adverse events and severe toxicity (grade ≥3, the group receiving the combined therapy

  15. Health-related quality of life in pain-free or mildly symptomatic patients with metastatic hormone-resistant prostate cancer following treatment with the specific endothelin A receptor antagonist zibotentan (ZD4054).

    Science.gov (United States)

    Dawson, Nancy; Payne, Heather; Battersby, Clare; Taboada, Maria; James, Nick

    2011-01-01

    Zibotentan (ZD4054) is a specific endothelin A receptor antagonist in clinical development for the treatment of hormone-resistant prostate cancer (HRPC). In a Phase II trial in patients with pain-free or mildly symptomatic metastatic HRPC, zibotentan was well tolerated with a promising signal for prolonged overall survival compared with placebo. As part of this trial, the impact of zibotentan compared with placebo on health-related quality of life (HRQoL) was assessed. Patients were randomized to receive once-daily oral zibotentan 10 or 15 mg, or matching placebo. Patients were allocated to one of two questionnaires; the Functional Assessment of Cancer Therapy-Prostate (FACT-P) or the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), supplemented by PR25, specific for prostate cancer. Questionnaires were completed at baseline and every 4 weeks until disease progression when study treatment was discontinued. Compliance with questionnaire completion was >90% (286 of 312 patients) of the intention-to-treat population at baseline. Of baseline completers who were available for assessment (i.e., had not clinically progressed), 89% (164 of 184) and 83% (73 of 88) completed questionnaires at 12 and 24 weeks, respectively. HRQoL scores from both questionnaires were high at baseline and remained high throughout the study, with scores being similar in the zibotentan and placebo groups. However, some floor and ceiling effects were seen in the EORTC QLQ-C30 questionnaire. High-baseline HRQoL scores were maintained throughout treatment with zibotentan. The FACT-P instrument was selected to further assess the impact of zibotentan on HRQoL in the Phase III clinical trial program.

  16. Oxidative stress and counteracting mechanisms in hormone receptor positive, triple-negative and basal-like breast carcinomas

    Directory of Open Access Journals (Sweden)

    Soini Ylermi

    2011-06-01

    Full Text Available Abstract Background Triple-negative breast cancer (TNBC and basal-like breast cancer (BLBC are breast cancer subtypes with an especially poor prognosis. 8-Hydroxydeoxyguanosine (8-OHdG is a widely used marker of oxidative stress and the redox-state-regulating enzymes peroxiredoxins (PRDXs are efficient at depressing excessive reactive oxygen species. NF-E2-related factor 2 (Nrf2 and Kelch-like ECH-associated protein 1 (Keap1 are redox-sensitive transcription factors that regulate PRDX expression. This is the first study to assess oxidative stress and or cell redox state-regulating enzymes in TNBC and BLBC. Methods We assessed immunohistochemical expression of 8-OHdG, Nrf2, Keap1, PRDX III and PRDX IV in 79 women with invasive ductal breast carcinomas. Of these tumors, 37 represented TNBC (grade II-III tumors with total lack of ER, PR and human epidermal growth factor receptor 2 [HER2] expression. Control cases (n = 42 were ER-positive, PR-positive and HER2-negative. Of the 37 TNBCs, 31 had BLBC phenotype (TNBC with expression of cytokeratin 5/6 or epidermal growth factor receptor 1. Results Patients with TNBC had worse breast cancer-specific survival (BCSS than the control group (p = 0.015. Expression of 8-OHdG was significantly lower in TNBC than in the non-TNBC group (p vs. the non-TNBC group (p = 0.022. Conclusions Cellular redox state markers may be promising targets when elucidating the pathogenesis of TNBC.

  17. Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance).

    Science.gov (United States)

    Bluethmann, Shirley M; Alfano, Catherine M; Clapp, Jonathan D; Luta, George; Small, Brent J; Hurria, Arti; Cohen, Harvey J; Sugarman, Steven; B Muss, Hyman; Isaacs, Claudine; Mandelblatt, Jeanne S

    2017-10-01

    To investigate the effects of cognitive function on discontinuation of hormonal therapy in breast cancer survivors ages 65+ ("older"). Older breast cancer survivors with invasive, non-metastatic disease, and no reported cognitive difficulties were recruited from 78 Alliance sites between 2004 and 2011. Eligible survivors (n = 1280) completed baseline interviews; follow-up was conducted annually for up to 7 years. Survivors with estrogen-receptor-positive (ER+) cancers who initiated hormonal therapy (n = 990) were included. Self-reported cognitive function was measured using the EORTC-QLQ30 scale; a difference of eight points on the 0-100 scale was considered clinically significant. Based on varying rates of discontinuation over time, discontinuation was evaluated separately for three time periods: early (3-5 years). Cox models for each time period were used to evaluate the effects of cognition immediately preceding discontinuation, controlling for age, chemotherapy, and other covariates. Survivors were 65-91 years old (mean 72.6 years), and 79% had stages 1 or 2A disease. Overall, 43% discontinued hormonal therapy before 5 years. Survivors who reported lower cognitive function in the period before discontinuation had greater hazards of discontinuing therapy at the treatment midpoint (HR 1.22 per 8-point difference, CI 1.09-1.40, p cognition was not related to discontinuation in the other periods. Self-reported cognitive problems were a significant risk factor for discontinuation of hormonal therapy 1-3 years post-initiation. Additional research is needed on the temporality of cognitive effects and hormonal therapy to support survivorship care needs of older survivors.

  18. Prognosis of metastatic breast cancer: are there differences between patients with de novo and recurrent metastatic breast cancer?

    Science.gov (United States)

    Lobbezoo, D J A; van Kampen, R J W; Voogd, A C; Dercksen, M W; van den Berkmortel, F; Smilde, T J; van de Wouw, A J; Peters, F P J; van Riel, J M G H; Peters, N A J B; de Boer, M; Peer, P G M; Tjan-Heijnen, V C G

    2015-04-28

    We aimed to determine the prognostic impact of time between primary breast cancer and diagnosis of distant metastasis (metastatic-free interval, MFI) on the survival of metastatic breast cancer patients. Consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight hospitals in the Southeast of the Netherlands were included and categorised based on MFI. Survival curves were estimated using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic impact of de novo metastatic breast cancer vs recurrent metastatic breast cancer (MFI ⩽24 months and >24 months), adjusted for age, hormone receptor and HER2 status, initial site of metastasis and use of prior (neo)adjuvant systemic therapy. Eight hundred and fifteen patients were included and divided in three subgroups based on MFI; 154 patients with de novo metastatic breast cancer, 176 patients with MFI 24 months. Patients with de novo metastatic breast cancer had a prolonged survival compared with patients with recurrent metastatic breast cancer with MFI 24 months (median, 29.4 vs 27.9 months, P=0.73). Adjusting for other prognostic factors, patients with MFI 24 months with de novo metastatic breast cancer no significant difference in mortality risk was found. The association between MFI and survival was seen irrespective of use of (neo)adjuvant systemic therapy. Patients with de novo metastatic breast cancer had a significantly better outcome when compared with patients with MFI 24 months, patients with de novo metastatic breast cancer had similar outcome.

  19. Placental Kisspeptins Differentially Modulate Vital Parameters of Estrogen Receptor-Positive and -Negative Breast Cancer Cells

    Science.gov (United States)

    Rasoulzadeh, Zahra; Ghods, Roya; Kazemi, Tohid; Mirzadegan, Ebrahim; Ghaffari-Tabrizi-Wizsy, Nassim; Rezania, Simin; Kazemnejad, Somaieh; Arefi, Soheila; Ghasemi, Jamileh; Vafaei, Sedigheh; Mahmoudi, Ahmad-Reza; Zarnani, Amir-Hassan

    2016-01-01

    Kisspeptins (KPs) are major regulators of trophoblast and cancer invasion. Thus far, limited and conflicting data are available on KP-mediated modulation of breast cancer (BC) metastasis; mostly based on synthetic KP-10, the most active fragment of KP. Here, we report for the first time comprehensive functional effects of term placental KPs on proliferation, adhesion, Matrigel invasion, motility, MMP activity and pro-inflammatory cytokine production in MDA-MB-231 (estrogen receptor-negative) and MCF-7 (estrogen receptor-positive). KPs were expressed at high level by term placental syncytiotrophoblasts and released in soluble form. Placental explant conditioned medium containing KPs (CM) significantly reduced proliferation of both cell types compared to CM without (w/o) KP (CM-w/o KP) in a dose- and time-dependent manner. In MDA-MB-231 cells, placental KPs significantly reduced adhesive properties, while increased MMP9 and MMP2 activity and stimulated invasion. Increased invasiveness of MDA-MB-231 cells after CM treatment was inhibited by KP receptor antagonist, P-234. CM significantly reduced motility of MCF-7 cells at all time points (2–30 hr), while it stimulated motility of MDA-MB-231 cells. These effects were reversed by P-234. Co-treatment with selective ER modulators, Tamoxifen and Raloxifene, inhibited the effect of CM on motility of MCF-7 cells. The level of IL-6 in supernatant of MCF-7 cells treated with CM was higher compared to those treated with CM-w/o KP. Both cell types produced more IL-8 after treatment with CM compared to those treated with CM-w/o KP. Taken together, our observations suggest that placental KPs differentially modulate vital parameters of estrogen receptor-positive and -negative BC cells possibly through modulation of pro-inflammatory cytokine production. PMID:27101408

  20. Placental Kisspeptins Differentially Modulate Vital Parameters of Estrogen Receptor-Positive and -Negative Breast Cancer Cells.

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    Zahra Rasoulzadeh

    Full Text Available Kisspeptins (KPs are major regulators of trophoblast and cancer invasion. Thus far, limited and conflicting data are available on KP-mediated modulation of breast cancer (BC metastasis; mostly based on synthetic KP-10, the most active fragment of KP. Here, we report for the first time comprehensive functional effects of term placental KPs on proliferation, adhesion, Matrigel invasion, motility, MMP activity and pro-inflammatory cytokine production in MDA-MB-231 (estrogen receptor-negative and MCF-7 (estrogen receptor-positive. KPs were expressed at high level by term placental syncytiotrophoblasts and released in soluble form. Placental explant conditioned medium containing KPs (CM significantly reduced proliferation of both cell types compared to CM without (w/o KP (CM-w/o KP in a dose- and time-dependent manner. In MDA-MB-231 cells, placental KPs significantly reduced adhesive properties, while increased MMP9 and MMP2 activity and stimulated invasion. Increased invasiveness of MDA-MB-231 cells after CM treatment was inhibited by KP receptor antagonist, P-234. CM significantly reduced motility of MCF-7 cells at all time points (2-30 hr, while it stimulated motility of MDA-MB-231 cells. These effects were reversed by P-234. Co-treatment with selective ER modulators, Tamoxifen and Raloxifene, inhibited the effect of CM on motility of MCF-7 cells. The level of IL-6 in supernatant of MCF-7 cells treated with CM was higher compared to those treated with CM-w/o KP. Both cell types produced more IL-8 after treatment with CM compared to those treated with CM-w/o KP. Taken together, our observations suggest that placental KPs differentially modulate vital parameters of estrogen receptor-positive and -negative BC cells possibly through modulation of pro-inflammatory cytokine production.

  1. Aromatase expression increases the survival and malignancy of estrogen receptor positive breast cancer cells.

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    Keya De Mukhopadhyay

    Full Text Available In postmenopausal women, local estrogen produced by adipose stromal cells in the breast is believed to support estrogen receptor alpha (ERα positive breast cancer cell survival and growth. This raises the question of how the ERα positive metastatic breast cancer cells survive after they enter blood and lymph circulation, where estrogen level is very low in postmenopausal women. In this study, we show that the aromatase expression increased when ERα positive breast cancer cells were cultured in suspension. Furthermore, treatment with the aromatase substrate, testosterone, inhibited suspension culture-induced apoptosis whereas an aromatase inhibitor attenuated the effect of testosterone suggesting that suspended circulating ERα positive breast cancer cells may up-regulate intracrine estrogen activity for survival. Consistent with this notion, a moderate level of ectopic aromatase expression rendered a non-tumorigenic ERα positive breast cancer cell line not only tumorigenic but also metastatic in female nude mice without exogenous estrogen supplementation. The increased malignant phenotype was confirmed to be due to aromatase expression as the growth of orthotopic tumors regressed with systemic administration of an aromatase inhibitor. Thus, our study provides experimental evidence that aromatase plays an important role in the survival of metastatic ERα breast cancer cells by suppressing anoikis.

  2. Current problems in the first-line treatment of metastatic breast cancer: focus on the role of docetaxel

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    Filippo Montemurro

    2010-09-01

    Full Text Available Metastatic breast cancer is a very heterogeneous disease, both from a clinical and a biological point of view. Despite being still incurable, the expanding therapeutic repertoire has determined a progressive increase in median survival. We describe the clinical course of a 67-year-old woman with a locally advanced, hormone-receptor positive breast cancer with synchronous liver metastases. Single-agent docetaxel at the dose of 100 mg/m2 for 8 cycles determined a pathological complete remission in the breast and a near complete remission of liver metastases. After more than 4 years from diagnosis, the patient is alive and without signs of tumour progression. Based on this clinical case, we discuss management issues like the choice of the initial treatment, the use of monochemotherapy vs polychemotherapy, the worth of surgery of the primary tumour in patients with stage IV disease, and the issue of maintenance endocrine therapy. Furthermore, we reviewed the pivotal role of docetaxel in the management of advanced breast cancer. Whether monochemotherapy or polychemotherapy is felt to be an adequate choice in the clinical practice, docetaxel qualifies as one of the most active and manageable agents. Single agent activity ranging from 20-48% in terms of response rate has been reported in several clinical trials in patients treated in various clinical settings. Docetaxel-based combinations with other cytotoxic agents have become established in the first line treatment both in patients with anthracycline-resistant and anthracycline-sensitive metastatic breast cancer. Finally, docetaxel has been shown to be an optimal companion drug for biologically targeted agents like trastuzumab or bevacizumab, resulting in further treatment options.

  3. Lineage-Biased Stem Cells Maintain Estrogen-Receptor-Positive and -Negative Mouse Mammary Luminal Lineages

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    Chunhui Wang

    2017-03-01

    Full Text Available Delineating the mammary differentiation hierarchy is important for the study of mammary gland development and tumorigenesis. Mammary luminal cells are considered a major origin of human breast cancers. However, how estrogen-receptor-positive (ER+ and ER− luminal cells are developed and maintained remains poorly understood. The prevailing model suggests that a common stem/progenitor cell generates both cell types. Through genetic lineage tracing in mice, we find that SOX9-expressing cells specifically contribute to the development and maintenance of ER− luminal cells and, to a lesser degree, basal cells. In parallel, PROM1-expressing cells give rise only to ER+ luminal cells. Both SOX9+ and PROM1+ cells specifically sustain their respective lineages even after pregnancy-caused tissue remodeling or serial transplantation, demonstrating characteristic properties of long-term repopulating stem cells. Thus, our data reveal that mouse mammary ER+ and ER− luminal cells are two independent lineages that are maintained by distinct stem cells, providing a revised mammary epithelial cell hierarchy.

  4. Mutational Profile of Metastatic Breast Cancers: A Retrospective Analysis.

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    Celine Lefebvre

    2016-12-01

    Full Text Available Major advances have been achieved in the characterization of early breast cancer (eBC genomic profiles. Metastatic breast cancer (mBC is associated with poor outcomes, yet limited information is available on the genomic profile of this disease. This study aims to decipher mutational profiles of mBC using next-generation sequencing.Whole-exome sequencing was performed on 216 tumor-blood pairs from mBC patients who underwent a biopsy in the context of the SAFIR01, SAFIR02, SHIVA, or Molecular Screening for Cancer Treatment Optimization (MOSCATO prospective trials. Mutational profiles from 772 primary breast tumors from The Cancer Genome Atlas (TCGA were used as a reference for comparing primary and mBC mutational profiles. Twelve genes (TP53, PIK3CA, GATA3, ESR1, MAP3K1, CDH1, AKT1, MAP2K4, RB1, PTEN, CBFB, and CDKN2A were identified as significantly mutated in mBC (false discovery rate [FDR] < 0.1. Eight genes (ESR1, FSIP2, FRAS1, OSBPL3, EDC4, PALB2, IGFN1, and AGRN were more frequently mutated in mBC as compared to eBC (FDR < 0.01. ESR1 was identified both as a driver and as a metastatic gene (n = 22, odds ratio = 29, 95% CI [9-155], p = 1.2e-12 and also presented with focal amplification (n = 9 for a total of 31 mBCs with either ESR1 mutation or amplification, including 27 hormone receptor positive (HR+ and HER2 negative (HER2- mBCs (19%. HR+/HER2- mBC presented a high prevalence of mutations on genes located on the mechanistic target of rapamycin (mTOR pathway (TSC1 and TSC2 as compared to HR+/HER2- eBC (respectively 6% and 0.7%, p = 0.0004. Other actionable genes were more frequently mutated in HR+ mBC, including ERBB4 (n = 8, NOTCH3 (n = 7, and ALK (n = 7. Analysis of mutational signatures revealed a significant increase in APOBEC-mediated mutagenesis in HR+/HER2- metastatic tumors as compared to primary TCGA samples (p < 2e-16. The main limitations of this study include the absence of bone metastases and the size of the cohort, which might

  5. Effects of obesity on transcriptomic changes and cancer hallmarks in estrogen receptor-positive breast cancer.

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    Fuentes-Mattei, Enrique; Velazquez-Torres, Guermarie; Phan, Liem; Zhang, Fanmao; Chou, Ping-Chieh; Shin, Ji-Hyun; Choi, Hyun Ho; Chen, Jiun-Sheng; Zhao, Ruiying; Chen, Jian; Gully, Chris; Carlock, Colin; Qi, Yuan; Zhang, Ya; Wu, Yun; Esteva, Francisco J; Luo, Yongde; McKeehan, Wallace L; Ensor, Joe; Hortobagyi, Gabriel N; Pusztai, Lajos; Fraser Symmans, W; Lee, Mong-Hong; Yeung, Sai-Ching Jim

    2014-07-01

    Obesity increases the risk of cancer death among postmenopausal women with estrogen receptor-positive (ER+) breast cancer, but the direct evidence for the mechanisms is lacking. The purpose of this study is to demonstrate direct evidence for the mechanisms mediating this epidemiologic phenomenon. We analyzed transcriptomic profiles of pretreatment biopsies from a prospective cohort of 137 ER+ breast cancer patients. We generated transgenic (MMTV-TGFα;A (y) /a) and orthotopic/syngeneic (A (y) /a) obese mouse models to investigate the effect of obesity on tumorigenesis and tumor progression and to determine biological mechanisms using whole-genome transcriptome microarrays and protein analyses. We used a coculture system to examine the impact of adipocytes/adipokines on breast cancer cell proliferation. All statistical tests were two-sided. Functional transcriptomic analysis of patients revealed the association of obesity with 59 biological functional changes (P cancer hallmarks. Gene enrichment analysis revealed enrichment of AKT-target genes (P = .04) and epithelial-mesenchymal transition genes (P = .03) in patients. Our obese mouse models demonstrated activation of the AKT/mTOR pathway in obesity-accelerated mammary tumor growth (3.7- to 7.0-fold; P obesity-induced secretion of adipokines and breast tumor formation and growth (0.5-fold, P = .04; 0.3-fold, P cancer cell proliferation and invasion. Metformin suppress adipocyte-induced cell proliferation and adipocyte-secreted adipokines in vitro. Adipokine secretion and AKT/mTOR activation play important roles in obesity-accelerated breast cancer aggressiveness in addition to hyperinsulinemia, estrogen signaling, and inflammation. Metformin and everolimus have potential for therapeutic interventions of ER+ breast cancer patients with obesity. © The Author 2014. Published by Oxford University Press.

  6. Low expression of a few genes indicates good prognosis in estrogen receptor positive breast cancer

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    Buechler Steven

    2009-07-01

    Full Text Available Abstract Background Many breast cancer patients remain free of distant metastasis even without adjuvant chemotherapy. While standard histopathological tests fail to identify these good prognosis patients with adequate precision, analyses of gene expression patterns in primary tumors have resulted in more successful diagnostic tests. These tests use continuous measurements of the mRNA concentrations of numerous genes to determine a risk of metastasis in lymph node negative breast cancer patients with other clinical traits. Methods A survival model is constructed from genes that are both connected with relapse and have expression patterns that define distinct subtypes, suggestive of different cellular states. This in silico study uses publicly available microarray databases generated with Affymetrix GeneChip technology. The genes in our model, as represented by array probes, have distinctive distributions in a patient cohort, consisting of a large normal component of low expression values; and a long right tail of high expression values. The cutoff between low and high expression of a probe is determined from the distribution using the theory of mixture models. The good prognosis group in our model consists of the samples in the low expression component of multiple genes. Results Here, we define a novel test for risk of metastasis in estrogen receptor positive (ER+ breast cancer patients, using four probes that determine distinct subtypes. The good prognosis group in this test, denoted AP4-, consists of the samples with low expression of each of the four probes. Two probes target MKI67, antigen identified by monoclonal antibody Ki-67, one targets CDC6, cell division cycle 6 homolog (S. cerevisiae, and a fourth targets SPAG5, sperm associated antigen 5. The long-term metastasis-free survival probability for samples in AP4- is sufficiently high to render chemotherapy of questionable benefit. Conclusion A breast cancer subtype defined by low

  7. Pre-metastatic niches

    DEFF Research Database (Denmark)

    Peinado, Héctor; Zhang, Haiying; Matei, Irina R.

    2017-01-01

    -secreted factors and tumour-shed extracellular vesicles that enable the 'soil' at distant metastatic sites to encourage the outgrowth of incoming cancer cells. In this Review, we summarize the main processes and new mechanisms involved in the formation of the pre-metastatic niche....

  8. Polymorphisms associated with everolimus pharmacokinetics, toxicity and survival in metastatic breast cancer.

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    Tomas Pascual

    Full Text Available Metastatic breast cancer (MBC progressing after endocrine therapy frequently activates PI3K/AKT/mTOR pathway. The BOLERO-2 trial showed that everolimus-exemestane achieves increased progression free survival (PFS compared with exemestane. However, there is great inter-patient variability in toxicity and response to exemestane-everolimus treatment. The objective of this study was to perform an exploratory study analyzing the implication of single nucleotide polymorphisms (SNPs on outcomes from this treatment through a pharmacogenetic analysis.Blood was collected from 90 postmenopausal women with hormone receptor-positive, HER2-negative MBC treated with exemestane-everolimus following progression after prior treatment with a non-steroidal aromatase inhibitor. Everolimus pharmacokinetics was measured in 37 patients. Twelve SNPs in genes involved in everolimus pharmacokinetics and pharmacodynamics were genotyped and associations assessed with drug plasma levels, clinically relevant toxicities (non-infectious pneumonitis, mucositis, hyperglycemia and hematological toxicities, dose reductions or treatment suspensions due to toxicity, progression free survival (PFS and overall survival.We found that CYP3A4 rs35599367 variant (CYP3A4*22 allele carriers had higher everolimus blood concentration compared to wild type patients (P = 0.019. ABCB1 rs1045642 was associated with risk of mucositis (P = 0.031, while PIK3R1 rs10515074 and RAPTOR rs9906827 were associated with hyperglycemia and non-infectious pneumonitis (P = 0.016 and 0.024, respectively. Furthermore, RAPTOR rs9906827 was associated with PFS (P = 0.006.CYP3A4*22 allele influenced plasma concentration of everolimus and several SNPs in PI3K/AKT/mTOR pathway genes were associated with treatment toxicities and prognosis. These results require replication, but suggest that germline variation could influence everolimus outcomes in MBC.

  9. Detection of ESR1 mutations in circulating cell-free DNA from patients with metastatic breast cancer treated with palbociclib and letrozole.

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    Gyanchandani, Rekha; Kota, Karthik J; Jonnalagadda, Amruth R; Minteer, Tanya; Knapick, Beth A; Oesterreich, Steffi; Brufsky, Adam M; Lee, Adrian V; Puhalla, Shannon L

    2017-09-15

    ESR1 mutations are frequently acquired in hormone-resistant metastatic breast cancer (MBC). CDK4/6 inhibition along with endocrine therapy is a promising strategy in hormone receptor-positive MBC. However, the incidence and impact of ESR1 mutations on clinical outcome in patients treated with CDK4/6 inhibitors have not been defined. In this study, we evaluated the frequency of ESR1 mutations in cfDNA from 16 patients with MBC undergoing palbociclib and letrozole therapy. Four common ESR1 mutations (D538G, Y537C, Y537N, and Y537S) were analyzed in serial blood draws using ddPCR. Mutation rate was 31.3% (5/16) (n=3; de novo, n=2; acquired). D538G was the most frequent mutation (n=3), followed by Y537N and Y537S (n=2). One patient showed multiple ESR1 mutations. Mutations were enriched during therapy. Progression-free survival (PFS) and overall survival (OS) were similar in patients with and without mutation detected at any given time during treatment. However, PFS was significantly shorter in patients with ESR1 mutation at initial blood draw (3.3 versus 9.0 months, P-value=0.038). In conclusion, ESR1 mutation prevalence is consistent with recent studies in hormone-refractory breast cancer. Further, treatment with palbociclib and letrozole does not prevent selection of ESR1 mutations in later lines of therapy. Larger studies are warranted to validate these findings.

  10. Dormancy Signatures and Metastasis in Estrogen Receptor Positive and Negative Breast Cancer

    Science.gov (United States)

    Kim, Ryung S.; Avivar-Valderas, Alvaro; Estrada, Yeriel; Bragado, Paloma; Sosa, Maria Soledad; Aguirre-Ghiso, Julio A.; Segall, Jeffrey E.

    2012-01-01

    Breast cancers can recur after removal of the primary tumor and treatment to eliminate remaining tumor cells. Recurrence may occur after long periods of time during which there are no clinical symptoms. Tumor cell dormancy may explain these prolonged periods of asymptomatic residual disease and treatment resistance. We generated a dormancy gene signature from published experimental models and applied it to both breast cancer cell line expression data as well as four published clinical studies of primary breast cancers. We found that estrogen receptor (ER) positive breast cell lines and primary tumors have significantly higher dormancy signature scores (P<0.0000001) than ER- cell lines and tumors. In addition, a stratified analysis combining all ER+ tumors in four studies indicated 2.1 times higher hazard of recurrence among patients whose tumors had low dormancy scores (LDS) compared to those whose tumors had high dormancy scores (HDS) (p<0.000005). The trend was shown in all four individual studies. Suppression of two dormancy genes, BHLHE41 and NR2F1, resulted in increased in vivo growth of ER positive MCF7 cells. The patient data analysis suggests that disseminated ER positive tumor cells carrying a dormancy signature are more likely to undergo prolonged dormancy before resuming metastatic growth. Furthermore, genes identified with this approach might provide insight into the mechanisms of dormancy onset and maintenance as well as dormancy models using human breast cancer cell lines. PMID:22530051

  11. Dormancy signatures and metastasis in estrogen receptor positive and negative breast cancer.

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    Ryung S Kim

    Full Text Available Breast cancers can recur after removal of the primary tumor and treatment to eliminate remaining tumor cells. Recurrence may occur after long periods of time during which there are no clinical symptoms. Tumor cell dormancy may explain these prolonged periods of asymptomatic residual disease and treatment resistance. We generated a dormancy gene signature from published experimental models and applied it to both breast cancer cell line expression data as well as four published clinical studies of primary breast cancers. We found that estrogen receptor (ER positive breast cell lines and primary tumors have significantly higher dormancy signature scores (P<0.0000001 than ER- cell lines and tumors. In addition, a stratified analysis combining all ER+ tumors in four studies indicated 2.1 times higher hazard of recurrence among patients whose tumors had low dormancy scores (LDS compared to those whose tumors had high dormancy scores (HDS (p<0.000005. The trend was shown in all four individual studies. Suppression of two dormancy genes, BHLHE41 and NR2F1, resulted in increased in vivo growth of ER positive MCF7 cells. The patient data analysis suggests that disseminated ER positive tumor cells carrying a dormancy signature are more likely to undergo prolonged dormancy before resuming metastatic growth. Furthermore, genes identified with this approach might provide insight into the mechanisms of dormancy onset and maintenance as well as dormancy models using human breast cancer cell lines.

  12. HER-2 amplification, HER-1 expression, and tamoxifen response in estrogen receptor-positive metastatic breast cancer: a southwest oncology group study.

    Science.gov (United States)

    Arpino, Grazia; Green, Stephanie J; Allred, D Craig; Lew, Dannika; Martino, Silvana; Osborne, C Kent; Elledge, Richard M

    2004-09-01

    Preclinical data indicate that expression of the ErbB family of receptors, such as HER-2 and HER-1 (EGFR) may be involved in endocrine resistance. Evidence of resistance from clinical studies has been inconsistent. The present study examined whether HER-2 gene amplification or HER-1 expression predicted response to tamoxifen. Three hundred and forty nine patients had estrogen receptor (ER)-positive breast cancer and received daily tamoxifen as initial therapy for advanced disease. HER-2 gene amplification, detected by fluorescence in situ hybridization, and HER-1 expression, evaluated by immunohistochemistry, was determined on 136 and 204 patients, respectively. HER-2 amplification was correlated with lower ER (P = 0.02), HER-1 positivity (P = 0.004), and HER-2 protein overexpression (P HER-1-negative versus 36% for HER-1-positive (P = 0.05). Time to treatment failure (TTF) was 7 months for non-amplified HER-2 tumors and 5 months (P = 0.007) for amplified HER-2 tumors, and there was a trend toward a better overall survival (OS) in patients with non-amplified HER-2 tumors (median 31 versus 25 months, respectively, P = 0.07). For positive versus negative HER-1 tumors, TTF was 4 versus 8 months (P = 0.08) and median survival was 24 versus 31 months (P = 0.41). Combining HER-1 expression and HER-2 gene status, patients with both negative HER-1 expression and non-amplified HER-2 had longer TTF (P = 0.001) and OS (P = 0.03) than if either were positive. In multivariate analysis, HER-2 was not an independent factor for TTF and OS, although HER-1 was significant for TTF only (P HER-1 expression had lower ER levels and were modestly less responsive to tamoxifen, suggesting that molecular events in addition to those involving the ErbB receptors are important in determining the endocrine-resistant phenotype.

  13. A Polymorphism at the 3'-UTR Region of the Aromatase Gene Is Associated with the Efficacy of the Aromatase Inhibitor, Anastrozole, in Metastatic Breast Carcinoma

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    Qing-Yuan Zhang

    2013-09-01

    Full Text Available Estrogen-related genes and the fat mass and obesity-associated (FTO gene play a critical role in estrogen metabolism, and those polymorphisms are associated with a poor prognosis in breast cancer. However, little is known about the association between these polymorphisms and the efficacy of anastrozole. The aim was to investigate the impact of the genetic polymorphisms, CYP19A1, 17-β-HSD-1 and FTO, on the response to anastrozole in metastatic breast carcinoma (MBC and to evaluate the impact of those polymorphisms on various clinicopathologic features. Two-hundred seventy-two women with hormone receptor-positive MBC treated with anastrozole were identified retrospectively. DNA was extracted from peripheral blood and genotyped for five variants in three candidate genes. Time to progression was improved in patients carrying the variant alleles of rs4646 when compared to patients with the wild-type allele (16.40 months versus 13.52 months; p = 0.049. The rs4646 variant alleles were significantly associated with longer overall survival (37.3 months versus 31.6 months; p = 0.007. This relationship was not observed with the rs10046, rs2830, rs9926298 and rs9939609 polymorphisms. The findings of this study indicate that rs4646 polymorphism in the CYP19A1 gene may serve as a prognostic maker of the response to anastrozole in patients with MBC who are treated with anastrozole.

  14. Metastatic brain tumor

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    ... JavaScript. A metastatic brain tumor is cancer that started in another part of the body ... of cancer rarely spread to the brain, such as colon cancer and prostate cancer. In other rare cases, a tumor can ...

  15. PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy—Safety and Efficacy in Asian Patients

    Directory of Open Access Journals (Sweden)

    Hiroji Iwata

    2017-08-01

    Full Text Available Purpose: To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy–resistant metastatic breast cancer. Patients and Methods: The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3 trial, a double-blind phase III study, included 521 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs were assessed on study treatment and at the end of treatment. Results: This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71 or placebo plus fulvestrant (n = 31. Palbociclib plus fulvestrant improved progression-free survival (PFS compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065. The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92% and leukopenia (29%; febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. Conclusion: This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study.

  16. Progesterone Negatively Regulates BCRP in Progesterone Receptor-Positive Human Breast Cancer Cells

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    Xiaojuan Wu

    2013-08-01

    Full Text Available Background/Aims: Breast cancer resistance protein (BCRP plays a crucial role in multidrug resistance (MDR. Previous studies have shown that steroid hormones, like progesterone (PROG, regulate BCRP expression. The presence of a progesterone response element (PRE in the BCRP promoter, suggests that PROG may regulate transcription of BCRP. Methods: To investigate the role of PROG in the regulation of BCRP expression, two constructs encoding full-length BCRP driven by either an endogenous PRE promoter or a constitutive CMV promoter, were transfected into T47D cells that express the progesterone receptor (PR or into PR-negative MDA-MB-231 cells. Results: After treatment with PROG, qPCR and Western blotting analyses indicated that BCRP mRNA and BCRP protein levels were significantly reduced in a dose-dependent manner in PR-positive cells, but PROG had no significant effect on BCRP levels in the PR-negative cells. The effect observed in PR-positive cells was reversed by co-treatment with RU-486, a specific PROG inhibitor. Cytometric analysis confirmed that BCRP-mediated drug efflux was inhibited and chemosensitivity to mitoxantrone was markedly increased by PROG treatment. Conclusion: These results suggest that PROG reverses BCRP-mediated MDR by down-regulating BCRP expression in breast cancer cells by affecting transcription from the PRE-containing BCRP promoter. Our studies suggest that breast cancer patients with BCRP-mediated MDR may be successfully treated with PROG.

  17. Preclinical Evaluation of 68Ga-DOTA-Minigastrin for the Detection of Cholecystokinin-2/Gastrin Receptor-Positive Tumors

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    Maarten Brom

    2011-03-01

    Full Text Available In comparison to somatostatin receptor scintigraphy, gastrin receptor scintigraphy using 111In-DTPA-minigastrin (MG0 showed added value in diagnosing neuroendocrine tumors. We investigated whether the 68Ga-labeled gastrin analogue DOTA-MG0 is suited for positron emission tomography (PET, which could improve image quality. Targeting of cholecystokinin-2 (CCK2/gastrin receptor-positive tumor cells with DOTA-MG0 labeled with either 111In or 68Ga in vitro was investigated using the AR42J rat tumor cell line. Biodistribution was examined in BALB/c nude mice with a subcutaneous AR42J tumor. In vivo PET imaging was performed using a preclinical PET-computed tomographic scanner. DOTA-MG0 showed high receptor affinity in vitro. Biodistribution studies revealed high tumor uptake of 68Ga-DOTA-MG0: 4.4 ± 1.3 %ID/g at 1 hour postinjection. Coadministration of an excess unlabeled peptide blocked the tumor uptake (0.7 ± 0.1 %ID/g, indicating CCK2/gastrin receptor-mediated uptake (p = .0005. The biodistribution of 68Ga-DOTA-MG0 was similar to that of 111In-DOTA-MG0. Subcutaneous and intraperitoneal tumors were clearly visualized by small-animal PET imaging with 5 MBq 68Ga-DOTA-MG0. 111In- and 68Ga-labeled DOTA-MG0 specifically accumulate in CCK2/gastrin receptor-positive AR42J tumors with similar biodistribution apart from the kidneys. AR42J tumors were clearly visualized by microPET. Therefore, 68Ga-DOTA-MG0 is a promising tracer for PET imaging of CCK2/gastrin receptor-positive tumors in humans.

  18. Breast density and parenchymal texture measures as potential risk factors for estrogen-receptor positive breast cancer

    Science.gov (United States)

    Keller, Brad M.; Chen, Jinbo; Conant, Emily F.; Kontos, Despina

    2014-03-01

    Accurate assessment of a woman's risk to develop specific subtypes of breast cancer is critical for appropriate utilization of chemopreventative measures, such as with tamoxifen in preventing estrogen-receptor positive breast cancer. In this context, we investigate quantitative measures of breast density and parenchymal texture, measures of glandular tissue content and tissue structure, as risk factors for estrogen-receptor positive (ER+) breast cancer. Mediolateral oblique (MLO) view digital mammograms of the contralateral breast from 106 women with unilateral invasive breast cancer were retrospectively analyzed. Breast density and parenchymal texture were analyzed via fully-automated software. Logistic regression with feature selection and was performed to predict ER+ versus ER- cancer status. A combined model considering all imaging measures extracted was compared to baseline models consisting of density-alone and texture-alone features. Area under the curve (AUC) of the receiver operating characteristic (ROC) and Delong's test were used to compare the models' discriminatory capacity for receptor status. The density-alone model had a discriminatory capacity of 0.62 AUC (p=0.05). The texture-alone model had a higher discriminatory capacity of 0.70 AUC (p=0.001), which was not significantly different compared to the density-alone model (p=0.37). In contrast the combined density-texture logistic regression model had a discriminatory capacity of 0.82 AUC (pmeasures may have the potential to identify women specifically at risk for estrogen-receptor positive breast cancer and could be useful in triaging women into appropriate risk-reduction strategies.

  19. Apparent diffusion coefficient in estrogen receptor-positive invasive ductal breast carcinoma: correlations with tumor-stroma ratio.

    Science.gov (United States)

    Ko, Eun Sook; Han, Boo-Kyung; Kim, Rock Bum; Cho, Eun Yoon; Ahn, Soomin; Nam, Seok Jin; Ko, Eun Young; Shin, Jung Hee; Hahn, Soo Yeon

    2014-04-01

    To determine whether apparent diffusion coefficient (ADC) values vary according to tumor-stroma ratio, dominant stroma type, or presence of central fibrosis in estrogen receptor-positive breast cancer. Institutional review board approval was obtained, and patient consent was waived. Sixty-one patients with estrogen receptor-positive invasive ductal carcinoma-not otherwise specified who underwent breast magnetic resonance (MR) imaging with diffusion-weighted (DW) imaging were included in this study. The ADC values of the lesions were measured. Two pathologists evaluated the tumor-stroma ratio, dominant stroma type (collagen, fibroblast, lymphocyte), and central fibrosis. Detectability on DW images was compared between the two groups according to the tumor-stroma ratio (stroma rich or stroma poor). Mean ADC values were retrospectively compared with the tumor-stroma ratio, dominant stroma type, and presence of a central fibrosis. Multiple linear regression analysis was performed to determine variables independently associated with ADC. On DW images, detectability was not significantly different between stroma-rich and stroma-poor groups (P = .244). ADC values were significantly lower in the stroma-poor group (P collagen-dominant type were lower than in fibroblast-dominant or lymphocyte-dominant types (P = .021). In multiple linear regression analysis, tumor-stroma ratio (P = .007), tumor size (P = .007), and dominant stroma type (collagen dominant, P = .029) were independently correlated with ADC. In estrogen receptor-positive breast cancers, ADC values showed significant differences according to the tumor-stroma ratio and dominant stroma type. RSNA, 2013

  20. Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer.

    Science.gov (United States)

    Prat, Aleix; Cheang, Maggie Chon U; Martín, Miguel; Parker, Joel S; Carrasco, Eva; Caballero, Rosalía; Tyldesley, Scott; Gelmon, Karen; Bernard, Philip S; Nielsen, Torsten O; Perou, Charles M

    2013-01-10

    Current immunohistochemical (IHC)-based definitions of luminal A and B breast cancers are imperfect when compared with multigene expression-based assays. In this study, we sought to improve the IHC subtyping by examining the pathologic and gene expression characteristics of genomically defined luminal A and B subtypes. Gene expression and pathologic features were collected from primary tumors across five independent cohorts: British Columbia Cancer Agency (BCCA) tamoxifen-treated only, Grupo Español de Investigación en Cáncer de Mama 9906 trial, BCCA no systemic treatment cohort, PAM50 microarray training data set, and a combined publicly available microarray data set. Optimal cutoffs of percentage of progesterone receptor (PR) -positive tumor cells to predict survival were derived and independently tested. Multivariable Cox models were used to test the prognostic significance. Clinicopathologic comparisons among luminal A and B subtypes consistently identified higher rates of PR positivity, human epidermal growth factor receptor 2 (HER2) negativity, and histologic grade 1 in luminal A tumors. Quantitative PR gene and protein expression were also found to be significantly higher in luminal A tumors. An empiric cutoff of more than 20% of PR-positive tumor cells was statistically chosen and proved significant for predicting survival differences within IHC-defined luminal A tumors independently of endocrine therapy administration. Finally, no additional prognostic value within hormonal receptor (HR) -positive/HER2-negative disease was observed with the use of the IHC4 score when intrinsic IHC-based subtypes were used that included the more than 20% PR-positive tumor cells and vice versa. Semiquantitative IHC expression of PR adds prognostic value within the current IHC-based luminal A definition by improving the identification of good outcome breast cancers. The new proposed IHC-based definition of luminal A tumors is HR positive/HER2 negative/Ki-67 less than 14

  1. Hormone-refractory prostate cancer and the skeleton

    NARCIS (Netherlands)

    Soerdjbalie-Maikoe, Vidija

    2006-01-01

    Prostate cancer is the second most common cancer in men in the UK. Androgen ablation with luteinising hormone-releasing hormone agonists (LHRH agonists) alone, or in combination with anti-androgens is the standard treatment for men with metastatic prostate cancer. Unfortunately, despite maximal

  2. Risk Factors That Increase Risk of Estrogen Receptor-Positive and -Negative Breast Cancer.

    Science.gov (United States)

    Kerlikowske, Karla; Gard, Charlotte C; Tice, Jeffrey A; Ziv, Elad; Cummings, Steven R; Miglioretti, Diana L

    2017-05-01

    Risk factors may differentially influence development of estrogen receptor (ER)-positive vs -negative breast cancer. We examined associations with strong, prevalent risk factors by ER subtype. Of 1 279 443 women age 35 to 74 years participating in the Breast Cancer Surveillance Consortium, 14 969 developed ER-positive and 3617 developed ER-negative invasive breast cancer. We calculated hazard ratios (HRs) using Cox regression and compared ER subtype hazard ratios at representative ages or by menopausal status using Wald tests. All statistical tests were two-sided. For women age 40 years, compared with no prior biopsy, ER-positive vs ER-negative HRs were 1.53 (95% CI = 1.30 to 1.81) vs 1.26 (95% CI = 0.90 to 1.76) for nonproliferative disease, 1.63 (95% CI = 1.23 to 2.17) vs 1.41 (95% CI = 0.78 to 2.57) for proliferative disease without atypia, and 4.47 (95% CI = 2.88 to 6.96) vs 0.20 (95% CI = 0.02 to 2.51) for proliferative disease with atypia. Benign disease proliferation risk was stronger for ER-positive than ER-negative cancer for women age 35 years (Wald P = .04), age 40 years (Wald P = .04), and age 50 years (Wald P = .06). Among pre/perimenopausal women, body mass index (BMI) had a stronger association with ER-negative than ER-positive cancer (obese II/III vs. normal weight: HR = 1.52, 95% CI = 1.19 to 1.94; vs 1.21, 95% CI = 1.08 to 1.36). Increasing BMI similarly increased ER-positive and ER-negative cancer risk among postmenopausal hormone users (Wald P = .15) and nonusers (Wald P = .08). Associations with ER subtype varied by race/ethnicity across all ages (P breast cancer and breast density for specific ages. Strength of risk factor associations differed by ER subtype. Separate risk models for ER subtypes may improve identification of women for targeted prevention strategies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. HORMONE THERAPY WITH USAGE OF AGONISTS AND ANTAGONISTS OF LUTEINIZING HORMONE RELEASING HORMONE IN PATIENTS WITH PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    K. M. Nyushko

    2014-01-01

    Full Text Available Prostate cancer (PC is one of the most actual problems of modern oncourology. Hormone therapy (HT using medical castration is the main method of treatment of patients with metastatic PC. HT with usage of the new class of drugs that block the receptors for luteinizing hormone releasing hormone (LHRH is a promising and effective method of castration therapy that has a number of significant advantages over the use of analogues LHRH. This article presents areview of studies that compared the effectiveness and side effects of HT using antagonists and analogues LHRH.

  4. Establishment of a normal-derived estrogen receptor-positive cell line comparable to the prevailing human breast cancer subtype

    DEFF Research Database (Denmark)

    Hopkinson, Branden Michael; Klitgaard, Marie Christine; Petersen, Ole William

    2017-01-01

    Understanding human cancer increasingly relies on insight gained from subtype specific comparisons between malignant and non-malignant cells. The most frequent subtype in breast cancer is the luminal. By far the most frequently used model for luminal breast cancer is the iconic estrogen receptor......-positive (ERpos) MCF7 cell line. However, luminal specific comparisons have suffered from the lack of a relevant non-malignant counterpart. Our previous work has shown that transforming growth factor-β receptor (TGFβR) inhibition suffices to propagate prospectively isolated ERpos human breast luminal cells from...... propose that iHBECERpos may serve to shed light on hitherto unappreciated differences in ER regulation and function between normal breast and breast cancer....

  5. Interaction between body mass index and hormone-receptor status as a prognostic factor in lymph-node-positive breast cancer.

    Directory of Open Access Journals (Sweden)

    Il Yong Chung

    Full Text Available The aim of this study was to determine the relationship between the body mass index (BMI at a breast cancer diagnosis and various factors including the hormone-receptor, menopause, and lymph-node status, and identify if there is a specific patient subgroup for which the BMI has an effect on the breast cancer prognosis. We retrospectively analyzed the data of 8,742 patients with non-metastatic invasive breast cancer from the research database of Asan Medical Center. The overall survival (OS and breast-cancer-specific survival (BCSS outcomes were compared among BMI groups using the Kaplan-Meier method and Cox proportional-hazards regression models with an interaction term. There was a significant interaction between BMI and hormone-receptor status for the OS (P = 0.029, and BCSS (P = 0.013 in lymph-node-positive breast cancers. Obesity in hormone-receptor-positive breast cancer showed a poorer OS (adjusted hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 0.92 to 2.48 and significantly poorer BCSS (HR = 1.80, 95% CI = 1.08 to 2.99. In contrast, a high BMI in hormone-receptor-negative breast cancer revealed a better OS (HR = 0.44, 95% CI = 0.16 to 1.19 and BCSS (HR = 0.53, 95% CI = 0.19 to 1.44. Being underweight (BMI < 18.50 kg/m2 with hormone-receptor-negative breast cancer was associated with a significantly worse OS (HR = 1.98, 95% CI = 1.00-3.95 and BCSS (HR = 2.24, 95% CI = 1.12-4.47. There was no significant interaction found between the BMI and hormone-receptor status in the lymph-node-negative setting, and BMI did not interact with the menopause status in any subgroup. In conclusion, BMI interacts with the hormone-receptor status in a lymph-node-positive setting, thereby playing a role in the prognosis of breast cancer.

  6. Evidence for the prevention of bone loss in elderly and old early non-metastatic breast cancer patients treated with aromatase inhibitors

    DEFF Research Database (Denmark)

    Gunmalm, V.; Jørgensen, N. R.; Abrahamsen, B.

    2017-01-01

    Breast cancer (BC) is the most common cancer amongst women worldwide. Bone health is emerging as an important issue for BC survivors. In this literature study, we focus on agents for preventing bone loss in early non-metastatic estrogen receptor positive BC in treatment with aromatase inhibitors...... (AI) and to assess the evidence for antiresorptive treatment of bone loss in early non-metastatic breast cancer. We included randomized controlled trials (RCT's) comparing: (a) bisphosphonates and control; (b) different bisphosphonates; (c) denosumab and control and (d) bisphosphonates vs. denosumab...... in early non-metastatic BC women in AI treatment. Among antiresorptives, zoledronic acid currently has the highest evidence for prevention of AI associated bone loss in early non-metastatic BC. Data on fracture prevention among all patients, elderly and old is sparse. More randomized controlled studies...

  7. Mortality rates among early-stage hormone receptor-positive breast cancer patients: a population-based cohort study in Denmark

    DEFF Research Database (Denmark)

    Christiansen, Peer; Bjerre, Karsten; Ejlertsen, Bent Laursen

    2011-01-01

    Indications for adjuvant endocrine treatment of breast cancer have gradually increased over the past several years. We aimed to define subgroups of patients who may or may not benefit from adjuvant endocrine therapy....

  8. Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial.

    Science.gov (United States)

    Sonke, Gabe S; Hart, Lowell L; Campone, Mario; Erdkamp, Frans; Janni, Wolfgang; Verma, Sunil; Villanueva, Cristian; Jakobsen, Erik; Alba, Emilio; Wist, Erik; Favret, Anne M; Bachelot, Thomas; Hegg, Roberto; Wheatley-Price, Paul; Souami, Farida; Sutradhar, Santosh; Miller, Michelle; Germa, Caroline; Burris, Howard A

    2017-10-22

    Determine the efficacy and safety of first-line ribociclib plus letrozole in elderly patients with HR+, HER2- advanced breast cancer. 668 postmenopausal women with HR+, HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021); 295 patients were aged ≥ 65 years. Patients were randomized to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.5 mg/day) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was PFS, which was evaluated in elderly (≥ 65 years) and younger ( 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm in both subgroups; most events were grade 1/2. In elderly patients, grade 1/2 anemia and fatigue were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm and discontinuation rates were similar in both arms. Addition of ribociclib to letrozole is a valid therapeutic option for elderly patients with HR+, HER2- advanced breast cancer in the first-line setting.

  9. A Role for MEK-Interacting Protein 1 (MP1) in Hormone Responsiveness of Estrogen Receptor-Positive Breast Cancer Cells

    Science.gov (United States)

    2008-07-01

    target gene. Flag epitope tagged MP1 (Flag-MP1) was subcloned into the ARGENT Target Gene Vector ( TGV ), and the resulting constructs were transfected...hygromycin (the TGV contains a hygromycin resistance gene), and screened for Flag-MP1 expression in the presence of AP. Although the initial screening...passage. The TGV contains retroviral LTRs as well as a viral packaging site, and can be reconstituted into an infectious retrovirus by transfecting the

  10. Mortality rates among early-stage hormone receptor-positive breast cancer patients: a population-based cohort study in Denmark

    DEFF Research Database (Denmark)

    Christiansen, Peer Michael; Bjerre, Karsten; Ejlertsen, Bent

    2011-01-01

    Indications for adjuvant endocrine treatment of breast cancer have gradually increased over the past several years. We aimed to define subgroups of patients who may or may not benefit from adjuvant endocrine therapy.......Indications for adjuvant endocrine treatment of breast cancer have gradually increased over the past several years. We aimed to define subgroups of patients who may or may not benefit from adjuvant endocrine therapy....

  11. High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease.

    Science.gov (United States)

    Minicozzi, Pamela; Berrino, Franco; Sebastiani, Federica; Falcini, Fabio; Vattiato, Rosa; Cioccoloni, Francesca; Calagreti, Gioia; Fusco, Mario; Vitale, Maria Francesca; Tumino, Rosario; Sigona, Aurora; Budroni, Mario; Cesaraccio, Rosaria; Candela, Giuseppa; Scuderi, Tiziana; Zarcone, Maurizio; Campisi, Ildegarda; Sant, Milena

    2013-12-01

    We investigated the effect of fasting blood glucose and body mass index (BMI) at diagnosis on risk of breast cancer death for cases diagnosed in five Italian cancer registries in 2003-2005 and followed up to the end of 2008. For 1607 Italian women (≥15 years) with information on BMI or blood glucose or diabetes, we analysed the risk of breast cancer death in relation to glucose tertiles (≤84.0, 84.1-94.0, >94.0 mg/dl) plus diabetic and unspecified categories; BMI tertiles (≤23.4, 23.5-27.3, >27.3 kg/m(2), unspecified), stage (T1-3N0M0, T1-3N+M0 plus T4anyNM0, M1, unspecified), oestrogen (ER) and progesterone (PR) status (ER+PR+, ER-PR-, ER and PR unspecified, other), age, chemotherapy and endocrine therapy, using multiple regression models. Separate models for ER+PR+ and ER-PR- cases were also run. Patients often had T1-3N0M0, ER+PR+ cancers and received chemotherapy or endocrine therapy; only 6% were M1 and 17% ER-PR-. Diabetic patients were older and had more often high BMI (>27 kg/m(2)), ER-PR-, M1 cancers than other patients. For ER+PR+ cases, with adjustment for other variables, breast cancer mortality was higher in women with high BMI than those with BMI 23.5-27.3 kg/m(2) (hazard ratio (HR)=2.9, 95% confidence interval (CI) 1.2-6.9). Breast cancer mortality was also higher in women with high (>94 mg/dl) blood glucose compared to those with glucose 84.1-94.0mg/dl (HR=2.6, 95% CI 1.2-5.7). Our results provide evidence that in ER+PR+ patients, high blood glucose and high BMI are independently associated with increased risk of breast cancer death. Detection and correction of these factors in such patients may improve prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Zoledronic acid in the management of metastatic bone disease

    Directory of Open Access Journals (Sweden)

    Thomas J Polascik

    2008-03-01

    Full Text Available Thomas J Polascik, Vladimir MouravievDuke Prostate Center and Division of Urologic Surgery, Duke University Medical Center, Durham, NC, USAAbstract: Many patients with advanced cancer experience decreased bone strength due to metastatic foci, underlying osteoporosis and/or cancer treatment induced bone loss. The clinical consequences of metastatic disease involving the skeleton are widespread. This review focuses on the efficacy, pharmacology, and safety when using intravenous biphosphonate such a zoledronic acid for cancer bone metastases. Zoledronic acid is the gold standard for the medical management of metastatic bone disease. The indications for treatment include prevention of skeletal relevant events (SRE, osteoporotic complications, and palliation of bone pain, among others. Zoledronic acid is the only bisphosphonate effective in decreasing SREs associated with bone metastases from advanced renal cell carcinoma and prostate cancer. Regarding prostate cancer, zoledronic acid effectively prevents both bone loss in patients with locally advanced disease receiving androgen deprivation therapy and SREs in men with hormone-refractory or hormonesensitive metastatic disease. Zoledronic acid has an acceptable safety profile and tolerability, and has been effective at significantly decreasing the incidence, delaying the onset, and reducing the overall risk of experiencing an SRE compared to placebo. It is the only bisphosphonate currently approved for the prevention and treatment of skeletal complications in patients with bone metastases due to all solid tumors.Keywords: zoledronic acid, metastatic bone disease, osteoporosis, skeletal relevant events, advanced prostate cancer

  13. Imaging of Spinal Metastatic Disease

    Directory of Open Access Journals (Sweden)

    Lubdha M. Shah

    2011-01-01

    Full Text Available Metastases to the spine can involve the bone, epidural space, leptomeninges, and spinal cord. The spine is the third most common site for metastatic disease, following the lung and the liver. Approximately 60–70% of patients with systemic cancer will have spinal metastasis. Materials/Methods. This is a review of the imaging techniques and typical imaging appearances of spinal metastatic disease. Conclusions. Awareness of the different manifestations of spinal metastatic disease is essential as the spine is the most common site of osseous metastatic disease. Imaging modalities have complimentary roles in the evaluation of spinal metastatic disease. CT best delineates osseous integrity, while MRI is better at assessing soft tissue involvement. Physiologic properties, particularly in treated disease, can be evaluated with other imaging modalities such as FDG PET and advanced MRI sequences. Imaging plays a fundamental role in not only diagnosis but also treatment planning of spinal metastatic disease.

  14. Estrogen Receptor- and Progesterone Receptor-Positive Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Yuichi Kinoshita

    2013-04-01

    Full Text Available The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC is a relatively rare tumor. We herein report the case of young woman with DSV-PTC who developed cervical lymph node recurrence 7 years after the initial surgery. A 15-year-old female patient with no medical or family history of thyroid tumors developed a thyroid neoplasm in the right lobe. Right thyroidectomy and regional lymphadenectomy were performed, and the tumor was diagnosed as DSV-PTC. She was followed up as an outpatient. Seven years after the surgery, cervical lymph node recurrence developed. On microscopic examination, the thyroid tumor showed a papillary growth pattern with numerous psammoma bodies and distinct fibrosis. Immunohistochemically, the tumor cells were estrogen receptor and progesterone receptor positive with reduced membranous expression of E-cadherin and were intermingled with S-100-positive dendritic/Langerhans cells. DSV-PTC is characterized by a strong tendency for invasion and metastasis. Thus, accurate diagnosis is clinically important, and a morphological and immunohistochemical understanding of DSV-PTC is necessary.

  15. Identification of orexin A- and orexin type 2 receptor-positive cells in the gastrointestinal tract of neonatal dogs

    Directory of Open Access Journals (Sweden)

    C Dall’Aglio

    2009-08-01

    Full Text Available The presence and distribution of cells positive to orexin A (OXA and to orexin type 2 receptor (OX2R were investigated in the gastrointestinal tract of neonatal dogs by means of immunohistochemical techniques. The orexin A-positive cells were identified with some of the endocrine cells in the stomach and in the duodenum; they were both of the open and closed type and were lacking in the large intestine. In the stomach, a large subset of orexin A-positive cells also showed gastrin-like immunoreactivity while, in the duodenum, many of them seemed to store serotonin. The orexin type 2 receptor-positive cells were evidenced all along the gastrointestinal tract examined, also in the large intestine, and they showed the same morphological characteristics as those positive to orexin A. Moreover, the immunohistochemical techniques revealed intense positivity for both orexin A and orexin type 2 receptor in the neurons and fibers of the enteric nervous system. A large subset of orexin A-positive neurons seemed to store substance P.

  16. Methylation of the claudin 1 promoter is associated with loss of expression in estrogen receptor positive breast cancer.

    Directory of Open Access Journals (Sweden)

    Francescopaolo Di Cello

    Full Text Available Downregulation of the tight junction protein claudin 1 is a frequent event in breast cancer and is associated with recurrence, metastasis, and reduced survival, suggesting a tumor suppressor role for this protein. Tumor suppressor genes are often epigenetically silenced in cancer. Downregulation of claudin 1 via DNA promoter methylation may thus be an important determinant in breast cancer development and progression. To investigate if silencing of claudin 1 has an epigenetic etiology in breast cancer we compared gene expression and methylation data from 217 breast cancer samples and 40 matched normal samples available through the Cancer Genome Atlas (TCGA. Moreover, we analyzed claudin 1 expression and methylation in 26 breast cancer cell lines. We found that methylation of the claudin 1 promoter CpG island is relatively frequent in estrogen receptor positive (ER+ breast cancer and is associated with low claudin 1 expression. In contrast, the claudin 1 promoter was not methylated in most of the ER-breast cancers samples and some of these tumors overexpress claudin 1. In addition, we observed that the demethylating agents, azacitidine and decitabine can upregulate claudin 1 expression in breast cancer cell lines that have a methylated claudin 1 promoter. Taken together, our results indicate that DNA promoter methylation is causally associated with downregulation of claudin 1 in a subgroup of breast cancer that includes mostly ER+ tumors, and suggest that epigenetic therapy to restore claudin 1 expression might represent a viable therapeutic strategy in this subtype of breast cancer.

  17. Effects of alpha-7 nicotinic acetylcholine receptor positive allosteric modulator on lipopolysaccharide-induced neuroinflammatory pain in mice.

    Science.gov (United States)

    Abbas, Muzaffar; Rahman, Shafiqur

    2016-07-15

    Evidence indicates that microglial activation contributes to the pathophysiology and maintenance of neuroinflammatory pain involving central nervous system alpha-7 nicotinic acetylcholine receptors. The objective of the present study was to determine the effects of 3a,4,5,9b-Tetrahydro-4-(1-naphthalenyl)-3H-cyclopentan[c]quinoline-8-sulfonamide (TQS), an alpha-7 nicotinic acetylcholine receptor positive allosteric modulator (PAM), on tactile allodynia and thermal hyperalgesia following lipopolysaccharide (LPS)-induced microglial activation in hippocampus, a neuroinflammatory pain model in mice. In addition, we examined the effects of TQS on microglial activation marker, an ionized calcium-binding adapter molecule 1 (Iba-1), in the hippocampus may be associated with neuroinflammatory pain. Pretreatment of TQS (4mg/kg) significantly reduced LPS (1mg/kg)-induced tactile allodynia and thermal hyperalgesia. Moreover, pretreatment of methyllycaconitine (3mg/kg) significantly reversed TQS-induced antiallodynic and antihyperalgesic responses indicating the involvement of alpha-7 nicotinic acetylcholine receptor. Pretreatment of TQS significantly decreased LPS-induced increased in hippocampal Iba-1 expression. Overall, these results suggest that TQS reduces LPS-induced neuroinflammatory pain like symptoms via modulating microglial activation likely in the hippocampus and/or other brain region by targeting alpha-7 nicotinic acetylcholine receptor. Therefore, alpha-7 nicotinic acetylcholine receptor PAM such as TQS could be a potential drug candidate for the treatment of neuroinflammatory pain. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for breast cancer

    Directory of Open Access Journals (Sweden)

    Robertson John FR

    2011-09-01

    Full Text Available Abstract Background It has been shown in in-vitro experiments that "withdrawal" of tamoxifen inhibits growth of tumor cells. However, evidence is scarce when this is extrapolated into clinical context. We report our experience to verify the clinical relevance of "withdrawal therapy". Methods Breast cancer patients since 1998 who fulfilled the following criteria were selected from the departmental database and the case-notes were retrospectively reviewed: (1 estrogen receptor positive, operable primary breast cancer in elderly (age > 70 years, locally advanced or metastatic breast cancer; (2 disease deemed suitable for treatment by hormonal manipulation; (3 disease assessable by UICC criteria; (4 received "withdrawal" from a prior endocrine agent as a form of therapy; (5 on "withdrawal therapy" for ≥ 6 months unless they progressed prior. Results Seventeen patients with median age of 84.3 (53.7-92.5 had "withdrawal therapy" as second to tenth line of treatment following prior endocrine therapy using tamoxifen (n = 10, an aromatase inhibitor (n = 5, megestrol acetate (n = 1 or fulvestrant (n = 1. Ten patients (58.8% had clinical benefit (CB (complete response/partial response/stable disease ≥ 6 months with a median duration of Clinical Benefit (DoCB of 10+ (7-27 months. Two patients remain on "withdrawal therapy" at the time of analysis. Conclusion "Withdrawal therapy" appears to produce sustained CB in a significant proportion of patients. This applies not only to "withdrawal" from tamoxifen, but also from other categories of endocrine agents. "Withdrawal" from endocrine therapy is, therefore, a viable intercalating option between endocrine agents to minimise resistance and provide additional line of therapy. It should be considered as part of the sequencing of endocrine therapy.

  19. Factors Associated with the Use of Gene Expression Profiles in Estrogen Receptor-Positive Early-Stage Breast Cancer Patients: A Nationwide Study

    NARCIS (Netherlands)

    Kuijer, A.; Schreuder, Kay; Elias, S.G.; Smorenburg, C.H.; Rutgers, E.J.T.; Siesling, Sabine; van Dalen, T.

    2016-01-01

    Background: Breast cancer guidelines suggest the use of gene expression profiles (GEPs) in estrogen receptor-positive (ER+) breast cancer patients in whom controversy exists regarding adjuvant chemotherapy benefit based on traditional prognostic factors alone. We evaluated the current use of GEPs in

  20. Factors Associated with the Use of Gene Expression Profiles in Estrogen Receptor-Positive Early-Stage Breast Cancer Patients : A Nationwide Study

    NARCIS (Netherlands)

    Kuijer, Anne; Schreuder, Kay; Elias, Sjoerd G|info:eu-repo/dai/nl/261632590; Smorenburg, Carolien H; Rutgers, Emiel J T; Siesling, Sabine; van Dalen, Thijs

    2016-01-01

    BACKGROUND: Breast cancer guidelines suggest the use of gene expression profiles (GEPs) in estrogen receptor-positive (ER+) breast cancer patients in whom controversy exists regarding adjuvant chemotherapy benefit based on traditional prognostic factors alone. We evaluated the current use of GEPs in

  1. Hormone Therapy

    Science.gov (United States)

    ... vaginal lining gets thinner, dryer, and less elas- tic. Vaginal dryness may cause pain during sexual intercourse . ... when a woman starts taking hormone therapy. Some research suggests that for women who start combined therapy ...

  2. Growth Hormone

    Science.gov (United States)

    ... of GHD and/or hypopituitarism , such as: Decreased bone density Fatigue Adverse lipid changes, such as high cholesterol Reduced exercise tolerance Other hormone testing, such as thyroid testing , ...

  3. Growth Hormone

    Science.gov (United States)

    ... High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV ... 003706.htm . Accessed October 2010. (© 1995-2010). Unit Code 8688: Growth Hormone, Serum. Mayo Clinic, Mayo Medical ...

  4. Hormone Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Hormones quantified from marine mammal and sea turtle tissue provide information about the status of each animal sampled, including its sex, reproductive status and...

  5. A multicentric observational trial of pegylated liposomal doxorubicin for metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Wischnik Arthur

    2010-01-01

    Full Text Available Abstract Background Pegylated liposomal doxorubicin (PLD is active in metastatic breast cancer. This observational study evaluated the efficacy and safety of PLD in patients treated during routine clinical practice. Methods Eligible patients had metastatic breast cancer and were treated with PLD according to the dose and schedule determined by their physician as part of routine practice. The primary objectives were to analyze the efficacy and toxicity of PLD therapy. Results 125 patients were assessable. Median age was 62 years, 78% had performance status 0-1, and 60% had estrogen-receptor-positive disease. PLD treatment was second- or third-line in 69% of patients. Prior anthracyclines (adjuvant or metastatic had been used in 56% of patients. The majority of patients (79% received PLD every 4 weeks at a median dose of 40 mg/m2. Overall response rate was 43% in all patients and 34% in those previously treated with anthracyclines. The most common grade 3/4 adverse events were skin toxicity/hand-foot syndrome (6%, and leukopenia (3%. Conclusions This observational study supports the activity and tolerability of PLD in metastatic breast cancer as demonstrated in PLD clinical trials.

  6. Discriminative Stimulus Effects of the GABAB Receptor-Positive Modulator rac-BHFF: Comparison with GABAB Receptor Agonists and Drugs of Abuse

    Science.gov (United States)

    Cheng, Kejun; Rice, Kenner C.

    2013-01-01

    GABAB receptor-positive modulators are thought to have advantages as potential medications for anxiety, depression, and drug addiction. They may have fewer side effects than GABAB receptor agonists, because selective enhancement of activated receptors could have effects different from nonselective activation of all receptors. To examine this, pigeons were trained to discriminate the GABAB receptor-positive modulator (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one (rac-BHFF) from its vehicle. The discriminative stimulus effects of rac-BHFF were not mimicked by the GABAB receptor agonists baclofen and γ-hydroxybutyrate (GHB), not by diazepam, and not by alcohol, cocaine, and nicotine, whose self-administration has been reported to be attenuated by GABAB receptor-positive modulators. The discriminative stimulus effects of rac-BHFF were not antagonized by the GABAB receptor antagonist 3-aminopropyl (diethoxymethyl)phosphinic acid (CGP35348) but were attenuated by the less efficacious GABAB receptor-positive modulator 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)phenol (CGP7930), suggesting the possibility that rac-BHFF produces its discriminative stimulus effects by directly activating GABAB2 subunits of GABAB receptors. At a dose 10-fold lower than the training dose, rac-BHFF enhanced the discriminative stimulus effects of baclofen, but not of GHB. This study provides evidence that the effects of GABAB receptor-positive modulators are not identical to those of GABAB receptor agonists. In addition, the results suggest that positive modulation of GABAB receptors does not produce discriminative stimulus effects similar to those of benzodiazepines, alcohol, cocaine, and nicotine. Finally, the finding that rac-BHFF enhanced effects of baclofen but not of GHB is consistent with converging evidence that the populations of GABAB receptors mediating the effects of baclofen and GHB are not identical. PMID:23275067

  7. Prospects of 2nd line chemotherapy personalization in patients with metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2016-01-01

    Full Text Available Prostate cancer (PC is one of the most challenging and pressing problems of modern oncourology because of high morbidity associated with the disease worldwide. About 1 100 000 new cases are diagnosed each year. The main approach to treatment of locally advanced and/or metastatic PC is hormonal therapy. Androgen deprivation therapy allows to achieve stabilization in more than 90 % of patients, but average time until progression after hormonal therapy in patients with metastatic PC is about 2 years. Then patients with tumor progression accompanied by castration level of testosterone enter the stage of so-called castration-resistant PC (CRPC. Prognosis for regional CRPC is unfavorable, and it substantially lowers patients’ quality of life. Taxane-based chemotherapy remains a standard method of treatment in this patient cohort. The article reviews studies of efficacy of different doses and regimes of 2nd line chemotherapy using cabazitaxel in patients with metastatic CRPC.

  8. Hormone Therapy Plus Chemotherapy for Metastatic Prostate Cancer

    Science.gov (United States)

    A trial of androgen deprivation therapy (ADT) plus six cycles of docetaxel versus ADT alone found that after a median follow-up of nearly 29 months, median overall survival was 13.6 months longer with the combination therapy than with ADT alone.

  9. Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance.

    Science.gov (United States)

    Arpino, Grazia; Weiss, Heidi; Lee, Adrian V; Schiff, Rachel; De Placido, Sabino; Osborne, C Kent; Elledge, Richard M

    2005-09-07

    Clinical data indicate that estrogen receptor-positive/progesterone receptor-negative (ER+/PR-) breast cancers are less sensitive to tamoxifen than are ER+/PR+ tumors. It has also been reported that tamoxifen may be less effective in tumors that overexpress either HER-2 or HER-1 (epidermal growth factor receptor) and that signaling through these receptors reduces PR expression in experimental models. We hypothesized that ER+/PR- breast tumors are more likely than ER+/PR+ breast tumors to have an aggressive phenotype, to express HER-1 and overexpress HER-2, and are less likely to benefit from tamoxifen adjuvant therapy. Clinical and biological features of 31 415 patients with ER+/PR+ tumors were compared with those of 13,404 patients with ER+/PR- tumors. Association between disease-free survival (DFS) and HER-1 and HER-2 status was analyzed in a subset of 11,399 patients receiving adjuvant tamoxifen therapy. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression or Kaplan-Meier analyses, and all statistical tests were two-sided. ER+/PR- tumors were more frequent in older patients, were larger in size, had a higher S-phase fraction, and were more likely to be aneuploid than ER+/PR+ tumors. Furthermore, three times as many ER+/PR- tumors as ER+/PR+ tumors expressed HER-1 (25% versus 8%; P HER-1-expressing tumors than with HER-1-negative tumors (HR = 1.9, 95% CI = 1.0 to 3.5; P = .05); a stronger association between worse DFS and HER-2 overexpression was observed (HR = 2.3, 95% CI = 1.2 to 4.3; P = .006). However, results varied by PR status. Among tamoxifen-treated women with ER+/PR+ tumors, HER-1 or HER-2 status was not associated with worse DFS. Among women with ER+/PR- tumors, however, both HER-1 expression (HR = 2.4, 95% CI = 1.0 to 5.4; P = .036) and HER-2 overexpression (HR = 2.6, 95% CI = 1.1 to 6.0; P = .022) were associated with a higher likelihood of recurrence. ER+/PR- tumors express higher levels of HER-1 and HER-2 and

  10. Metastatic pituitary carcinoma in a patient with acromegaly: a case report.

    LENUS (Irish Health Repository)

    Sreenan, Seamus

    2012-01-01

    Asymptomatic pituitary abnormalities occur in about 10% of cranial magnetic resonance imaging scans, but metastatic carcinoma of the pituitary gland is rare: 133 cases have been reported. Two thirds secreted either prolactin or adrenocorticotropic hormone, and another 24% were non-secreting.

  11. A case of metastatic follicular thyroid carcinoma complicated with Graves' disease after total thyroidectomy.

    Science.gov (United States)

    Aoyama, Mariko; Takizawa, Hiromitsu; Tsuboi, Mitsuhiro; Nakagawa, Yasushi; Tangoku, Akira

    2017-12-28

    Thyroid cancer and Graves' disease may present simultaneously in one patient. The incidence of the development of hyperthyroidism from metastatic differentiated thyroid carcinoma is rare. We herein report a case of metastatic follicular carcinoma complicated with Graves' disease after total thyroidectomy. A 57-year-old woman underwent right hemithyroidectomy for follicular carcinoma. Metastatic lesions appeared in the lungs and skull two years after the first surgery, and remnant thyroidectomy was performed for radioactive iodine-131 (RAI) therapy, during which the TSH receptor antibody (TRAb) was found to be negative. The patient was treated with RAI therapy four times for four years and was receiving levothyroxine suppressive therapy. Although radioiodine uptake was observed in the lesions after the fourth course of RAI therapy, metastatic lesions had progressed. Four years after the second surgery, she had heart palpitations and tremors. Laboratory data revealed hyperthyroidism and positive TRAb. She was diagnosed with Graves' disease and received a fifth course of RAI therapy. 131I scintigraphy after RAI therapy showed strong radioiodine uptake in the metastatic lesions. As a result, the sizes and numbers of metastatic lesions decreased, and thyroid function improved. Metastatic lesions produced thyroid hormone and caused hyperthyroidism. RAI therapy was effective for Graves' disease and thyroid carcinoma.

  12. Sorafenib for Metastatic Thyroid Cancer

    Science.gov (United States)

    A summary of results from an international phase III trial that compared sorafenib (Nexavar®) and a placebo for the treatment of locally advanced or metastatic differentiated thyroid cancer that is no longer responding to treatment with radioactive iodine

  13. Hormone impostors

    Energy Technology Data Exchange (ETDEWEB)

    Colborn, T.; Dumanoski, D.; Myers, J.P.

    1997-01-01

    This article discusses the accumulating evidence that some synthetic chemicals disrupt hormones in one way or another. Some mimic estrogen and others interfere with other parts of the body`s control or endocrine system such as testosterone and thyroid metabolism. Included are PCBs, dioxins, furans, atrazine, DDT. Several short sidebars highlight areas where there are or have been particular problems.

  14. Types of hormone therapy

    Science.gov (United States)

    ... your doctor for regular checkups when taking HT. Alternative Names HRT- types; Estrogen replacement therapy - types; ERT- types of hormone therapy; Hormone replacement therapy - types; Menopause - types of hormone therapy; HT - types; Menopausal hormone ...

  15. Bioidentical Hormones and Menopause

    Science.gov (United States)

    ... Endocrinologist Search Featured Resource Menopause Map™ View Bioidentical Hormones January 2012 Download PDFs English Espanol Editors Howard ... take HT for symptom relief. What are bioidentical hormones? Bioidentical hormones are identical to the hormones that ...

  16. Aromatase Inhibitor-Induced Erythrocytosis in a Patient Undergoing Hormonal Treatment for Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sri Lakshmi Hyndavi Yeruva

    2015-01-01

    Full Text Available Aromatase inhibitors (AIs are most commonly used for breast cancer patients with hormone receptor positive disease. Although the side effect profile of aromatase inhibitors is well known, including common side effects like arthralgia, bone pain, arthritis, hot flashes, and more serious problems like osteoporosis, we present a case of an uncommon side effect of these medications. We report the case of a postmenopausal woman on adjuvant hormonal therapy with anastrozole after completing definitive therapy for stage IIIB estrogen receptor-positive breast cancer, who was referred to hematology service for evaluation of persistent erythrocytosis. Primary and known secondary causes of polycythemia were ruled out. On further evaluation, we found that her erythrocytosis began after initiation of anastrozole and resolved after it was discontinued. We discuss the pathophysiology of aromatase inhibitor-induced erythrocytosis and reference of similar cases reported in the literature.

  17. Palbociclib for Advanced Breast Cancer

    Science.gov (United States)

    An interim analysis of the PALOMA3 trial shows that women with hormone receptor-positive metastatic breast cancer who received palbociclib plus fulvestrant had longer progression-free survival rates than women who received a placebo plus fulvestrant.

  18. Ribociclib and Doxorubicin in Treating Patients With Metastatic or Advanced Soft Tissue Sarcomas That Cannot Be Removed by Surgery

    Science.gov (United States)

    2017-10-31

    Metastatic Angiosarcoma; Metastatic Epithelioid Sarcoma; Metastatic Fibrosarcoma; Metastatic Leiomyosarcoma; Metastatic Liposarcoma; Metastatic Malignant Peripheral Nerve Sheath Tumor; Metastatic Synovial Sarcoma; Metastatic Undifferentiated Pleomorphic Sarcoma; Myxofibrosarcoma; Pleomorphic Rhabdomyosarcoma; Stage III Soft Tissue Sarcoma; Stage IV Soft Tissue Sarcoma; Undifferentiated (Embryonal) Sarcoma

  19. Metastatic Carcinoid Tumor Presenting As Right Sided Heart Failure

    Science.gov (United States)

    Martinez-Quintana, Efren; Avila-Gonzalez, Maria Del Mar; Suarez-Castellano, Laura; Rodriguez-Gonzalez, Fayna

    2013-01-01

    Carcinoid tumor is a slow-growing type of neuroendocrine tumor, originating in the enterochromaffin cells and secreting mainly serotonin. The diagnosis is based on clinical symptoms, hormone levels, radiological and nuclear imaging, and histological confirmation. The clinical symptoms are characterized by flushing, diarrhea, abdominal pain, telangiectasia and/or bronchoconstriction. However, most patients have metastatic disease at diagnosis because the clinic goes unnoticed or are ascribed to other abdominal conditions. We report the clinical symptoms, hormone levels, radiological and nuclear imaging, histological diagnosis, treatment and evaluation of a 44-year-old female patient with congestive heart failure secondary to carcinoid heart disease in the context of liver metastases of an ileum carcinoid tumor. PMID:23825984

  20. The modified Geller-Seifter test in rats was insensitive to GABAB receptor positive modulation or blockade, or 5-HT1A receptor activation.

    Science.gov (United States)

    Paterson, Neil E; Hanania, Taleen

    2010-03-17

    Both the GABA(B) receptor positive modulator GS39783 and the GABA(B) receptor antagonist CGP46381 exhibit anxiolytic-like properties in animal models. In the present studies, the effects of GS39783 and CGP46381 in the modified Geller-Seifter task were assessed. First, the predictive validity of the task was confirmed by assessing the effects of multiple anxiolytic and non-anxiolytic compounds on punished and unpunished responding. Rats were trained in the modified Geller-Seifter task. After successful acquisition of the task, chlordiazepoxide, diazepam, MPEP, haloperidol, GS39783, 8-OH-DPAT, alprazolam and CGP46381 were tested consecutively. For each test compound, doses were administered in a randomized, counter-balanced, within-subjects design. Drug tests were performed only when rats exhibited baseline performance (the punished and time-out response rates were less than 10% of the unpunished response rate). Chlordiazepoxide, diazepam, alprazolam and MPEP released punished responding with variable effects on unpunished responding. Haloperidol had a small but significant effect on punished responding at an intermediate dose, and decreased unpunished responding at the highest dose tested. In contrast, administration of the GABA(B) receptor positive modulator GS398783 or the GABA(B) receptor antagonist CGP46381 at doses up to 30 mg/kg had no effects on either punished or unpunished responding. The 5-HT(1A) agonist 8-OH-DPAT did not release punished responding, but significantly decreased unpunished responding at the highest dose tested. The modified Geller-Seifter task generally exhibits good predictive validity for anxiolytic-like compounds. Neither GABA(B) receptor positive allosteric modulation nor blockade exhibited anxiolytic-like properties in the modified Geller-Seifter task. The 5-HT(1A) partial agonist buspirone was similarly ineffective. Copyright 2009 Elsevier B.V. All rights reserved.

  1. Repeated administration of the GABAB receptor positive modulator BHF177 decreased nicotine self-administration, and acute administration decreased cue-induced reinstatement of nicotine seeking in rats.

    Science.gov (United States)

    Vlachou, Styliani; Guery, Sebastien; Froestl, Wolfgang; Banerjee, Deboshri; Benedict, Jessica; Finn, M G; Markou, Athina

    2011-05-01

    γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the modulation of central reward processes. Acute or chronic administration of GABA(B) receptor agonists or positive modulators decreased self-administration of various drugs of abuse. Furthermore, GABA(B) receptor agonists inhibited cue-induced reinstatement of nicotine- and cocaine-seeking behavior. Because of their fewer adverse side effects compared with GABA(B) receptor agonists, GABA(B) receptor positive modulators are potentially improved therapeutic compounds for the treatment of drug dependence compared with agonists. We examined whether the acute effects of the GABA(B) receptor positive modulator N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-2-methyl-5-[4-(trifluoromethyl)phenyl]-4-pyrimidinamine (BHF177) on nicotine self-administration and food-maintained responding under a fixed-ratio 5 schedule of reinforcement were maintained after repeated administration. The effects of acute BHF177 administration on cue-induced nicotine- and food-seeking behavior, a putative animal model of relapse, were also examined. Repeated administration of BHF177 for 14 days decreased nicotine self-administration, with small tolerance observed during the last 7 days of treatment, whereas BHF177 minimally affected food-maintained responding. Acute BHF177 administration dose-dependently blocked cue-induced reinstatement of nicotine-, but not food-, seeking behavior after a 10-day extinction period. These results showed that BHF177 selectively blocked nicotine self-administration and prevented cue-induced reinstatement of nicotine seeking, with minimal effects on responding for food and no effect on cue-induced reinstatement of food seeking. Thus, GABA(B) receptor positive modulators could be useful therapeutics for the treatment of different aspects of nicotine dependence by facilitating smoking cessation by decreasing nicotine intake and preventing relapse to smoking in humans.

  2. Alterations in Circulating miRNA Levels following Early-Stage Estrogen Receptor-Positive Breast Cancer Resection in Post-Menopausal Women

    DEFF Research Database (Denmark)

    Kodahl, Annette R; Zeuthen, Pernille; Binder, Harald

    2014-01-01

    these alterations were also observed in an independent data set. METHODS: Global miRNA analysis was performed on prospectively collected serum samples from 24 post-menopausal women with estrogen receptor-positive early-stage breast cancer before surgery and 3 weeks after tumor resection using global LNA...... design and the same qPCR profiling platform, resulting in limited agreement. CONCLUSIONS: A panel of 4 circulating miRNAs exhibited significantly altered levels following radical resection of primary ER+ breast cancers in post-menopausal women. These specific miRNAs may be involved in tumorigenesis...

  3. The estrogen receptor negative-progesterone receptor positive breast carcinoma is a biological entity and not a technical artifact.

    Science.gov (United States)

    Ng, Char Hong; Pathy, Nirmala Bhoo; Taib, Nur Aishah; Mun, Kein Seong; Rhodes, Anthony; Yip, Cheng Har

    2012-01-01

    The ER-/PR+ breast tumor may be the result of a false ER negative result. The aim of this study was to investigate whether there is a difference in patient and tumor characteristics of the ER-/PR+ phenotype in an Asian setting. A total of 2629 breast cancer patients were categorized on the basis of their age, ethnicity, tumor hormonal receptor phenotype, grade and histological type. There were 1230 (46.8%) ER+/PR+, 306 (11.6%) ER+/PR-, 122 (4.6%) ER-/PR+ and 972 (37%) ER-/PR-. ER-/PR+ tumors were 2.5 times more likely to be younger than 50 years at diagnosis (OR: 2.52; 95% CI: 1.72-3.67). Compared to ER+/PR+ tumors, the ER-/ PR+ phenotype was twice more likely to be associated with grade 3 tumors (OR:2.02; 95%CI: 1.00-4.10). In contrast, compared to ER-/PR- tumors, the ER-/PR+ phenotype was 90% less likely to be associated with a grade 3 tumor (OR: 0.12; 95%CI:0.05-0.26), and more likely to have invasive lobular than invasive ductal histology (OR: 3.66; 95%CI: 1.47-9.11). These results show that the ER-/PR+ phenotype occurs in a younger age group and is associated with intermediate histopathological characteristics compared to ER+/PR+ and ER-/PR- tumors. This may imply that it is a distinct entity and not a technical artifact.

  4. Biopsy confirmation of metastatic sites in breast cancer patients: clinical impact and future perspectives

    Science.gov (United States)

    2014-01-01

    Determination of hormone receptor (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2 status in the primary tumor is clinically relevant to define breast cancer subtypes, clinical outcome, and the choice of therapy. Retrospective and prospective studies suggest that there is substantial discordance in receptor status between primary and recurrent breast cancer. Despite this evidence and current recommendations, the acquisition of tissue from metastatic deposits is not routine practice. As a consequence, therapeutic decisions for treatment in the metastatic setting are based on the features of the primary tumor. Reasons for this attitude include the invasiveness of the procedure and the unreliable outcome of biopsy, in particular for biopsies of lesions at complex visceral sites. Improvements in interventional radiology techniques mean that most metastatic sites are now accessible by minimally invasive methods, including surgery. In our opinion, since biopsies are diagnostic and changes in biological features between the primary and secondary tumors can occur, the routine biopsy of metastatic disease needs to be performed. In this review, we discuss the rationale for biopsy of suspected breast cancer metastases, review issues and caveats surrounding discordance of biomarker status between primary and metastatic tumors, and provide insights for deciding when to perform biopsy of suspected metastases and which one (s) to biopsy. We also speculate on the future translational implications for biopsy of suspected metastatic lesions in the context of clinical trials and the establishment of bio-banks of biopsy material taken from metastatic sites. We believe that such bio-banks will be important for exploring mechanisms of metastasis. In the future, advances in targeted therapy will depend on the availability of metastatic tissue. PMID:25032257

  5. An Ectopic ACTH Secreting Metastatic Parotid Tumour

    Directory of Open Access Journals (Sweden)

    Thomas Dacruz

    2016-01-01

    Full Text Available A 60-year old woman presented with features of Cushing’s syndrome (CS secondary to an ectopic adrenocorticotropic hormone (ACTH secreting metastatic parotid tumour 3 years after excision of the original tumour. She subsequently developed fatal intestinal perforation and unfortunately died despite best possible medical measures. Ectopic ACTH secretion accounts for 5–10% of all patients presenting with ACTH dependent hypercortisolism; small cell carcinoma of lung (SCLC and neuroendocrine tumours (NET account for the majority of such cases. Although there are 4 previous case reports of ectopic ACTH secreting salivary tumours in literature, to our knowledge this is the first published case report in which the CS developed after 3 years of what was deemed as a successful surgical excision of primary salivary tumour. Our patient initially had nonspecific symptoms which may have contributed to a delay in diagnosis. Perforation of sigmoid colon is a recognised though underdiagnosed complication associated with steroid therapy and hypercortisolism. This case demonstrates the challenges faced in diagnosis as well as management of patients with CS apart from the practical difficulties faced while trying to identify source of ectopic ACTH.

  6. Metastatic renal cell carcinoma management

    Directory of Open Access Journals (Sweden)

    Flavio L. Heldwein

    2009-06-01

    Full Text Available PURPOSE: To assess the current treatment of metastatic renal cell carcinoma, focusing on medical treatment options. MATERIAL AND METHODS: The most important recent publications have been selected after a literature search employing PubMed using the search terms: advanced and metastatic renal cell carcinoma, anti-angiogenesis drugs and systemic therapy; also significant meeting abstracts were consulted. RESULTS: Progress in understanding the molecular basis of renal cell carcinoma, especially related to genetics and angiogenesis, has been achieved mainly through of the study of von Hippel-Lindau disease. A great variety of active agents have been developed and tested in metastatic renal cell carcinoma (mRCC patients. New specific molecular therapies in metastatic disease are discussed. Sunitinib, Sorafenib and Bevacizumab increase the progression-free survival when compared to therapy with cytokines. Temsirolimus increases overall survival in high-risk patients. Growth factors and regulatory enzymes, such as carbonic anhydrase IX may be targets for future therapies. CONCLUSIONS: A broader knowledge of clear cell carcinoma molecular biology has permitted the beginning of a new era in mRCC therapy. Benefits of these novel agents in terms of progression-free and overall survival have been observed in patients with mRCC, and, in many cases, have become the standard of care. Sunitinib is now considered the new reference first-line treatment for mRCC. Despite all the progress in recent years, complete responses are still very rare. Currently, many important issues regarding the use of these agents in the management of metastatic renal cancer still need to be properly addressed.

  7. Growth hormone test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003706.htm Growth hormone test To use the sharing features on this page, please enable JavaScript. The growth hormone test measures the amount of growth hormone in ...

  8. Growth hormone suppression test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  9. Upper Gastrointestinal Bleeding as a Metastatic Manifestation of Breast Cancer: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Tony Reiman

    2001-01-01

    Full Text Available CASE PRESENTATION: 64-year-old woman with known metastatic lobular breast cancer presented with fever, epigastric pain, hematemesis and melena. A bleeding, ulcerated gastric metastasis was found and was treated with endoscopic therapy, omeprazole and hormonal therapy; the patient was alive and well 13 months later. The bleeding was probably precipitated by necrosis of the lesion during chemotherapy.

  10. Sipuleucel-T: Autologous Cellular Immunotherapy for Men with Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Robert B. Sims

    2011-01-01

    Full Text Available Sipuleucel T is an autologous cellular immunotherapy designed to stimulate an immune response in men diagnosed with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory prostate cancer. Sipuleucel T improves overall survival and provides an additional treatment option for this patient population.

  11. Efficacy and safety of endocrine monotherapy as first-line treatment for hormone-sensitive advanced breast cancer: A network meta-analysis.

    Science.gov (United States)

    Zhang, Jingwen; Huang, Yanhong; Wang, Changyi; He, Yuanfang; Zheng, Shukai; Wu, Kusheng

    2017-08-01

    Endocrine therapy was recommended as the preferred first-line treatment for hormone receptor-positive (HR+, i.e., ER+ and/or PgR+), human epidermal growth factor receptor-2-negative (HER2-) postmenopausal advanced breast cancer (ABC), but which endocrine monotherapy is optimal lacks consensus. We aimed to identify the optimal endocrine monotherapy with a network meta-analysis. We performed a network meta-analysis for a comprehensive analysis of 6 first-line endocrine monotherapies (letrozole, anastrozole, exemestane, tamoxifen, fulvestrant 250 mg and 500 mg) for HR+ HER2- metastatic or locally advanced breast cancer in postmenopausal patients. The main outcomes were objective response rate (ORR), time to progression (TTP), and progression-free survival (PFS). Secondary outcomes were adverse events. We identified 27 articles of 8 randomized controlled trials including 3492 patients in the network meta-analysis. For ORR, the treatments ranked in descending order of effectiveness were letrozole > exemestane > anastrozole > fulvestrant 500 mg > tamoxifen > fulvestrant 250 mg. For TTP/PFS, the order was fulvestrant 500 mg > letrozole > anastrozole > exemestane > tamoxifen > fulvestrant 250 mg. We directly compared adverse events and found that tamoxifen produced more hot flash events than fulvestrant 250 mg. Fulvestrant 500 mg and letrozole might be optimal first-line endocrine monotherapy choices for HR+ HER2- ABC because of efficacious ORR and TTP/PFS, with a favorable tolerability profile. However, direct comparisons among endocrine monotherapies in the first-line therapy setting are still required to robustly demonstrate any differences among these endocrine agents. Clinical choices should also depend on the specific disease situation and duration of endocrine therapy.

  12. Metastatic prostate cancer in transsexual diagnosed after three decades of estrogen therapy

    Science.gov (United States)

    Turo, Rafal; Jallad, Samer; Prescott, Stephen; Cross, William Richard

    2013-01-01

    The incidence of prostate cancer in transsexual patients is very low with only few reported cases. Many years before presenting with prostate cancer, these patients receive hormone ablation as a part of their gender therapy. Their disease is already defined as castrate resistant, and the treatment and follow-up of such patients remains a challenge. We report a case of a male-to-female transgender woman who was diagnosed with metastatic prostate cancer, 31 years post-feminization. PMID:24032068

  13. Chemotherapy of metastatic colon cancer

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2012-01-01

    Full Text Available Colorectal cancer is one of the leading causes of cancer incidence and mortality. In 2008 inRussian Federation55 719 new cases of colorectal cancer were diagnosed and 37 911 patients died of this disease. A significant progress was achieved in metastatic colorectal cancer treatment during the last decades. A lot of treatment options became available: from 5-fluoruracil monotherapy to combined treatment treatment schemes including surgery. A group of patients with isolated liver metastases was distinguished, who can achieve 5-year survival rate of 40 % after systemic treatment and surgery. Today, based on clinical data and molecular analysis, we come close to individualized treatment of this patient group. In this literature review results of metastatic colorectal cancer chemotherapy are being analyzed and rational treatment tactic is proposed based on therapy goals. 

  14. Immunotherapy of distant metastatic disease

    DEFF Research Database (Denmark)

    Schadendorf, D; Algarra, S M; Bastholt, L

    2009-01-01

    vaccines based on dendritic cells and peptides is driven by advances in understanding antigen presentation and processing, and by new techniques of vaccine preparation, stabilisation and delivery. Several agents that have shown promising activity in metastatic melanoma including IL-21 and monoclonal......Immunotherapy of metastatic melanoma consists of various approaches leading to specific or non-specific immunomodulation. The use of FDA-approved interleukin (IL)-2 alone, in combination with interferon alpha, and/or with various chemotherapeutic agents (biochemotherapy) is associated...... with significant toxicity and poor efficacy that does not improve overall survival of 96% of patients. Many studies with allogeneic and autologous vaccines have demonstrated no clinical benefit, and some randomised trials even showed a detrimental effect in the vaccine arm. The ongoing effort to develop melanoma...

  15. Immunolymphoscintigraphy for Metastatic Sentinel Nodes

    DEFF Research Database (Denmark)

    Chakera, A.H.; Nielsen, B.S.; Madsen, J.

    2011-01-01

    Aim. To develop a method and obtain proof-of-principle for immunolymphoscintigraphy for identification of metastatic sentinel nodes. Methods. We selected one of four tumour-specific antibodies against human breast cancer and investigated (1), in immune- deficient (nude) mice with xenograft human...... in healthy rabbits. Results and Conclusion. Our paper suggests the theoretical possibility of a model of dual isotope immuno-lymphoscintigraphy for noninvasive, preoperative, malignant sentinel node imaging....

  16. Metastatic hidradenocarcinoma: Surgery and chemotherapy.

    Science.gov (United States)

    Amel, Trabelsi; Olfa, Gharbi; Faten, Hammedi; Makrem, Hochlef; Slim, Ben Ahmed; Moncef, Mokni

    2009-12-01

    Hidradenocarcinoma is a rare carcinoma of high malignant potential. It most metastasizes to regional lymph nodes and distant viscera. We report a case of 52-year-old woman who presented with an invasive hidradenocarcinoma of the finger, treated with surgical excision. The patient presented with skin and lymph node metastases four years after, treated by chemotherapy. Hidradenocarcinoma is an aggressive tumor. It seems important to use adjuvant therapies particularly for recurrent and metastatic forms.

  17. Emergency Surgery for Metastatic Melanoma

    Directory of Open Access Journals (Sweden)

    Dimitrios Mantas

    2014-01-01

    Full Text Available Visceral metastases from malignant melanoma (stage M1c confer a very poor prognosis, as documented on the most recent revised version of the TNM/AJCC staging system. Emergency surgery for intra-abdominal complications from the disease is rare. We report on our 5-year single institution experience with surgical management of metastatic melanoma to the viscera in the emergent setting. From 2009 to 2013, 14 patients with metastatic melanoma were admitted emergently due to an acute abdomen. Clinical manifestations encompassed intestinal obstruction and bleeding. Surgical procedures involved multiple enterectomies with primary anastomoses in 8 patients, and one patient underwent splenectomy, one adrenalectomy, one right colectomy, one gastric wedge resection, one gastrojejunal anastomosis, and one transanal debulking, respectively. The 30-day mortality was 7 percent. Median follow-up was 14 months. Median overall survival was 14 months. Median disease free survival was 7.5 months. One-year overall survival was 64.2 percent and 2-year overall survival was 14.2 percent. Emergency surgery for metastatic melanoma to the viscera is rare. Elective curative surgery combined with novel cytotoxic systemic therapies is under investigation in an attempt to grant survival benefit in melanoma patients with visceral disease.

  18. Hormones and absence epilepsy

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Tolmacheva, E.A.; Budziszewska, B.

    2017-01-01

    Hormones have an extremely large impact on seizures and epilepsy. Stress and stress hormones are known to reinforce seizure expression, and gonadal hormones affect the number of seizures and even the seizure type. Moreover, hormonal concentrations change drastically over an individual's lifetime,

  19. Hormones and absence epilepsy

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Budziszewska, B.; Tolmacheva, E.A.

    2009-01-01

    Hormones have an extremely large impact on seizures and epilepsy. Stress and stress hormones are known to reinforce seizure expression, and gonadal hormones affect the number of seizures and even the seizure type. Moreover, hormonal concentrations change drastically over an individual's lifetime,

  20. Regulation of Metastatic Breast Cancer Dormancy

    Science.gov (United States)

    2015-09-01

    to begin to unravel the complex resistance seen with metastatic breast cancer , particularly the fear of recurrence 5-10 years after apparent cure...AWARD NUMBER: W81XWH-14-1-0062 TITLE: Regulation of Metastatic Breast Cancer Dormancy PRINCIPAL INVESTIGATOR: Sarah Wheeler CONTRACTING...Metastatic Breast Cancer Dormancy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0062 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Sarah Wheeler 5d

  1. Hormone therapy in acne

    Directory of Open Access Journals (Sweden)

    Chembolli Lakshmi

    2013-01-01

    Full Text Available Underlying hormone imbalances may render acne unresponsive to conventional therapy. Relevant investigations followed by initiation of hormonal therapy in combination with regular anti-acne therapy may be necessary if signs of hyperandrogenism are present. In addition to other factors, androgen-stimulated sebum production plays an important role in the pathophysiology of acne in women. Sebum production is also regulated by other hormones, including estrogens, growth hormone, insulin, insulin-like growth factor-1, glucocorticoids, adrenocorticotropic hormone, and melanocortins. Hormonal therapy may also be beneficial in female acne patients with normal serum androgen levels. An understanding of the sebaceous gland and the hormonal influences in the pathogenesis of acne would be essential for optimizing hormonal therapy. Sebocytes form the sebaceous gland. Human sebocytes express a multitude of receptors, including receptors for peptide hormones, neurotransmitters and the receptors for steroid and thyroid hormones. Various hormones and mediators acting through the sebocyte receptors play a role in the orchestration of pathogenetic lesions of acne. Thus, the goal of hormonal treatment is a reduction in sebum production. This review shall focus on hormonal influences in the elicitation of acne via the sebocyte receptors, pathways of cutaneous androgen metabolism, various clinical scenarios and syndromes associated with acne, and the available therapeutic armamentarium of hormones and drugs having hormone-like actions in the treatment of acne.

  2. Metastatic Breast Carcinoma Presenting as a Sigmoid Stricture: Report of a Case and Review of the Literature

    Directory of Open Access Journals (Sweden)

    A. Nikkar-Esfahani

    2013-03-01

    Full Text Available Metastatic spread of breast carcinoma to the colon and rectum is rare. We report the case of a patient treated for lobular breast carcinoma presenting 17 years later with metastatic breast cancer of the colon. A 63-year-old lady with a past history of right-sided invasive lobular carcinoma of the breast presented with persistent diarrhoea. Colonoscopy with biopsies revealed a benign-looking stricture at the rectosigmoid junction. A CT scan of the abdomen and pelvis revealed a benign-looking stricture in keeping with a probable diverticular stricture. A Hartmann procedure was performed and histology revealed a metastatic lobular carcinoma with oestrogen and progesterone receptor-positive status. Treatment was commenced with letrozole and the patient remains well under clinical surveillance. In a patient with a history of breast carcinoma who presents with gastrointestinal symptoms the possibility of gastrointestinal tract spread should always be considered. Endoscopic diagnosis may be misleading with pathological diagnosis only being made following surgical resection. A history of breast carcinoma must be declared to the histopathologist following surgical resection so that an accurate diagnosis is made and appropriate treatment is commenced.

  3. Expression of glucocorticoid receptor is associated with aggressive primary endometrial cancer and increases from primary to metastatic lesions.

    Science.gov (United States)

    Tangen, Ingvild L; Veneris, Jennifer Taylor; Halle, Mari K; Werner, Henrica M; Trovik, Jone; Akslen, Lars A; Salvesen, Helga B; Conzen, Suzanne D; Fleming, Gini F; Krakstad, Camilla

    2017-12-01

    Glucocorticoid receptor (GR) has emerged as an important steroid nuclear receptor in hormone dependent cancers, however few data are available regarding a potential role of GR in endometrial cancer. The aim of this study was to investigate expression of GR in primary and metastatic endometrial cancer lesions, and to assess the relationship between GR expression and clinical and histopathological variables and survival. Expression of GR was investigated by IHC in 724 primary tumors and 289 metastatic lesions (from 135 patients), and correlations with clinical and histopathological data and survival were explored. Expression of GR was significantly increased in non-endometrioid tumors compared to endometrioid tumors, and was associated with markers of aggressive disease and poor survival both in univariate and multivariate analysis after correcting for age, FIGO stage and histologic grade. Within the subgroups of hormone receptor negative tumors (loss of androgen receptor, estrogen receptor or progesterone receptor) expression of GR was highly significantly associated with poor disease specific survival. There was an overall increase in GR expression from primary to metastatic lesions, and the majority of metastases expressed GR. GR expression in primary endometrial cancer is associated with aggressive disease and poor survival. The majority of metastatic endometrial cancer lesions express GR; therefore GR may represent a therapeutic target in the adjuvant therapy of poor prognosis early-stage as well as metastatic endometrial cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Radiolabeled high affinity peptidomimetic antagonist selectively targets {alpha}{sub v}{beta}{sub 3} receptor-positive tumor in mice

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Beom-Su [Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Lim, Esther [Department of Radiology, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Hee Park, Seung [Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Shin, In Soo [Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Danthi, S. Narasimhan [Department of Radiology, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Hwang, In Sook [Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Le, Nhat [Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Yu, Sarah [Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Xie Jianwu [Department of Radiology, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Li, King C.P. [Department of Radiology, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Carrasquillo, Jorge A. [Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Paik, Chang H. [Department of Nuclear Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States)]. E-mail: cpaik@mail.nih.gov

    2007-05-15

    Objectives: The aim of this research was to synthesize radiolabeled peptidomimetic integrin {alpha}{sub v}{beta}{sub 3} antagonists that selectively target integrin {alpha}{sub v}{beta}{sub 3} receptor and clear rapidly from the whole body. Methods: Integrin {alpha}{sub v}{beta}{sub 3} antagonists, 4-[2-(3,4,5,6-tetrahydropyrimidine-2-ylamino) ethyloxy]benzoyl-2-(S)-aminoethylsulfonyl-amino-{beta}-alanine (IA) and 4-[2-(3,4,5,6-tetrahydro-pyrimidin-2-ylamino)-ethyloxy]benzoyl-2-(S)-[N- (3-amino-neopenta-1-carbamyl)]-aminoethylsulfonylamino-{beta}-alanine hydrochloride (IAC), a hydrophobic carbamate derivative of IA, were conjugated with 2-p-isothiocyanatobenzyl-DOTA at the amino terminus and labeled with {sup 111}In. The {sup 111}In labeled IA and IAC were subjected to in vitro receptor binding, biodistribution and imaging studies using nude mice bearing the receptor-positive M21 human melanoma xenografts. Results: The {sup 111}In-labeled IA (40%) and -IAC (72%) specifically bound in vitro to {alpha}{sub v}{beta}{sub 3} (0.8 {mu}M) at a molar excess. This receptor binding was completely blocked by a molar excess of cold IA to {alpha}{sub v}{beta}{sub 3}. The higher receptor-binding affinity of the {sup 111}In-labeled IAC was reflected in higher tumor uptake and retention: 5.6{+-}1.4 and 4.5{+-}0.7 %ID/g vs. 3.8{+-}0.9 and 2.0{+-}0.3 %ID/g for the {sup 111}In-labeled IA at 0.33 and 2 h. The tumor uptakes were inhibited by the co-injection of 200 {mu}g of IA, indicating that the uptake was receptor mediated. These antagonists were excreted primarily via the renal system. The {sup 111}In activity retained in the whole body was quite comparable between the {sup 111}In-labeled IA (24% ID) and the {sup 111}In-labeled IAC (33% ID) at 2 h. The higher peak tumor uptake and longer retention resulted in higher tumor-to-background ratios for the {sup 111}In-labeled IAC at 2 h with 9.7, 2.3, 0.8, 1.9, 7.1, 2.2, 0.9, 3.7 and 9.9 for blood, liver, kidney, lung, heart, stomach

  5. Role of surgery in advanced/metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Suresh Bhat

    2010-01-01

    Full Text Available Metastatic renal cell cancer (RCC is a malignant disease without curative treatment. These patients are usually symptomatic and desperate for effective palliative treatment. Radiotherapy, chemotherapy, and hormonal therapy are not effective in these patients. A multimodal approach consisting of cytoreductive nephrectomy, systemic therapy (which includes cytokines or targeted molecules, and metastasectomy have been shown to be useful in prolonging the survival and improving the quality of life in a select group of patients with metastatic renal cancer. Patients with oligometastatic disease, good performance status, and delayed presentation of the secondaries have better results following this integrated approach. Although there is some controversy regarding the order in which nephrectomy and systemic therapy are to be instituted, well-controlled studies like the South West Oncology Group and European organization research and treatment of cancer have shown that upfront nephrectomy gives better survival compared to neoadjuvant systemic therapy followed by nephrectomy. This order is the standard presently. Of late, with better understanding of the genetic basis and the biology of the various subtypes of renal cell carcinoma, targeted molecular therapies have emerged as an equally effective alternative therapy to cytokines. Recent reports have proven that targeted therapy is more effective with comparable side effects. Metastasectomy in a subgroup of patients improves survival and quality of life specifically in those with lung secondaries and painful bone metastases.

  6. Targeted treatment of advanced and metastatic breast cancer with lapatinib

    Directory of Open Access Journals (Sweden)

    Brendan Corkery

    2008-09-01

    Full Text Available Brendan Corkery1,2, Norma O’Donovan2, John Crown1,21St. Vincent’s University Hospital, Dublin, Ireland; 2National Institute for Cellular Biotechnology, Dublin City University, Dublin, IrelandAbstract: Improved molecular understanding of breast cancer in recent years has led to the discovery of important drug targets such as HER-2 and EGFR. Lapatinib is a potent dual inhibitor of HER-2 and EGFR. Preclinical and phase I studies have shown activity with lapatinib in a number of cancers, including breast cancer, and the drug is well tolerated. The main known drug interactions are with paclitaxel and irinotecan. The most significant side-effects of lapatinib are diarrhea and adverse skin events. Rates of cardiotoxicity compare favorably with trastuzumab, a monoclonal antibody against HER-2. This paper focuses on lapatinib in advanced and metastatic breast cancer, which remains an important therapeutic challenge. Phase II and III studies show activity as monotherapy, and in combination with chemotherapy or hormonal agents. Results from these studies suggest that the main benefit from lapatinib is in the HER-2 positive breast cancer population. Combinations of lapatinib and trastuzumab are also being studied and show encouraging results, particularly in trastuzumab-refractory metastatic breast cancer. Lapatinib may have a specific role in treating HER-2 positive CNS metastases. The role of lapatinib as neoadjuvant therapy and in early breast cancer is also being evaluated.Keywords: HER-2, EGFR, erbB, lapatinib, Tykerb®, tyrosine kinase

  7. The changing natural history of metastatic prostate cancer.

    Science.gov (United States)

    Alva, Ajjai; Hussain, Maha

    2013-01-01

    Since 1941, the understanding of prostate cancer pathogenesis and therapy has undergone a significant transformation. Rigorous translational research has identified multiple mechanisms underlying castration resistance, the fatal clinical state of the disease. Therapeutic approaches targeting these mechanisms in metastatic castration-resistant prostate cancer have now been clinically validated in the clinic including high-potency androgen signaling inhibition, novel cytotoxic chemotherapy, and bone-targeted therapies. Despite these advances, cure remains an elusive goal. The natural history of metastatic prostate cancer has evolved particularly in the last 2 decades in step with improved management of age-associated comorbidities, improved imaging, and the expansion of novel therapies, thus providing new opportunities and challenges. It is also important to note that the advent of prostate-specific antigen testing caused a stage shift in the disease spectrum, thus leading to earlier interventions and potentially positively impacting survival. The optimal sequencing and combinations of available therapies, predictive biomarkers, and better understanding of mechanisms of resistance remain high priority. Further refinement of the clinical niche for novel therapies in hormone-sensitive and castration-resistant disease through rationally designed clinical trials incorporating molecular, clinical, and imaging biomarkers and quality-of-life correlatives is of paramount importance.

  8. Basic Concepts in Metastatic Cardiac Disease

    OpenAIRE

    Vlachostergios, Panagiotis J.; Daliani, Danai D.; Papandreou, Christos N.

    2012-01-01

    The involvement of the heart in metastatic cancer is a rare clinical diagnosis, as it may be asymptomatic or symptoms, when present, may be attributed to other causes. Issues regarding incidence, intracardiac location, clinical presentation, diagnosis and treatment of metastatic cardiac tumors will be discussed here.

  9. REPORT OF SEVEN CASES OF METASTATIC TUMOURS

    African Journals Online (AJOL)

    Major Adebayo

    Abstract. Background: Metastatic tumours make up approximately one per cent of all oral malignancies. Such tumours may present in the jawbones and oral soft tissues. The commonest oral site is the mandible. Nigerian reports of metastatic tumours to the jaws are very rare. Method: This is a retrospective study of six cases ...

  10. CT of metastatic spinal tumor

    Energy Technology Data Exchange (ETDEWEB)

    Sakata, T. (Osaka Medical Coll., Takatsuki (Japan))

    1980-12-01

    CT findings of metastatic spinal tumor were classified into 6 types, i.e., consolidation, dissolution, mottle, doughnut, and ring types, and mixed type of these, and that of no findings. Some statistically significant relationship was found between prostatic cancer and consolidation type, and unknown primary cancer and dissolution type. Abnormal findings of bone scintigraphy was suspected to have metastatic spinal tumor by plain radiography and CT scan in 64/128 (50.0%) and 113/145 (78.6%), respectively. There was some relationship between plain radiographic findings and CT findings; between consolidation type of the former and consolidation type of the latter, dissolution type and dissolution type, compression fracture type and mixed type, the type of no findings and consolidation or mixed type. Most of the lesions detected by CT as consolidation or mixed type were revealed by plain radiography. Changes in Ca amount was not detected by plain radiography and CT scan if it was approximately less than 30% and 18% of the initial Ca respectively.

  11. [The metastatic tumor and immunotherapy].

    Science.gov (United States)

    Fuchimoto, S; Orita, K

    1989-04-01

    Metastasis is one of the great characteristics of malignant tumors. On the basis of our data, we reported here the immunotherapy for hematogenous metastasis. A randomized controlled study of preoperative transendoscopic intratumoral injection of BRM into gastro-intestinal cancer, which was performed in our Department, revealed a decreasing tendency of distant metastases in lymph node for the injection group, suggesting the disappearance of micro-metastasis due to the injection, namely, systemic immuno-enhancement due to the local effect, leading to diminution of hematogenous metastasis. Next, a mixture of natural human TNF-alpha (nHuTNF-alpha) and natural human IFn-alpha(nHuIFN-alpha), the so-called OH-1, was described. The results of a clinical study dealing with the antitumor effect on advanced and recurrent malignant tumors made it clear that all of the effective results (72 cases) such as CR and PR were obtained by an administration schedule with a maintenance dose of more than 200 X 10(4)U; rate of efficacy was 19.4% (4 cases of CR, 10 of PR and 4 of MR). By disease, breast cancer, renal cancer and liver cancer evidenced the most remarkable effects. Examination of the antitumor effect by metastatic organ revealed the effectiveness on hematogenous metastasic tumor of lung, bone and liver, though dependent upon underlying diseases. Finally, being based on our in vitro and in vivo results, we discussed the role of these immunotherapies for metastatic tumors.

  12. Prognostic Impacts of Metastatic Site and Pain on Progression to Castrate Resistance and Mortality in Patients with Metastatic Prostate Cancer.

    Science.gov (United States)

    Koo, Kyo Chul; Park, Sang Un; Kim, Ki Hong; Rha, Koon Ho; Hong, Sung Joon; Yang, Seung Choul; Chung, Byung Ha

    2015-09-01

    To investigate predictors of progression to castration-resistant prostate cancer (CRPC) and cancer-specific mortality (CSM) in patients with metastatic prostate cancer (mPCa). A retrospective analysis was performed on 440 consecutive treatment-naïve patients initially diagnosed with mPCa between August 2000 and June 2012. Patient age, body mass index (BMI), Gleason score, prostate-specific antigen (PSA), PSA nadir, American Joint Committee on Cancer stage, Visual Analogue Scale pain score, Eastern Cooperative Oncology Group performance score (ECOG PS), PSA response to hormone therapy, and metastatic sites were assessed. Cox-proportional hazards regression analyses were used to evaluate survivals and predictive variables of men with bone metastasis stratified according to the presence of pain, compared to men with visceral metastasis. Metastases were most often found in bone (75.4%), followed by lung (16.3%) and liver (8.3%) tissues. Bone metastasis, pain, and high BMI were associated with increased risks of progression to CRPC, and bone metastasis, pain, PSA nadir, and ECOG PS≥1 were significant predictors of CSM. During the median follow-up of 32.0 (interquartile range 14.7-55.9) months, patients with bone metastasis with pain and patients with both bone and visceral metastases showed the worst median progression to CRPC-free and cancer-specific survivals, followed by men with bone metastasis without pain. Patients with visceral metastasis had the best median survivals. Metastatic spread and pain patterns confer different prognosis in patients with mPCa. Bone may serve as a crucial microenvironment in the development of CRPC and disease progression.

  13. Deciding about hormone therapy

    Science.gov (United States)

    ... to continue seeing your doctor for regular checkups. Alternative Names HRT - deciding; Estrogen replacement therapy - deciding; ERT- deciding; Hormone replacement therapy - deciding; Menopause - deciding; HT - deciding; Menopausal hormone therapy - deciding; MHT - ...

  14. Hormones and Hypertension

    Science.gov (United States)

    Fact Sheet Hormones and Hypertension What is hypertension? Hypertension, or chronic (long-term) high blood pressure, is a main cause of ... tobacco, alcohol, and certain medications play a part. Hormones made in the kidneys and in blood vessels ...

  15. Menopause and Hormones

    Science.gov (United States)

    ... Consumer Information by Audience For Women Menopause and Hormones: Common Questions Share Tweet Linkedin Pin it More ... reproduction and distribution. Learn More about Menopause and Hormones Menopause--Medicines to Help You Links to other ...

  16. Antidiuretic hormone blood test

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003702.htm Antidiuretic hormone blood test To use the sharing features on this page, please enable JavaScript. Antidiuretic blood test measures the level of antidiuretic hormone (ADH) in ...

  17. Tumor-infiltrating lymphocytes are significantly associated with better overall survival and disease-free survival in triple-negative but not estrogen receptor-positive breast cancers.

    Science.gov (United States)

    Krishnamurti, Uma; Wetherilt, Ceyda Sonmez; Yang, Jing; Peng, Limin; Li, Xiaoxian

    2017-06-01

    Correlation between tumor-infiltrating lymphocytes (TILs) and complete pathological response (pCR) in breast cancers in neoadjuvant settings have been reported. In this study, we analyzed the association between TILs and diagnostic and prognostic parameters in estrogen receptor-positive (ER+) and triple-negative breast cancer (TNBC) without neoadjuvant treatments. Three hundred forty-four (344) patients who underwent mastectomy for breast cancer (187 ER+ and 157 TNBC) without neoadjuvant treatments were evaluated. Percentage of overall and peripheral TILs were correlated with lymphovascular invasion (LVI), Nottingham histologic grade (NHG, 1/2 versus 3), stage, lymph node status (LN), overall survival (OS), and disease-free survival (DFS). In TNBC, both peripheral and overall TILs were significantly associated with NHG 3 (PP=.0354) and DFS (HR: 0.95; 95% CI: 0.91-1.00; P=.0314) in univariate and multivariate analysis. In ER+ breast cancer, only peripheral TILs were associated with NHG 3 (P=.018) but not with OS or DFS (both P>.05). In ER+ breast cancer, there was a negative association between Oncotype DX recurrence score and both overall (P=.0007) and peripheral TILs (P=.0119). In conclusion, peripheral but not overall TILs correlate with better OS and DFS in TNBC, indicating the location of TILs may be important in TNBC. The negative association between TILs and Oncotype DX score in ER+ may indicate the possible prognostic value of TILs in ER+ breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Oxidative Stress-Mediated Apoptosis Induced by Ethanolic Mango Seed Extract in Cultured Estrogen Receptor Positive Breast Cancer MCF-7 Cells

    Directory of Open Access Journals (Sweden)

    Al-Shwyeh Hussah Abdullah

    2015-02-01

    Full Text Available Breast cancer has become a global health issue requiring huge expenditures for care and treatment of patients. There is a need to discover newer cost-effective alternatives for current therapeutic regimes. Mango kernel is a waste product with potential as a source of anti-cancer phytochemicals, especially since it is non-toxic towards normal breast cell lines at concentrations for which it induces cell death in breast cancer cells. In this study, the anti-cancer effect of mango kernel extract was determined on estrogen receptor-positive human breast carcinoma (MCF-7 cells. The MCF-7 cells were cultured and treated with 5, 10 and 50 μg/mL of mango kernel extract for 12 and 24 h. In response to treatment, there were time- and dose-dependent increases in oxidative stress markers and pro-apoptotic factors; Bcl-2-like protein 4 (BAX, p53, cytochrome c and caspases (7, 8 and 9 in the MCF-7 cells treated with the extract. At the same time, there were decreases in pro-survival markers (Bcl-2 and glutathione as the result of the treatments. The changes induced in the MCF-7 cells by mango kernel extract treatment suggest that the extract can induce cancer cell apoptosis, likely via the activation of oxidative stress. These findings need to be evaluated further to determine whether mango kernel extract can be developed as an anti-breast cancer agent.

  19. Oxidative stress-mediated apoptosis induced by ethanolic mango seed extract in cultured estrogen receptor positive breast cancer MCF-7 cells.

    Science.gov (United States)

    Abdullah, Al-Shwyeh Hussah; Mohammed, Abdulkarim Sabo; Rasedee, Abdullah; Mirghani, Mohamed Elwathig Saeed

    2015-02-05

    Breast cancer has become a global health issue requiring huge expenditures for care and treatment of patients. There is a need to discover newer cost-effective alternatives for current therapeutic regimes. Mango kernel is a waste product with potential as a source of anti-cancer phytochemicals, especially since it is non-toxic towards normal breast cell lines at concentrations for which it induces cell death in breast cancer cells. In this study, the anti-cancer effect of mango kernel extract was determined on estrogen receptor-positive human breast carcinoma (MCF-7) cells. The MCF-7 cells were cultured and treated with 5, 10 and 50 μg/mL of mango kernel extract for 12 and 24 h. In response to treatment, there were time- and dose-dependent increases in oxidative stress markers and pro-apoptotic factors; Bcl-2-like protein 4 (BAX), p53, cytochrome c and caspases (7, 8 and 9) in the MCF-7 cells treated with the extract. At the same time, there were decreases in pro-survival markers (Bcl-2 and glutathione) as the result of the treatments. The changes induced in the MCF-7 cells by mango kernel extract treatment suggest that the extract can induce cancer cell apoptosis, likely via the activation of oxidative stress. These findings need to be evaluated further to determine whether mango kernel extract can be developed as an anti-breast cancer agent.

  20. Testosterone-receptor positive hepatocellular carcinoma in a 29-year old bodybuilder with a history of anabolic androgenic steroid abuse: a case report.

    Science.gov (United States)

    Solbach, Philipp; Potthoff, Andrej; Raatschen, Hans-Jürgen; Soudah, Bisharah; Lehmann, Ulrich; Schneider, Andrea; Gebel, Michael J; Manns, Michael P; Vogel, Arndt

    2015-05-20

    Continuous use of anabolic androgenic steroid in high-doses is associated with substantial health risks, including hepatocellular adenoma. Malignant transformation from hepatocellular adenoma to hepatocellular carcinoma after anabolic androgenic steroid abuse has been rarely reported. The morphological distinction of adenoma from well-differentiated hepatocellular carcinoma is challenging and requires elaborated imaging techniques and histology. We report about a 29-year old male professional bodybuilder who presented with mid-epigastric pain at the emergency unit. Ultrasound showed a severe hepatomegaly with multiple lesions. Contrast-enhanced ultrasound revealed a heterogeneous pattern with signs of hepatocellular carcinoma. CT scan of the abdomen confirmed multiple hypervascular lesions and central areas of necrosis without contrast enhancement. Subsequent diagnostics included fine needle aspiration (FNA) of suspicious lesions and mini-laparoscopy to establish the diagnosis of a β-catenin and testosterone-receptor positive hepatocellular carcinoma embedded in multiple adenomas. The patient was subsequently treated by liver transplantation and remains tumor-free 27 month after surgery. Hepatocellular carcinoma occurring in association with anabolic androgenic steroid abuse should sensitize physicians and especially professional bodybuilders for the harmful use of high doses of steroids.

  1. Identification of Potential Glycoprotein Biomarkers in Estrogen Receptor Positive (ER+ and Negative (ER- Human Breast Cancer Tissues by LC-LTQ/FT-ICR Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Suzan M. Semaan, Xu Wang, Alan G. Marshall, Qing-Xiang Amy Sang

    2012-01-01

    Full Text Available Breast cancer is the second most fatal cancer in American women. To increase the life expectancy of patients with breast cancer new diagnostic and prognostic biomarkers and drug targets must be identified. A change in the glycosylation on a glycoprotein often causes a change in the function of that glycoprotein; such a phenomenon is correlated with cancerous transformation. Thus, glycoproteins in human breast cancer estrogen receptor positive (ER+ tissues and those in the more advanced stage of breast cancer, estrogen receptor negative (ER- tissues, were compared. Glycoproteins showing differences in glycosylation were examined by 2-dimensional gel electrophoresis with double staining (glyco- and total protein staining and identified by reversed-phase nano-liquid chromatography coupled with a hybrid linear quadrupole ion trap/ Fourier transform ion cyclotron resonance mass spectrometer. Among the identified glycosylated proteins are alpha 1 acid glycoprotein, alpha-1-antitrypsin, calmodulin, and superoxide dismutase mitochondrial precursor that were further verified by Western blotting for both ER+ and ER- human breast tissues. Results show the presence of a possible glycosylation difference in alpha-1-antitrypsin, a potential tumor-derived biomarker for breast cancer progression, which was expressed highest in the ER- samples.

  2. Risk estimation of distant metastasis in node-negative, estrogen receptor-positive breast cancer patients using an RT-PCR based prognostic expression signature

    Directory of Open Access Journals (Sweden)

    Gray Joe

    2008-11-01

    Full Text Available Abstract Background Given the large number of genes purported to be prognostic for breast cancer, it would be optimal if the genes identified are not confounded by the continuously changing systemic therapies. The aim of this study was to discover and validate a breast cancer prognostic expression signature for distant metastasis in untreated, early stage, lymph node-negative (N- estrogen receptor-positive (ER+ patients with extensive follow-up times. Methods 197 genes previously associated with metastasis and ER status were profiled from 142 untreated breast cancer subjects. A "metastasis score" (MS representing fourteen differentially expressed genes was developed and evaluated for its association with distant-metastasis-free survival (DMFS. Categorical risk classification was established from the continuous MS and further evaluated on an independent set of 279 untreated subjects. A third set of 45 subjects was tested to determine the prognostic performance of the MS in tamoxifen-treated women. Results A 14-gene signature was found to be significantly associated (p Conclusion The 14-gene signature is significantly associated with risk of distant metastasis. The signature has a predominance of proliferation genes which have prognostic significance above that of Ki-67 LI and may aid in prioritizing future mechanistic studies and therapeutic interventions.

  3. Growth Hormone Deficiency in Adults

    Science.gov (United States)

    ... Balance › Growth Hormone Deficiency in Adults Patient Guide Growth Hormone Deficiency in Adults June 2011 Download PDFs English ... depression, or moodiness What are the benefits of growth hormone therapy? Growth hormone treatment involves injections (shots) of ...

  4. iTRAQ Quantitative Proteomic Comparison of Metastatic and Non-Metastatic Uveal Melanoma Tumors.

    Directory of Open Access Journals (Sweden)

    John W Crabb

    Full Text Available Uveal melanoma is the most common malignancy of the adult eye. The overall mortality rate is high because this aggressive cancer often metastasizes before ophthalmic diagnosis. Quantitative proteomic analysis of primary metastasizing and non-metastasizing tumors was pursued for insights into mechanisms and biomarkers of uveal melanoma metastasis.Eight metastatic and 7 non-metastatic human primary uveal melanoma tumors were analyzed by LC MS/MS iTRAQ technology with Bruch's membrane/choroid complex from normal postmortem eyes as control tissue. Tryptic peptides from tumor and control proteins were labeled with iTRAQ tags, fractionated by cation exchange chromatography, and analyzed by LC MS/MS. Protein identification utilized the Mascot search engine and the human Uni-Prot/Swiss-Protein database with false discovery ≤ 1%; protein quantitation utilized the Mascot weighted average method. Proteins designated differentially expressed exhibited quantitative differences (p ≤ 0.05, t-test in a training set of five metastatic and five non-metastatic tumors. Logistic regression models developed from the training set were used to classify the metastatic status of five independent tumors.Of 1644 proteins identified and quantified in 5 metastatic and 5 non-metastatic tumors, 12 proteins were found uniquely in ≥ 3 metastatic tumors, 28 were found significantly elevated and 30 significantly decreased only in metastatic tumors, and 31 were designated differentially expressed between metastatic and non-metastatic tumors. Logistic regression modeling of differentially expressed collagen alpha-3(VI and heat shock protein beta-1 allowed correct prediction of metastasis status for each of five independent tumor specimens.The present data provide new clues to molecular differences in metastatic and non-metastatic uveal melanoma tumors. While sample size is limited and validation required, the results support collagen alpha-3(VI and heat shock protein beta-1 as

  5. Extended adjuvant endocrine therapy in hormone dependent breast cancer: the paradigm of the NCIC-CTG MA.17/BIG 1-97 trial.

    Science.gov (United States)

    Higgins, Michaela J; Liedke, Pedro E R; Goss, Paul E

    2013-04-01

    Early hormone-receptor-positive breast cancer is a chronic relapsing disease that can remain clinically silent for many years. The NCIC-CTG MA.17/BIG 1-97 trial randomized disease-free early breast cancer patients who had received five years of adjuvant tamoxifen to either letrozole or placebo and was the first to demonstrate a benefit with extended endocrine therapy. MA.17/BIG 1-97 was stopped at the first interim analysis because disease free survival was strongly prolonged in the letrozole arm. Subsequent subset analyses and longer follow up have shown that this therapy improved survival across all groups, particularly among women with node-positive disease and those that were pre-menopausal at time of study enrolment. The MA.17/BIG 1-97 study should be considered a paradigm for extended adjuvant endocrine therapy in hormone-receptor-positive early breast cancer. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  6. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer.

    Science.gov (United States)

    Schiavon, Gaia; Hrebien, Sarah; Garcia-Murillas, Isaac; Cutts, Rosalind J; Pearson, Alex; Tarazona, Noelia; Fenwick, Kerry; Kozarewa, Iwanka; Lopez-Knowles, Elena; Ribas, Ricardo; Nerurkar, Ashutosh; Osin, Peter; Chandarlapaty, Sarat; Martin, Lesley-Ann; Dowsett, Mitch; Smith, Ian E; Turner, Nicholas C

    2015-11-11

    Acquired ESR1 mutations are a major mechanism of resistance to aromatase inhibitors (AIs). We developed ultra high-sensitivity multiplex digital polymerase chain reaction assays for ESR1 mutations in circulating tumor DNA (ctDNA) and investigated the clinical relevance and origin of ESR1 mutations in 171 women with advanced breast cancer. ESR1 mutation status in ctDNA showed high concordance with contemporaneous tumor biopsies and was accurately assessed in samples shipped at room temperature in preservative tubes. ESR1 mutations were found exclusively in estrogen receptor-positive breast cancer patients previously exposed to AI. Patients with ESR1 mutations had a substantially shorter progression-free survival on subsequent AI-based therapy [hazard ratio, 3.1; 95% confidence interval (CI), 1.9 to 23.1; P = 0.0041]. ESR1 mutation prevalence differed markedly between patients who were first exposed to AI during the adjuvant and metastatic settings [5.8% (3 of 52) versus 36.4% (16 of 44), respectively; P = 0.0002]. In an independent cohort, ESR1 mutations were identified in 0% (0 of 32; 95% CI, 0 to 10.9) tumor biopsies taken after progression on adjuvant AI. In a patient with serial sampling, ESR1 mutation was selected during metastatic AI therapy to become the dominant clone in the cancer. ESR1 mutations can be robustly identified with ctDNA analysis and predict for resistance to subsequent AI therapy. ESR1 mutations are rarely acquired during adjuvant AI but are commonly selected by therapy for metastatic disease, providing evidence that mechanisms of resistance to targeted therapy may be substantially different between the treatment of micrometastatic and overt metastatic cancer. Copyright © 2015, American Association for the Advancement of Science.

  7. Tattoo pigment mimicking metastatic malignant melanoma.

    Science.gov (United States)

    Anderson, L L; Cardone, J S; McCollough, M L; Grabski, W J

    1996-01-01

    The benefits of elective lymph node dissection (ELND) in the treatment of melanoma remain controversial, however, it may be beneficial in some patients. Tattoo pigment from decorative tattoos may migrate to the regional lymph nodes. In patients who develop malignant melanoma and who have been tattooed, this pigment may clinically mimic metastatic disease. We wish to alert clinicians that pigment from tattoos may migrate to the regional lymph nodes. In the unusual instance of a tattooed patient who develops malignant melanoma, when undergoing ELND, surgeons should rely on histologic confirmation of metastatic disease before altering operative plans. ELND for malignant melanoma, in a patient with a history of decorative tattoos that had been removed by dermabrasion, was performed. Black lymph nodes that clinically resembled metastatic disease were identified. Subsequent histologic examination revealed normal lymph node architecture with a heavy collection of black pigment. Mass spectrophotometry showed this pigment to be consistent with tattoo dye. A patient who had undergone dermabrasion for removal of decorative tattoos developed malignant melanoma in the same extremity. Clinically suspicious black lymph nodes were identified during ELND. Histologic examination did not reveal metastatic disease. Additional therapy was not considered intra- or postoperatively even though the clinical suspicion of metastatic disease was high. The patient was not subjected to any unnecessary emotional or physical distress pending histologic confirmation. Tattoo pigment in the lymph nodes may clinically mimic metastatic melanoma. Histologic confirmation of metastatic disease should always be obtained before additional therapy is considered.

  8. Up-regulation of the oligosaccharide sialyl LewisX: a new prognostic parameter in metastatic prostate cancer.

    Science.gov (United States)

    Jørgensen, T; Berner, A; Kaalhus, O; Tveter, K J; Danielsen, H E; Bryne, M

    1995-05-01

    Metastatic prostate cancer has an unpredictable long-term prognosis. At present, there are few specific predictors to indicate the outcome for the individual patient. We have studied immunoreactivity for type-2 carbohydrate structures, known to be involved in various cell adhesion processes, in patients with metastatic prostate cancer. One group of patients (n = 26) did not progress within 3 years after orchiectomy, while another group of patients (n = 33) progressed within 1 year following castration and survived less than 2 years. Among the parameters studied, sialyl LewisX carbohydrate up-regulation was the only variable showing significant association with poor prognosis (P < 0.01). Sialyl LewisX discriminated between these two outcome groups with 71% predictability and 96% specificity. Our results indicate that up-regulation of sialyl LewisX is associated with hormonal-resistant, aggressive disease. This prognostic marker may, therefore, have an important role in selecting proper treatment for patients with metastatic prostate cancer.

  9. CDK9 inhibitors selectively target estrogen receptor-positive breast cancer cells through combined inhibition of MYB and MCL-1 expression.

    Science.gov (United States)

    Mitra, Partha; Yang, Ren-Ming; Sutton, James; Ramsay, Robert G; Gonda, Thomas J

    2016-02-23

    Our previous studies showed that MYB is required for proliferation of, and confers protection against apoptosis on, estrogen receptor-positive (ER(+ve)) breast cancer cells, which are almost invariably also MYB(+ve). We have also shown that MYB expression in ER(+ve) breast cancer cells is regulated at the level of transcriptional elongation and as such, is suppressed by CDK9i. Here we examined the effects of CDK9i on breast cancer cells and the involvement of MYB in these effects. ER(+ve) breast cancer cell lines including MCF-7 were much more sensitive (> 10 times) to killing by CDK9i than ER(-ve)/MYB(-ve) cells. Moreover, surviving cells showed a block at the G2/M phase of the cell cycle. Importantly, ectopic MYB expression conferred resistance to apoptosis induction, cell killing and G2/M accumulation. Expression of relevant MYB target genes including BCL2 and CCNB1 was suppressed by CDK9 inhibition, and this too was reversed by ectopic MYB expression. Nevertheless, inhibition of BCL2 alone either by MYB knockdown or by ABT-199 treatment was insufficient for significant induction of apoptosis. Further studies implied that suppression of MCL-1, a well-documented target of CDK9 inhibition, was additionally required for apoptosis induction, while maximal levels of apoptosis induced by CDK9i are likely to also involve inhibition of BCL2L1 expression. Taken together these data suggest that MYB regulation of BCL2 underlies the heightened sensitivity of ER(+ve) compared to ER(-ve) breast cancer cells to CDK9 inhibition, and that these compounds represent a potential therapeutic for ER(+ve) breast cancers and possibly other MYB-dependent cancers.

  10. Reproductive factors and risk of estrogen receptor positive, triple-negative, and HER2-neu overexpressing breast cancer among women 20-44 years of age.

    Science.gov (United States)

    Li, Christopher I; Beaber, Elisabeth F; Tang, Mei-Tzu Chen; Porter, Peggy L; Daling, Janet R; Malone, Kathleen E

    2013-01-01

    Aspects of reproductive history are among the most well-established breast cancer risk factors. However, relatively little is known about how they influence risk of different molecular subtypes of breast cancer, particularly among younger women. Using data from a population-based case-control study of women 20-44 years of age, we assessed the relationships between various reproductive factors and risk of estrogen receptor positive (ER+), triple-negative, and HER2-overexpressing breast cancers. Detailed reproductive histories were obtained through structured interviewer administered in-person questionnaires. Reproductive histories among control women (n = 941) were compared to those of ER+ cases (n = 781), triple-negative cases (n = 180), and HER2-overexpressing cases (n = 60) using polytomous logistic regression. Age at menarche, parity, and number of full-term pregnancies were similarly associated with risk of all three breast cancer subtypes. In contrast, age at first live birth, the interval between age at menarche and age at first birth, and breastfeeding were inversely associated with risk of triple-negative breast cancer (P values for trend 0.002, 0.006 and 0.018, respectively), but were not associated with risk of ER+ or HER2-overexpressing cancers. A strong inverse association between breastfeeding and risk of triple-negative breast cancer has now been consistently observed across numerous studies, and at present it is the most well-established protective factor for this aggressive and lethal form of breast cancer. Further studies clarifying the biological mechanisms underlying this relationship and confirming our results with respect to age at first birth and the interval between age at menarche and age at first birth are needed.

  11. Rapid synthesis and in vitro and in vivo evaluation of folic acid derivatives labeled with fluorine-18 for PET imaging of folate receptor-positive tumors

    Energy Technology Data Exchange (ETDEWEB)

    Jammaz, I. Al, E-mail: jammaz@kfshrc.edu.sa; Al-Otaibi, B.; Amer, S.; Okarvi, S.M.

    2011-10-15

    In an attempt to visualize folate receptors that overexpress on many cancers, [{sup 18}F]-fluorobenzene and pyridinecarbohydrazide-folate/methotrexate conjugates ([{sup 18}F]-1, [{sup 18}F]-2-folates and [{sup 18}F]-8, [{sup 18}F]-9-MTXs) were synthesized by the nucleophilic displacement reactions using ethyl-trimethylammonium-benzoate and pyridinecarboxylate precursors. The intermediates ethyl [{sup 18}F]-fluorinated benzene and pyridine esters were reacted with hydrazine to produce the [{sup 18}F]-fluorobenzene and pyridinecarbohydrazides, followed by coupling with N-hydroxysuccinimide-folate/MTX. Radiochemical yields were greater than 80% (decay corrected), with total synthesis time of less than 45 min. Radiochemical purities were always greater than 97% without high-performance liquid chromatography purification. These synthetic approaches hold considerable promise as rapid and simple method for the radiofluorination of folate derivatives with high radiochemical yield in short synthesis time. In vitro tests on KB cell line showed that significant amount of the radioconjugates were associated with cell fractions, and in vivo characterization in normal Balb/c mice revealed rapid blood clearance of these radioconjugates with excretion predominantly by the urinary and partially by the hepatobiliary systems. Biodistribution studies in nude mice bearing human KB cell line xenografts demonstrated significant tumor uptake and favorable biodistribution profile for [{sup 18}F]-2-folate over the other conjugates. The uptake in the tumors was blocked by excess coinjection of folic acid, suggesting a receptor-mediated process. Micro-positron emission tomography images of nude mice bearing human KB cell line xenografts confirmed these observations. These results demonstrate that [{sup 18}F]-2-folate may be useful as molecular probe for detecting and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis as well as monitoring tumor response

  12. Rapid synthesis and in vitro and in vivo evaluation of folic acid derivatives labeled with fluorine-18 for PET imaging of folate receptor-positive tumors.

    Science.gov (United States)

    Al Jammaz, I; Al-Otaibi, B; Amer, S; Okarvi, S M

    2011-10-01

    In an attempt to visualize folate receptors that overexpress on many cancers, [(18)F]-fluorobenzene and pyridinecarbohydrazide-folate/methotrexate conjugates ([(18)F]-1, [(18)F]-2-folates and [(18)F]-8, [(18)F]-9-MTXs) were synthesized by the nucleophilic displacement reactions using ethyl-trimethylammonium-benzoate and pyridinecarboxylate precursors. The intermediates ethyl [(18)F]-fluorinated benzene and pyridine esters were reacted with hydrazine to produce the [(18)F]-fluorobenzene and pyridinecarbohydrazides, followed by coupling with N-hydroxysuccinimide-folate/MTX. Radiochemical yields were greater than 80% (decay corrected), with total synthesis time of less than 45 min. Radiochemical purities were always greater than 97% without high-performance liquid chromatography purification. These synthetic approaches hold considerable promise as rapid and simple method for the radiofluorination of folate derivatives with high radiochemical yield in short synthesis time. In vitro tests on KB cell line showed that significant amount of the radioconjugates were associated with cell fractions, and in vivo characterization in normal Balb/c mice revealed rapid blood clearance of these radioconjugates with excretion predominantly by the urinary and partially by the hepatobiliary systems. Biodistribution studies in nude mice bearing human KB cell line xenografts demonstrated significant tumor uptake and favorable biodistribution profile for [(18)F]-2-folate over the other conjugates. The uptake in the tumors was blocked by excess coinjection of folic acid, suggesting a receptor-mediated process. Micro-positron emission tomography images of nude mice bearing human KB cell line xenografts confirmed these observations. These results demonstrate that [(18)F]-2-folate may be useful as molecular probe for detecting and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis as well as monitoring tumor response to treatment. Copyright © 2011

  13. Novel synthesis and preclinical evaluation of folic acid derivatives labeled with (18)F-[FDG] for PET imaging of folate receptor-positive tumors.

    Science.gov (United States)

    Al Jammaz, I; Al-Otaibi, B; Amer, S; Al-Hokbany, N; Okarvi, S

    2012-08-01

    There is a need to develop more potent radiofluorinated folic acid conjugates for a better visualization of folate receptors that overexpress on many human cancers. Due to the clinical importance of [(18)F]-fluoro-2-deoxy-d-glucose ([(18)F]-FDG) and its availability in almost every positron-emission tomography center, new radiofluorinated [(18)F]-FDG-folate and methotrexate conjugates ([(18)F]-5 and [(18)F]-8) were synthesized using [(18)F]-FDG as a prosthetic group. In a convenient and simple one-step radiosynthesis, [(18)F]-5 and [(18)F]-8 conjugates were prepared in high radiochemical yields (>80%) with total synthesis time of almost 20 min, and radiochemical purities were found to be greater than 98% without high-performance liquid chromatography purification, which make these approaches amenable for automation. In vitro tests on KB cell line showed that a significant amount of the radioconjugates were associated with the cell fractions. In vivo characterization in normal Balb/c mice revealed rapid blood clearance of these radioconjugates with excretion predominantly by the urinary and hepatobiliary systems for [(18)F]-5 and [(18)F]-8 conjugates, respectively. Biodistribution studies in nude mice-bearing human KB cell line xenografts demonstrated significant tumor uptake and favorable kinetics profile for [(18)F]-5 over the other conjugate. The uptake in the tumors was blocked by the excess coinjection of cold folic acid, suggesting the receptor-mediated process. These results demonstrate that [(18)F]-5 may be useful as a molecular probe for detecting and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis, as well as monitoring tumor response to the treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Phospho-aspirin-2 (MDC-22 inhibits estrogen receptor positive breast cancer growth both in vitro and in vivo by a redox-dependent effect.

    Directory of Open Access Journals (Sweden)

    Liqun Huang

    Full Text Available Phospho-aspirin (PA-2 is a novel aspirin derivative that exhibits promising anticancer properties and is considerably safer than conventional aspirin. In this study, we investigated the chemotherapeutic efficacy of PA-2 in preclinical models of estrogen receptor positive (ER+ breast cancer and elucidated its mechanism of action. PA-2 inhibited the growth of ER+ cells more potently than aspirin in vitro, and exerted a triple cytokinetic effect that includes induction of apoptosis and cell cycle arrest as well as the inhibition of cell proliferation. PA-2 is highly efficacious in vivo, as treatment of established MCF7 xenografts with PA-2 induced tumor stasis (98.2% inhibition, p<0.01. PA-2 triggered the activation of p53-dependent apoptosis via two distinct mechanisms: 1 acetylation of p53 (at K373, which disrupts its interaction with its transcription repressor MDM2, and 2 translocation of p53 to the mitochondria leading to the dissipation of mitochondrial transmembrane potential (ΔΨ(m. Consistent with these observations, both the RNAi-mediated knockdown of p53 and forced deactylation via HDAC1 over-expression attenuated the anticancer effect of PA-2 in MCF7 cells. An upstream mediator of the signaling effects of PA-2 is RONS. PA-2 induced oxidative stress in vitro and in mice bearing MCF7 xenografts; its induction effect appears to be tumor-specific. Crucially, administration of N-acetylcysteine, a ROS scavenger, abrogated the effect of PA-2 on p53 acetylation and mitochondria translocation, thus identifying RONS as proximal molecules mediating the anticancer effect of PA-2. In summary, our findings demonstrate that PA-2 is a promising antineoplastic compound against ER+ breast cancer, warranting further evaluation as an anticancer agent.

  15. Phospho-aspirin-2 (MDC-22) inhibits estrogen receptor positive breast cancer growth both in vitro and in vivo by a redox-dependent effect.

    Science.gov (United States)

    Huang, Liqun; Wong, Chi C; Cheng, Ka W; Rigas, Basil

    2014-01-01

    Phospho-aspirin (PA-2) is a novel aspirin derivative that exhibits promising anticancer properties and is considerably safer than conventional aspirin. In this study, we investigated the chemotherapeutic efficacy of PA-2 in preclinical models of estrogen receptor positive (ER+) breast cancer and elucidated its mechanism of action. PA-2 inhibited the growth of ER+ cells more potently than aspirin in vitro, and exerted a triple cytokinetic effect that includes induction of apoptosis and cell cycle arrest as well as the inhibition of cell proliferation. PA-2 is highly efficacious in vivo, as treatment of established MCF7 xenografts with PA-2 induced tumor stasis (98.2% inhibition, pmechanisms: 1) acetylation of p53 (at K373), which disrupts its interaction with its transcription repressor MDM2, and 2) translocation of p53 to the mitochondria leading to the dissipation of mitochondrial transmembrane potential (ΔΨ(m)). Consistent with these observations, both the RNAi-mediated knockdown of p53 and forced deactylation via HDAC1 over-expression attenuated the anticancer effect of PA-2 in MCF7 cells. An upstream mediator of the signaling effects of PA-2 is RONS. PA-2 induced oxidative stress in vitro and in mice bearing MCF7 xenografts; its induction effect appears to be tumor-specific. Crucially, administration of N-acetylcysteine, a ROS scavenger, abrogated the effect of PA-2 on p53 acetylation and mitochondria translocation, thus identifying RONS as proximal molecules mediating the anticancer effect of PA-2. In summary, our findings demonstrate that PA-2 is a promising antineoplastic compound against ER+ breast cancer, warranting further evaluation as an anticancer agent.

  16. Genomic growth hormone, growth hormone receptor and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-07-20

    Lei et al., 2007). Recently, the effects of bovine growth hormone gene polymorphism at codon 127 and 172 were determined on carcass traits and fatty acid compositions in Japanese Black cattle using allele specific-multiplex ...

  17. Treatment sequencing in metastatic castrate-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Oliver Sartor

    2014-06-01

    Full Text Available Six different treatments have demonstrated improved survival in phase III trials targeted to patients with metastatic castration-resistant prostate cancer (mCRPC. Front-line therapeutic options for mCRPC include docetaxel, sipuleucel-T, abiraterone and radium-223. Post-docetaxel options include cabazitaxel, abiraterone, enzalutamide and radium-223. Despite much progress in recent years, much is yet unknown and debates occur over optimal treatment choices and sequences. None of the new agents have been compared to one another, thus physicians in practice today must make choices based on non-randomized comparisons, toxicity considerations and various assumptions. Abiraterone is now moving into the front line mCRPC space given recent regulatory approvals and enzalutamide will follow soon. Both of the hormonal agents have less toxicity when compared to chemotherapeutic options and both of these hormonal agents are expected to be used in a considerable number of mCRPC patients in the years ahead. Little data are available for the post-abiraterone or post-enzalutamide setting. In this review the currently available sequencing data are summarized and interpreted. It is now clear that cross resistance is a potential issue between various treatments, especially those agents that target the androgen axis. This review highlights the need for additional studies to optimize the current treatments for these patients.

  18. Treatment sequencing in metastatic castrate-resistant prostate cancer

    Science.gov (United States)

    Sartor, Oliver; Gillessen, Silke

    2014-01-01

    Six different treatments have demonstrated improved survival in phase III trials targeted to patients with metastatic castration-resistant prostate cancer (mCRPC). Front-line therapeutic options for mCRPC include docetaxel, sipuleucel-T, abiraterone and radium-223. Post-docetaxel options include cabazitaxel, abiraterone, enzalutamide and radium-223. Despite much progress in recent years, much is yet unknown and debates occur over optimal treatment choices and sequences. None of the new agents have been compared to one another, thus physicians in practice today must make choices based on non-randomized comparisons, toxicity considerations and various assumptions. Abiraterone is now moving into the front line mCRPC space given recent regulatory approvals and enzalutamide will follow soon. Both of the hormonal agents have less toxicity when compared to chemotherapeutic options and both of these hormonal agents are expected to be used in a considerable number of mCRPC patients in the years ahead. Little data are available for the post-abiraterone or post-enzalutamide setting. In this review the currently available sequencing data are summarized and interpreted. It is now clear that cross resistance is a potential issue between various treatments, especially those agents that target the androgen axis. This review highlights the need for additional studies to optimize the current treatments for these patients. PMID:24675654

  19. Metastatic calcification of floor of the mouth secondary to chronic renal failure-report of a rare case with atypical presentation.

    Science.gov (United States)

    Verma, D K; Thelekkat, Y; Bansal, S

    2015-01-01

    Soft-tissue calcification is always pathological. Metastatic calcification is calcification of soft tissues owing to hyperphosphataemia with or without hypercalcaemia. Metastatic calcification of oral cavity is extremely rare. A case report of metastatic calcification of the floor of the mouth with atypical radiologic and clinical picture is presented here along with a review of earlier reports. A chance finding of the granular oral mucosa on palpation led to a radiographic examination revealing granular calcifications of the floor of the mouth. Blood chemistry and hormone analysis revealed chronic renal failure and hyperparathyroidism. A diagnosis of metastatic calcification secondary to renal failure was made and the treatment was aimed at correcting the renal failure without any intervention for the asymptomatic calcifications. Key differences between the present case and other cases reported in the literature are outlined.

  20. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Science.gov (United States)

    A multinational phase III trial found that the drug abiraterone acetate prolonged the median survival of patients with metastatic castration-resistant prostate cancer by 4 months compared with patients who received a placebo.

  1. Radiotherapy for metastatic fibrolamellar hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Justin G. Peacock

    2013-07-01

    Full Text Available Fibrolamellar hepatocellular carcinoma (FLHCC is a rare variant of hepatocellular carcinoma (HCC that commonly affects young individuals without a prior history of liver disease. FLHCC commonly results in a better prognosis than HCC; however, the risk of recurrence and metastatic disease is high. FLHCC is typically treated by primary resection of the tumor with 50-75% cure rates. The use of radiation therapy in FLHCC has not been assessed on its own, and may show some success in a very few reported combination therapy cases. We report on the successful use of radiation therapy in a case of metastatic FLHCC to the lung following primary and secondary resections. Our treatment of the large, metastatic, pulmonary FLHCC tumor with 40 Gy in 10 fractions resulted in an 85.9% tumor volume decrease over six months. This suggests FLHCC may be a radiosensitive tumor and radiotherapy may be valuable in unresectable or metastatic tumors.

  2. [Role of surgery in metastatic breast cancer].

    Science.gov (United States)

    Medina-Franco, Heriberto; Suárez-Bobadilla, Yoli Lizbeth

    2012-01-01

    Breast cancer is the most common malignant tumor in Mexican women and very often patients present with advanced stages. Patients with metastatic breast cancer have limited therapeutic options and the mainstay of treatment in this disease stage is systemic chemotherapy Traditionally, the role of surgery in this context is limited to symptom palliation. The increase in efficiency of chemotherapy drugs and the new endocrine and molecular targeted therapy has prolonged the life expectancy of this group of patients and has expanded surgical indications beyond palliation. Some recent institutional reports suggest increasing survival of patients who undergo resection of limited metastatic disease. On another hand, there are reports of survival benefit when the primary tumor is removed even in presence of metastatic disease. We conducted a systematic review of the literature with the objective to analyze the role of surgery in the multidisciplinary management of metastatic breast cancer in order to improve the prognosis of this increasing group of patients.

  3. Case for diagnosis. Metastatic Crohn's disease.

    Science.gov (United States)

    Gontijo, João Renato Vianna; Leidenz, Franciele Antonieta Bianchi; Sousa, Maria Silvia Laborne Alves de

    2016-01-01

    Metastatic Crohn's disease is a rare skin manifestation, defined by granulomatous skin lesions that are discontinuous to the affected gastrointestinal tract and histopathologically resembling inflammatory bowel lesions. Up to 44% of patients with Crohn's disease have cutaneous manifestations, of which metastatic lesions are the least common. We present a case of an adolescent with refractory Crohn's disease and persistent papules and plaques on the skin.

  4. Case for diagnosis. Metastatic Crohn's disease

    OpenAIRE

    Gontijo, João Renato Vianna; Leidenz, Franciele Antonieta Bianchi; Sousa,Maria Silvia Laborne Alves de

    2016-01-01

    Abstract: Metastatic Crohn's disease is a rare skin manifestation, defined by granulomatous skin lesions that are discontinuous to the affected gastrointestinal tract and histopathologically resembling inflammatory bowel lesions. Up to 44% of patients with Crohn's disease have cutaneous manifestations, of which metastatic lesions are the least common. We present a case of an adolescent with refractory Crohn's disease and persistent papules and plaques on the skin.

  5. Case for diagnosis. Metastatic Crohn's disease*

    Science.gov (United States)

    Gontijo, João Renato Vianna; Leidenz, Franciele Antonieta Bianchi; de Sousa, Maria Silvia Laborne Alves

    2016-01-01

    Metastatic Crohn's disease is a rare skin manifestation, defined by granulomatous skin lesions that are discontinuous to the affected gastrointestinal tract and histopathologically resembling inflammatory bowel lesions. Up to 44% of patients with Crohn's disease have cutaneous manifestations, of which metastatic lesions are the least common. We present a case of an adolescent with refractory Crohn's disease and persistent papules and plaques on the skin. PMID:27579756

  6. Standardization of hormone determinations.

    Science.gov (United States)

    Stenman, Ulf-Håkan

    2013-12-01

    Standardization of hormone determinations is important because it simplifies interpretation of results and facilitates the use of common reference values for different assays. Progress in standardization has been achieved through the introduction of more homogeneous hormone standards for peptide and protein hormones. However, many automated methods for determinations of steroid hormones do not provide satisfactory result. Isotope dilution-mass spectrometry (ID-MS) has been used to establish reference methods for steroid hormone determinations and is now increasingly used for routine determinations of steroids and other low molecular weight compounds. Reference methods for protein hormones based on MS are being developed and these promise to improve standardization. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Hormonal therapy for acne.

    Science.gov (United States)

    George, Rosalyn; Clarke, Shari; Thiboutot, Diane

    2008-09-01

    Acne affects more than 40 million people, of which more than half are women older than 25 years of age. These women frequently fail traditional therapy and have high relapse rates even after isotretinoin. Recent advances in research have helped to delineate the important role hormones play in the pathogenesis of acne. Androgens such as dihydrotestosterone and testosterone, the adrenal precursor dehydroepiandrosterone sulfate, estrogens, growth hormone, and insulin-like growth factors may all contribute to the development of acne. Hormonal therapy remains an important part of the arsenal of acne treatments available to the clinician. Women dealing with acne, even those without increased serum androgens, may benefit from hormonal treatments. The mainstays of hormonal therapy include oral contraceptives and antiandrogens such as spironolactone, cyproterone acetate, or flutamide. In this article, we discuss the effects of hormones on the pathogenesis of acne, evaluation of women with suspected endocrine abnormalities, and the myriad of treatment options available.

  8. Epigenetic alterations in metastatic cutaneous carcinoma.

    Science.gov (United States)

    Darr, Owen A; Colacino, Justin A; Tang, Alice L; McHugh, Jonathan B; Bellile, Emily L; Bradford, Carol R; Prince, Mark P; Chepeha, Douglas B; Rozek, Laura S; Moyer, Jeffrey S

    2015-07-01

    Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the 2 most common cutaneous carcinomas. Molecular profiles predicting metastasis of these cancers have not been identified. Epigenetic profiles of 37 primary cases of cutaneous SCC and BCC were quantified via the Illumina Goldengate Cancer Panel. Differential protein expression by metastatic potential was analyzed in 110 total cases by immunohistochemical (IHC) staining. Unsupervised hierarchical clustering analysis revealed that metastatic BCCs had a methylation profile resembling cutaneous SCCs. Metastatic cutaneous SCCs were found to be hypermethylated at FRZB (median methylation: 46.7% vs 4.7%; p = 4 × 10(-5) ). Metastatic BCCs were found to be hypomethylated at MYCL2 (median methylation: 3.8% vs 83.4%; p = 1.9 × 10(-6) ). Immunohistochemical staining revealed few differences between metastatic and nonmetastatic cancers. Metastatic primary BCCs and cutaneous SCCs had distinct epigenetic profiles when compared to their nonmetastatic counterparts. Epigenetic profiling may prove useful in future diagnosis and prevention of advanced nonmelanoma skin cancers. © 2014 Wiley Periodicals, Inc.

  9. METASTATIC MELANOMA WITHOUT CLINICALLY EVIDENT PRIMARY TUMOR

    Directory of Open Access Journals (Sweden)

    V. Sh. Rzaeva

    2017-01-01

    Full Text Available The purpose of the study was to systematize the data available in the modern literature on the diagnosis and treatment of metastatic melanoma without clinically evident primary tumor. Materials and methods. The results of laboratory-instrumental diagnostics, surgical and drug treatment presented in randomized clinical trials, published over the past 10 years in Medline, Embase and the Cochrane Library were analyzed. Results. Despite continuous improvement in imaging techniques, melanoma accounts for up to 12.6 % of all cases of metastatic cancer with an unknown primary site. Metastatic melanoma without clinical evidence of primary tumor accounts for approximately 1% to 8% of all melanoma cases. Conclusion. Metastatic melanoma without clinically evident primary tumor has not been extensively studied. Until now, only a few reports on metastatic melanoma without clinically evident primary tumor have been available. Therefore, further prospective studies of clinical course and optimization of diagnosis and treatment of patients with metastatic melanoma without clinically evident primary tumor are needed. 

  10. Treatment of metastatic brain lesion

    Directory of Open Access Journals (Sweden)

    A. M. Zaytsev

    2015-01-01

    Full Text Available Objective. Increasing survival in patients with secondary brain damage, and identifying the factors of favorable and adverse prognosis.Material and method. In P. A. Hertsen Moscow Oncology Research Institute from 2007 to 2013 there were treated 268 patients with brain metastases. The mean age was 55.8 years (from 24 to 81 years. Metastases of colorectal cancer identified in 7.8%, cases of lung cancer in 34%, melanoma 9.3 %, breast cancer in 26%, kidney cancer in 11%, with non-identified primary tumor in 4.5%, other tumors accounted for 6.7%. Solitary metastasis was diagnosed in 164 (61,19% patients, oligometastasis (2-3 - 72 (26,87% patients with polymetastasis (more than 3 – 32 (11,94% patients. In 106 (39,55% of patients with brain metastases it was the only manifestation of the generalization process. To control the radical removal of the tumor in 93 (34,7% patients we used the method of fluorescence navigation (FN with the drug Alasens. In 66 (24,6% patients intraoperatively was held a session of photodynamic therapy (PDT. In 212 (79,1% cases, the removal of metastasis performed totally, 55 (20,9% patients stated Subtotal removal.Results. The observation period for the patients ranged from 3 to 79 months. Survival median among the entire group of patients with metastatic brain lesion was 12 months. Overall survival was significantly dependent on RPA class, the volume of postoperative treatment, histological type of primary tumor, number of intracerebral metastases and the timing of the relapse-free period.Conclusions. Factors that affects the overall survival are the features of the histology of the primary lesion, multiplicity of metastatic lesions, RPA class and the synchronous nature of the metastasis. The median of overall survival of patients who did not receive after surgical treatment of a particular type of therapy was only 4 months. If to use the combined treatment (surgical treatment with the irradiation of the whole brain median

  11. Sex hormones and hypertension

    OpenAIRE

    Dubey, Raghvendra K; Oparil, Suzanne; Imthurn, Bruno; Jackson, Edwin K.

    2017-01-01

    Gender has an important influence on blood pressure, with premenopausal women having a lower arterial blood pressure than age-matched men. Compared with premenopausal women, postmenopausal women have higher blood pressures, suggesting that ovarian hormones may modulate blood pressure. However, whether sex hormones are responsible for the observed gender-associated differences in arterial blood pressure and whether ovarian hormones account for differences in blood pressure in premenopausal ver...

  12. Evidence that the 5p12 Variant rs10941679 Confers Susceptibility to Estrogen-Receptor-Positive Breast Cancer through FGF10 and MRPS30 Regulation.

    Science.gov (United States)

    Ghoussaini, Maya; French, Juliet D; Michailidou, Kyriaki; Nord, Silje; Beesley, Jonathan; Canisus, Sander; Hillman, Kristine M; Kaufmann, Susanne; Sivakumaran, Haran; Moradi Marjaneh, Mahdi; Lee, Jason S; Dennis, Joe; Bolla, Manjeet K; Wang, Qin; Dicks, Ed; Milne, Roger L; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Muir, Kenneth; Lophatananon, Artitaya; Fasching, Peter A; Beckmann, Matthias W; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Benitez, Javier; González-Neira, Anna; Alonso, M Rosario; Pita, Guillermo; Neuhausen, Susan L; Anton-Culver, Hoda; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Tessier, Daniel C; Vincent, Daniel; Nevanlinna, Heli; Khan, Sofia; Matsuo, Keitaro; Ito, Hidemi; Dörk, Thilo; Bogdanova, Natalia V; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Wu, Anna H; Van Den Berg, David; Lambrechts, Diether; Floris, Giuseppe; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Barile, Monica; Couch, Fergus J; Hallberg, Emily; Giles, Graham G; Haiman, Christopher A; Le Marchand, Loic; Goldberg, Mark S; Teo, Soo H; Yip, Cheng Har; Borresen-Dale, Anne-Lise; Zheng, Wei; Cai, Qiuyin; Winqvist, Robert; Pylkäs, Katri; Andrulis, Irene L; Devilee, Peter; Tollenaar, Rob A E M; García-Closas, Montserrat; Figueroa, Jonine; Hall, Per; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Eriksson, Mikael; Hooning, Maartje J; Koppert, Linetta B; Li, Jingmei; Shu, Xiao-Ou; Zheng, Ying; Cox, Angela; Cross, Simon S; Shah, Mitul; Rhenius, Valerie; Choi, Ji-Yeob; Kang, Daehee; Hartman, Mikael; Chia, Kee Seng; Kabisch, Maria; Torres, Diana; Luccarini, Craig; Conroy, Don M; Jakubowska, Anna; Lubinski, Jan; Sangrajrang, Suleeporn; Brennan, Paul; Olswold, Curtis; Slager, Susan; Shen, Chen-Yang; Hou, Ming-Feng; Swerdlow, Anthony; Schoemaker, Minouk J; Simard, Jacques; Pharoah, Paul D P; Kristensen, Vessela; Chenevix-Trench, Georgia; Easton, Douglas F; Dunning, Alison M; Edwards, Stacey L

    2016-10-06

    Genome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,495-45,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen-receptor-positive (ER+) breast cancer (per-g allele OR ER+ = 1.15; 95% CI 1.13-1.18; p = 8.35 × 10-30). After adjustment for rs10941679, we detected signal 2, consisting of 38 SNPs more strongly associated with ER-negative (ER-) breast cancer (lead SNP rs6864776: per-a allele OR ER- = 1.10; 95% CI 1.05-1.14; p conditional = 1.44 × 10-12), and a single signal 3 SNP (rs200229088: per-t allele OR ER+ = 1.12; 95% CI 1.09-1.15; p conditional = 1.12 × 10-05). Expression quantitative trait locus analysis in normal breast tissues and breast tumors showed that the g (risk) allele of rs10941679 was associated with increased expression of FGF10 and MRPS30. Functional assays demonstrated that SNP rs10941679 maps to an enhancer element that physically interacts with the FGF10 and MRPS30 promoter regions in breast cancer cell lines. FGF10 is an oncogene that binds to FGFR2 and is overexpressed in ∼10% of human breast cancers, whereas MRPS30 plays a key role in apoptosis. These data suggest that the strongest signal of association at 5p12 is mediated through coordinated activation of FGF10 and MRPS30, two candidate genes for breast cancer pathogenesis. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Risk estimation of distant metastasis in node-negative, estrogen receptor-positive breast cancer patients using an RT-PCR based prognostic expression signature

    Science.gov (United States)

    Tutt, Andrew; Wang, Alice; Rowland, Charles; Gillett, Cheryl; Lau, Kit; Chew, Karen; Dai, Hongyue; Kwok, Shirley; Ryder, Kenneth; Shu, Henry; Springall, Robert; Cane, Paul; McCallie, Blair; Kam-Morgan, Lauren; Anderson, Steve; Buerger, Horst; Gray, Joe; Bennington, James; Esserman, Laura; Hastie, Trevor; Broder, Samuel; Sninsky, John; Brandt, Burkhard; Waldman, Fred

    2008-01-01

    Background Given the large number of genes purported to be prognostic for breast cancer, it would be optimal if the genes identified are not confounded by the continuously changing systemic therapies. The aim of this study was to discover and validate a breast cancer prognostic expression signature for distant metastasis in untreated, early stage, lymph node-negative (N-) estrogen receptor-positive (ER+) patients with extensive follow-up times. Methods 197 genes previously associated with metastasis and ER status were profiled from 142 untreated breast cancer subjects. A "metastasis score" (MS) representing fourteen differentially expressed genes was developed and evaluated for its association with distant-metastasis-free survival (DMFS). Categorical risk classification was established from the continuous MS and further evaluated on an independent set of 279 untreated subjects. A third set of 45 subjects was tested to determine the prognostic performance of the MS in tamoxifen-treated women. Results A 14-gene signature was found to be significantly associated (p < 0.05) with distant metastasis in a training set and subsequently in an independent validation set. In the validation set, the hazard ratios (HR) of the high risk compared to low risk groups were 4.02 (95% CI 1.91–8.44) for the endpoint of DMFS and 1.97 (95% CI 1.28 to 3.04) for overall survival after adjustment for age, tumor size and grade. The low and high MS risk groups had 10-year estimates (95% CI) of 96% (90–99%) and 72% (64–78%) respectively, for DMFS and 91% (84–95%) and 68% (61–75%), respectively for overall survival. Performance characteristics of the signature in the two sets were similar. Ki-67 labeling index (LI) was predictive for recurrent disease in the training set, but lost significance after adjustment for the expression signature. In a study of tamoxifen-treated patients, the HR for DMFS in high compared to low risk groups was 3.61 (95% CI 0.86–15.14). Conclusion The 14

  14. Metastatic Crohn's disease in pediatrics

    Directory of Open Access Journals (Sweden)

    Javier Blasco-Alonso

    Full Text Available Introduction: Metastatic Crohn's disease (MCD is an extraintestinal manifestation of Crohn's disease, with biopsy as fundamental diagnostic tool. There are few References to MCD in children, with a 0.5-1% estimated incidence in adults. There is no consensus about its therapeutic approach. We describe our diagnostic and therapeutic experience in MCD. Case Reports: Four cases of MCD are described in our Pediatric Gastroenterology Unit in a tertiary care hospital. The age at diagnosis was between 7 and 13 years. Lesions appeared before the diagnosis of Crohn's disease in three of them, and during the course of the disease in another one, with genital location in three patients and bilateral pretibial region in the other. All four cases demonstrated non-caseificant granulomas on biopsy. Only two patients used exclusive enteral nutrition therapy with complete resolution, while other two cases received a combination of therapies (corticosteroids, azathioprine, tacrolimus, infliximab and adalimumab because of recurrence. Only one case required surgery after poor clinical control. Discussion: The MCD is infrequent but must always be included in the differential diagnosis of cutaneous lesions in Crohn's disease, considering it could be the debut of the disease. We will rely on biopsy anyway for definitive diagnosis. In this series the genital region is verified as the most commonly affected in children. The therapeutic approach does not differ from the management of intestinal involvement.

  15. Post-Transcriptional Regulation of Chemokine Receptor CXCR4 by Estrogen in HER2 Overexpressing, Estrogen Receptor-Positive Breast Cancer Cells

    Science.gov (United States)

    Sengupta, Surojeet; Schiff, Rachel; Katzenellenbogen, Benita S.

    2008-01-01

    Expression of the chemokine receptor CXCR4, a G protein-coupled receptor, and HER2, a receptor tyrosine kinase, strongly correlates with the aggressive and metastatic potential of breast cancer cells. We studied estrogen regulation of CXCR4 in estrogen receptor (ER)-positive MCF-7 breast cancer cells overexpressing HER2 (MCF7-HER2). Although estrogen evoked no change in CXCR4 mRNA levels, CXCR4 protein was significantly up-regulated after estrogen treatment of these cells, whereas estrogen had no effect on CXCR4 protein level in parental MCF7 cells that are low in HER2. Use of the CXCR4 specific inhibitor, AMD 3100, indicated that this increase in CXCR4 protein was partially responsible for the increase in estrogen-induced migration of these cells. The estrogen-induced increase in CXCR4 protein in MCF-7-HER2 cells was abrogated by the antiestrogen ICI 182780 and by gefitinib (Iressa; a phosphotyrosine kinase inhibitor), indicating an ER-mediated effect and confirming involvement of receptor tyrosine kinases, respectively. Using specific pathway inhibitors, we show that the estrogen-induced increase in CXCR4 involves PI3K/AKT, MAPK and mTOR pathways. PI3K/AKT and MAPK pathways are known to result in the phosphorylation and functional inactivation of tuberin (TSC2) of tuberous sclerosis complex thereby negating its inhibitory effects on mTOR, which in turn stimulates the translational machinery. Small interfering RNA (siRNA) mediated knockdown of tuberin elevated the level of CXCR4 protein in MCF7-HER2 cells and also nullified further estrogen up-regulation of CXCR4. This study suggests a pivotal role of PI3K, MAPK and mTOR pathways, via tuberin, in post-transcriptional control of CXCR4, initiated through estrogen-stimulated crosstalk between ER and HER2. Thus, post-transcriptional regulation of CXCR4 by estrogens acting through ER via kinase pathways may play a critical role in determining the metastatic potential of breast cancer cells. PMID:18807177

  16. Systematic review and network meta-analysis comparing palbociclib with chemotherapy agents for the treatment of postmenopausal women with HR-positive and HER2-negative advanced/metastatic breast cancer.

    Science.gov (United States)

    Wilson, Florence R; Varu, Abhishek; Mitra, Debanjali; Cameron, Chris; Iyer, Shrividya

    2017-11-01

    To compare palbociclib + letrozole and palbociclib + fulvestrant with chemotherapy agents in postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (ABC/MBC) who had no prior systemic treatment for advanced disease (first line) or whose disease progressed after prior endocrine therapy or chemotherapy (second line). A systematic search identified randomized controlled trials (RCTs) published from January 2000 to January 2016 that compared endocrine-based therapies, chemotherapy agents, and/or chemotherapy agents + biological therapies in the first- and second-line treatment of postmenopausal women with HR+/HER2- ABC/MBC. The main outcome of interest was progression-free survival (PFS)/time to progression (TTP). Bayesian network meta-analyses (NMAs) and pairwise meta-analyses were conducted. Heterogeneity and inconsistency were assessed. Sixty RCTs met eligibility criteria and were stratified by line of therapy. In the first line, palbociclib + letrozole showed statistically significant improvements in PFS/TTP versus capecitabine [intermittent: HR 0.28 (95% CrI 0.11-0.72)] and mitoxantrone [HR 0.28 (0.13-0.61)], and trended toward improvements versus paclitaxel [HR 0.59 (0.19-1.96)], docetaxel [HR 0.51 (0.14-2.03)] and other monotherapy or combination agents (HRs ranging from 0.24 to 0.99). In the second line, palbociclib + fulvestrant showed statistically significant improvements in PFS/TTP versus capecitabine [intermittent: HR 0.28 (0.13-0.65)], mitoxantrone [HR 0.26 (0.12-0.53)], and pegylated liposomal doxorubicin [HR 0.19 (0.07-0.50)], and trended toward improvements versus paclitaxel [HR 0.48 (0.16-1.44)], docetaxel [HR 0.71 (0.24-2.13)] and other monotherapy or combination agents (HRs ranging from 0.23-0.89). NMA findings aligned with direct evidence and were robust to sensitivity analyses. Palbociclib + letrozole and palbociclib

  17. Chemotherapy in the treatment of metastatic prostate cancer: the present state of the problem

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2015-01-01

    Full Text Available The paper reviews the current possibilities of cytostatic chemotherapy in patients with metastatic prostate cancer. It gives the data of studies dealing with the early use of docetaxel in patents with hormone-susceptible tumors and analyzes approaches to sequential therapy with docetaxel, cabazitaxel, and antiandrogens (abiraterone, enzalutamide in patients with castration-refractory prostate cancer. Assessment of the prognostic role of different clinical and biological factors could provide an algorithm for the choice of first- and second-line therapy in patients with castration resistance.

  18. 10-year survival of a patient with metastatic prostate cancer: Case report and literature review.

    Science.gov (United States)

    Krpina, Kristian; Markić, Dean; Rahelić, Dražen; Ahel, Juraj; Rubinić, Nino; Španjol, Josip

    2015-09-30

    Prostate cancer is the most common malignancy in men. The 5-year relative survival for all stages combined is 98.8%. Patients diagnosed with metastatic prostate cancer have median survival from 2 to 3 years. We describe a case of 64-year old man who clinically presented with inguinal lymphadenopathy. Because of elevated PSA levels biopsy of prostate was done and adenocarcinoma was diagnosed. Biopsy of inguinal lymph nodes confirmed the diagnosis of prostate cancer. Hormonal treatment was started and at the most recent follow-up, 10 years later, the patient is asymptomatic with no clinical signs of disseminated disease.

  19. 10-year survival of a patient with metastatic prostate cancer: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Kristian Krpina

    2015-09-01

    Full Text Available Prostate cancer is the most common malignancy in men. The 5-year relative survival for all stages combined is 98.8%. Patients diagnosed with metastatic prostate cancer have median survival from 2 to 3 years. We describe a case of 64-year old man who clinically presented with inguinal lymphadenopathy. Because of elevated PSA levels biopsy of prostate was done and adenocarcinoma was diagnosed. Biopsy of inguinal lymph nodes confirmed the diagnosis of prostate cancer. Hormonal treatment was started and at the most recent follow-up, 10 years later, the patient is asymptomatic with no clinical signs of disseminated disease.

  20. Sex hormones and urticaria.

    Science.gov (United States)

    Kasperska-Zajac, A; Brzoza, Z; Rogala, B

    2008-11-01

    Chronic urticaria is characterized by mast cells/basophils activation which initiate the inflammatory response. Pathogenetically, the disease may in many cases represent an autoimmune phenomenon. Altered function of the neuro-endocrine-immune system due to stress and other factors has also been implicated its pathogenesis. Sex hormones modulate immune and inflammatory cell functions, including mast cell secretion, and are regarded as responsible for gender and menstrual cycle phase-associated differential susceptibility and severity of some autoimmune and inflammatory diseases. Chronic urticaria is approximately twice more frequent in women than in men. In addition, urticaria may be associated with some diseases and conditions characterized by hormonal changes, including endocrinopathy, menstrual cycle, pregnancy, menopause and hormonal contraceptives or hormone replacement therapy. Hypersensitivity reactions to endogenous or exogenous female sex hormones have been implicated in the pathogenesis of urticarial lesions associated with estrogen and autoimmune progesterone dermatitis. We observed lower serum dehydroepiandrosterone sulfate (DHEA-S) concentration in patients with chronic urticaria with positive and negative response to autologous serum skin test. Thus, the influence of fluctuations in the hormonal milieu and altered sex hormone expression on the triggering-off, maintenance or aggravation of urticaria should be taken into account. In addition, the possible impact of estrogen mimetics, in the environment and in food, on the development of disease associated with mast cell activation must be considered. This review endeavours to outline what is known about the possible influence of sex hormones in the expression of urticaria.

  1. Parathyroid Hormone Injection

    Science.gov (United States)

    ... have any questions about how to inject this medication.Parathyroid hormone injection comes in a cartridge to be mixed in ... and vitamin D while you are taking this medication.Parathyroid hormone injection controls hypoparathyroidism but does not cure it. Continue ...

  2. Apparent diffusion coefficient for discriminating metastatic from non-metastatic lymph nodes in primary rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Een Young, E-mail: seirosera@naver.com; Kim, Seung Ho, E-mail: radiresi@gmail.com; Yoon, Jung-Hee, E-mail: radyjh@hanmail.net; Lee, Yedaun, E-mail: chosai@hanmail.net; Lim, Yun-Jung, E-mail: iihiye@hanmail.net; Kim, Seon-Jeong, E-mail: bluesingirl@naver.com; Baek, Hye Jin, E-mail: sartre81@gmail.com; Eun, Choong Ki, E-mail: ilovegod@chollian.net

    2013-11-01

    Objective: To investigate whether the apparent diffusion coefficient (ADC) could be used to discriminate metastatic from non-metastatic lymph nodes (LNs) in patients with primary rectal cancer. Methods: This study investigated 34 patients (male: 12, female: 22, mean: 62.7, range: 37–82) who underwent 1.5-T MRI with diffusion-weighted imaging (DWI) and subsequent surgical resection. A blinded radiologist measured the ADC value in each regional LN after referring to the T2-weighted images and DWI. The t-test was used to compare the mean ADC values of the metastatic and non-metastatic LNs. A ROC analysis was performed to calculate the diagnostic performance and obtain the optimal cut-off. The histopathological results were used as the reference standard. Results: 114 LNs (46 metastatic and 68 non-metastatic) were matched and analyzed. The mean ADC of the metastatic LNs was significantly lower than that of the non-metastatic LNs (0.9 ± 0.15 × 10{sup −3} mm{sup 2}/s; 1.1 ± 0.22 × 10{sup −3} mm{sup 2}/s, P < 0.0001). The area under the ROC curve was 0.734 (95% confidence interval, 0.644–0.812). When an ADC value of 1.0 × 10{sup −3} mm{sup 2}/s was used as the cut-off, a maximum accuracy of 72% was calculated (sensitivity, 78%; specificity, 67%). Conclusions: Although ADC could be used to discriminate metastatic from non-metastatic LNs, the diagnostic accuracy is approximately 70%.

  3. Heart, lipids and hormones

    Directory of Open Access Journals (Sweden)

    Peter Wolf

    2017-05-01

    Full Text Available Cardiovascular disease is the leading cause of death in general population. Besides well-known risk factors such as hypertension, impaired glucose tolerance and dyslipidemia, growing evidence suggests that hormonal changes in various endocrine diseases also impact the cardiac morphology and function. Recent studies highlight the importance of ectopic intracellular myocardial and pericardial lipid deposition, since even slight changes of these fat depots are associated with alterations in cardiac performance. In this review, we overview the effects of hormones, including insulin, thyroid hormones, growth hormone and cortisol, on heart function, focusing on their impact on myocardial lipid metabolism, cardiac substrate utilization and ectopic lipid deposition, in order to highlight the important role of even subtle hormonal changes for heart function in various endocrine and metabolic diseases.

  4. Aging changes in hormone production

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/004000.htm Aging changes in hormone production To use the sharing ... that produce hormones are controlled by other hormones. Aging also changes this process. For example, an endocrine ...

  5. Hormone therapy for prostate cancer

    Science.gov (United States)

    ... gov/ency/patientinstructions/000908.htm Hormone therapy for prostate cancer To use the sharing features on this page, ... the growth of prostate cancer. Male Hormones and Prostate Cancer Androgens are male sex hormones. Testosterone is one ...

  6. Growth Hormone Deficiency in Children

    Science.gov (United States)

    ... c m y one in Children What is growth hormone deficiency? Growth hormone deficiency (GHD) is a rare condition in which the body does not make enough growth hormone (GH). GH is made by the pituitary gland, ...

  7. Vinorelbine induced perforation of a metastatic gastric lesion.

    Science.gov (United States)

    Mullally, W J; O'Súilleabháin, C B; Brady, C; O'Reilly, S

    2016-12-30

    Breast carcinoma metastasis to the gastrointestinal tract is rare and more frequently associated with lobular than ductal carcinoma (Borst and Ingold, Surg 114(4):637-641 [1]). The purpose of this article is to present a case based review of a unique gastrointestinal metastasis and literature review. A 46 year old lady with metastatic invasive ductal breast cancer was admitted to A&E with sudden onset of epigastric and left shoulder pain. She completed the first cycle of capecitabine/vinorelbine 1 week previously. Clinical examination revealed a tender epigastrium with rigidity in the upper abdomen. Free air under the diaphragm and a positive Rigler's sign was radiologically identified. A laparoscopy demonstrated a fibrinous exudate in the left upper quadrant consistent with a walled off lesser curvature gastric perforation. A subsequent oesophagogastroduodenoscopy (OGD) demonstrated a healed gastric ulcer of benign appearance; however the pathology confirmed metastatic breast carcinoma. Literature review confirmed no previously reported cases of vinorelbine induced gastric perforation. Four cases of metastatic breast cancer with gastric metastasis presenting with perforation were identified; three of these cases (Fra et al., Presse Med 25(26):1215 (1996) [2], Solis-Caxaj et al., Gastroenterol Clin Biol 28(1):91-92 (2004) [3], Ghosn et al., Bull Cancer 78(11):1071-1073 (1991) [4]), were in the French medical literature, including one male patient (Fra et al., Presse Med 25(26):1215 (1996) [2]) and at least one ductal breast carcinoma (Solis-Caxaj et al., Gastroenterol Clin Biol 28(1):91-92 (2004) [3]). The fourth case (van Geel et al., Ned Tijdschr Geneeskd 144(37):1761-1763 (2000) [5]), was in the Dutch medical literature and a lobular breast carcinoma. This case represents a rare complication of breast cancer chemotherapy, the subsequent significant benefit the patient received from treatment is consistent with the chemosensitivity to therapy that also resulted

  8. Intralesional and systemic immunotherapy for metastatic melanoma.

    Science.gov (United States)

    Luu, Carrie; Khushalani, Nikhil I; Zager, Jonathan S

    2016-12-01

    Immunotherapy has revolutionized the treatment of metastatic melanoma and dramatically improved patient outcomes. Ipilimumab, an inhibitor of cytotoxic T-lymphocyte antigen-4 (CTLA-4), was the first immunotherapeutic agent to demonstrate improved survival in advanced melanoma. More recently, other immune checkpoint inhibitors, including the programmed death-1 (PD-1) inhibitors pembrolizumab and nivolumab, have demonstrated efficacy in locally advanced unresectable and metastatic melanoma. In addition to systemically delivered immunotherapies, intralesional therapies such as talimogene laherparepvec (TVEC) play an important role in the treatment of locoregionally advanced and metastatic melanoma. Areas covered: This review provides an overview of the mechanisms behind immune checkpoint inhibitors. Clinical evidence of their efficacy is presented and discussion of new patterns of response and associated immune related adverse events associated with immunotherapy are provided. Expert opinion: Treatment options for locally advanced and metastatic melanoma are expanding with new developments in immunotherapy and immune checkpoint inhibitors. The utility of these novel therapies in the adjuvant setting is currently being explored. The ideal treatment of metastatic melanoma continues to be multimodal, combining systemic treatments, intralesional and regional therapies, surgery and radiotherapy to achieve optimal outcomes.

  9. Family history and breast cancer hormone receptor status in a Spanish cohort.

    Directory of Open Access Journals (Sweden)

    Xuejuan Jiang

    Full Text Available BACKGROUND: Breast cancer is a heterogenous disease that impacts racial/ethnic groups differently. Differences in genetic composition, lifestyles, reproductive factors, or environmental exposures may contribute to the differential presentation of breast cancer among Hispanic women. MATERIALS AND METHODS: A population-based study was conducted in the city of Santiago de Compostela, Spain. A total of 645 women diagnosed with operable invasive breast cancer between 1992 and 2005 participated in the study. Data on demographics, breast cancer risk factors, and clinico-pathological characteristics of the tumors were collected. Hormone receptor negative tumors were compared with hormone receptor postive tumors on their clinico-pathological characteristics as well as risk factor profiles. RESULTS: Among the 645 breast cancer patients, 78% were estrogen receptor-positive (ER+ or progesterone receptor-positive (PR+, and 22% were ER-&PR-. Women with a family history of breast cancer were more likely to have ER-&PR- tumors than women without a family history (Odds ratio, 1.43; 95% confidence interval, 0.91-2.26. This association was limited to cancers diagnosed before age 50 (Odds ratio, 2.79; 95% confidence interval, 1.34-5.81. CONCLUSIONS: An increased proportion of ER-&PR- breast cancer was observed among younger Spanish women with a family history of the disease.

  10. Enzalutamide in metastatic prostate cancer before chemotherapy

    DEFF Research Database (Denmark)

    Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana E

    2014-01-01

    BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have...... the most common clinically relevant adverse events associated with enzalutamide treatment. CONCLUSIONS: Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas...... skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P

  11. Atypical Radiological Manifestation of Pulmonary Metastatic Calcification

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Eun Hae; Kim, Eun Sun; Kim, Chul Hwan; Ham, Soo Youn; Oh, Yu Whan [Korea University College of Medicine, Seoul (Korea, Republic of)

    2008-04-15

    Metastatic pulmonary calcification is a condition of calcium deposition in the normal pulmonary parenchyma, and this is secondary to abnormal calcium metabolism without any prior soft tissue damage. The predisposing factors for this condition include chronic renal failure, hypercalcemia and increased tissue alkalinity. The most common radiologic manifestation consists of poorly defined nodular opacities in the upper lung zone. These opacities reflect the deposition of calcium salts in the pulmonary interstitium. We present here a case of metastatic pulmonary calcification in a patient who recovered from pneumonia with sepsis and whose high-resolution CT (HRCT) images demonstrated localized parenchymal airspace calcification that was limited to the bilateral lower lobes. These lower lobes had been involved with pneumonic consolidation without calcification, as seen on the previous CT scan. In summary, we report here on an atypical presentation of metastatic pulmonary calcification that showed dense airspace consolidation localized to the bilateral lower lobes in a patient with primary hyperparathyroidism and pneumonia.

  12. PARANEOPLASTIC VITELLIFORM MACULOPATHY ASSOCIATED WITH METASTATIC MELANOMA.

    Science.gov (United States)

    Rahimi, Mansour; Navajas, Eduardo V; Sarraf, David

    2017-11-22

    To report a case of paraneoplastic vitelliform maculopathy in a patient with metastatic melanoma of unknown primary site. Case report. Main outcome measures include funduscopic examination, fluorescein angiography, fundus autofluorescence, and spectral domain optical coherence tomography. A 44-year-old man with a known history of metastatic melanoma was referred for ophthalmic evaluation because of bilateral vision loss. Funduscopic examination was remarkable for vitelliform maculopathy that was confirmed with fundus autofluorescence and spectral domain optical coherence tomography. We describe a rare case of paraneoplastic vitelliform maculopathy. There are many etiologies of acquired vitelliform retinal lesions in the retina. Multimodal retinal imaging, including fundus autofluorescence and spectral domain optical coherence tomography, can be best used to identify these lesions. A history of systemic metastatic melanoma should be ruled out in patients with vitelliform maculopathy.

  13. Recent Advances in Immunotherapy in Metastatic NSCLC.

    Directory of Open Access Journals (Sweden)

    Pranshu Bansal

    2016-11-01

    Full Text Available Non-small cell lung cancer (NSCLC is one of most common malignancies and the leading cause of cancer deaths worldwide. Despite advances in targeted therapies, majority of NSCLC patients do not have targetable genomic alterations. Nevertheless, recent discovery that NSCLC is an immunogenic tumor type, and several breakthroughs in immunotherapies have led to rapid expansion of this new treatment modality in NSCLC with recent FDA approvals of PD-1 inhibitors, nivolumab and pembrolizumab. Here, we review promising immunotherapeutic approaches in metastatic NSCLC, including checkpoint inhibitors, agents with other mechanisms of action, and immunotherapy combinations with other drugs. With advent of immunotherapy, therapeutic options in metastatic NSCLC are rapidly expanding with the hope to further expand life expectancy in metastatic lung cancer.

  14. Dietary administration of δ- and γ-tocopherol inhibits tumorigenesis in the animal model of estrogen receptor-positive, but not HER-2 breast cancer.

    Science.gov (United States)

    Smolarek, Amanda K; So, Jae Young; Burgess, Brenda; Kong, Ah-Ng Tony; Reuhl, Kenneth; Lin, Yong; Shih, Weichung Joe; Li, Guangxun; Lee, Mao-Jung; Chen, Yu-Kuo; Yang, Chung S; Suh, Nanjoo

    2012-11-01

    Tocopherol, a member of the vitamin E family, consists of four forms designated as α, β, γ, and δ. Several large cancer prevention studies with α-tocopherol have reported no beneficial results, but recent laboratory studies have suggested that δ- and γ-tocopherol may be more effective. In two different animal models of breast cancer, the chemopreventive activities of individual tocopherols were assessed using diets containing 0.3% of tocopherol (α-, δ-, or γ-) or 0.3% of a γ-tocopherol rich mixture (γ-TmT). Although administration of tocopherols did not prevent human epidermal growth factor receptor 2 (HER2/neu)-driven tumorigenesis, δ- and γ-tocopherols inhibited hormone-dependent mammary tumorigenesis in N-methyl-N-nitrosourea (NMU)-treated female Sprague-Dawley rats. NMU-treated rats showed an average tumor burden of 10.6 ± 0.8 g in the control group at 11 weeks, whereas dietary administration of δ- and γ-tocopherols significantly decreased tumor burden to 7.2 ± 0.8 g (P < 0.01) and 7.1 ± 0.7 g (P < 0.01), respectively. Tumor multiplicity was also reduced in δ- and γ-tocopherol treatment groups by 42% (P < 0.001) and 32% (P < 0.01), respectively. In contrast, α-tocopherol did not decrease tumor burden or multiplicity. In mammary tumors, the protein levels of proapoptotic markers (BAX, cleaved caspase-9, cleaved caspase-3, cleaved PARP) were increased, whereas antiapoptotic markers (Bcl-2, XIAP) were inhibited by δ-tocopherol, γ-tocopherol, and γ-TmT. Furthermore, markers of cell proliferation (PCNA, PKCα), survival (PPAR-γ, PTEN, phospho-Akt), and cell cycle (p53, p21) were affected by δ- and γ-tocopherols. Both δ- and γ-tocopherols, but not α-tocopherol, seem to be promising agents for the prevention of hormone-dependent breast cancer.

  15. General Information about Metastatic Squamous Neck Cancer with Occult Primary

    Science.gov (United States)

    ... Head and Neck Cancer Patient Hypopharyngeal Cancer Treatment Laryngeal Cancer Treatment Lip & Oral Cavity Treatment Metastatic Squamous Neck ... Oropharyngeal Cancer Screening Health Professional Hypopharyngeal Cancer Treatment Laryngeal Cancer Treatment Lip & Oral Cavity Treatment Metastatic Squamous Neck ...

  16. Stages of Metastatic Squamous Neck Cancer with Occult Primary

    Science.gov (United States)

    ... Head and Neck Cancer Patient Hypopharyngeal Cancer Treatment Laryngeal Cancer Treatment Lip & Oral Cavity Treatment Metastatic Squamous Neck ... Oropharyngeal Cancer Screening Health Professional Hypopharyngeal Cancer Treatment Laryngeal Cancer Treatment Lip & Oral Cavity Treatment Metastatic Squamous Neck ...

  17. Treatment Option Overview (Metastatic Squamous Neck Cancer with Occult Primary)

    Science.gov (United States)

    ... Head and Neck Cancer Patient Hypopharyngeal Cancer Treatment Laryngeal Cancer Treatment Lip & Oral Cavity Treatment Metastatic Squamous Neck ... Oropharyngeal Cancer Screening Health Professional Hypopharyngeal Cancer Treatment Laryngeal Cancer Treatment Lip & Oral Cavity Treatment Metastatic Squamous Neck ...

  18. Metastatic intraocular hemangiopericytoma in a dog | Pucket | Open ...

    African Journals Online (AJOL)

    Therapeutic and diagnostic enucleation of the left eye was performed and histopathologic examination demonstrated the presence of a presumed metastatic spindle cell sarcoma. Further immunohistochemical staining confirmed the intraocular neoplasia to be metastatic spread from the previously removed flank mass.

  19. Growth hormone releasing hormone or growth hormone treatment in growth hormone insufficiency?

    OpenAIRE

    Smith, P J; Brook, C G

    1988-01-01

    Sixteen prepubertal children who were insufficient for growth hormone were treated with growth hormone releasing hormone (GHRH) 1-40 and GHRH 1-29 for a mean time of nine months (range 6-12 months) with each peptide. Eleven children received GHRH 1-40 in four subcutaneous nocturnal pulses (dose 4-8 micrograms/kg/day) and eight (three of whom were also treated with GHRH 1-40) received GHRH 1-29 twice daily (dose 8-16 micrograms/kg/day). Altogether 73% of the children receiving GHRH 1-40 and 63...

  20. [Hormonal contraception in men].

    Science.gov (United States)

    de Ronde, W; Meuleman, E J H

    2007-11-17

    Over the past few decades, female hormonal contraception has been seen to be very successful. However, this has still not resulted in a hormonal contraceptive for men. Certain injectable combinations ofandrogens and progestagens have been found to suppress spermatogenesis. All combinations that have been tested so far suffer from a relative lack of efficacy, a long lag time to achieve azoospermia, requiring the user to undergo one or more semen analyses, a moderate user friendliness, and concerns about the long-term safety and reversibility. It is not to be expected that male hormonal contraception will become a serious alternative to the already existing female equivalent during the coming 5 years.

  1. Transcriptome analysis reveals a role for the endothelial ANP-GC-A signaling in interfering with pre-metastatic niche formation by solid cancers.

    Science.gov (United States)

    Nojiri, Takashi; Arai, Miki; Suzuki, Yutaka; Kumazoe, Motofumi; Tokudome, Takeshi; Miura, Koichi; Hino, Jun; Hosoda, Hiroshi; Miyazato, Mikiya; Okumura, Meinoshin; Kawaoka, Shinpei; Kangawa, Kenji

    2017-09-12

    Cancer establishes a microenvironment called the pre-metastatic niche in distant organs where disseminated cancer cells can efficiently metastasize. Pre-metastatic niche formation requires various genetic factors. Previous studies suggest that inhibiting a single niche-factor is insufficient to completely block pre-metastatic niche formation especially in human patients. Here we show that the atrial natriuretic peptide (ANP), an endogenous hormone produced by the heart, inhibits pre-metastatic niche formation and metastasis of murine solid cancer models when pharmacologically supplied in vivo . On the basis of a wealth of comprehensive RNA-seq data, we demonstrated that ANP globally suppressed expression of cancer-induced genes including known niche-factors in the lung. The lungs of mice overexpressing GC-A, a receptor for ANP in endothelial cells, were conferred resistance against pre-metastatic niche formation. Importantly, neither ANP administration nor GC-A overexpression had a detrimental effect on lung gene expression in a cancer-free condition. The current study establishes endothelial ANP-GC-A signaling as a therapeutic target to control the pre-metastatic niche.

  2. Metastatic lung malignancy to mandibular gingiva

    Directory of Open Access Journals (Sweden)

    Moharil Rohit

    2010-01-01

    Full Text Available Metastatic tumors of oral cavity are uncommon and may occur in oral soft tissues or jaw bones. Because of their rarity, metastasis to oral cavity are challenging to diagnose and difficult to treat. They often have vague symptoms that mimic dental infections. These lesions generally show poorly differentiated histopathologic picture and have poor prognosis. We reported a case of a 40-year-old male patient of metastatic lesion to the oral cavity and brain with primary tumor, diagnosed as an undifferentiated epithelial malignancy of lung.

  3. Metastatic angiosarcoma of the lung : HRCT findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Young; Lim, Byung Sung; Oh, Mee Hye [Sejong General Hospital, Seoul (Korea, Republic of); Im, Jung Gi [Seoul National Univ. College of Medicine and the Institute of Radiation Medicine, SNUMRC, Seoul (Korea, Republic of)

    1999-03-01

    We describe a case of cavitary metastasis to the lungs from a small angiosarcoma of the scalp, in which the metastatic lesions were complicated by pneumothorax and pulmonary hemorrhage. On high-resolution CT, the lesions simulated the findings of Langerhans cell histiocytosis. Thin-walled cavitary metastatic lesions were similar to those of thin walled air cysts in Langerhans cell histiocytosis. Ground-glass opacity simulated the findings of smoker's respiratory bronchiolitis in Langerhans cell histiocytosis but histologically represented hemorrhage during metastasis of the angiosarcoma.

  4. An Unusual Course of Metastatic Gastroesophageal Cancer

    Directory of Open Access Journals (Sweden)

    William H. Smith

    2015-01-01

    Full Text Available We are reporting on a case of a 41-year-old woman who presented with metastatic gastroesophageal junction cancer and who achieved prolonged survival with a multimodal treatment approach. After initially experiencing robust response to chemotherapy, she was treated for distant recurrence with palliative radiation to the gastrohepatic and supraclavicular lymph nodes and subsequently, given her unusual near-complete response, with reirradiation to the abdomen with curative intent for residual disease. The case presented is unique due to the patient’s atypical treatment course, including technically difficult reirradiation to the abdomen, and the resulting prolonged survival despite metastatic presentation.

  5. Flow cytometry analysis of hormone receptors on human peripheral blood mononuclear cells to identify stress-induced neuroendocrine effects

    Science.gov (United States)

    Meehan, R. T.

    1986-01-01

    Understanding the role of circulating peptide hormones in the pathogenesis of space-flight induced disorders would be greatly facilitated by a method which monitors chronic levels of hormones and their effects upon in vivo cell physiology. Single and simultaneous multiparameter flow cytometry analysis was employed to identify subpopulations of mononuclear cells bearing receptors for ACTH, Endorphin, and Somatomedin-C using monoclonal antibodies and monospecific antisera with indirect immunofluorescence. Blood samples were obtained from normal donors and subjects participating in decompression chamber studies (acute stress), medical student academic examination (chronic stress), and a drug study (Dexamethasone). Preliminary results indicate most ACTH and Endorphin receptor positive cells are monocytes and B-cells, exhibit little diurnal variation but the relative percentages of receptor positive cells are influenced by exposure to various stressors and ACTH inhibition. This study demonstrates the capability of flow cytometry analysis to study cell surface hormone receptor regulation which should allow insight into neuroendocrine modulation of the immune and other cellular systems during exposure to stress or microgravity.

  6. A rare presentation of prostate adenocarcinoma metastatic to the maxilla

    Directory of Open Access Journals (Sweden)

    Venkata S Prathi

    2017-01-01

    Full Text Available Metastatic tumors of the orofacial region are uncommon and may occur in the oral soft tissues and jaw bones. The occurrence of prostate as the primary site for jaw metastasis is extremely rare. Mandible and palate are the common prostate metastatic sites. Here, we present a rare case of prostate adenocarcinoma metastatic to maxilla.

  7. ADH (Antidiuretic Hormone) Test

    Science.gov (United States)

    ... Hormone Binding Globulin (SHBG) Shiga toxin-producing Escherichia coli Sickle Cell Tests Sirolimus Smooth Muscle Antibody (SMA) ... Ratio Valproic Acid Vancomycin Vanillylmandelic Acid (VMA) VAP Vitamin A Vitamin B12 and Folate Vitamin D Tests ...

  8. ACTH (Adrenocorticotropic Hormone) Test

    Science.gov (United States)

    ... Hormone Binding Globulin (SHBG) Shiga toxin-producing Escherichia coli Sickle Cell Tests Sirolimus Smooth Muscle Antibody (SMA) ... Ratio Valproic Acid Vancomycin Vanillylmandelic Acid (VMA) VAP Vitamin A Vitamin B12 and Folate Vitamin D Tests ...

  9. Hormonal effects in newborns

    Science.gov (United States)

    ... can cause an infection under the skin ( abscess ). Hormones from the mother may also cause some fluid to leak from the infant's nipples. This is called witch's milk. It is common and most often goes away ...

  10. Protein Hormones and Immunity‡

    Science.gov (United States)

    Kelley, Keith W.; Weigent, Douglas A.; Kooijman, Ron

    2007-01-01

    A number of observations and discoveries over the past 20 years support the concept of important physiological interactions between the endocrine and immune systems. The best known pathway for transmission of information from the immune system to the neuroendocrine system is humoral in the form of cytokines, although neural transmission via the afferent vagus is well documented also. In the other direction, efferent signals from the nervous system to the immune system are conveyed by both the neuroendocrine and autonomic nervous systems. Communication is possible because the nervous and immune systems share a common biochemical language involving shared ligands and receptors, including neurotransmitters, neuropeptides, growth factors, neuroendocrine hormones and cytokines. This means that the brain functions as an immune-regulating organ participating in immune responses. A great deal of evidence has accumulated and confirmed that hormones secreted by the neuroendocrine system play an important role in communication and regulation of the cells of the immune system. Among protein hormones, this has been most clearly documented for prolactin (PRL), growth hormone (GH), and insulin-like growth factor-1 (IGF-I), but significant influences on immunity by thyroid stimulating hormone (TSH) have also been demonstrated. Here we review evidence obtained during the past 20 years to clearly demonstrate that neuroendocrine protein hormones influence immunity and that immune processes affect the neuroendocrine system. New findings highlight a previously undiscovered route of communication between the immune and endocrine systems that is now known to occur at the cellular level. This communication system is activated when inflammatory processes induced by proinflammatory cytokines antagonize the function of a variety of hormones, which then causes endocrine resistance in both the periphery and brain. Homeostasis during inflammation is achieved by a balance between cytokines and

  11. INTERMITTENT HORMONE THERAPY WITH ELIGARD IN PATIENTS WITH PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2014-07-01

    Full Text Available Prostate cancer (PC is one of the most burning problems of modern urologic oncology, which is attributable to the fact that the incidence of this pathology remains high. Hormone therapy (HT is a basic treatment in patients with metastatic PC. Intermittent HT (IHT is an effective and safe method for hormonal exposure in PC patients, as supported by the results of many trials. IHT may be recommended in the therapy of patients with PC in different clinical situations, including in patients with distant metastases. Eligard is recognized to be an effective and safe medicament to treat this category of patients. Its injection formulation once three or six months is easy-to-use for IHT.

  12. INTERMITTENT HORMONE THERAPY WITH ELIGARD IN PATIENTS WITH PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2014-01-01

    Full Text Available Prostate cancer (PC is one of the most burning problems of modern urologic oncology, which is attributable to the fact that the incidence of this pathology remains high. Hormone therapy (HT is a basic treatment in patients with metastatic PC. Intermittent HT (IHT is an effective and safe method for hormonal exposure in PC patients, as supported by the results of many trials. IHT may be recommended in the therapy of patients with PC in different clinical situations, including in patients with distant metastases. Eligard is recognized to be an effective and safe medicament to treat this category of patients. Its injection formulation once three or six months is easy-to-use for IHT.

  13. Body segments and growth hormone.

    OpenAIRE

    Bundak, R; Hindmarsh, P C; Brook, C G

    1988-01-01

    The effects of human growth hormone treatment for five years on sitting height and subischial leg length of 35 prepubertal children with isolated growth hormone deficiency were investigated. Body segments reacted equally to treatment with human growth hormone; this is important when comparing the effect of growth hormone on the growth of children with skeletal dysplasias or after spinal irradiation.

  14. Dietary administration of δ- and γ-tocopherol inhibits tumorigenesis in the animal model of estrogen-receptor positive, but not HER-2 breast cancer

    Science.gov (United States)

    Smolarek, Amanda K.; So, Jae Young; Burgess, Brenda; Kong, Ah-Ng Tony; Reuhl, Kenneth; Lin, Yong; Shih, Weichung Joe; Li, Guangxun; Lee, Mao-Jung; Chen, Yu-Kuo; Yang, Chung S.; Suh, Nanjoo

    2012-01-01

    Tocopherol, a member of the vitamin E family, consists of four forms designated as α, β, γ, and δ. Several large cancer prevention studies with α-tocopherol have reported no beneficial results, but recent laboratory studies have suggested that δ- and γ-tocopherol may be more effective. In two different animal models of breast cancer, the chemopreventive activities of individual tocopherols were assessed using diets containing 0.3% of tocopherol (α-, δ- or γ-) or 0.3% of a γ-tocopherol rich mixture (γ-TmT). While administration of tocopherols did not prevent human epidermal growth factor receptor 2 (HER2/neu)-driven tumorigenesis, δ- and γ-tocopherols inhibited hormone-dependent mammary tumorigenesis in N-methyl-N-nitrosourea (NMU)-treated female Sprague Dawley rats. NMU-treated rats showed an average tumor burden of 10.6 ± 0.8 g in the control group at 11 weeks, whereas dietary administration of δ- and γ-tocopherols significantly decreased tumor burden to 7.2 ± 0.8 g (p<0.01) and 7.1 ± 0.7 g (p<0.01), respectively. Tumor multiplicity was also reduced in δ- and γ-tocopherol treatment groups by 42% (p<0.001) and 32% (p<0.01), respectively. In contrast, α-tocopherol did not decrease tumor burden or multiplicity. In mammary tumors, the protein levels of pro-apoptotic markers (BAX, cleaved-caspase 9, cleaved-caspase 3, cleaved-PARP) were increased, while anti-apoptotic markers (Bcl2, XIAP) were inhibited by δ-tocopherol, γ-tocopherol and γ-TmT. Furthermore, markers of cell proliferation (PCNA, PKC α), survival (PPARγ, PTEN, phospho-Akt) and cell cycle (p53, p21) were affected by δ- and γ-tocopherols. Both δ- and γ-tocopherols, but not α-tocopherol, appear to be promising agents for the prevention of hormone-dependent breast cancer. PMID:22964476

  15. Pathogenesis of Metastatic Calcification and Acute Pancreatitis in Adult T-Cell Leukemia under Hypercalcemic State

    Directory of Open Access Journals (Sweden)

    Masachika Senba

    2012-01-01

    Full Text Available Human T-cell leukemia virus type-1 (HTLV-1 is the causative agent of adult T-cell leukemia (ATL. Hypercalcemia is common in patients with ATL. These patients rarely develop metastatic calcification and acute pancreatitis. The underlying pathogenesis of this condition is osteoclast hyperactivity with associated overproduction of parathyroid hormone-related protein, which results in hypercalcemia in association with bone demineralization. The discovery of the osteoclast differentiation factor receptor activator of nuclear factor-κB ligand (RANKL, its receptor RANK, and its decoy receptor osteoprotegerin (OPG, enhanced our understanding of the mechanisms of ATL-associated hypercalcemia. Macrophage inflammatory protein-1-α, tumor necrosis factor-α, interleukin-1, and interleukin-6 are important molecules that enhance the migration and differentiation of osteoclasts and the associated enhanced production of RANKL for osteoblast formation. In this paper, we focus on metastatic calcification and acute pancreatitis in ATL, highlighting recent advances in the understanding of the molecular role of the RANKL/RANK/OPG system including its interaction with various cytokines and calciotropic hormones in the regulation of osteoclastogenesis for bone resorption in hypercalcemic ATL patients.

  16. Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer.

    Science.gov (United States)

    Kim, Esther S; Scott, Lesley J

    2017-06-01

    Oral palbociclib (Ibrance®) is a first-in-class, highly selective inhibitor of cyclin-dependent kinases 4 and 6 (i.e. a CDK4/6 inhibitor). It is indicated for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, in combination with an aromatase inhibitor as initial endocrine-based therapy, and in combination with fulvestrant (with or without a luteinizing hormone-releasing hormone agonist) in those previously treated with endocrine therapy. In clinical trials, palbociclib in combination with letrozole as initial endocrine-based therapy in postmenopausal women (PALOMA-1 and PALOMA-2), or in combination with fulvestrant in pre-, peri-, or postmenopausal women with disease progression after endocrine therapy (PALOMA-3), significantly prolonged progression-free survival (PFS) and improved clinical benefit response (CBR) rates. Neutropenia was the most commonly reported any-grade and grade ≥ 3 adverse event. It was infrequently associated with febrile neutropenia (palbociclib dose delay, interruption or reduction, without the routine use of growth factors, and without affecting efficacy. In conclusion, oral palbociclib combination therapy is a valuable emerging option for use in patients with HR-positive, HER2-negative advanced or metastatic breast cancer.

  17. [Cabazitaxel after docetaxel: a new option in metastatic castration-resistant prostate cancer].

    Science.gov (United States)

    Lheureux, Stéphanie; Joly, Florence

    2012-09-01

    The management of patients with metastatic castration-resistant prostate cancer is a real challenge. Indeed, after a first line chemotherapy with docetaxel, there was no standard because the treatments were ineffective. Today, several therapeutic options are available with the development of new therapies. Among them, cabazitaxel, semi-synthetic derivative of a natural taxoid, has been developed to its low recognition by the MDR system and power distribution including brain. This new chemotherapy was assessed in patients with metastatic castration-resistant prostate cancer whose disease has progressed during or after docetaxel-based therapy. Treatment with cabazitaxel plus prednisone has improved overall survival of 2.4 months compared to mitoxantrone in the TROPIC phase III. However, hematologic toxicity may be limiting with a risk of febrile neutropenia; hematopoietic growth factors are advised in case of significant neutropenia. The cabazitaxel, Jevtana(®), has been approved in second line after docetaxel. Its position in relation to new types of hormone therapy, as abiraterone acetate, in the same indication requires further investigations, including predictive factors of response. Studies are on going in first line indication (compared to docetaxel) and associated to other new hormone therapies.

  18. Differential Expression of Ccn4 and Other Genes Between Metastatic and Non-metastatic EL4 Mouse Lymphoma Cells.

    Science.gov (United States)

    Chahal, Manpreet S; Ku, H Teresa; Zhang, Zhihong; Legaspi, Christian M; Luo, Angela; Hopkins, Mandi M; Meier, Kathryn E

    Previous work characterized variants of the EL4 murine lymphoma cell line. Some are non-metastatic, and others metastatic, in syngenic mice. In addition, metastatic EL4 cells were stably transfected with phospholipase D2 (PLD2), which further enhanced metastasis. Microarray analyses of mRNA expression was performed for non-metastatic, metastatic, and PLD2-expressing metastatic EL4 cells. Many differences were observed between non-metastatic and metastatic cell lines. One of the most striking new findings was up-regulation of mRNA for the matricellular protein WNT1-inducible signaling pathway protein 1 (CCN4) in metastatic cells; increased protein expression was verified by immunoblotting and immunocytochemistry. Other differentially expressed genes included those for reproductive homeobox 5 (Rhox5; increased in metastatic) and cystatin 7 (Cst7; decreased in metastatic). Differences between PLD2-expressing and parental cell lines were limited but included the signaling proteins Ras guanyl releasing protein 1 (RGS18; increased with PLD2) and suppressor of cytokine signaling 2 (SOCS2; decreased with PLD2). The results provide insights into signaling pathways potentially involved in conferring metastatic ability on lymphoma cells. Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

  19. Metastatic Insulinoma Following Resection of Nonsecreting Pancreatic Islet Cell Tumor

    Directory of Open Access Journals (Sweden)

    Anoopa A. Koshy MD

    2013-01-01

    Full Text Available A 56-year-old woman presented to our clinic for recurrent hypoglycemia after undergoing resection of an incidentally discovered nonfunctional pancreatic endocrine tumor 6 years ago. She underwent a distal pancreatectomy and splenectomy, after which she developed diabetes and was placed on an insulin pump. Pathology showed a pancreatic endocrine neoplasm with negative islet hormone immunostains. Two years later, computed tomography scan of the abdomen showed multiple liver lesions. Biopsy of a liver lesion showed a well-differentiated neuroendocrine neoplasm, consistent with pancreatic origin. Six years later, she presented to clinic with 1.5 years of recurrent hypoglycemia. Laboratory results showed elevated proinsulin, insulin levels, and c-peptide levels during a hypoglycemic episode. Computed tomography scan of the abdomen redemonstrated multiple liver lesions. Repeated transarterial catheter chemoembolization and microwave thermal ablation controlled hypoglycemia. The unusual features of interest of this case include the transformation of nonfunctioning pancreatic endocrine tumor to a metastatic insulinoma and the occurrence of atrial flutter after octreotide for treatment.

  20. Metastatic bronchogenic carcinoma masquerading as a felon.

    Science.gov (United States)

    Rose, B A; Wood, F M

    1983-05-01

    This report describes a rare occurrence of a subcutaneous metastatic bronchogenic carcinoma to the distal fingertip. The original clinical presentation suggested an infectious process. Subsequent roentgenograms, sterile cultures, and positive biopsy material revealed that the lesion started as a subcutaneous metastasis that secondarily involved adjacent bone. Amputation of the digit was performed.

  1. Metastatic leiomyosarcoma of the intrapancreatic bile duct.

    Science.gov (United States)

    Perysinakis, Iraklis; Katopodi, Aggeliki; Avlonitis, Spyridon; Georgiadou, Despoina; Choreftaki, Theodosia; Christopoulos, George; Margaris, Ilias

    2013-01-01

    We report the case of a patient with a history of surgically treated pulmonary leiomyosarcoma, presenting with recurrent acute cholangitis and metastatic leiomyosarcoma of the common bile duct. Preoperative examinations had revealed a high grade malignant neoplasm and bilateral lung metastases. The patient underwent pylorus-preserving pancreaticoduodenectomy and survived for 5.5 years after the first diagnosis.

  2. Delayed presentation and diagnosis of metastatic hepatocellular ...

    African Journals Online (AJOL)

    during pregnancy.[2,3] The finding of a hepatic lesion in pregnancy is often incidental, and the diagnosis of early-stage HCC may be delayed as the symptoms are often nonspecific.[4] We ... presentation and diagnosis of metastatic HCC in pregnancy. ... found to have a thrombocytopenia of 86 × 109/L and a haemoglobin of.

  3. Metastatic Bronchogenic Carcinoma to the Mandible

    African Journals Online (AJOL)

    metastatic or secondary carcinoma is the most common malignant tumor of bone (9). However, metastasis to mandible are very rare (10). Lung cancer is the leading cause of cancer-related death worldwide and the second most common cancer in both men and women and accounts for. 1.8% of all the cancers registered by ...

  4. Coexistent intracerebral metastatic melanoma and meningioma.

    Science.gov (United States)

    Shinde, Sweety V; Shenoy, Asha S; Savant, Hemant V; Balasubramaniam, Srikant B

    2017-01-01

    Coexistence of multifocal neural crest tumors, namely meningioma, melanoma, and nerve sheath tumors, is termed as neurocristopathy. Neurofibromatosis is the commonest form of neurocristopathy. We report a rare case of frontal lobe metastatic melanoma coexistent with a parietal lobe meningioma, in the absence of any stigmata of neurofibromatosis.

  5. Angiogenic and Metastatic Determinants of Malignant Melanoma

    NARCIS (Netherlands)

    A. Mooppilmadham Das (Asha)

    2015-01-01

    markdownabstractCutaneous melanoma or malignant melanoma of the skin is a highly metastatic disease, with an increasing rate of incidence, poor prognosis and high resistance to therapeutic intervention. Although early diagnosis and surgical resection of the primary lesion could significantly improve

  6. Functional metastatic parathyroid adenocarcinoma in a dog

    OpenAIRE

    Kishi, Erin N.; Holmes, Shannon P.; Abbott, Jeffrey R.; Bacon, Nicholas J.

    2014-01-01

    A 12-year-old dachshund dog was presented for persistent hypercalcemia and hyperparathyroidism despite bilateral parathyroidectomy. Magnetic resonance imaging of the head, neck, and cranial mediastinum identified an increased number of cranial mediastinal lymph nodes with heterogeneous signal intensity. Hypercalcemia and hyperparathyroidism resolved after surgery to remove multiple cranial mediastinal lymph nodes, one of which contained presumed metastatic parathyroid tissue.

  7. Metastatic Malignant Melanoma Mimicking Benign Breast Cysts

    OpenAIRE

    Marius Lund-Iversen; Olav Inge Håskjold; Hiep Phuc Dong; Aasmund Berner

    2011-01-01

    Benign cysts are one of the most common mass-occupying lesions of the breast and are often investigated with triple diagnostic trial (clinical examination, radiology, and cytology). Malignant melanoma is one of medicine's imitators, and metastatic disease can mimic cysts. Thorough investigation of any breast mass is essential to clarify its nature.

  8. Radiation therapy for metastatic spinal tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kida, Akio; Fukuda, Haruyuki [Osaka City Univ. (Japan). Medical School; Taniguchi, Shuji; Sakai, Kazuaki

    2000-02-01

    The results of radiation therapy for metastatic spinal tumors were evaluated in terms of pain relief, improvement of neurological impairment, and survival. Between 1986 and 1995, 52 symptomatic patients with metastatic spinal tumors treated with radiation therapy were evaluated. The patients all received irradiation of megavoltage energy. Therapeutic efficacy was evaluated in terms of pain relief and improvement of neurological impairment. Pain relief was observed in 29 (61.7%) of 47 patients with pain. Therapy was effective for 17 (70.8%) of 24 patients without neurological impairment, and efficacy was detected in 12 (52.2%) of 23 patients with neurological impairment. Improvement of neurological symptoms was obtained in seven (25.0%) of 28 patients with neurological impairment. Radiation therapy was effective for pain relief in patients with metastatic spinal tumors. In patients with neurological impairment, less pain relief was observed than in those without impairment. Improvement of neurological impairment was restricted, but radiation therapy was thought to be effective in some cases in the early stage of neurological deterioration. Radiation therapy for metastatic spinal tumors contraindicated for surgery was considered effective for improvement of patients' activities of daily living. (author)

  9. Sorafenib makes headway on metastatic thyroid cancer.

    Science.gov (United States)

    2013-07-01

    In a randomized phase III clinical trial, patients with metastatic differentiated cancer of the thyroid who were treated with sorafenib achieved median progression-free survival of 10.8 months, compared with 5.8 months among patients treated with placebo.

  10. Epidemiology and therapies for metastatic sarcoma

    Directory of Open Access Journals (Sweden)

    Amankwah EK

    2013-05-01

    Full Text Available Ernest K Amankwah,1 Anthony P Conley,2 Damon R Reed2 1Department of Cancer Epidemiology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 2Sarcoma Department, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA Abstract: Sarcomas are cancers arising from the mesenchymal layer that affect children, adolescents, young adults, and adults. Although most sarcomas are localized, many display a remarkable predilection for metastasis to the lungs, liver, bones, subcutaneous tissue, and lymph nodes. Additionally, many sarcoma patients presenting initially with localized disease may relapse at metastatic sites. While localized sarcomas can often be cured through surgery and often radiation, controversies exist over optimal management of patients with metastatic sarcoma. Combinations of chemotherapy are the most effective in many settings, and many promising new agents are under active investigation or are being explored in preclinical models. Metastatic sarcomas are excellent candidates for novel approaches with additional agents as they have demonstrated chemosensitivity and affect a portion of the population that is motivated toward curative therapy. In this paper, we provide an overview on the common sarcomas of childhood (rhabdomyosarcoma, adolescence, and young adults (osteosarcoma, Ewing sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor and older adults (leiomyosarcoma, liposarcoma, and undifferentiated high grade sarcoma in terms of the epidemiology, current therapy, promising therapeutic directions and outcome with a focus on metastatic disease. Potential advances in terms of promising therapy and biologic insights may lead to more effective and safer therapies; however, more clinical trials and research are needed for patients with metastatic sarcoma. Keywords: chemotherapy, pediatric sarcoma, rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, synovial sarcoma

  11. Hormonal therapy in the treatment of mandibular metastasis of breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ehlinger, P.; Peeters, L.C.; Fossion, E. (Department of Maxillo-Facial Surgery, Algemeen Ziekenhuis Middelheim, Antwerp (Belgium)); Servais, J. (Department of Oncology and Radiation Therapy, Algemeen Ziekenhuis Middelheim, Antwerp (Belgium))

    1993-01-01

    We present the clinical history of a 39-year-old woman, who has survived for over 10 years with metastatic breast cancer. After combined surgery and radiotherapy of the primary tumor and the regional lymph nodes, all bone metastases gradually disappeared under chemotherapy and continuing hormonal treatment. This complete remission included a large mandibular metastasis, which had received additional radiotherapy of 21 Gy. Spontaneous reossification was observed in this location. (au) (7 refs.).

  12. Hormone-sensing cells require Wip1 for paracrine stimulation in normal and premalignant mammary epithelium.

    Science.gov (United States)

    Tarulli, Gerard A; De Silva, Duvini; Ho, Victor; Kunasegaran, Kamini; Ghosh, Kakaly; Tan, Bryan C; Bulavin, Dmitry V; Pietersen, Alexandra M

    2013-01-31

    The molecular circuitry of different cell types dictates their normal function as well as their response to oncogene activation. For instance, mice lacking the Wip1 phosphatase (also known as PPM1D; protein phosphatase magnesium-dependent 1D) have a delay in HER2/neu (human epidermal growth factor 2), but not Wnt1-induced mammary tumor formation. This suggests a cell type-specific reliance on Wip1 for tumorigenesis, because alveolar progenitor cells are the likely target for transformation in the MMTV(mouse mammary tumor virus)-neu but not MMTV-wnt1 breast cancer model. In this study, we used the Wip1-knockout mouse to identify the cell types that are dependent on Wip1 expression and therefore may be involved in the early stages of HER2/neu-induced tumorigenesis. We found that alveolar development during pregnancy was reduced in Wip1-knockout mice; however, this was not attributable to changes in alveolar cells themselves. Unexpectedly, Wip1 allows steroid hormone-receptor-positive cells but not alveolar progenitors to activate STAT5 (signal transducer and activator of transcription 5) in the virgin state. In the absence of Wip1, hormone-receptor-positive cells have significantly reduced transcription of RANKL (receptor activator of nuclear factor kappa-B ligand) and IGF2 (insulin-like growth factor 2), paracrine stimulators of alveolar development. In the MMTV-neu model, HER2/neu activates STAT5 in alveolar progenitor cells independent of Wip1, but HER2/neu does not override the defect in STAT5 activation in Wip1-deficient hormone-sensing cells, and paracrine stimulation remains attenuated. Moreover, ERK (extracellular signal-regulated kinase) activation by HER2/neu in hormone-sensing cells is also Wip1 dependent. We identified Wip1 as a potentiator of prolactin and HER2/neu signaling strictly in the molecular context of hormone-sensing cells. Furthermore, our findings highlight that hormone-sensing cells convert not only estrogen and progesterone but also

  13. Re-Appraisal of Estrogen Receptor Negative/Progesterone Receptor Positive (ER-/PR+) Breast Cancer Phenotype: True Subtype or Technical Artefact?

    Science.gov (United States)

    Foley, Niamh M; Coll, J M; Lowery, A J; Hynes, S O; Kerin, M J; Sheehan, M; Brodie, C; Sweeney, K J

    2017-09-11

    Expression of the ER and PR receptors is routinely quantified in breast cancer as a predictive marker of response to hormonal therapy. Accurate determination of ER and PR status is critical to the optimal selection of patients for targeted therapy. The existence of an ER-/PR+ subtype is controversial, with debate centred on whether this represents a true phenotype or a technical artefact on immunohistochemistry (IHC). The aim of this study was to investigate the true incidence and clinico-pathological features of ER-/PR+ breast cancers in a tertiary referral symptomatic breast unit. Clinico-pathological data were collected on invasive breast cancers diagnosed between 1995 and 2005. IHC for ER and PR receptors was repeated on all cases which were ER-/PR+, with the same paraffin block used for the initial diagnostic testing. Concordance between the diagnostic and repeat IHC was determined using validated testing. Complete data, including ER and PR status were available for 697 patients diagnosed during the study period. On diagnostic IHC, the immunophenotype of the breast tumours was: ER+/PR+ in 396 (57%), ER-/PR- in 157 (23%), ER+/PR- in 88 (12%) and ER-/PR+ in 56 (8.6%) patients. On repeat IHC of 48/56 ER-/PR+ tumours 45.8% were ER+/PR+, 6% were ER+/PR- and 43.7% were ER-/PR- None of the cases were confirmed to be ER-/PR+. The ER-/PR+ phenotypic breast cancer is likely to be the result of technical artefact. Prompt reassessment of patients originally assigned to this subtype who re-present with symptoms should be considered to ensure appropriate clinical management.

  14. Headache And Hormones

    Directory of Open Access Journals (Sweden)

    Shukla Rakesh

    2002-01-01

    Full Text Available There are many reasons to suggest a link between headache and hormones. Migraine is three times common in women as compared to men after puberty, cyclic as well as non-cyclic fluctuations in sex hormone levels during the entire reproductive life span of a women are associated with changes in frequency or severity of migraine attack, abnormalities in the hypothalamus and pineal gland have been observed in cluster headache, oestrogens are useful in the treatment of menstrual migraine and the use of melatonin has been reported in various types of primary headaches. Headache associated with various endocrinological disorders may help us in a better understanding of the nociceptive mechanisms involved in headache disorders. Prospective studies using headache diaries to record the attacks of headache and menstrual cycle have clarified some of the myths associated with menstrual migraine. Although no change in the absolute levels of sex hormones have been reported, oestrogen withdrawal is the most likely trigger of the attacks. Prostaglandins, melatonin, opioid and serotonergic mechanisms may also have a role in the pathogenesis of menstrual migraine. Guidelines have been published by the IHS recently regarding the use of oral contraceptives by women with migraine and the risk of ischaemic strokes in migraineurs on hormone replacement therapy. The present review includes menstrual migraine, pregnancy and migraine, oral contraceptives and migraine, menopause and migraine as well as the hormonal changes in chronic migraine.

  15. Evaluation of dual energy spectral CT in differentiating metastatic from non-metastatic lymph nodes in rectal cancer: Initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Huanhuan [Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Department of Radiology, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine (China); Yan, Fuhua; Pan, Zilai; Lin, Xiaozhu; Luo, Xianfu; Shi, Cen [Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Chen, Xiaoyan [Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Wang, Baisong [Department of Biomedical Statistics, Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China); Zhang, Huan, E-mail: huanzhangy@126.com [Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai 200025 (China)

    2015-02-15

    Highlights: • Colorectal cancer is the third most prevalent cancer and the status of the regional lymph nodes in rectal cancer is considered to be one of the most powerful prognostic factor in the absence of distant metastatic disease. Detecting LNs metastasis is still a challenging problem due to the presence of microscopic metastasis or inflammatory swelling of LNs. • We investigated the value of dual energy spectral CT in differentiating metastatic from non-metastatic lymph nodes in rectal cancer. Our study demonstrated that the quantitative normalized iodine concentration (nIC) could be useful for differentiating metastatic and non-metastatic lymph nodes. The combination of nIC in portal venous phase and conventional size criterion could improve the diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of rectal cancer. - Abstract: Objectives: To investigate the value of dual energy spectral CT (DEsCT) imaging in differentiating metastatic from non-metastatic lymph nodes in rectal cancer. Methods: Fifty-five patients with rectal cancer underwent the arterial phase (AP) and portal venous phase (PP) contrast-enhanced DEsCT imaging. The virtual monochromatic images and iodine-based material decomposition images derived from DEsCT imaging were interpreted for lymph nodes (LNs) measurement. The short axis diameter and the normalized iodine concentration (nIC) of metastatic and non-metastatic LNs were measured. The two-sample t test was used to compare the short axis diameters and nIC values of metastatic and non-metastatic LNs. ROC analysis was performed to assess the diagnostic performance. Results: One hundred and fifty two LNs including 92 non-metastatic LNs and 60 metastatic LNs were matched using the radiological-pathological correlation. The mean short axis diameter of metastatic LNs was significantly larger than that of the non-metastatic LNs (7.28 ± 2.28 mm vs. 4.90 ± 1.64 mm, P < 0.001). The mean n

  16. Stress and hormones

    Directory of Open Access Journals (Sweden)

    Salam Ranabir

    2011-01-01

    Full Text Available In the modern environment one is exposed to various stressful conditions. Stress can lead to changes in the serum level of many hormones including glucocorticoids, catecholamines, growth hormone and prolactin. Some of these changes are necessary for the fight or flight response to protect oneself. Some of these stressful responses can lead to endocrine disorders like Graves′ disease, gonadal dysfunction, psychosexual dwarfism and obesity. Stress can also alter the clinical status of many preexisting endocrine disorders such as precipitation of adrenal crisis and thyroid storm.

  17. Sex Hormones and Tendon

    DEFF Research Database (Denmark)

    Hansen, Mette; Kjaer, Michael

    2016-01-01

    The risk of overuse and traumatic tendon and ligament injuries differ between women and men. Part of this gender difference in injury risk is probably explained by sex hormonal differences which are specifically distinct during the sexual maturation in the teenage years and during young adulthood....... The effects of the separate sex hormones are not fully elucidated. However, in women, the presence of estrogen in contrast to very low estrogen levels may be beneficial during regular loading of the tissue or during recovering after an injury, as estrogen can enhance tendon collagen synthesis rate. Yet...

  18. Viral Therapy In Treating Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Cancer or Metastatic Breast Cancer

    Science.gov (United States)

    2018-02-16

    Estrogen Receptor Negative; Estrogen Receptor Positive; Head and Neck Squamous Cell Carcinoma; HER2/Neu Negative; HER2/Neu Positive; Invasive Breast Carcinoma; Progesterone Receptor Negative; Progesterone Receptor Positive; Recurrent Head and Neck Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  19. Ovarian hormones and obesity.

    Science.gov (United States)

    Leeners, Brigitte; Geary, Nori; Tobler, Philippe N; Asarian, Lori

    2017-05-01

    Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role. We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE. Articles in English indexed in PubMed through January 2016 were searched using keywords related to: (i) reproductive hormones, (ii) weight regulation and (iii) central nervous system. We sought to identify emerging research foci with clinical translational potential rather than to provide a comprehensive review. We find that estrogens play a leading role in the causes and consequences of female obesity. With respect to adiposity, estrogens synergize with AT genes to increase gluteofemoral subcutaneous AT mass and decrease central AT mass in reproductive-age women, which leads to protective cardiometabolic effects. Loss of estrogens after menopause, independent of aging, increases total AT mass and decreases lean body mass, so that there is little net effect on body weight. Menopause also partially reverses women's protective AT distribution. These effects can be counteracted by estrogen treatment. With respect to eating, increasing estrogen levels progressively decrease eating during the follicular and peri-ovulatory phases of the menstrual cycle. Progestin levels are associated with eating during the luteal phase, but there does not appear to be a causal relationship. Progestins may increase binge eating and eating stimulated by negative emotional states during the luteal phase. Pre-clinical research indicates that one mechanism for the pre-ovulatory decrease in eating is a

  20. Intra-abdominal splenosis mimicking metastatic cancer.

    Science.gov (United States)

    Short, Nicholas J; Hayes, Teresa G; Bhargava, Peeyush

    2011-03-01

    Splenosis, the heterotopic autotransplantion of splenic tissue, is a common benign condition among patients with a history of splenic trauma. Most cases of splenosis are intra-abdominal due to direct seeding of surrounding structures, although these ectopic rests may occur almost anywhere in the body, and its diffuse nature may raise the suspicion of metastatic cancer. Confirmation of splenic tissue can be made by technetium-99m (Tc-99m) sulfur colloid scintigraphy or with Tc-99m heat-damaged red blood cells; however, in some cases, biopsy may be required for definitive diagnosis. Here, the authors present a patient with a remote history of posttraumatic splenectomy who was discovered to have multiple intra-abdominal nodules by CT scan. A diagnosis of diffuse metastatic disease was initially considered before a diagnosis of intraabdominal splenosis was ultimately made with the aid of Tc-99m sulfur colloid single-positron emission computed tomography (SPECT) and computed tomography imaging.

  1. Duodenal Bleeding from Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Tarun Rustagi

    2011-04-01

    Full Text Available Massive upper gastrointestinal bleeding due to malignancy is relatively uncommon and the duodenum is the least frequently involved site. Duodenal metastasis is rare in renal cell carcinoma (RCC and early detection, especially in case of a solitary mass, helps in planning further therapy. We report a case of intractable upper gastrointestinal bleeding from metastatic RCC to the duodenum. The patient presented with melena and anemia, 13 years after nephrectomy for RCC. On esophagogastroduodenoscopy, a submucosal mass was noted in the duodenum, biopsies of which revealed metastatic RCC. In conclusion, metastasis from RCC should be considered in nephrectomized patients presenting with gastrointestinal symptoms and a complete evaluation, especially endoscopic examination followed by biopsy, is suggested.

  2. Metastatic urachal cancer responding to FOLFOX chemotherapy.

    Science.gov (United States)

    Tran, Ben; McKendrick, Joe

    2010-04-01

    Metastatic urachal cancer is a rare disease and subsequently, does not have a defined systemic treatment. Although urachal cancer is most commonly adenocarcinoma and histologically similar to colon cancer, treatment selection is usually based upon location (the proximity of the urachus to the bladder) with bladder cancer regimens the most commonly prescribed. We report a case of metastatic urachal cancer where the immunohistochemical profile's similarities to colon cancer led to treatment with colon cancer specific chemotherapy. Our case is the first to report urachal cancer treated with and responding to modified FOLFOX6. In the age of targeted therapy, where molecular biology drives treatment selection, our case highlights that in rare tumors, when evidence is often lacking, a common sense approach can often prevail.

  3. Ziv-aflibercept in metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Patel A

    2013-12-01

    Full Text Available Anuj Patel, Weijing Sun Division of Hematology-Oncology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Abstract: The combination of cytotoxic chemotherapy and antiangiogenic agents has become a conventional treatment option for patients with metastatic colorectal cancer. Ziv-aflibercept is a fusion protein which acts as a decoy receptor for vascular endothelial growth factor (VEGF-A, VEGF-B, and placental growth factor (PlGF; it was approved in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI for the treatment of patients with metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing fluoropyrimidine-based regimen. Herein we review the role of tumor angiogenesis as the rationale for antiangiogenic therapy, the clinical data associated with ziv-aflibercept, and its current role as a treatment option compared to other antiangiogenic agents, such as bevacizumab and regorafenib. Keywords: aflibercept, angiogenesis, colorectal cancer

  4. Metastatic melanoma masquerading as a furuncle

    Directory of Open Access Journals (Sweden)

    Imran Aslam

    2017-10-01

    Full Text Available Melanoma metastasizes to the skin in about 10-17% of patients. Although there are reports of metastatic melanoma masquerading as panniculitis and erysipelas, it is very uncommon for it to present as an inflammatory skin lesion. When malignant melanoma cells invade the superficial dermal lymphatic vessels it can result in erythema, edema and induration of the overlying skin. This presentation can be problematic for clinicians if they do not suspect melanoma and choose not to biopsy the lesion. We report a case of an elderly man with a history of invasive melanoma who presented with a furuncle-like lesion that was found to be in-transit metastatic melanoma.

  5. Thoracoabdominal actinomycosis mimicking metastatic disease: case report

    Energy Technology Data Exchange (ETDEWEB)

    Ros, L.H.; Villacampa, V.M. [Hospital Miguel Servet, Dept. of Radiology, Zaragoza (Spain); Torres, G.M. [Univ. of Florida, Dept. of Radiology, Gainesville, Florida (United States); Ros, P.R. [Harvard Medical School, Brigham and Women' s Hospital, Dept. of Radiology, Boston, Massachusetts (United States)

    1999-12-01

    Actinomycosis is a chronic suppurative infection with bacteria of the Actinomycetaceae family, characterized by the formation of abundant granular tissue and multiple abscesses. It is a rare entity, and clinical and radiological findings are similar to those in other inflammatory and in neoplastic processes. Actinomycosis should be considered in the differential diagnosis in high-risk patients with predisposing factors, such as alcoholism, poor oral hygiene, maxillofacial trauma, tuberculosis, chronic obstructive pulmonary disease, steroid ingestion or immunodeficiency, and in patients in whom the disease history does not correlate with widespread metastatic involvement. Early diagnosis is important, to prevent disease progression and unnecessary surgery, since the response to drug treatment is very good. We present a case of diffuse actinomycosis involving multiple organs (liver, kidneys, colon, and lungs) that simulated metastatic disease on radiography and computed tomography (CT). (author)

  6. Metastatic intraocular hemangiopericytoma in a dog

    Directory of Open Access Journals (Sweden)

    Jonathan D. Pucket

    2017-05-01

    Full Text Available A 10-year-old Labrador Retriever who had been undergoing therapy for a recurrent hemangiopericytoma of the right flank presented to the Kansas State University Ophthalmology service for evaluation of a painful left eye. Examination revealed secondary glaucoma and irreversible blindness of the affected eye and multifocal chorioretinal lesions in the fellow eye. Therapeutic and diagnostic enucleation of the left eye was performed and histopathologic examination demonstrated the presence of a presumed metastatic spindle cell sarcoma. Further immunohistochemical staining confirmed the intraocular neoplasia to be metastatic spread from the previously removed flank mass. Rapid progression in size and number of chorioretinal lesions in the right eye was noted in the post-operative period until the patient was euthanized one month after surgery. This case report is the first to document intraocular metastasis of hemangiopericytoma in a veterinary patient.

  7. Colon Cancer Metastatic to the Biliary Tree

    OpenAIRE

    Strauss, Alexandra T.; Clayton, Steven B.; Markow, Michael; Mamel, Jay

    2016-01-01

    Metastasis of colon adenocarcinoma is commonly found in the lung, liver, or peritoneum. Common bile duct (CBD) tumors related to adenomas from familial adenomatous polyposis metastasizing from outside of the gastrointestinal tract have been reported. We report a case of biliary colic due to metastatic colon adenocarcinoma to the CBD. Obstructive jaundice with signs of acalculous cholecystitis on imaging in a patient with a history of colon cancer should raise suspicion for metastasis to CBD.

  8. Spontaneous regression of metastatic Merkel cell carcinoma.

    LENUS (Irish Health Repository)

    Hassan, S J

    2010-01-01

    Merkel cell carcinoma is a rare aggressive neuroendocrine carcinoma of the skin predominantly affecting elderly Caucasians. It has a high rate of local recurrence and regional lymph node metastases. It is associated with a poor prognosis. Complete spontaneous regression of Merkel cell carcinoma has been reported but is a poorly understood phenomenon. Here we present a case of complete spontaneous regression of metastatic Merkel cell carcinoma demonstrating a markedly different pattern of events from those previously published.

  9. Quantitative Method of Measuring Metastatic Activity

    Science.gov (United States)

    Morrison, Dennis R. (Inventor)

    1999-01-01

    The metastatic potential of tumors can be evaluated by the quantitative detection of urokinase and DNA. The cell sample selected for examination is analyzed for the presence of high levels of urokinase and abnormal DNA using analytical flow cytometry and digital image analysis. Other factors such as membrane associated uroldnase, increased DNA synthesis rates and certain receptors can be used in the method for detection of potentially invasive tumors.

  10. Roles of metalloproteases in metastatic niche.

    Science.gov (United States)

    Rucci, N; Sanità, P; Angelucci, A

    2011-11-01

    Metalloproteinases (MMPs) are a cluster of at least 23 enzymes belonging to the more wide family of endopeptidases called Metzincins, whose structure is characterized by the presence of a zinc ion at the catalytic site. Although the general view of MMPs as physiologic scissors involved in extracellular matrix (ECM) degradation and tissue remodeling is still valid, additional functions have recently emerged, including the ability to cleave non ECM molecules such as growth factors, cytokines and chemokines from their membrane-anchored proforms. These functions are utilized by tumor cells and are fundamental in the determination of tumor progression and invasion. The effect of MMPs activity in cancer progression has been traditionally associated with the acquisition by tumor cells of an invasive phenotype, an indispensable requisite for the metastatic spreading of cancer cells. In addition to the traditional view, a new role for MMPs in creating a favourable microenvironment has been proposed, so that MMPs are not only involved in cell invasion, but also in signaling pathways that control cell growth, inflammation, or angiogenesis. Finally, recent evidence suggest a role of MMPs in the so called "pre-metastatic niche" that is the hypothesis of an early distant modification of the premetastatic site by primary cancer cells. This new hypothesis is changing our traditional view about MMPs and provides important insights into the effective time window for the therapeutic use of MMP inhibitors. In this review we provide the main available data about the ability of MMPs in creating a suitable microenvironment for tumor growth in metastatic sites and we indicate the implication of these data on the potential use of MMP inhibitors in the metastatic therapy.

  11. Metastatic malignant melanoma of the gastrointestinal tract.

    Science.gov (United States)

    Liang, Kelly V; Sanderson, Schuyler O; Nowakowski, Grzegorz S; Arora, Amindra S

    2006-04-01

    Malignant melanoma is one of the most common malignancies to metastasize to the gastrointestinal (GI) tract. Metastases to the GI tract can present at the time of primary diagnosis or decades later as the first sign of recurrence. Symptoms may include abdominal pain, dysphagia, small bowel obstruction, hematemesis, and melena. We report 2 cases of malignant melanoma metastatic to the GI tract, followed by a review of the literature. The first case is a 72-year-old man who underwent resection of superficial spreading melanoma on his back 13 years previously who presented with dysphagia. A biopsy specimen of a mucosal fold in a gastric fundus noted during endoscopy was taken and revealed metastatic malignant melanoma, which was resected 1 month later. Three weeks later, the patient was found to have an ulcerated jejunal metastatic melanoma mass, which was also resected. The second case is a 63-year-old man with an ocular melanoma involving the chorold of the left eye that had been diagnosed 4 years previously, which had been excised several times, who presented with anorexia, dizziness, and fatigue. He was found to have cerebellar and stomach metastases. He underwent adjuvant radiation therapy, chemotherapy, and surgical resection of the gastric melanoma metastasis. In patients with a history of melanoma, a high index of suspicion for metastasis must be maintained if they present with seemingly unrelated symptoms. Diagnosis requires careful inspection of the mucosa for metastatic lesions and biopsy with special immunohistochemical stains. Management may include surgical resection, chemotherapy, immunotherapy, observation, or enrollment in clinical trials. Prognosis is poor, with a median survival of 4 to 6 months.

  12. Metastatic Uveal Melanoma: Biology and Emerging Treatments

    OpenAIRE

    Scott E Woodman

    2012-01-01

    Uveal melanoma is the most common primary intraocular cancer in adults. Nearly half of primary uveal melanoma tumors metastasize, but there are currently no effective therapies for metastatic uveal melanoma. The recent discovery of mutations that underlie uveal melanoma metastasis, growth and survival provide a key to the molecular understanding of this disease. Much work is now underway to leverage this knowledge to develop effective therapies. This review summarizes recently discovered mole...

  13. Metastatic breast cancer: The Odyssey of personalization.

    Science.gov (United States)

    Sonnenblick, A; Pondé, N; Piccart, M

    2016-10-01

    Metastatic breast cancer is the most frequent cause of cancer death for women worldwide. In the last 15 years, a large number of new agents have entered clinical use, a result of the dramatic increase in our understanding of the molecular underpinnings of metastatic breast cancer. However, while these agents have led to better outcomes, they are also at the root cause of increasing financial pressure on healthcare systems. Moreover, decision making in an era where every year new agents are added to the therapeutic armamentarium has also become a significant challenge for medical oncologists. In the present article, we will provide an ample review on the most recent developments in the field of treatment of the different subtypes of metastatic breast cancer with a critical discussion on the slow progress made in identifying response biomarkers. New hopes in the form of ctDNA monitoring and functional imaging will be presented. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  14. Metastatic urachal carcinoma in bronchial brush cytology

    Directory of Open Access Journals (Sweden)

    Fatima Zahra Aly

    2013-01-01

    Full Text Available Urachal carcinoma is rare comprising less than 1% of all bladder carcinomas. Metastases of urachal carcinoma have been reported to meninges, brain, ovary, lung, and maxilla. Cytologic features of metastatic urachal carcinoma have not been previously reported. We present a case of metastatic urachal adenocarcinoma in bronchial brushings and review the use of immunohistochemistry in its diagnosis. A 47-year-old female was seen initially in 2007 with adenocarcinoma of the bladder dome for which she underwent partial cystectomy. She presented in 2011 with a left lung mass and mediastinal adenopathy. Bronchoscopy showed an endobronchial lesion from which brushings were obtained. These showed numerous groups of columnar cells with medium sized nuclei and abundant cytoplasm. The cells were positive for CK20 and CDX2 and negative for CK7. The cytomorphological findings were similar to those in the previous resection specimen and concurrent biopsy. This is the first case report of bronchial brushings containing metastatic urachal carcinoma. No specific immunohistochemical profile is available for its diagnosis. The consideration of a second primary was a distinct possibility in this case due to the lapse of time from primary resection, absence of local disease, and lack of regional metastases.

  15. LUTEINIZING HORMONE (LH)

    African Journals Online (AJOL)

    ... period and ovulation in rats.J. Endocr. 57,235. JOcHLE, W., 1969. Latest trends and practical problems arising during oestrus synchronisation. Proc. S. Afr. Soc. Anim. Prod. 8,23. KANN, G., 1971. Variations des concentrations plasmatiques de l'hormone luteinisant et de la prolactin au cours du cycle oestrien de la brebis.

  16. Thyroid hormone and obesity.

    Science.gov (United States)

    Pearce, Elizabeth N

    2012-10-01

    To review several of the most recent and most important clinical studies regarding the effects of thyroid treatments on weight change, associations between thyroid status and weight, and the effects of obesity and weight change on thyroid function. Weight decreases following treatment for hypothyroidism. However, following levothyroxine treatment for overt hypothyroidism, weight loss appears to be modest and mediated primarily by loss of water weight rather than fat. There is conflicting evidence about the effects of thyroidectomy on weight. In large population studies, even among euthyroid individuals, serum thyroid-stimulating hormone is typically positively associated with body weight and BMI. Both serum thyroid-stimulating hormone and T3 are typically increased in obese compared with lean individuals, an effect likely mediated, at least in part, by leptin. Finally, there is no consistent evidence that thyroid hormone treatment induces weight loss in obese euthyroid individuals, but thyroid hormone analogues may eventually be useful for weight loss. The interrelationships between body weight and thyroid status are complex.

  17. Hormones and postpartum cardiomyopathy.

    NARCIS (Netherlands)

    Clapp, C.; Thebault, S.C.; Martinez de la Escalera, G.M.

    2007-01-01

    Prolactin, a hormone fundamental for lactation, was recently shown to mediate postpartum cardiomyopathy, a life-threatening disease in late-term and lactating mothers. The detrimental effect of prolactin results from myocardial upregulation of cathepsin-D, which in turn cleaves prolactin to a 16 kDa

  18. Extracellular vesicles secreted by highly metastatic clonal variants of osteosarcoma preferentially localize to the lungs and induce metastatic behaviour in poorly metastatic clones.

    Science.gov (United States)

    Macklin, Rebecca; Wang, Haolu; Loo, Dorothy; Martin, Sally; Cumming, Andrew; Cai, Na; Lane, Rebecca; Ponce, Natalia Saenz; Topkas, Eleni; Inder, Kerry; Saunders, Nicholas A; Endo-Munoz, Liliana

    2016-07-12

    Osteosarcoma (OS) is the most common pediatric bone tumor and is associated with the emergence of pulmonary metastasis. Unfortunately, the mechanistic basis for metastasis remains unclear. Tumor-derived extracellular vesicles (EVs) have been shown to play critical roles in cell-to-cell communication and metastatic progression in other cancers, but their role in OS has not been explored. We show that EVs secreted by cells derived from a highly metastatic clonal variant of the KHOS cell line can be internalized by a poorly metastatic clonal variant of the same cell line and induce a migratory and invasive phenotype. This horizontal phenotypic transfer is unidirectional and provides evidence that metastatic potential may arise via interclonal co-operation. Proteomic analysis of the EVs secreted by highly metastatic OS clonal variants results in the identification of a number of proteins and G-protein coupled receptor signaling events as potential drivers of OS metastasis and novel therapeutic targets. Finally, multiphoton microscopy with fluorescence lifetime imaging in vivo, demonstrated a preferential seeding of lung tissue by EVs derived from highly metastatic OS clonal variants. Thus, we show that EVs derived from highly metastatic clonal variants of OS may drive metastatic behaviour via interclonal co-operation and preferential colonization of the lungs.

  19. Luteinizing hormone (LH) blood test

    Science.gov (United States)

    ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... to temporarily stop medicines that may affect the test results. Be sure to tell your provider about ...

  20. Hormonal contraception and venous thromboembolism

    DEFF Research Database (Denmark)

    Lidegaard, Øjvind; Milsom, Ian; Geirsson, Reynir Tomas

    2012-01-01

    New studies about the influence of hormonal contraception on the risk of venous thromboembolism (VTE) have been published.......New studies about the influence of hormonal contraception on the risk of venous thromboembolism (VTE) have been published....

  1. Gastrointestinal hormones and their targets

    DEFF Research Database (Denmark)

    Rehfeld, Jens F.

    2014-01-01

    Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone producing organ in the body. Modern biology makes...... it feasible to conceive the hormones under five headings: The structural homology groups a majority of the hormones into nine families, each of which is assumed to originate from one ancestral gene. The individual hormone gene often has multiple phenotypes due to alternative splicing, tandem organization......, or differentiated maturation of the prohormone. By a combination of these mechanisms, more than 100 different hormonally active peptides are released from the gut. Gut hormone genes are also widely expressed in cells outside the gut, some only in extraintestinal endocrine cells and neurons but others also in other...

  2. Hormone Therapy for Breast Cancer

    Science.gov (United States)

    ... hormones? Hormones are substances that function as chemical messengers in the body. They affect the actions of ... at the National Institutes of Health FOLLOW US Facebook Twitter Instagram YouTube Google+ LinkedIn GovDelivery RSS CONTACT ...

  3. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... Links Patient Resources For Health Professionals Subscribe Search Sex Hormone Binding Globulin (SHBG) Send Us Your Feedback ... As Testosterone-estrogen Binding Globulin TeBG Formal Name Sex Hormone Binding Globulin This article was last reviewed ...

  4. Docetaxel in hormone-sensitive advanced prostate cancer; GENESIS-SEFH evaluation reporta

    Directory of Open Access Journals (Sweden)

    Emilio Jesús Alegre del Rey

    2017-07-01

    Full Text Available Prostate cancer (PC is the most common urogenital malignancy in older men and the second leading cause of death by cancer in men in Europe. Current therapeutic practice considers Androgen Deprivation Therapy (ADT as first line treatment for clinically localized prostate cancer at high-risk, either locally advanced or metastatic. ADT can be achieved through orchiectomy (surgical castration, luteinizing hormone-releasing hormone (LHRH agonists, or through complete androgen blockade (LHRH agonist combined with an anti-androgen. Docetaxel in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone-refractory metastatic prostate cancer. The CHAARTED and STAMPEDE clinical trials studied the effect of bringing forward the use of docetaxel added on to ADT in the context of hormone-sensitive patients. The CHAARTED clinical trial showed a significant increase in a variable with maximum relevance such as Overall Survival (OS, with a difference of 13.6 months between medians. There was also clinical benefit in the secondary variables: median time until castration-resistant disease or until clinical progression. In the STAMPEDE clinical trial, which included 39% of non-metastatic patients, a 10-month difference between medians was demonstrated in OS, and 17 months in the primary co-variable of Progression Free Survival. The most frequent adverse events were: neutropenia, febrile neutropenia, leucopenia, and general disorders such as asthenia, lethargy or fever. According to data from the CHAARTED and STAMPEDE studies, and the incremental cost of € 3 196.98 for adding on docetaxel to standard treatment, the estimated additional cost for each year of life gained is compatible with an incremental cost-effectiveness ratio between € 2 267.36 and € 3 851.78. In view of the efficacy and safety results, the proposed positioning is: to advance the use of docetaxel added to androgen deprivation therapy to first

  5. Melatonin – apleiotropic hormone

    Directory of Open Access Journals (Sweden)

    Maciej Brzęczek

    2016-06-01

    Full Text Available Melatonin, a tryptophan derivative, is synthesised in mammals mainly in the pineal gland. It coordinates the biological clock by regulating the circadian rhythm. Its production is dependent on light and its concentrations change with age. Thanks to its specific chemical structure, melatonin is capable of crossing all biological barriers in the organism and affecting other tissues and cells, both in indirect and direct ways. Its mechanism of action involves binding with membrane receptors, nuclear receptors and intracellular proteins. Melatonin shows antioxidant activity. Moreover, its immunomodulatory and antilipid effects as well as its role in secreting other hormones, such as prolactin, luteinizing hormone, follicle-stimulating hormone, somatotropin, thyroliberin, adrenocorticotropin hormone or corticosteroids, are essential. In the recent years, research studies have been mainly focussed on the potential influence of melatonin on the aetiology and development of various disease entities, such as sleep disorders, gastrointestinal diseases, cancers, psychiatric and neurological conditions, cardiovascular diseases or conditions with bone turnover disorders. Indications for melatonin use in paediatrics are being discussed more and more frequently. Among others, authors debate on its use in dyssomnias in children with neurodevelopmental disorders, such as attention deficit hyperactivity disorder, supportive treatment in febrile seizures and epilepsy as well as potential use in paediatric anaesthesia. The molecular mechanism and broad-spectrum action of melatonin have not been sufficiently researched and its clinical relevance is often underestimated. This hormone is a promising link in achieving alternative therapeutic solutions.

  6. Targeted therapy after complete resection of metastatic lesions in metastatic renal cell carcinoma.

    Science.gov (United States)

    Park, Yong Hyun; Jung, Jin-Woo; Lee, Byung Ki; Lee, Sangchul; Jeong, Seong Jin; Byun, Seok-Soo; Lee, Sang Eun

    2015-02-01

    To evaluate the efficacy of targeted therapy after complete resection of metastatic lesions in patients with metastatic renal cell carcinoma. We retrospectively reviewed the medical records of 53 patients with metastatic renal cell carcinoma who underwent complete surgical resection of metastatic lesions between January 2006 and December 2012. Immediate postoperative targeted therapy was given to a subgroup of patients. Progression-free survival and cancer-specific survival were assessed. All patients underwent curative surgery for a primary tumor. A total of 13 patients (24.5%) had metastatic disease at initial diagnosis, and 49 (92.5%) had single-organ involvement at the time of first metastasis. None of the patients met the poor-risk criteria. Of the 19 patients who received immediate postoperative targeted therapy, five (26.3%) experienced relapse. Of the 34 patients who did not receive immediate postoperative targeted therapy, 27 (79.4%) experienced disease recurrence. Targeted therapy was restarted in 30 patients (93.8%) after relapse with excellent disease control rates (complete response: 3.3%, partial response: 36.7%, stable disease: 46.7%). Immediate postoperative targeted therapy was associated with better median progression-free survival (not reached vs 20.0 months; P = 0.017), but not better cancer-specific survival. Postoperative targeted therapy after complete metastasectomy seems to be associated with better progression-free survival in patients with metastatic renal cell carcinoma, but not with cancer-specific survival. © 2014 The Japanese Urological Association.

  7. Hormone Profiling in Plant Tissues.

    Science.gov (United States)

    Müller, Maren; Munné-Bosch, Sergi

    2017-01-01

    Plant hormones are for a long time known to act as chemical messengers in the regulation of physiological processes during a plant's life cycle, from germination to senescence. Furthermore, plant hormones simultaneously coordinate physiological responses to biotic and abiotic stresses. To study the hormonal regulation of physiological processes, three main approaches have been used (1) exogenous application of hormones, (2) correlative studies through measurements of endogenous hormone levels, and (3) use of transgenic and/or mutant plants altered in hormone metabolism or signaling. A plant hormone profiling method is useful to unravel cross talk between hormones and help unravel the hormonal regulation of physiological processes in studies using any of the aforementioned approaches. However, hormone profiling is still particularly challenging due to their very low abundance in plant tissues. In this chapter, a sensitive, rapid, and accurate method to quantify all the five "classic" classes of plant hormones plus other plant growth regulators, such as jasmonates, salicylic acid, melatonin, and brassinosteroids is described. The method includes a fast and simple extraction procedure without time consuming steps as purification or derivatization, followed by optimized ultrahigh-performance liquid chromatography coupled to electrospray ionization-tandem mass spectrometry (UHPLC-MS/MS) analysis. This protocol facilitates the high-throughput analysis of hormone profiling and is applicable to different plant tissues.

  8. Estrogen and Progestin (Hormone Replacement Therapy)

    Science.gov (United States)

    ... Estrogen and progestin are two female sex hormones. Hormone replacement therapy works by replacing estrogen hormone that is no ... menopausal women. Progestin is added to estrogen in hormone replacement therapy to reduce the risk of uterine cancer in ...

  9. Multiple urinary bladder masses from metastatic prostate adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Richard Choo

    2010-12-01

    Full Text Available We present an unusual case of metastatic prostate adenocarcinoma that manifested with multiple exophytic intravesical masses, mimicking a multifocal primary bladder tumor. Biopsy with immunohistochemical analysis confirmed metastatic prostate adenocarcinoma. The patient was treated palliatively with external beam radiotherapy to prevent possible symptoms from local tumor progression. This case illustrates that when a patient with known prostate cancer presents with multifocal bladder tumors, the possibility of metastatic prostate cancer should be considered.

  10. Metastatic Malignant Melanoma Presenting as an Appendiceal Mucocele

    Directory of Open Access Journals (Sweden)

    A. A. Alduaij

    2011-01-01

    Full Text Available Melanoma metastatic to the appendix is extremely rare. Here we describe a case of a 31-year-old female from Bolivia with a remote history of metastatic malignant melanoma first diagnosed as a cutaneous malignant melanoma ten years prior to this presentation. The patient was being followed for a mucocele which on resection was found to be metastatic melanoma. “Mucocele” is a generic diagnosis that warrants further characterization and treatment.

  11. EVALUATION OF STEROID HORMONES AND THEIR RECEPTORS IN DEVELOPMENT AND PROGRESSION OF RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Nigel Bennett

    2014-06-01

    Full Text Available Steroid hormones and their receptors have important roles in normal kidney biology, and alterations in their expression and function help explain the differences in development of kidney diseases, such as nephrotic syndrome and chronic kidney disease. The distinct gender difference in incidence of renal cell carcinoma (RCC, with males having almost twice the incidence as females globally, also suggests a role for sex hormones or their receptors in RCC development and progression. There was a peak in interest in evaluating the roles of androgen and estrogen receptors in RCC pathogenesis in the late 20th century, with some positive outcomes for RCC therapy that targeted estrogen receptors, especially for metastatic disease. Since that time, however, there have been few studies that look at use of steroid hormone modulators for RCC, especially in the light of new therapies such as the tyrosine kinase inhibitors and new immune therapies, which are having some success for treatment of metastatic RCC. This review summarises past and current literature and attempts to stimulate renewed interest in research into the steroid hormones and their receptors, which might be used to effect, for example, in combination with the other newer targeted therapies for RCC.

  12. Bone scintigraphy predicts the risk of spinal cord compression in hormone-refractory prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Soerdjbalie-Maikoe, Vidija; Pelger, Rob C.M.; Nijeholt, Guus A.B. Lycklama [Department of Urology, Leiden University Medical Center, Leiden (Netherlands); Arndt, Jan-Willem [Department of Nuclear Medicine, Leiden University Medical Center, Leiden (Netherlands); Zwinderman, Aeilko H. [Department of Medical Statistics, Leiden University Medical Center, Leiden (Netherlands); Bril, Herman [Department of Pathology, Reinier de Graaf Hospital, Delft (Netherlands); Papapoulos, Socrates E.; Hamdy, Neveen A.T. [Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden (Netherlands)

    2004-07-01

    In prostate cancer, confirmation of metastatic involvement of the skeleton has traditionally been achieved by bone scintigraphy, although the widespread availability of prostate-specific antigen (PSA) measurements has tended to eliminate the need for this investigation. The potential of bone scintigraphy to predict skeletal-related events, particularly spinal cord compression, after the onset of hormone refractoriness has never been investigated. The aim of this study was to establish whether a new method of evaluating bone scintigraphy would offer a better predictive value for this complication of the metastatic process than is achieved with currently available grading methods. We studied 84 patients with hormone-refractory prostate cancer who had undergone bone scintigraphy at the time of hormone escape. Tumour grading and parameters of tumour load (PSA and alkaline phosphatase activity) were available in all patients. The incidence of spinal cord compression was documented and all patients were followed up until death. Bone scintigraphy was evaluated by the conventional Soloway grading and by an additional analysis determining total or partial involvement of individual vertebrae. In contrast to the Soloway method, the new method was able to predict spinal cord compression at various spinal levels. Our data suggest that there is still a place for bone scintigraphy in the management of hormone-refractory prostate cancer. (orig.)

  13. First line chemotherapy plus trastuzumab in metastatic breast cancer ...

    African Journals Online (AJOL)

    First line chemotherapy plus trastuzumab in metastatic breast cancer HER2 positive - Observational institutional study. Meryem Aitelhaj, Siham Lkhoyaali, Ghizlane Rais, Saber Boutayeb, Hassan Errihani ...

  14. Gastric obstruction secondary to metastatic breast cancer: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Hussain Tasadooq

    2012-08-01

    Full Text Available Abstract Introduction Gastrointestinal tract soft tissues metastasis is a well-known occurrence with invasive lobular breast cancer subtypes. Gastric involvement is more common, with reports of both diffuse and localized involvements. Usually, a gastric localized involvement presents as wall thickening with an appearance similar to that of a gastrointestinal stromal tumour; rarely does a localized metastatic deposit grow aggressively to present as a large tumour causing obstructive symptoms. Our case highlights one such unusual presentation in a patient presenting with non-specific gastrointestinal symptoms. To the best of our knowledge, there have been no previous reports on a similar presentation occurring from a localized metastasis. Case presentation A 65-year-old Caucasian woman awaiting an outpatient oral gastroduodenoscopy for symptoms of intermittent vomiting, epigastric pains and weight loss of six weeks’ duration presented acutely with symptoms of haematemesis and abdominal distension. An initial contrast-enhanced computed tomography scan showed a grossly dilated stomach with a locally advanced stenosing tumour mass at the pylorus. Our patient had a history of left mastectomy and axillary clearance followed by adjuvant endocrine therapy for an oestrogen receptor- and progesterone receptor-positive, grade 2, invasive lobular breast cancer. The oral gastroduodenoscopy confirmed the computed tomography findings; biopsies of the pyloric mass on immunohistochemistry stains were strongly positive for pancytokeratin and gross cystic disease fluid proteins, consistent with an invasive lobular breast cancer metastasis. She received a palliative gastrojejunal bypass and her adjuvant endocrine treatment was switched over to exemestane. Conclusion Our case highlights the aggressive behaviour of a localized gastric metastasis that is unusual and unexpected. Gastrointestinal symptomatology can be non-specific and, at times, non-diagnostic on

  15. Benzimidazole as Novel Therapy for Hormone-Refractory Metastatic Prostate Cancer

    Science.gov (United States)

    2011-05-01

    6):705-8. 31. Lanusse CE, Prichard RK. Clinical pharmacokinetics and metabolism of benzimidazole anthelmintics in ruminants . Drug Metab Rev 1993;25...hepatocellular carcinoma. Ann Oncol 1998;9(2):217-9. 43. Sri-Pathmanathan RM, Plumb JA, Fearon KC. Clofazimine alters the energy metabolism and inhibits the

  16. Gut hormones and gastric bypass

    DEFF Research Database (Denmark)

    Holst, Jens J.

    2016-01-01

    Gut hormone secretion in response to nutrient ingestion appears to depend on membrane proteins expressed by the enteroendocrine cells. These include transporters (glucose and amino acid transporters), and, in this case, hormone secretion depends on metabolic and electrophysiological events elicited...... that determines hormone responses. It follows that operations that change intestinal exposure to and absorption of nutrients, such as gastric bypass operations, also change hormone secretion. This results in exaggerated increases in the secretion of particularly the distal small intestinal hormones, GLP-1, GLP-2......, oxyntomodulin, neurotensin and peptide YY (PYY). However, some proximal hormones also show changes probably reflecting that the distribution of these hormones is not restricted to the bypassed segments of the gut. Thus, cholecystokinin responses are increased, whereas gastric inhibitory polypeptide responses...

  17. Hormonal Control of Lactation

    OpenAIRE

    青野, 敏博; Toshihiro, AONO; 徳島大学; Department of Obstetrics and Gynecology, University of Tokushima, School of Medicine

    1990-01-01

    We studied the mechanism of normal lactation, especially the roles of prolactin (PRL) and oxytocin (OXT) in the initiation of lactation, the lactation in the women complicated with endocrinological disorders, and medical therapies for stimulation and suppression of lactation. The level of serum PRL increases as pregnancy progresses, and reachs to a peak on the day of delivery. Despite high PRL level, milk secretion does not appear during pregnancy, because the sex steroid hormones suppress bi...

  18. Enzalutamide monotherapy: Phase II study results in patients with hormone-naive prostate cancer

    DEFF Research Database (Denmark)

    Tombal, Bertrand; Borre, Michael; Rathenborg, Per Zier

    2013-01-01

    studies that exclusively enrolled patients with CRPC receiving androgen deprivation therapy (ie, testosterone (T) levels #50 ng/dL), this phase II study assessed the efficacy and safety of ENZA monotherapy in patients who had never received hormone therapy; presenting with non-castrate T levels ($230 ng......Background: Enzalutamide (ENZA) is an oral androgen receptor inhibitor that has been approved in the US and shown to increase overall survival by 4.8 months over a placebo (HR,0.63) in patients with metastatic castration resistant prostate cancer (CRPC) previously treated with docetaxel (Scher et....../dL). Methods: This was a 25-wk, open-label, single-arm study of patients with hormone-naïve, histologically confirmed prostate cancer (all stages) requiring hormonal treatment, an ECOG PS score of 0,and a life expectancy .1 y. All patients received ENZA 160 mg/d without concomitment castration. Primary endpoint...

  19. Cediranib for Metastatic Alveolar Soft Part Sarcoma

    Science.gov (United States)

    Kummar, Shivaani; Allen, Deborah; Monks, Anne; Polley, Eric C.; Hose, Curtis D.; Ivy, S. Percy; Turkbey, Ismail B.; Lawrence, Scott; Kinders, Robert J.; Choyke, Peter; Simon, Richard; Steinberg, Seth M.; Doroshow, James H.; Helman, Lee

    2013-01-01

    Purpose Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor, for which no effective standard systemic treatment exists for patients with unresectable disease. Cediranib is a potent, oral small-molecule inhibitor of all three vascular endothelial growth factor receptors (VEGFRs). Patients and Methods We conducted a phase II trial of once-daily cediranib (30 mg) given in 28-day cycles for patients with metastatic, unresectable ASPS to determine the objective response rate (ORR). We also compared gene expression profiles in pre- and post-treatment tumor biopsies and evaluated the effect of cediranib on tumor proliferation and angiogenesis using positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging. Results Of 46 patients enrolled, 43 were evaluable for response at the time of analysis. The ORR was 35%, with 15 of 43 patients achieving a partial response. Twenty-six patients (60%) had stable disease as the best response, with a disease control rate (partial response + stable disease) at 24 weeks of 84%. Microarray analysis with validation by quantitative real-time polymerase chain reaction on paired tumor biopsies from eight patients demonstrated downregulation of genes related to vasculogenesis. Conclusion In this largest prospective trial to date of systemic therapy for metastatic ASPS, we observed that cediranib has substantial single-agent activity, producing an ORR of 35% and a disease control rate of 84% at 24 weeks. On the basis of these results, an open-label, multicenter, randomized phase II registration trial is currently being conducted for patients with metastatic ASPS comparing cediranib with another VEGFR inhibitor, sunitinib. PMID:23630200

  20. MOLECULAR MARKERS FOR METASTATIC PROSTATE ADENOCARCINOMA

    Directory of Open Access Journals (Sweden)

    I. S. Kunin

    2012-01-01

    Full Text Available The search of molecular markers of metastasing and prognosis in prostate cancer remains an urgent task. In this study, we investigated the relationship of gene expression heparanase-1 (HPSE1 and D-glucuronil C5-epimerase (GLCE with early disease relapse and metastasis of a 2,5−3 years after diagnosis. It was shown that the ratio of the expression levels of genes HPSE1/GLCE > 1 may serve as a prognostic relapse marker and trends of the tumour to metastasis. The data obtained suggest to use this option as a molecular marker for the diagnostics of metastatic process and the disease prognosis.

  1. Central skeletal sarcoidosis mimicking metastatic disease

    Energy Technology Data Exchange (ETDEWEB)

    Talmi, Danit; Smith, Stacy; Mulligan, Michael E. [University of Maryland School of Medicine, Department of Radiology, Baltimore, MD (United States)

    2008-08-15

    Sarcoidosis is a systemic disease that histologically typically shows non-caseating granulomas. The most common radiologic finding is hilar and mediastinal adenopathy. Patients with widely disseminated disease may show involvement of the peripheral appendicular skeleton in 1-13% of such cases. A primary skeletal presentation without other manifestations typical of the disease is rare. We present a case of sarcoidosis in a middle-aged Caucasian man in whom the disease presented with widespread lytic lesions in the axial skeleton and long bones, mimicking metastatic disease. There was no involvement of the peripheral skeleton, skin or lungs. (orig.)

  2. Pulmonary metastatic calcification: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Bozi, Lilian Christine Franchiotti [Radiology, Hospital Universitario Antonio Pedro (HUAP), Niteroi, RJ (Brazil); Melo, Alessandro Severo Alves de; Marchiori, Edson, E-mail: edmarchiori@gmail.com [Department of Radiology, School of Medicine, Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil)

    2012-09-15

    The present report describes the case of a 48-year-old female patient suffering from chronic renal failure on dialysis for 13 years. She presented with hemoptysis, fever, productive cough and dyspnoea. Chest radiography showed predominance of ill-defined opacities in the middle and lower lung fields, bilaterally. Chest computed tomography showed ground glass opacities associated with poorly defined centrilobular nodules with ground-glass attenuation. The patient was submitted to bronchoalveolar lavage that was negative for mycobacteria and fungi. On the basis of such findings, open lung biopsy was performed, which revealed metastatic pulmonary calcification. (author)

  3. Radiation therapy for metastatic choroidal tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ochiai, Yuko; Sunakawa, Mitsuko (National Kyoto Hospital (Japan)); Hiraoka, Masahiro

    1992-03-01

    We treated 3 eyes in 2 cases of metastatic choroidal malignancy by applying x-ray angled 5deg from a linear accelerator. One case was a 35-year-old female with breast cancer metastasized in both choroids. The second was a 59-year-old male with choroidal metastasis in one eye from malignant lymphoma of the cerebellum. Immediate regression of the tumor followed in all the eyes with resolution of secondary retinal detachment. The treatment was free of complications including cataract or corneal erosion. (author).

  4. Paclitaxel and doxorubicin in metastatic breast cancer

    DEFF Research Database (Denmark)

    Gehl, J; Boesgaard, M; Paaske, T

    1996-01-01

    For the past decades the anthracyclines have been regarded as among the most active drugs for the treatment of metastatic breast cancer. However, the 5-year survival rate in patients with stage IV breast cancer continues to be below 20%, and new active drugs and drug combinations clearly must...... be explored. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been demonstrated to be highly effective in treating patients with advanced breast cancer, including those with anthracycline-resistant breast cancer, a fact that has led to efforts to combine paclitaxel and anthracyclines...

  5. Predictors of Metastatic Disease After Prostate Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Forsythe, Kevin [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States); Burri, Ryan [Department of Radiation Oncology, New York-Presbyterian Hospital, New York, NY (United States); Stone, Nelson [Department of Urology, Mount Sinai School of Medicine, New York, NY (United States); Stock, Richard G., E-mail: richard.stock@moutsinai.org [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States)

    2012-06-01

    Purpose: To identify predictors of metastatic disease after brachytherapy treatment for prostate cancer. Methods and Materials: All patients who received either brachytherapy alone (implant) or brachytherapy in combination with external beam radiation therapy for treatment of localized prostate cancer at The Mount Sinai Hospital between June 1990 and March 2007 with a minimum follow-up of 2 years were included. Univariate and multivariable analyses were performed on the following variables: risk group, Gleason score (GS), clinical T stage, pretreatment prostate-specific antigen level, post-treatment prostate-specific antigen doubling time (PSA-DT), treatment type (implant vs. implant plus external beam radiation therapy), treatment era, total biological effective dose, use of androgen deprivation therapy, age at diagnosis, and race. PSA-DT was analyzed in the following ordinate groups: 0 to 90 days, 91 to 180 days, 180 to 360 days, and greater than 360 days. Results: We included 1,887 patients in this study. Metastases developed in 47 of these patients. The 10-year freedom from distant metastasis (FFDM) rate for the entire population was 95.1%. Median follow-up was 6 years (range, 2-15 years). The only two significant predictors of metastatic disease by multivariable analyses were GS and PSA-DT (p < 0.001 for both variables). Estimated 10-year FFDM rates for GS of 6 or less, GS of 7, and GS of 8 or greater were 97.9%, 94.3%, and 76.1%, respectively (p < 0.001). Estimated FFDM rates for PSA-DT of 0 to 90 days, 91 to 180 days, 181 to 360 days, and greater than 360 days were 17.5%, 67.9%, 74%, and 94.8%, respectively (p < 0.001). Estimated 10-year FFDM rates for the low-, intermediate-, and high-risk groups were 98.6%, 96.2%, and 86.7%, respectively. A demographic shift to patients presenting with higher-grade disease in more recent years was observed. Conclusions: GS and post-treatment PSA-DT are both statistically significant independent predictors of metastatic

  6. Cetuximab in treatment of metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Guren, Tormod Kyrre; Thomsen, Maria Morandi; Kure, Elin H

    2017-01-01

    BACKGROUND: The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival......, neither on progression-free nor overall survival. However, the outcomes in a subset of patients, which, after the first eight treatment cycles, received cetuximab alone, suggested a beneficial effect of cetuximab monotherapy. CONCLUSIONS: Adding cetuximab to Nordic FLOX did not provide any clinical...

  7. Breast Angiosarcoma Metastatic to the Ovary

    Directory of Open Access Journals (Sweden)

    Frederico F. Souza

    2009-01-01

    Full Text Available Ovarian masses are common findings in general gynecological practice. Approximately 5%–10% of ovarian malignancies are diagnosed as metastatic tumors. Primary angiosarcoma can arise anywhere in the body and when it arises in the breast, it usually affects women in their 3rd and 4th decades and accounts for one in 1700–2300 cases of primary breast cancer. Although unusual, breast angiosarcomas tend to metastasize hematogenously rather than lymphogenously, have high rates of local recurrence, that often develop metastases soon after treatment, and have a dismal prognosis. We present a case of a solitary ovarian metastasis from angiosarcoma of the breast.

  8. Total Thyroidectomy for Thyroid Cancer Followed by Thyroid Storm due to Thyrotropin Receptor Antibody Stimulation of Metastatic Thyroid Tissue

    DEFF Research Database (Denmark)

    Folkestad, Lars; Brandt, Frans; Brix, Thomas

    2017-01-01

    BACKGROUND: Graves disease (GD) is an autoimmune condition characterized by the presence of antibodies against the thyrotropin receptor (TRAB), which stimulate the thyroid gland to produce excess thyroid hormone. Theoretically, TRAB could stimulate highly differentiated thyroid cancer tissue and....../or metastases to produce thyroid hormone. CASE: A 68-year-old male, with weight loss and palpitations, was diagnosed with thyrotoxicosis. A later MRI, due to persistent shoulder pain, revealed multiple bone metastases. A biopsy was diagnostic for follicular variant of papillary thyroid carcinoma, and total...... treatment continued until after the fourth RAI dose. Hypothyroidism did not occur until following the fifth RAI treatment. SUMMARY AND CONCLUSIONS: We present a patient initially diagnosed with thyrotoxicosis and subsequently with metastatic follicular variant of papillary thyroid cancer. It is suggested...

  9. Understanding prostate-specific antigen dynamics in monitoring metastatic castration-resistant prostate cancer: implications for clinical practice

    Directory of Open Access Journals (Sweden)

    Atsushi Mizokami

    2017-01-01

    Full Text Available Availability of novel hormonal therapies as well as docetaxel and cabazitaxel treatment for metastatic castration-resistant prostate cancer (CRPC has changed the outlook for this group of patients with improvements in progression-free survival and overall survival. Physicians often diagnose the progression of prostate cancer using serum prostate-specific antigen (PSA. However, serum PSA is not always correlated with the clinical status in CRPC. To evaluate the PSA dynamics with greater precision, understanding of the control of PSA and of the mechanisms of development of CRPC is needed. Moreover, it is necessary to use new hormonal therapies with an appropriate timing to optimally improve the prognosis and the QOL of the patients. In the present review, we ascertain the PSA dynamics and the mechanisms of the development of CRPC to assist in optimal utilization of the new treatments for mCRPC.

  10. Inverse Relationship Between Leydig Cell Density and Metastatic Potential of Prostatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    W. John Wang

    1999-01-01

    Full Text Available Purpose: Evaluate the relationship between metastatic potential of prostatic adenocarcinoma (PC and testicular Leydig cell density. Materials and methods: Tissue samples from 111 men, age 52–85, with PC and bilateral orchiectomy were evaluated for Leydig cell density. The patients were divided into two groups: Group A were patients with metastasis (n=36 and Group B were patients without metastasis (n=75. Leydig cell density was determined by direct manual microscopic cell count on the tissue sections. The means of cell counts by four pathologists, expressed as cell/0.78 mm2 were used for analysis. The normally distributed data were analyzed by two‐tail Student’s t‐test. Thirty‐eight age‐compatible autopsy cases who died of unrelated causes served as normal controls. Results: The mean of Leydig cell count in group A patients was 14.43 (14.43 ± 1.19 SE. Mean of Group B was 47.05 (47.05 ± 4.05 SE whereas normal controls displayed a mean of 48.66 (48.66 ± 2.94 SE. Group A was significantly different from control (p0.75. Conclusions: Patients with metastatic adenocarcinoma of prostate, as a group, have a significantly lower Leydig cell density than patients without metastasis or patients without PC in compatible age groups. The hormonal relationship between this observation is however unknown. One possible explanation is that PC subpopulation with metastatic potential may require different level of endogenous androgen or are androgen‐independent.

  11. Interleukin-2 based immunotherapy in patients with metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Donskov, Frede

    2007-01-01

    The present thesis consists of 8 published articles focusing on interleukin-2 based immunotherapy in metastatic renal cell carcinoma (mRCC). This disease represents a significant challenge, as the tumor is resistant to current chemotherapy, hormonal therapy and radiation therapy. However, IL-2......, an estimated 5-year survival rate of 16% was observed. From the blood and tumor analysis, an understanding emerged that IL-2 based immunotherapy is a "targeted therapy" requiring intratumoral immune cells (CD4+, CD8+, CD56+, CD57+ T- and NK cells) for treatment effect. In contrast, monocytes and neutrophils...... were harmful for the outcome of IL-2 based immunotherapy. In progressing patients, the leukocyte subsets in blood and tumor tissue remained unaffected by cytokine therapy. The fate of a patient with mRCC prior to IL-2 and IFN-alpha based immunotherapy cannot be determined by measuring baseline tumor...

  12. Complete Response to Bicalutamide Withdrawal Prolonged for Almost 2 Years in Patients With Metastatic Prostate Cancer☆

    Science.gov (United States)

    Hongo, Hiroshi; Kosaka, Takeo; Oya, Mototsugu

    2014-01-01

    This is the first case report describing a complete response to bicalutamide withdrawal that lasted for almost 2 years in a patient with metastatic prostate cancer. An 80-year-old man who had prostate-specific antigen (PSA) level elevation (168.1 ng/mL) visited our hospital in February 2010. Bone scintigraphy showed pelvic metastases. We started hormonal therapy with leuprorelin and bicalutamide. The PSA concentration decreased to <0.1 ng/mL but started increasing again and reached 1.64 ng/mL in October 2012, at which time bicalutamide administration was discontinued. The PSA concentration decreased again and has remained below the limit of sensitivity for almost 2 years. PMID:26958470

  13. Complete Response to Bicalutamide Withdrawal Prolonged for Almost 2 Years in Patients With Metastatic Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Hiroshi Hongo

    2014-09-01

    Full Text Available This is the first case report describing a complete response to bicalutamide withdrawal that lasted for almost 2 years in a patient with metastatic prostate cancer. An 80-year-old man who had prostate-specific antigen (PSA level elevation (168.1 ng/mL visited our hospital in February 2010. Bone scintigraphy showed pelvic metastases. We started hormonal therapy with leuprorelin and bicalutamide. The PSA concentration decreased to <0.1 ng/mL but started increasing again and reached 1.64 ng/mL in October 2012, at which time bicalutamide administration was discontinued. The PSA concentration decreased again and has remained below the limit of sensitivity for almost 2 years.

  14. Non-metastatic squamous cell carcinoma in two Hermann’s tortoises (Testudo hermanni

    Directory of Open Access Journals (Sweden)

    Marie-Charlotte von Deetzen

    2012-02-01

    Full Text Available Squamous cell carcinomas (SCC are malignant tumors of the epidermal cells with varying degrees of keratinocyte differentiation. They are common tumors in mammalian and avian species but there are, however, only two description of SCC in tortoises. In this case report we describe two cases of non-metastatic squamous cell carcinomas of the carapax and the plastron in Hermann’s tortoises with evidence of humoral hypercalcemia of malignancy (HHM in one case. HHM is thought to be associated with SCC in mammals due to de novo secretion of parathyroid hormone-related protein (PTHrP by the tumor cells or tumor induced osteolysis but has not been described in reptiles so far.

  15. Discordance of the estrogen receptor and HER-2/neu in breast cancer from primary lesion to first and second metastatic site.

    Science.gov (United States)

    Lower, Elyse E; Khan, Shagufta; Kennedy, Diane; Baughman, Robert P

    2017-01-01

    Hormone receptor and HER-2/neu discordance between the primary lesion and first metastasis has been reported. This study was performed to determine further biomarker discordance rates between the first and subsequent metastatic breast cancer lesions. We performed a retrospective review of paired biomarkers from primary breast cancers compared to first reported and subsequent metastases from 103 patients with breast cancer. The estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu status were reported at all three time points. In addition, hormone, cytotoxic, and targeted treatments were recorded for primary and metastatic disease, and survival was determined. Between the primary and first metastases, discordance rates for ER, PR, and HER-2/neu were 15.8%, 33.7%, and 14.3%, respectively. There was discordance between the first and second metastases for the ER receptor in 18.8%, PR receptor in 19.8%, and HER-2/neu in 10.7%. Overall, there was discordance between the primary tumor and either the first or second metastases for ER in 27.7%, PR receptor in 40.7%, and HER-2/neu in 19.6% of cases. Discordance of either ER or PR affected survival, with worse survival experienced by those patients with all three hormone receptors remaining negative, and intermediate survival reported for those with discordant tumors (ER χ2=14.27, p=0.0008; PR χ2=11.31, p=0.0035). There was no difference in survival for patients whose HER-2/neu tumors were discordant. This study demonstrated that continued metastatic disease evolution may be associated with different tumor biology and that studies of metastatic lesions appear warranted, especially if targeted therapy is an option.

  16. Matrix rigidity induces osteolytic gene expression of metastatic breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Nazanin S Ruppender

    Full Text Available Nearly 70% of breast cancer patients with advanced disease will develop bone metastases. Once established in bone, tumor cells produce factors that cause changes in normal bone remodeling, such as parathyroid hormone-related protein (PTHrP. While enhanced expression of PTHrP is known to stimulate osteoclasts to resorb bone, the environmental factors driving tumor cells to express PTHrP in the early stages of development of metastatic bone disease are unknown. In this study, we have shown that tumor cells known to metastasize to bone respond to 2D substrates with rigidities comparable to that of the bone microenvironment by increasing expression and production of PTHrP. The cellular response is regulated by Rho-dependent actomyosin contractility mediated by TGF-ß signaling. Inhibition of Rho-associated kinase (ROCK using both pharmacological and genetic approaches decreased PTHrP expression. Furthermore, cells expressing a dominant negative form of the TGF-ß receptor did not respond to substrate rigidity, and inhibition of ROCK decreased PTHrP expression induced by exogenous TGF-ß. These observations suggest a role for the differential rigidity of the mineralized bone microenvironment in early stages of tumor-induced osteolysis, which is especially important in metastatic cancer since many cancers (such as those of the breast and lung preferentially metastasize to bone.

  17. First-line capecitabine monotherapy for slowly progressing metastatic breast cancer: do we need aggressive treatment?

    Science.gov (United States)

    Debled, Marc; Madranges, Nicolas; Trainaud, Alexandra; Floquet, Anne; Donamaria, Catherine; Brouste, Véronique; Durand, Michel; Mauriac, Louis

    2009-01-01

    Primary treatment goals in less aggressive metastatic breast cancer (MBC) are prolonged survival, good quality of life and control of the disease and its symptoms. High activity, oral administration and no alopecia make capecitabine monotherapy attractive in slowly evolving disease. We retrospectively analysed 226 patients who had received single-agent capecitabine as 1st-line chemotherapy at our institution. The median interval between breast cancer diagnosis and MBC was 52 months (range 0-479); 76% had received endocrine therapy for MBC, 58% had visceral involvement and 30% had 3 or more metastatic sites. The median starting dose was 1,000 mg/m(2) twice daily. Disease was improved in 56% of the patients (median duration: 13.2 months) and stabilised in 20%. Median time to treatment failure was 8.8 months (95% CI: 7.1-10.5); median overall survival from initiating capecitabine was 23.6 months (95% CI: 19.7-27.4). Prior adjuvant chemotherapy, endocrine therapy for MBC, visceral disease, hormone receptor status and initial capecitabine dose did not influence time to treatment failure. Among 161 patients <75 years, 90% received further chemotherapy. Based on these findings, 1st-line capecitabine should be considered in slowly progressing disease, offering an active, well-tolerated oral treatment with minimal toxicity and no alopecia. More toxic treatments may be reserved for more aggressive disease. Copyright 2009 S. Karger AG, Basel.

  18. Phase II Trial of Angiotensin-(1-7) for the Treatment of Patients with Metastatic Sarcoma.

    Science.gov (United States)

    Savage, Paul D; Lovato, James; Brosnihan, K Bridget; Miller, Antonius A; Petty, W Jeffrey

    2016-01-01

    Background. Angiotensin-(1-7) [Ang-(1-7)] is an endogenous antiangiogenic hormone with anticancer activity. In a phase I study of Ang-(1-7), two of three patients with metastatic sarcoma experienced disease stabilization. This phase II study examined clinical and biomarker outcomes for patients with metastatic sarcoma. Methods. Ang-(1-7) was administered by subcutaneous injection at a dose of 20 mg daily. If excessive toxicities occurred in the first cohort, a dose deescalation cohort was allowed. Blood samples were obtained to measure changes in biomarkers. Results. Treatment was well-tolerated and the dose deescalation cohort was not required. Plasma PlGF concentrations following treatment were not statistically significantly changed. A significant increase in plasma Ang-(1-7) was observed at 4 hours after injection. The median progression-free survival was 2.7 months (95% CI; 1.4 to 4.1 months), and the median overall survival was 10.2 months (95% CI; 5.3 to 18.3 months). Two patients with vascular sarcomas demonstrated prolonged disease stabilization of 10 months (hemangiopericytoma) and 19 months (epithelioid hemangioendothelioma). Conclusions. Ang-(1-7) at a dose of 20 mg daily was well-tolerated. This prospective phase II study failed to confirm the PlGF biomarker effect identified in the prior phase I study. Prolonged disease stabilization in hemangiopericytoma and epithelioid hemangioendothelioma may warrant further investigation.

  19. Phase II Trial of Angiotensin-(1-7 for the Treatment of Patients with Metastatic Sarcoma

    Directory of Open Access Journals (Sweden)

    Paul D. Savage

    2016-01-01

    Full Text Available Background. Angiotensin-(1-7 [Ang-(1-7] is an endogenous antiangiogenic hormone with anticancer activity. In a phase I study of Ang-(1-7, two of three patients with metastatic sarcoma experienced disease stabilization. This phase II study examined clinical and biomarker outcomes for patients with metastatic sarcoma. Methods. Ang-(1-7 was administered by subcutaneous injection at a dose of 20 mg daily. If excessive toxicities occurred in the first cohort, a dose deescalation cohort was allowed. Blood samples were obtained to measure changes in biomarkers. Results. Treatment was well-tolerated and the dose deescalation cohort was not required. Plasma PlGF concentrations following treatment were not statistically significantly changed. A significant increase in plasma Ang-(1-7 was observed at 4 hours after injection. The median progression-free survival was 2.7 months (95% CI; 1.4 to 4.1 months, and the median overall survival was 10.2 months (95% CI; 5.3 to 18.3 months. Two patients with vascular sarcomas demonstrated prolonged disease stabilization of 10 months (hemangiopericytoma and 19 months (epithelioid hemangioendothelioma. Conclusions. Ang-(1-7 at a dose of 20 mg daily was well-tolerated. This prospective phase II study failed to confirm the PlGF biomarker effect identified in the prior phase I study. Prolonged disease stabilization in hemangiopericytoma and epithelioid hemangioendothelioma may warrant further investigation.

  20. Successful treatment of metastatic Crohn's disease with cyclosporine.

    Science.gov (United States)

    Carranza, Dafnis C; Young, Lorraine

    2008-08-01

    Metastatic Crohn's disease refers to cutaneous granulomatous lesions that are noncontiguous to the gastrointestinal tract. The treatment of cutaneous Crohn's disease is challenging. A patient with metastatic Crohn's disease whose lesions cleared after a 3-month course of cyclosporine is reported.

  1. Prognosis in patients with symptomatic metastatic spinal cord compression

    DEFF Research Database (Denmark)

    Morgen, Søren Schmidt; Lund-Andersen, Casper; Larsen, Claus Falck

    2013-01-01

    A retrospective cohort study of 2321 patients consecutively admitted to one center and diagnosed with acute symptoms of metastatic spinal cord compression (MSCC).......A retrospective cohort study of 2321 patients consecutively admitted to one center and diagnosed with acute symptoms of metastatic spinal cord compression (MSCC)....

  2. Characterizing the outcomes of metastatic papillary renal cell carcinoma

    DEFF Research Database (Denmark)

    Connor Wells, John; Donskov, Frede; Fraccon, Anna P

    2017-01-01

    Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly characterized in the era of targeted therapy. A total of 5474 patients with metastatic renal cell carcinoma (mRCC) in the International mRCC Database Consortium (IMDC) were retrospectively analyzed. Outcomes were com...

  3. CASE REPORT Metastatic melanoma to the small bowel ...

    African Journals Online (AJOL)

    evaluation. Most recently, positron emission tomography - computed tomography (PET/CT) has been used to identify sites of metastatic melanoma. CT sensitivity is between 60 and 70%.2,5. Metastatic lesions may be intraluminal masses, ulcerating lesions (as in our case), diffusely infiltrating lesions or mesenteric implants.

  4. Duodenal Obstruction as First Presentation of Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sami Khairy

    2015-01-01

    Full Text Available The metastatic breast cancer to the duodenum is rare in spite of common breast cancer. In this paper, we are reporting a rare case of 50-year-old lady who presented with intestinal obstruction as result of metastatic breast cancer which completely responds to chemotherapy. The tumor presents again as brain metastasis after stop of Herceptin due to cardiac toxicity.

  5. Organtropic Metastatic Secretomes and Exosomes in Breast Cancer

    Science.gov (United States)

    2016-10-01

    breast cancer cell lines. We also plan to isolate miRNAs from the 4T1 series of mouse mammary tumor cell lines with progressively higher lung metastatic...identified distinct protein profiles (Lyden) of breast cancer cell lines with differential lung metastatic capabilities whose pathological relevance

  6. Hypertrophic osteoarthropathy associated with metastatic melanoma.

    Science.gov (United States)

    Thompson, Michael A; Warner, Noranna B; Hwu, Wen-Jen

    2005-12-01

    Hypertrophic osteoarthropathy (HOA) is one of the paraneoplastic syndromes most commonly associated with non-small-cell lung cancer. Although pulmonary metastasis is the second most common initial site of melanoma metastasis, HOA is rarely detected in patients with metastatic melanoma in the lung. We report a case of a 45-year-old woman with advanced melanoma who developed HOA after her disease had progressed through first-line systemic therapy. The patient's diagnosis of HOA was made on the basis of digital clubbing, arthralgia, pain, joint effusion and periosteal bone formation on X-ray with negative rheumatologic laboratory studies. Only six cases of HOA in metastatic melanoma have been reported previously. This diagnosis should be considered with lung metastases and the presentation of polyarthralgia with appropriate laboratory and imaging findings. Interestingly, the patient responded to bisphosphonates and second-line chemotherapy with carboplatin and paclitaxel, which is commonly used for lung cancer, not advanced melanoma. As with many paraneoplastic syndromes, successful treatment of the underlying disease was associated with a rapid resolution of the symptoms.

  7. Radioisotopes in management of metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Amar Raval

    2016-01-01

    Full Text Available Introduction: Metastatic prostate cancer continues to be a leading cause of morbidity and mortality in men with prostate cancer. Over the last decade, the treatment landscape for patients with castrate-resistant disease has drastically changed, with several novel agents demonstrating an improvement in overall survival in large, multi-institutional randomized trials. Traditional treatment with radioisotopes has largely been in the palliative setting. However, the first in class radiopharmaceutical radium-223 has emerged as the only bone-directed treatment option demonstrating an improvement in overall survival. Methods: Medline publications from 1990 to 2016 were searched and reviewed to assess the use of currently approved radioisotopes in the management of prostate cancer including emerging data regarding integration with novel systemic therapies. New positron emission tomography-based radiotracers for advanced molecular imaging of prostate cancer were also queried. Results: Radioisotopes play a crucial role in the diagnosis and treatment of prostate cancer in the definitive and metastatic setting. Molecular imaging of prostate cancer and theranostics are currently being investigated in the clinical arena. Conclusions: The use of modern radioisotopes in selected patients with mCRPC is associated with improvements in overall survival, pain control, and quality of life.

  8. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    Directory of Open Access Journals (Sweden)

    Yeliz Bilir

    2014-01-01

    Full Text Available Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts, the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  9. Local-regional radiotherapy and surgery is associated with a significant survival advantage in metastatic breast cancer patients.

    Science.gov (United States)

    Ly, Bevan Hong; Vlastos, Georges; Rapiti, Elisabetta; Vinh-Hung, Vincent; Nguyen, Nam Phong

    2010-01-01

    There is growing evidence of a survival benefit for metastatic breast cancer patients receiving surgery of the primary tumor. We investigated whether or not adjuvant radiotherapy can improve survival. Women diagnosed between 1988 and 2003 with metastatic, histologically confirmed unilateral primary breast cancer were selected from the SEER Program. Overall survival and specific survival were computed by the Kaplan-Meier method. Treatment hazard ratios of breast-conserving surgery or mastectomy versus no surgery, and radiotherapy versus none, were computed by Cox regression adjusting for period of diagnosis, age, marital status, race, histology, grade, and hormone receptors. Of 8761 women, radiotherapy was given to 1473 of 3905 who did not undergo surgery, to 882 of 2070 who underwent breast-conserving surgery, and to 1103 of 2786 mastectomy patients. Median overall survival was: for no surgery, 14 months; for breast-conserving surgery, 23 months; and for mastectomy, 28 months (P < 0.0001). The median overall survival of radiotherapy versus none was respectively 16 vs. 13 months without surgery (P = 0.0003), 28 vs. 20 months for breast-conserving surgery patients (P < 0.0001), and 28 vs. 28 months among mastectomy patients (P = 0.895). Multivariate analysis showed relative mortality reductions of 28% by breast-conserving surgery, 42% by mastectomy, and 10% by radiotherapy. Specific survival showed comparable results. Surgery and radiotherapy were associated with a significant survival advantage. We argue that local therapy should be considered even in metastatic disease.

  10. PTEN expression as a predictor for the response to trastuzumab-based therapy in Her-2 overexpressing metastatic breast cancer

    Science.gov (United States)

    Tan, Yen Y.; Fuchs, Eva-Maria; Hudelist, Gernot; Köstler, Wolfgang J.; Reiner, Angelika; Leser, Carmen; Salama, Mohamed; Attems, Johannes; Deutschmann, Christine; Zielinski, Christoph C.; Singer, Christian F.

    2017-01-01

    Background Even though trastuzumab is an effective therapy in early stage Her-2+ breast cancer, 40–50% of advanced Her-2+ breast cancer patients develop trastuzumab resistance. A potential resistance mechanism is aberrant downstream signal transmission due to loss of phosphatase and tensin homologue (PTEN). This study investigated the relationship between the expression of PTEN and trastuzumab response in Her-2 overexpressing metastatic breast cancer patients. Methods Between 2000 and 2007, 164 patients with Her-2+ metastatic breast cancer received trastuzumab-based therapy in our institution. We analyzed PTEN status by immunohistochemistry of 115 available tumor tissues and analyzed associations with other histopathological parameters, response rate, progression free survival (PFS) and overall survival (OS) with a median follow-up of 60 months. Results Eighty patients were PTEN positive (69.6%) and 35 patients PTEN negative (30.4%). We found a significant association of the expression of PTEN and p53 (p = 0.041), while there was no association with grading, hormone receptor status, IGFR or MIB. We found significantly more cases with progressive disease under trastuzumab-based therapy in patients with PTEN positive breast cancers (p = 0.018), while there was no significant correlation with PFS or OS. Conclusion In Her-2-positive metastatic breast cancers, PTEN positivity was significantly associated with progressive disease, but not with PFS or OS. PMID:28253285

  11. PTEN expression as a predictor for the response to trastuzumab-based therapy in Her-2 overexpressing metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    Daphne Gschwantler-Kaulich

    Full Text Available Even though trastuzumab is an effective therapy in early stage Her-2+ breast cancer, 40-50% of advanced Her-2+ breast cancer patients develop trastuzumab resistance. A potential resistance mechanism is aberrant downstream signal transmission due to loss of phosphatase and tensin homologue (PTEN. This study investigated the relationship between the expression of PTEN and trastuzumab response in Her-2 overexpressing metastatic breast cancer patients.Between 2000 and 2007, 164 patients with Her-2+ metastatic breast cancer received trastuzumab-based therapy in our institution. We analyzed PTEN status by immunohistochemistry of 115 available tumor tissues and analyzed associations with other histopathological parameters, response rate, progression free survival (PFS and overall survival (OS with a median follow-up of 60 months.Eighty patients were PTEN positive (69.6% and 35 patients PTEN negative (30.4%. We found a significant association of the expression of PTEN and p53 (p = 0.041, while there was no association with grading, hormone receptor status, IGFR or MIB. We found significantly more cases with progressive disease under trastuzumab-based therapy in patients with PTEN positive breast cancers (p = 0.018, while there was no significant correlation with PFS or OS.In Her-2-positive metastatic breast cancers, PTEN positivity was significantly associated with progressive disease, but not with PFS or OS.

  12. PTEN expression as a predictor for the response to trastuzumab-based therapy in Her-2 overexpressing metastatic breast cancer.

    Science.gov (United States)

    Gschwantler-Kaulich, Daphne; Tan, Yen Y; Fuchs, Eva-Maria; Hudelist, Gernot; Köstler, Wolfgang J; Reiner, Angelika; Leser, Carmen; Salama, Mohamed; Attems, Johannes; Deutschmann, Christine; Zielinski, Christoph C; Singer, Christian F

    2017-01-01

    Even though trastuzumab is an effective therapy in early stage Her-2+ breast cancer, 40-50% of advanced Her-2+ breast cancer patients develop trastuzumab resistance. A potential resistance mechanism is aberrant downstream signal transmission due to loss of phosphatase and tensin homologue (PTEN). This study investigated the relationship between the expression of PTEN and trastuzumab response in Her-2 overexpressing metastatic breast cancer patients. Between 2000 and 2007, 164 patients with Her-2+ metastatic breast cancer received trastuzumab-based therapy in our institution. We analyzed PTEN status by immunohistochemistry of 115 available tumor tissues and analyzed associations with other histopathological parameters, response rate, progression free survival (PFS) and overall survival (OS) with a median follow-up of 60 months. Eighty patients were PTEN positive (69.6%) and 35 patients PTEN negative (30.4%). We found a significant association of the expression of PTEN and p53 (p = 0.041), while there was no association with grading, hormone receptor status, IGFR or MIB. We found significantly more cases with progressive disease under trastuzumab-based therapy in patients with PTEN positive breast cancers (p = 0.018), while there was no significant correlation with PFS or OS. In Her-2-positive metastatic breast cancers, PTEN positivity was significantly associated with progressive disease, but not with PFS or OS.

  13. Radium-223 Therapy for Patients with Metastatic Castrate-Resistant Prostate Cancer: An Update on Literature with Case Presentation

    Science.gov (United States)

    Appleman, Leonard J.; Mountz, James M.

    2016-01-01

    Background and Purpose. Radium-223 dichloride (Xofigo®, Bayer HealthCare Pharmaceuticals Inc.) is the first α-particle emitter therapeutic agent approved by the FDA, with benefits in overall survival and delay in symptomatic skeletal event for patients with metastatic castrate-resistant prostate cancer (CRPC). Recent post hoc analyses of the phase III ALSYMPCA trial support the previously established safety profile as well as therapeutic effect and clinical outcome of Radium-223. Currently, Radium-223 is approved as a single agent therapy for metastatic CRPC. Clinical trials are currently investigating Radium-223 in additional clinical settings such as earlier asymptomatic disease and in combination with other agents including hormonal therapeutic agents and immunotherapeutic as well as chemotherapeutic agents. Trials are also ongoing in patients with other primary cancers such as breast cancer, thyroid cancer, and renal cancer metastatic to bone. In this article, the physics and radiobiology, as well as a literature update on the use of Radium-223, are provided along with case presentations, aiming at a better appreciation of research data as well as the assimilation of research data into clinical practice. PMID:27774318

  14. Growth Hormone and Aging

    Science.gov (United States)

    2000-08-01

    34Retrasos de crecimiento " 2a Ed., Diaz de al 1999), together with an increase in physical Santos. Madrid. pp 365-376 (1996). capacity (Jorgensen et al 1991...A, Marrama P, Agnati LF, Moiller EE. "Retrasos de crecimiento " 2’ Ed., Diaz de Reduced growth hormone releasing factor Santos. Madrid. pp 377-396...P, Skakkeback, Christiansen JS. variantes en (Moreno y Tresguerres dir). Three years of GH treatment in GH deficient "Retrasos de crecimiento " 2a Ed

  15. The use of hormone therapy and its alternatives in women with a history of hormone dependent cancer.

    Science.gov (United States)

    Sekar, Hashviniya; Singhal, Tasneem; Holloway, Debra; Rymer, Janice

    2013-03-01

    Treating the effects of menopause in women with history of oestrogen-dependent cancers presents a clinical dilemma. Endocrine adjuvant agents like tamoxifen and other cancer treatments, often induce premature menopause. Vasomotor, psychological and somatic symptoms may be more severe in these women. The risk of hormone therapy (HT) and its efficacy must be balanced. Currently, there are no consensus guidelines for the management of these patients. This is a retrospective study carried out between 10/01/2011 and 27/01/2012 in a tertiary referral menopausal clinic. Data was collected about cancer type and treatment, symptoms, prior use of T, bone density analyses and menopause treatments. 590 patient records were scanned and 146 patients (24.7%) had a history of cancer. Of these, 45.9% were younger than 50 years old. 67.1% comprised breast cancer patients, of which 69.4% were on adjuvant endocrine agents. 24.7% consisted of gynaecological cancer patients who were predominantly treated with surgery in conjunction with adjuvant therapies. 90.4% of the women had at least one menopause-related symptom, vasomotor symptoms being most prevalent, followed by psychological and vaginal symptoms. Women used a variety of HT and non-HRT therapies for their symptoms. Of the 77 women who had a personal history of oestrogen receptor positive cancers, 19.5% chose to take HT in spite of it being contraindicated. Prescribing HT to women with a history of hormone dependent cancer remains controversial. Patient 'Quality of Life' must be considered. More research is required in this area. 2013 © The Author(s).

  16. Association between lifetime exposure to passive smoking and risk of breast cancer subtypes defined by hormone receptor status among non-smoking Caucasian women.

    Science.gov (United States)

    Strumylaite, Loreta; Kregzdyte, Rima; Poskiene, Lina; Bogusevicius, Algirdas; Pranys, Darius; Norkute, Roberta

    2017-01-01

    Tobacco smoking is inconsistently associated with breast cancer. Although some studies suggest that breast cancer risk is related to passive smoking, little is known about the association with breast cancer by tumor hormone receptor status. We aimed to explore the association between lifetime passive smoking and risk of breast cancer subtypes defined by estrogen receptor and progesterone receptor status among non-smoking Caucasian women. A hospital-based case-control study was performed in 585 cases and 1170 controls aged 28-90 years. Information on lifetime passive smoking and other factors was collected via a self-administered questionnaire. Logistic regression was used for analyses restricted to the 449 cases and 930 controls who had never smoked actively. All statistical tests were two-sided. Adjusted odds ratio of breast cancer was 1.01 (95% confidence interval (CI): 0.72-1.41) in women who experienced exposure to passive smoking at work, 1.88 (95% CI: 1.38-2.55) in women who had exposure at home, and 2.80 (95% CI: 1.84-4.25) in women who were exposed at home and at work, all compared with never exposed regularly. Increased risk was associated with longer exposure: women exposed ≤ 20 years and > 20 years had 1.27 (95% CI: 0.97-1.66) and 2.64 (95% CI: 1.87-3.74) times higher risk of breast cancer compared with never exposed (Ptrend passive smoking with hormone receptor-positive breast cancer did not differ from that with hormone receptor-negative breast cancer (Pheterogeneity > 0.05). There was evidence of interaction between passive smoking intensity and menopausal status in both overall group (P = 0.02) and hormone receptor-positive breast cancer group (P passive smoking is associated with the risk of breast cancer independent of tumor hormone receptor status with the strongest association in postmenopausal women.

  17. Ductal carcinoma In-Situ in turner syndrome patient undergoing hormone replacement therapy: A case report

    Directory of Open Access Journals (Sweden)

    Rashmi Bawa

    2016-03-01

    Full Text Available Turner’s syndrome is a rare congenital disease which affects about 1 in every 2500-3000 live-born females. This happens due to chromosomal abnormalities in a phenotypic female, causing increased gonadotropin concentrations and low concentrations of estrogens from infancy. As a result, hormone replacement therapy is started in most adolescent Turner syndrome patients to initiate and sustain sexual maturation. Accordingly, most Turner’s syndrome patients undergo several decades of estrogen replacement therapy, from puberty to post-menopausal age. The highly publicized findings of the Women’s Health Initiative have called into question the appropriateness of hormone replacement therapy in adolescents with Turner’s syndrome. Those concerns were mostly theoretical extrapolations, as few prospective studies of cancer occurrence in women with Turner syndrome have been reported. Consequently, several recent publications have challenged those extrapolations, based on the assertion that the levels of hormone replacement in Turner syndrome patients are well below the physiologic levels observed in normal menstruating women, as well as the fact that these women are significantly younger than those studied by the Women’s Health Initiative. In discord to those reports, we present a case of ductal carcinoma in-situ in a 40-year-old Turner patient, who had undergone over two decades of combined hormone replacement therapy. The patient underwent an elective excisional biopsy for a palpable mass, with histopathology revealing a complex fibroadenoma with a nidus of ductal carcinoma in-situ. The lesion was noted to be estrogen receptor positive and progesterone receptor negative, with heavy staining for HER-2/Neu receptor. The patient was treated with tamoxifen. While a rare case, it is imperative for the astute clinician to keep in mind the consequences of long-term hormone replacement therapy in Turner’s syndrome patients in order to avoid missed

  18. Medullary Thyroid Carcinoma with Ectopic Adrenocorticotropic Hormone Syndrome

    Directory of Open Access Journals (Sweden)

    Hong Seok Choi

    2014-03-01

    Full Text Available Ectopic adrenocorticotropic hormone (ACTH syndrome is caused most frequently by a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid carcinoma (MTC is a rare etiology of ectopic ACTH syndrome. We describe a case of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy, cervical lymph node dissection and a series of metastasectomies. MTC was confirmed by the pathological examination of the thyroid and metastatic mediastinal lymph node tissues. Two years after his last surgery, he developed Cushingoid features, such as moon face and central obesity, accompanied by uncontrolled hypertension and new-onset diabetes. The laboratory results were compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the clinical and laboratory findings that were associated with Cushing syndrome. This is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea.

  19. Hormonal Regulation of Adipogenesis.

    Science.gov (United States)

    Lee, Mi-Jeong

    2017-09-12

    Adipose tissue includes multiple anatomical depots that serve as an energy reserve that can expand or contract to maintain metabolic homeostasis. During normal growth and in response to overnutrition, adipose tissue expands by increasing the volume of preexisting adipocytes (hypertrophy) and/or by generating new adipocytes (hyperplasia) via recruitment and differentiation of adipose progenitors. This so-called healthy expansion through hyperplasia is thought to be beneficial in that it protects against obesity associated metabolic disorders by allowing for the "safe" storage of excess energy. Remodeling adipose tissue to replace dysfunctional adipocytes that accumulate with obesity and age also requires new fat cell formation and is necessary to maintain metabolic health. Adipogenesis is the process by which adipose progenitors become committed to an adipogenic lineage and differentiate into mature adipocytes. This transition is regulated by complex array of transcriptional factors and numerous autocrine, paracrine, and endocrine signals. We will focus on hormonal factors that regulate adipocyte differentiation and their molecular mechanisms of actions on adipogenesis as studied in vitro and in vivo. Accumulating evidence indicates that adipose progenitors isolated from different adipose tissues exhibit intrinsic differences in adipogenic potential that may contribute to the depot and sex differences in adipose expansion and remodeling capacity. We will put special emphasis on the hormonal factors that are known to depot-dependently affect body fat accumulation and adipocyte development. © 2017 American Physiological Society. Compr Physiol 7:1151-1195, 2017. Copyright © 2017 John Wiley & Sons, Inc.

  20. Specific sites of metastases in invasive lobular carcinoma: a retrospective cohort study of metastatic breast cancer.

    Science.gov (United States)

    Inoue, Masayuki; Nakagomi, Hiroshi; Nakada, Haruka; Furuya, Kazushige; Ikegame, Kou; Watanabe, Hideki; Omata, Masao; Oyama, Toshio

    2017-09-01

    Invasive lobular carcinoma (ILC) is known to be the second most common histological type following invasive ductal carcinoma (IDC). Definitive clinical features of ILC are controversial. We retrospectively analyzed a cohort of 330 patients with metastatic breast cancer, 303 of IDC, 19 of ILC, and 8 of others. We compared the patient age and tumor-node-metastasis factors, disease-free survival (DFS), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression at the primary site between ILC and IDC. We then selected the patients in the ER+ or PR+/HER2- subtype specifically and compared sites of recurrence, and the survival curve starting from the point of development of metastatic disease. The clinical stage was significantly higher in the ILC patients than in the IDC (p = 0.001). The mean (±SD) of DFS for the ILC and IDC patients was 2.6 ± 0.6 and 2.4 ± 0.3 years, respectively, with no significant difference (p = 0.18). However, the hormone receptor status was same between both groups; the rate of HER2 positivity was significantly lower in the ILC group (0%) than in the IDC group (16.2%) (p = 0.05). In ER+ or PR+/HER2- subtype, the mean DFS for the ILC and IDC was 2.9 ± 0.6 and 3.1 ± 0.3 years, and the median survival time after the recurrence for ILC and IDC patients was 4.2 ± 0.7 and 5.6 ± 0.7 years, respectively, with no significant difference (p = 0.77). The frequency of lung metastases was significantly lower in the ILC group (6.3%) than in the IDC group (53.7%) (p note, the prognosis after the diagnosis of peritoneal metastases was poor, with a median survival time of 19 ± 9 months and resistance to hormone therapy. The extremely high rate (68.8%) of peritoneal metastases was observed in long-term follow-up for the metastatic breast cancer patients with ILC. We need to reveal the definitive feature of ILC and develop new therapeutic strategies to prevent the dissemination of ILCs.

  1. Phase II Randomized Preoperative Window-of-Opportunity Study of the PI3K Inhibitor Pictilisib Plus Anastrozole Compared With Anastrozole Alone in Patients With Estrogen Receptor-Positive Breast Cancer.

    Science.gov (United States)

    Schmid, Peter; Pinder, Sarah E; Wheatley, Duncan; Macaskill, Jane; Zammit, Charles; Hu, Jennifer; Price, Robert; Bundred, Nigel; Hadad, Sirwan; Shia, Alice; Sarker, Shah-Jalal; Lim, Louise; Gazinska, Patrycja; Woodman, Natalie; Korbie, Darren; Trau, Matt; Mainwaring, Paul; Gendreau, Steven; Lackner, Mark R; Derynck, Mika; Wilson, Timothy R; Butler, Hannah; Earl, Gemma; Parker, Peter; Purushotham, Arnie; Thompson, Alastair

    2016-06-10

    Preclinical data support a key role for the PI3K pathway in estrogen receptor-positive breast cancer and suggest that combining PI3K inhibitors with endocrine therapy may overcome resistance. This preoperative window study assessed whether adding the PI3K inhibitor pictilisib (GDC-0941) can increase the antitumor effects of anastrozole in primary breast cancer and aimed to identify the most appropriate patient population for combination therapy. In this randomized, open-label phase II trial, postmenopausal women with newly diagnosed operable estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers were recruited. Participants were randomly allocated (2:1, favoring the combination) to 2 weeks of preoperative treatment with anastrozole 1 mg once per day (n = 26) or the combination of anastrozole 1 mg with pictilisib 260 mg once per day (n = 49). The primary end point was inhibition of tumor cell proliferation as measured by change in Ki-67 protein expression between tumor samples taken before and at the end of treatment. There was significantly greater geometric mean Ki-67 suppression of 83.8% (one-sided 95% CI, ≥ 79.0%) for the combination and 66.0% (95% CI, ≤ 75.4%) for anastrozole (geometric mean ratio [combination:anastrozole], 0.48; 95% CI, ≤ 0.72; P = .004). PIK3CA mutations were not predictive of response to pictilisib, but there was significant interaction between response to treatment and molecular subtype (P = .03); for patients with luminal B tumors, the combination:anastrozole geometric mean ratio of Ki-67 suppression was 0.37 (95% CI, ≤ 0.67; P = .008), whereas no significant Ki-67 response was observed for pictilisib in luminal A tumors (1.01; P = .98). Multivariable analysis confirmed Ki-67 response to the combination treatment of patients with luminal B tumors irrespective of progesterone receptor status or baseline Ki-67 expression. Adding pictilisib to anastrozole significantly increases suppression

  2. Metastatic renal cell carcinoma to the thyroid gland.

    Science.gov (United States)

    Duggal, Neal Murari; Horattas, Mark C

    2008-11-01

    To examine the presentation, diagnosis, and appropriate management of renal clear cell carcinoma metastasis to the thyroid gland. We describe a clinical case of solitary thyroid metastasis from renal clear cell carcinoma and present a comprehensive review of the related English-language literature. Common patterns of presentation and generalized overall management recommendations are evaluated and summarized. Eight years after nephrectomy for renal carcinoma at age 61 years, a man presented with a thyroid mass. Cytology and histopathologic surgical findings were consistent with a solitary metastasis most compatible with metastatic clear cell carcinoma from his previous renal carcinoma. After left thyroid lobectomy and isthmusectomy, the patient remains disease-free 5 years later. Although uncommon, nearly 150 cases of clinically recognized metastatic renal cell carcinoma to the thyroid have been reported in the English-language literature. Metastatic disease from the kidney to the thyroid gland can occur more than 20 years after nephrectomy with the average time interval being 7.5 years. Obtaining a full clinical history in any patient who presents with a thyroid nodule is essential to allow consideration of possible metastatic disease from previous primary tumor. Metastatic disease to the thyroid gland can be correctly diagnosed preoperatively. If metastatic renal cancer is limited to the thyroid gland only, prompt, appropriate surgical intervention can be curative. Metastatic renal carcinoma to the thyroid should be considered in any patient presenting with a thyroid mass and a medical history of renal cell carcinoma.

  3. Combination of rapamycin, CI-1040, and 17-AAG inhibits metastatic capacity of prostate cancer via Slug inhibition.

    Directory of Open Access Journals (Sweden)

    Guanxiong Ding

    Full Text Available Though prostate cancer (PCa has slow progression, the hormone refractory (HRCP and metastatic entities are substantially lethal and lack effective treatments. Transcription factor Slug is critical in regulating metastases of various tumors including PCa. Here we studied targeted therapy against Slug using combination of 3 drugs targeting 3 pathways respectively converging via Slug and further regulating PCa metastasis. Using in vitro assays we confirmed that Slug up-regulation incurred inhibition of E-cadherin that was anti-metastatic, and inhibited Bim-regulated cell apoptosis in PCa. Upstream PTEN/Akt, mTOR, Erk, and AR/Hsp90 pathways were responsible for Slug up-regulation and each of these could be targeted by rapamycin, CI-1040, and 17-AAG respectively. In 4 PCa cell lines with different traits in terms of PTEN loss and androgen sensitivity we tested the efficacy of mono- and combined therapy with the drugs. We found that metastatic capacity of the cells was maximally inhibited only when all 3 drugs were combined, due to the crosstalk between the pathways. 17-AAG decreases Slug expression via blockade of HSP90-dependent AR stability. Combination of rapamycin and CI-1040 diminishes invasiveness more potently in PCa cells that are androgen insensitive and with PTEN loss. Slug inhibited Bim-mediated apoptosis that could be rescued by mTOR/Erk/HSP90 inhibitors. Using mouse models for circulating PCa DNA quantification, we found that combination of mTOR/Erk/HSP90 inhibitors reduced circulating PCa cells in vivo significantly more potently than combination of 2 or monotherapy. Conclusively, combination of mTOR/Erk/Hsp90 inhibits metastatic capacity of prostate cancer via Slug inhibition.

  4. Metastatic Medulloblastoma in Childhood: Chang's Classification Revisited

    Directory of Open Access Journals (Sweden)

    Christelle Dufour

    2012-01-01

    Patients and Methods. This population-based study concerned 117 newly diagnosed children with disseminated medulloblastoma treated at the Institute Gustave Roussy between 1988 and 2008. Metastatic disease was assessed using the Chang staging system, their form (positive cerebrospinal fluid (CSF, nodular or laminar, and their extension (positive cerebrospinal fluid, local, extensive. All patients received preirradiation chemotherapy. Results. The overall survival did not differ according to Chang M-stage. The 5-year overall survival was 59% in patients with nodular metastases compared to 35% in those with laminar metastases. The 5-year overall survival was 76% in patients without disease at the end of pre-irradiation chemotherapy compared to 34% in those without a complete response (P=0.0008. Conclusions. Radiological characteristics of metastases correlated with survival in patients with medulloblastoma. Complete response to sandwich chemotherapy was a strong predictor of survival.

  5. [Benign intraperitoneal metastatic leiomyomatosis: A case report].

    Science.gov (United States)

    García, Paz; Errázuriz, Juan Ignacio; Fernández, Carlos; Arteaga, Eugenio

    2017-02-01

    Benign intraperitoneal metastatic leiomyomatosis is a rare benign disease that is observed when a leiomyoma is present in the peritoneal surface. Women who have undergone hysterectomy for leiomyomas are most commonly affected. Patients are usually asymptomatic at presentation, being frequently an incidental finding in imaging studies. Ultrasound and CT play an important role in the diagnosis. The lesions are histologically identical to their uterine counterparts. There are different theories about the pathogenesis of the disease, including peritoneal seeding after laparoscopic hysterectomy. Others support the hypothesis of multiple independent foci of smooth muscle proliferation. Treatment, as in uterine leiomyomatosis, is generally conservative. We report a 53-year-old hysterectomized woman with intraperitoneal leiomyomas detected in a routine physical examination as mobile abdominal masses who underwent successful laparoscopic resection.

  6. Markers of metastatic carcinoma of breast origin.

    Science.gov (United States)

    Gown, Allen M; Fulton, Regan S; Kandalaft, Patricia L

    2016-01-01

    This review summarizes the three major breast-associated markers that can be of assistance in evaluating metastatic carcinomas for which a breast primary diagnosis is entertained. These markers include gross cystic disease fluid protein-15 (GCDFP-15), mammaglobin, and GATA3. The first two are cytoplasmic markers that show comparable sensitivities for breast cancer, although relatively few of the published studies have employed the same antibodies against the target molecule, making direct comparisons challenging. GATA3 is a nuclear transcription factor that shows superior sensitivity to GCDFP-15 and mammaglobin. However, the specificity of GATA3 can pose challenges, inasmuch as carcinomas of the bladder and other sites can show significant levels of positivity. Determination of the optimal panel of antibodies employed in a given clinical setting will thus depend on the non-breast tumours included in the differential diagnosis. © 2015 John Wiley & Sons Ltd.

  7. Metastatic mammary carcinoma in a cow

    Directory of Open Access Journals (Sweden)

    Manoela Marchezan Piva

    Full Text Available ABSTRACT: Mammary gland neoplasms in cattle are rarely observed in the field veterinary diagnostics routine. Therefore, the objective of this study is to report a metastatic mammary carcinoma in a fourteen-year-old Holstein cow in the state of Santa Catarina, Brazil. The animal was diagnosed by the field veterinarian with clinical mastitis that was unresponsive to treatment, and was euthanized due to the poor prognosis. At the necropsy, multiple yellow, firm, and sometimes friable nodules, ranging from 0.1 to 20cm were observed in all mammary glands, lymph nodes, kidneys, spleen, liver, pancreas, mediastinal lymph nodes, heart, and lungs. The final diagnosis of mammary carcinoma was established through the association of clinical, necropsy, histopathological, and immunohistochemical findings. Differential diagnoses included diseases such as bovine tuberculosis and chronic fungal or bacterial mastitis.

  8. Unusual presentation of metastatic gall bladder cancer

    Directory of Open Access Journals (Sweden)

    Piyush Shukla

    2014-01-01

    Full Text Available To report the first case of rare isolated breast metastasis from carcinoma gall bladder. Single patient case report. A 35-year-old pre-menopausal female presented with 2 FNx01 2 cm right upper outer quadrant breast lump. Post-mastectomy, histology confirmed it to be metastatic adenocarcinoma positive for both Cytokeratin (CK 7 and CK20. Past history as told by the patient revealed that 2 years back, cholecystectomy was performed for gall stones, of which no histology reports were present; she had a port site scar recurrence which showed it to be adenocarcinoma. Adjuvant chemotherapy and radiotherapy was advised which the patient did not complete. This is probably the first case reported of isolated breast metastasis from gall bladder carcinoma, diagnosed retrospectively. It also highlights the importance of adjuvant treatment in gall bladder malignancy.

  9. Metastatic malignant subungal melanoma: Importance of FNAC

    Directory of Open Access Journals (Sweden)

    Radhika Punshi Nandwani

    2014-01-01

    Full Text Available Subungual melanoma is a rare type of skin cancer. It is an uncommon form of acral lentiginous melanoma. Approximately 85% of cases are misdiagnosed initially, and it is generally associated with a poor prognosis. Herein, we describe a case of metastatic subungal melanoma to the axillary lymph node in a 45-year-old male. Diagnosis of metastasis was made based on cytology, where the clinicians were guided to search for primary. This case report highlights the role of fine-needle aspiration cytology (FNAC in the diagnosis of this entity to draw the attention of the reader to the possible underreporting of melanoma because of a variant that evades diagnosis and our reluctance to think about its existence.

  10. Molecularly targeted drugs for metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Cheng YD

    2013-11-01

    Full Text Available Ying-dong Cheng, Hua Yang, Guo-qing Chen, Zhi-cao Zhang Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China Abstract: The survival rate of patients with metastatic colorectal cancer (mCRC has significantly improved with applications of molecularly targeted drugs, such as bevacizumab, and led to a substantial improvement in the overall survival rate. These drugs are capable of specifically targeting the inherent abnormal pathways in cancer cells, which are potentially less toxic than traditional nonselective chemotherapeutics. In this review, the recent clinical information about molecularly targeted therapy for mCRC is summarized, with specific focus on several of the US Food and Drug Administration-approved molecularly targeted drugs for the treatment of mCRC in the clinic. Progression-free and overall survival in patients with mCRC was improved greatly by the addition of bevacizumab and/or cetuximab to standard chemotherapy, in either first- or second-line treatment. Aflibercept has been used in combination with folinic acid (leucovorin–fluorouracil–irinotecan (FOLFIRI chemotherapy in mCRC patients and among patients with mCRC with wild-type KRAS, the outcomes were significantly improved by panitumumab in combination with folinic acid (leucovorin–fluorouracil–oxaliplatin (FOLFOX or FOLFIRI. Because of the new preliminary studies, it has been recommended that regorafenib be used with FOLFOX or FOLFIRI as first- or second-line treatment of mCRC chemotherapy. In summary, an era of new opportunities has been opened for treatment of mCRC and/or other malignancies, resulting from the discovery of new selective targeting drugs. Keywords: metastatic colorectal cancer (mCRC, antiangiogenic drug, bevacizumab, aflibercept, regorafenib, cetuximab, panitumumab, clinical trial, molecularly targeted therapy

  11. Transcriptome analysis of the hormone-sensing cells in mammary epithelial reveals dynamic changes in early pregnancy.

    Science.gov (United States)

    De Silva, Duvini; Kunasegaran, Kamini; Ghosh, Sujoy; Pietersen, Alexandra M

    2015-01-27

    Alveoli, the milk-producing units of the mammary gland, are generated during pregnancy by collaboration of different epithelial cell types. We present the first analysis of transcriptional changes within the hormone sensing population during pregnancy. Hormone-receptor positive (HR+) cells play a key role in the initiation of alveologenesis as they sense systemic hormonal changes and translate these into local instructions for neighboring HR- cells. We recently showed that IGF2 is produced specifically by HR+ cells in early pregnancy, but is undetectable in the virgin state. Here, we define the transcriptome of HR+ cells in early pregnancy with the aim to elucidate additional changes that are unique for this dynamic developmental time window. We harvested mammary glands from virgin, 3-day and 7-day pregnant mice and isolated a few hundred hormone-sensing cells per animal by FACS for microarray analysis. There was a high concordance between animals with a clear induction of cell cycle progression genes at day 3 of pregnancy and molecules involved in paracrine signalling at day 7. These findings underscore the proliferative capacity of HR+ cells upon specific stimuli and elucidate developmentally-restricted changes in cellular communication. Since the majority of breast cancers are HR+, with a variable proportion of HR+ cells per tumor, we anticipate that this data set will aid further studies into the regulation of HR+ cell proliferation and the role of heterotypic signalling within tumors.

  12. Self-renewal of CD133(hi) cells by IL6/Notch3 signalling regulates endocrine resistance in metastatic breast cancer.

    Science.gov (United States)

    Sansone, Pasquale; Ceccarelli, Claudio; Berishaj, Marjan; Chang, Qing; Rajasekhar, Vinagolu K; Perna, Fabiana; Bowman, Robert L; Vidone, Michele; Daly, Laura; Nnoli, Jennifer; Santini, Donatella; Taffurelli, Mario; Shih, Natalie N C; Feldman, Michael; Mao, Jun J; Colameco, Christopher; Chen, Jinbo; DeMichele, Angela; Fabbri, Nicola; Healey, John H; Cricca, Monica; Gasparre, Giuseppe; Lyden, David; Bonafé, Massimiliano; Bromberg, Jacqueline

    2016-02-09

    The mechanisms of metastatic progression from hormonal therapy (HT) are largely unknown in luminal breast cancer. Here we demonstrate the enrichment of CD133(hi)/ER(lo) cancer cells in clinical specimens following neoadjuvant endocrine therapy and in HT refractory metastatic disease. We develop experimental models of metastatic luminal breast cancer and demonstrate that HT can promote the generation of HT-resistant, self-renewing CD133(hi)/ER(lo)/IL6(hi) cancer stem cells (CSCs). HT initially abrogates oxidative phosphorylation (OXPHOS) generating self-renewal-deficient cancer cells, CD133(hi)/ER(lo)/OXPHOS(lo). These cells exit metabolic dormancy via an IL6-driven feed-forward ER(lo)-IL6(hi)-Notch(hi) loop, activating OXPHOS, in the absence of ER activity. The inhibition of IL6R/IL6-Notch pathways switches the self-renewal of CD133(hi) CSCs, from an IL6/Notch-dependent one to an ER-dependent one, through the re-expression of ER. Thus, HT induces an OXPHOS metabolic editing of luminal breast cancers, paradoxically establishing HT-driven self-renewal of dormant CD133(hi)/ER(lo) cells mediating metastatic progression, which is sensitive to dual targeted therapy.

  13. Reproductive hormones as psychotropic agents?

    African Journals Online (AJOL)

    QuickSilver

    need to understand the role of reproductive hormones in psy- chiatric disorders. There is much research on the interaction between mood and endocrine factors that is impacting on the practice of women's health. Hormone fluctuations are linked to behavioural changes as well as the onset and recurrence of mood disorders.

  14. Hormonal contraception, thrombosis and age

    DEFF Research Database (Denmark)

    Lidegaard, Øjvind

    2014-01-01

    INTRODUCTION: This paper reviews the risk of thrombosis with use of different types of hormonal contraception in women of different ages. AREAS COVERED: Combined hormonal contraceptives with desogestrel, gestodene, drospirenone or cyproterone acetate (high-risk products) confer a sixfold increased...

  15. Hormones and β-Agonists

    NARCIS (Netherlands)

    Ginkel, van L.A.; Bovee, T.F.H.; Blokland, M.H.; Sterk, S.S.; Smits, N.G.E.; Pleadin, Jelka; Vulić, Ana

    2016-01-01

    This chapter provides some updated information on contemporary methods for hormone and β-agonist analyses. It deals with the classical approaches for the effective detection and identification of exogenous hormones. The chapter examines specific problems related to control strategies for natural

  16. Sex hormones and cardiometabolic risk

    NARCIS (Netherlands)

    Brand, J.S.M.

    2012-01-01

    In this thesis, we set out to investigate the complex relationship between endogenous sex hormones and cardiometabolic risk in men and women. The first part of this thesis is devoted to studies in women, and the second part describes the association between sex hormones and cardiometabolic risk in

  17. Metastatic Renal Cell Carcinoma to Jejunum: An Unusual Case Presentation

    Directory of Open Access Journals (Sweden)

    Igor Medic

    2017-07-01

    Full Text Available The small intestine is a very uncommon and peculiar site for metastasis from renal cell carcinoma (RCC. We present a clinical presentation of insidious and unusual development of a jejunal metastasis while having stable disease in a remainder of metastatic sites, in a patient undergoing immunotherapy with nivolumab. Due to the extreme rarity of metastatic renal cell carcinoma to the lumen of the small bowel, it is easy to overlook and misdiagnose symptoms of this pathologic entity, particularly when the remainder of metastatic disease responds well to ongoing therapy.

  18. Oxytocin - The Sweet Hormone?

    Science.gov (United States)

    Leng, Gareth; Sabatier, Nancy

    2017-05-01

    Mammalian neurons that produce oxytocin and vasopressin apparently evolved from an ancient cell type with both sensory and neurosecretory properties that probably linked reproductive functions to energy status and feeding behavior. Oxytocin in modern mammals is an autocrine/paracrine regulator of cell function, a systemic hormone, a neuromodulator released from axon terminals within the brain, and a 'neurohormone' that acts at receptors distant from its site of release. In the periphery oxytocin is involved in electrolyte homeostasis, gastric motility, glucose homeostasis, adipogenesis, and osteogenesis, and within the brain it is involved in food reward, food choice, and satiety. Oxytocin preferentially suppresses intake of sweet-tasting carbohydrates while improving glucose tolerance and supporting bone remodeling, making it an enticing translational target. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. [Hormonal treatment of transsexual persons].

    Science.gov (United States)

    Tinkanen, Helena; Das, Pia

    2015-01-01

    The primary investigations and starting the hormonal treatment of transsexual persons takes place in Helsinki and Tampere University hospitals as part of the real life period. The hormones used are estrogen and anti-androgen for MtoF and testosterone for FtoM persons. The medication suppresses the endogenous sex-hormone production and brings about the desired features of the other sex. While the recommended doses result in physiological hormone levels, higher doses do not hasten or increase the desired changes and are a health risk. After the transition period, the follow up is referred to the person's home district. The physical and psychological status and laboratory values are evaluated at the yearly follow-up doctor visits. Although the hormone doses are lowered and percutaneous administration route is favored upon aging, stopping the medication is not recommended.

  20. Factors associated with prolonged time to treatment failure with fulvestrant 500 mg in patients with postmenopausal estrogen receptor-positive advanced breast cancer: a subgroup analysis of the JBCRG-C06 Safari study.

    Science.gov (United States)

    Kawaguchi, Hidetoshi; Masuda, Norikazu; Nakayama, Takahiro; Aogi, Kenjiro; Anan, Keisei; Ito, Yoshinori; Ohtani, Shoichiro; Sato, Nobuaki; Saji, Shigehira; Takano, Toshimi; Tokunaga, Eriko; Nakamura, Seigo; Hasegawa, Yoshie; Hattori, Masaya; Fujisawa, Tomomi; Morita, Satoshi; Yamaguchi, Miki; Yamashita, Hiroko; Yamashita, Toshinari; Yamamoto, Yutaka; Yotsumoto, Daisuke; Toi, Masakazu; Ohno, Shinji

    2017-11-02

    The JBCRG-C06 Safari study showed that earlier fulvestrant 500 mg (F500) use, a longer time from diagnosis to F500 use, and no prior palliative chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with estrogen receptor-positive (ER+) advanced breast cancer (ABC). The objective of this subgroup analysis was to further examine data from the Safari study, focusing on ER+ and human epidermal growth factor receptor-negative (HER2-) cases. The Safari study (UMIN000015168) was a retrospective, multicenter cohort study, conducted in 1072 patients in Japan taking F500 for ER+ ABC. The subanalysis included only patients administered F500 as second-line or later therapy (n = 960). Of these, 828 patients were HER2-. Multivariate analysis showed that advanced age (≥65 years; p = 0.035), longer time (≥3 years) from AMBC ABC diagnosis to F500 use (p < 0.001), no prior chemotherapy (p < 0.001), and F500 treatment line (p < 0.001) were correlated with prolonged TTF (median 5.39 months). In ER+/HER2- patients receiving F500 as a second-line or later therapy, treatment line, advanced age, no prior palliative chemotherapy use, and a longer period from ABC diagnosis to F500 use were associated with longer TTF.

  1. Headaches and Hormones: What's the Connection?

    Science.gov (United States)

    ... make headaches worse. Though fluctuating hormone levels can influence headache patterns, you're not completely at the mercy of your hormones. Your doctor can help you treat — or prevent — hormone-related ...

  2. Growth hormone stimulation test - series (image)

    Science.gov (United States)

    The growth hormone (GH) is a protein hormone released from the anterior pituitary gland under the control of the hypothalamus. ... performed on infants and children to identify human growth hormone (hGH) deficiency as a cause of growth retardation. ...

  3. Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice

    Science.gov (United States)

    Peroni, Cibele N.; Hayashida, Cesar Y.; Nascimento, Nancy; Longuini, Viviane C.; Toledo, Rodrigo A.; Bartolini, Paolo; Bowers, Cyril Y.; Toledo, Sergio P.A.

    2012-01-01

    OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormone-releasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/lit mice, which represent a model of GH deficiency arising from mutated growth hormone-releasing hormone-receptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice. RESULTS: After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (pgrowth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions. CONCLUSIONS: Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a. PMID:22473409

  4. Gastrointestinal hormone research - with a Scandinavian annotation

    DEFF Research Database (Denmark)

    Rehfeld, Jens F

    2015-01-01

    Gastrointestinal hormones are peptides released from neuroendocrine cells in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gut, which makes it the largest hormone-producing organ in the body. Modern biology makes it feasible to conceive the hormones un......, but also constitute regulatory systems operating in the whole organism. This overview of gut hormone biology is supplemented with an annotation on some Scandinavian contributions to gastrointestinal hormone research....

  5. HORMONE THERAPY IN ADVANCED ER+/HER2- NEGATIVE BREAST CANCER WITH PI3K INHIBITORS: A REVIEW OF THE LITERATURE

    Directory of Open Access Journals (Sweden)

    Ivan Inkov

    2016-08-01

    Full Text Available Breast cancer is a heterogenous disease, showing as several different clinical and histologic types. Most of breast cancers express hormone receptors for estrogen and progesterone, which are considered as estrogen receptor-positive and progesterone-receptor-positive, respectively. Endocrine therapy was the first class of target-directed therapy approved for treating breast cancer and is still very important for the treatment of HR+ breast cancer because of its effectiveness and good toxicity profile. It targets receptor-mediated signaling pathways implicated in cell survival and proliferation, such as those mediated by hormone receptors. Although these approaches have improved the management of advanced breast cancer, many patients either fail to respond to initial therapy (primary or de novo resistance or eventually become resistant to treatment (secondary or acquired resistance. To expand the use of existing endocrine treatments and their efficiency, new methods are needed. Such new approaches would boost the benefit of existing endocrine therapy by extending time to disease progression, avoiding or overcoming resistance to endocrine treatment, and delaying the use of chemotherapy. This article will review the central role of the PI3K inhibitors in driving ER+/HER2- breast tumors. Also, schemes to combine pathway inhibitors with endocrine therapy for better patient outcome, and approaches to identify patient populations that would benefit most from inhibition of the PI3K/AKT/mTOR pathway will be assessed.

  6. Estrogen-biosynthesis gene CYP17 and its interactions with reproductive, hormonal and lifestyle factors in breast cancer risk: results from the Long Island Breast Cancer Study Project.

    Science.gov (United States)

    Chen, Yu; Gammon, Marilie D; Teitelbaum, Susan L; Britton, Julie A; Terry, Mary Beth; Shantakumar, Sumitra; Eng, Sybil M; Wang, Qiao; Gurvich, Irina; Neugut, Alfred I; Santella, Regina M; Ahsan, Habibul

    2008-04-01

    The genes that are involved in estrogen biosynthesis, cellular binding and metabolism may contribute to breast cancer susceptibility. We examined the effect of the CYP17 promoter T --> C polymorphism and its interactions with the reproductive history, exogenous hormone use and selected lifestyle risk factors on breast cancer risk among 1037 population-based incident cases and 1096 population-based controls in the Long Island Breast Cancer Study Project. Overall, there were no associations between the CYP17 genotype and breast cancer risk. Among postmenopausal women, the joint exposure to higher body mass index (BMI) and the variant C allele was associated with an increased risk of breast cancer [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.15-2.22]. The joint exposure to the variant C allele and long-term use of hormone replacement therapy (HRT) (>51 months) was related to an increased risk of breast cancer (OR, 1.51; 95% CI, 0.99-2.31) especially estrogen receptor-positive, progesterone receptor-positive breast cancer (OR, 1.87; 95% CI, 1.08-3.25). Among the control population, the CYP17 variant C allele was inversely associated with long-term use of postmenopausal HRT and a higher BMI in postmenopausal women. In conclusion, the findings suggest that the CYP17 variant C allele may increase breast cancer risk in conjunction with long-term HRT use and high BMI in postmenopausal women.

  7. Cytoreductive surgery for men with metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Nikolas Katelaris

    2016-09-01

    Conclusions: This data supports recent findings demonstrating that radical prostatectomy for metastatic prostate cancer is feasible. Further studies are needed to explore the role of cytoreductive surgery with regards to the potential oncological benefit.

  8. Metastatic leiomyosarcoma presenting as bilateral, multifocal breast masses

    Science.gov (United States)

    Vasan, Neil; Saglam, Ozlen; Killelea, Brigid K

    2012-01-01

    Here we describe a case of metastatic leiomyosarcoma presenting as bilateral, multifocal breast masses. This case represents the convergence of three rare entities: leiomyosarcoma of unknown primary origin, metastases to the breast and bilateral, multicentric breast disease. PMID:23220834

  9. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer

    NARCIS (Netherlands)

    Tol, J.; Koopman, M.; Cats, A.; Rodenburg, C.J.; Creemers, G.J.M.; Schrama, J.G.; Erdkamp, F.L.G.; Vos, A.H.; van Groeningen, C.J.; Sinnige, H.A.M.; Richel, D.J.; Voest, E.E.; Dijkstra, J.R.; Vink-Börger, M.E.; Antonini, N.F.; Mol, L.; van Krieken, J.H.J.M.; Dalesio, O.; Punt, C.J.A.

    2009-01-01

    Background: Fluoropyrimidine- based chemotherapy plus the anti - vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first- line treatment for metastatic colorectal cancer. We studied the effect of adding the anti - epidermal growth factor receptor (EGFR) antibody cetuximab to

  10. Metastatic choriocarcinoma in the small bowel: a case report

    Directory of Open Access Journals (Sweden)

    Zohreh Yousefi

    2014-08-01

    Conclusion: In abnormal postpartum hemorrhage, we should consider the possibility of choriocarcinoma. Although, it is important to note rare manifestations of metastatic choriocarcinoma of small bowel in massive gastrointestinal hemorrhage.

  11. Pazopanib Hydrochloride in Treating Patients With Metastatic Kidney Cancer

    Science.gov (United States)

    2017-09-07

    Carcinoma of the Collecting Ducts of Bellini; Chromophobe Renal Cell Carcinoma; Kidney Medullary Carcinoma; Kidney Oncocytoma; Metastatic Renal Cell Cancer; Papillary Renal Cell Carcinoma; Recurrent Renal Cell Carcinoma; Sarcomatoid Renal Cell Carcinoma; Stage IV Renal Cell Cancer

  12. General Information about Metastatic Squamous Neck Cancer with Occult Primary

    Science.gov (United States)

    ... lymph nodes in the neck or around the collarbone , it is called metastatic squamous neck cancer. The ... of the neck between the jawbone and the collarbone , including the following: All lymph nodes . The jugular ...

  13. Epidermotropic metastatic melanoma with perilesional depigmentation in an Indian male

    Directory of Open Access Journals (Sweden)

    Bhavana Doshi

    2013-01-01

    Full Text Available Melanoma is a rare form of cutaneous malignancy encountered in the dark skin population. Epidermotropic metastatic melanoma is a rare form of cutaneous metastatic melanoma which can mimic primary melanoma on histopathology. Hence its differentiation is of immense prognostic importance. The occurrence of rim of depigmentation around the primary cutaneous melanoma has previously been reported to portend a bad prognosis. The occurrence of vitiligo like lesions in patients with metastatic melanoma in comparison has a better prognosis. However the occurrence of depigmentation around the secondaries is rare and its importance is not well known. Hence we wish to report a case of epidermotropic metastatic melanoma with perilesional depigmentation in a 78 year old Indian male.

  14. Sexual function in patients with metastatic midgut carcinoid tumours

    NARCIS (Netherlands)

    van der Horst-Schrivers, Anouk N. A.; van Ieperen, Ellen; Wymenga, A. N. Machteld; Boezen, H. Marike; Weijmar-Schultz, Willibrord C. M.; Kema, Ido P.; Meijer, Wim G.; de Herder, Wouter W.; Willemse, Pax H. B.; Links, Thera P.; de Vries, Elisabeth G. E.

    2009-01-01

    Background: Sexual dysfunction is a poorly studied aspect of quality of life in patients with midgut carcinoid tumours. We investigated whether carcinoid patients experience sexual problems. Methods: Patients with metastatic midgut carcinoid tumours filled in a validated questionnaire for sexual

  15. Chromosomal instability predicts metastatic disease in patients with insulinomas

    NARCIS (Netherlands)

    Jonkers, YMH; Claessen, SMH; Perren, A; Schmid, S; Komminoth, P; Verhofstad, AA; Hofland, LJ; de Krijger, RR; Slootweg, PJ; Ramaekers, FCS; Speel, EJM

    Endocrine pancreatic tumors (EPTs) comprise a highly heterogeneous group of tumors with different clinical behavior and genetic makeup. Insulinomas represent the predominant syndromic subtype of EPTs. The metastatic potential of insulinomas can frequently not be predicted using histopathological

  16. Pseudocirrhosis: A Case Series and Literature Review

    Directory of Open Access Journals (Sweden)

    Abimbola Adike

    2016-07-01

    Full Text Available Pseudocirrhosis describes morphological changes of the liver that closely mimic cirrhosis, without the typical histopathological changes seen in cirrhosis. It most commonly occurs in patients with metastatic breast cancer, although it has been reported in other malignancies as well. Like in cirrhosis, portal hypertension is often seen in patients with pseudocirrhosis. Pseudocirrhosis is a rare but important complication of metastatic cancer. In this case series and literature review, we describe 6 patients with hormone-receptor-positive metastatic breast cancer. We report the significant morbidity associated with pseudocirrhosis in the course of treatment in patients with metastatic breast cancer.

  17. Palbociclib as a first-line treatment in oestrogen receptor-positive, HER2-negative, advanced breast cancer not cost-effective with current pricing: a health economic analysis of the Swiss Group for Clinical Cancer Research (SAKK).

    Science.gov (United States)

    Matter-Walstra, K; Ruhstaller, T; Klingbiel, D; Schwenkglenks, M; Dedes, K J

    2016-07-01

    Endocrine therapy continues to be the optimal systemic treatment for metastatic ER(+)HER2(-) breast cancer. The CDK4/6 inhibitor palbociclib combined with letrozole has recently been shown to significantly improve progression-free survival. Here we examined the cost-effectiveness of this regimen for the Swiss healthcare system. A Markov cohort simulation based on the PALOMA-1 trial (Finn et al. in Lancet Oncol 16:25-35, 2015) was used as the clinical course. Input parameters were based on summary trial data. Costs were assessed from the Swiss healthcare system perspective. Adding palbociclib to letrozole (PALLET) compared to letrozole monotherapy was estimated to cost an additional CHF342,440 and gain 1.14 quality-adjusted life years, resulting in an incremental cost-effectiveness ratio (ICER) of CHF301,227/QALY gained. In univariate sensitivity analyses, no tested variation in key parameters resulted in an ICER below a willingness-to-pay threshold of CHF100,000/QALY. PALLET had a 0 % probability of being cost-effective in probabilistic sensitivity analyses. Lowering PALLET's price by 75 % resulted in an ICER of CHF73,995/QALY and a 73 % probability of being cost-effective. At current prices, PALLET would cost the Swiss healthcare system an additional CHF155 million/year. Palbociclib plus letrozole cannot be considered cost-effective for the first-line treatment of patients with metastatic breast cancer in the Swiss healthcare system.

  18. Cellular traction stresses increase with increasing metastatic potential.

    Directory of Open Access Journals (Sweden)

    Casey M Kraning-Rush

    Full Text Available Cancer cells exist in a mechanically and chemically heterogeneous microenvironment which undergoes dynamic changes throughout neoplastic progression. During metastasis, cells from a primary tumor acquire characteristics that enable them to escape from the primary tumor and migrate through the heterogeneous stromal environment to establish secondary tumors. Despite being linked to poor prognosis, there are no direct clinical tests available to diagnose the likelihood of metastasis. Moreover, the physical mechanisms employed by metastatic cancer cells to migrate are poorly understood. Because metastasis of most solid tumors requires cells to exert force to reorganize and navigate through dense stroma, we investigated differences in cellular force generation between metastatic and non-metastatic cells. Using traction force microscopy, we found that in human metastatic breast, prostate and lung cancer cell lines, traction stresses were significantly increased compared to non-metastatic counterparts. This trend was recapitulated in the isogenic MCF10AT series of breast cancer cells. Our data also indicate that increased matrix stiffness and collagen density promote increased traction forces, and that metastatic cells generate higher forces than non-metastatic cells across all matrix properties studied. Additionally, we found that cell spreading for these cell lines has a direct relationship with collagen density, but a biphasic relationship with substrate stiffness, indicating that cell area alone does not dictate the magnitude of traction stress generation. Together, these data suggest that cellular contractile force may play an important role in metastasis, and that the physical properties of the stromal environment may regulate cellular force generation. These findings are critical for understanding the physical mechanisms of metastasis and the role of the extracellular microenvironment in metastatic progression.

  19. Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2016-10-01

    Mary Bowen Project Role: Research Assistance on animal work Researcher Identifier: Nearest person month worked: 2 Contributions to Project: Ms...AD______________ AWARD NUMBER: W81XWH-14-1-0552 TITLE: Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer PRINCIPAL INVESTIGATOR...5a. CONTRACT NUMBER Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-14-1-0552 5c. PROGRAM ELEMENT NUMBER

  20. Amiodarone-induced pulmonary toxicity mimicking metastatic lung disease.

    Science.gov (United States)

    Patel, P; Honeybourne, D; Watson, R D

    1987-05-01

    A 65 year old man developed atrial arrhythmias secondary to a congestive cardiomyopathy which were resistant to quinidine and disopyramide. Amiodarone controlled the paroxysmal atrial tachycardia but 4 months after starting the drug he developed increasing dyspnoea and radiological changes highly suggestive of metastatic lung disease. Lung biopsy showed change of drug-induced pneumonitis and 4 months after stopping amiodarone his symptoms resolved and the chest X-ray had cleared. Amiodarone may cause pulmonary toxicity mimicking metastatic lung disease.

  1. Intrahepatic therapy for liver-dominant metastatic colorectal cancer

    OpenAIRE

    De Groote, Kerlijne; Prenen, Hans

    2015-01-01

    In patients with metastatic colorectal cancer, the liver is the most common site of metastatic disease. In patients with liver-dominant disease, consideration needs to be given to locoregional treatments such as hepatic arterial infusion chemotherapy, transarterial chemoembolisation and selective internal radiation therapy because hepatic metastases are a major cause of liver failure especially in chemorefractory disease. In this review we provide insights on the published literature for loco...

  2. Bilateral choroidal tumors consistent with metastatic malignant paraganglioma.

    Science.gov (United States)

    Aaberg, Thomas M; Benjamin, Erin P; Biscotti, Charles V; Singh, Arun D

    2013-01-01

    To report a patient with bilateral choroidal metastasis from a malignant paraganglioma. Clinicopathologic case report and literature review. A 68-year-old woman presented with bilateral amelanotic focal choroidal lesions. A thorough systemic work-up for a primary cancer revealed a paraganglioma (extraadrenal pheochromocytoma) and a pheochromocytoma of the left adrenal gland. Fine-needle aspiration biopsy of the choroidal lesion was consistent with metastatic paraganglioma. Metastatic paraganglioma, although rare, has the ability to metastasize to the choroid.

  3. Compounded bioidentical menopausal hormone therapy.

    Science.gov (United States)

    2012-08-01

    Although improvement in long-term health is no longer an indication for menopausal hormone therapy, evidence supporting fewer adverse events in younger women, combined with its high overall effectiveness, has reinforced its usefulness for short-term treatment of menopausal symptoms. Menopausal therapy has been provided not only by commercially available products but also by compounding, or creation of an individualized preparation in response to a health care provider's prescription to create a medication tailored to the specialized needs of an individual patient. The Women's Health Initiative findings, coupled with an increase in the direct-to-consumer marketing and media promotion of compounded bioidentical hormonal preparations as safe and effective alternatives to conventional menopausal hormone therapy, have led to a recent increase in the popularity of compounded bioidentical hormones as well as an increase in questions about the use of these preparations. Not only is evidence lacking to support superiority claims of compounded bioidentical hormones over conventional menopausal hormone therapy, but these claims also pose the additional risks of variable purity and potency and lack efficacy and safety data. The Committee on Gynecologic Practice of the American College of Obstetricians and Gynecologists and the Practice Committee of the American Society for Reproductive Medicine provide an overview of the major issues of concern surrounding compounded bioidentical menopausal hormone therapy and provide recommendations for patient counseling. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  4. Vitamins as hormones.

    Science.gov (United States)

    Reichrath, J; Lehmann, B; Carlberg, C; Varani, J; Zouboulis, C C

    2007-02-01

    Vitamins A and D are the first group of substances that have been reported to exhibit properties of skin hormones, such as organized metabolism, activation, inactivation, and elimination in specialized cells of the tissue, exertion of biological activity, and release in the circulation. Vitamin A and its two important metabolites, retinaldehyde and retinoic acids, are fat-soluble unsaturated isoprenoids necessary for growth, differentiation and maintenance of epithelial tissues, and also for reproduction. In a reversible process, vitamin A is oxidized IN VIVO to give retinaldehyde, which is important for vision. The dramatic effects of vitamin A analogues on embryogenesis have been studied by animal experiments; the clinical malformation pattern in humans is known. Retinoic acids are major oxidative metabolites of vitamin A and can substitute for it in vitamin A-deficient animals in growth promotion and epithelial differentiation. Natural vitamin A metabolites are vitamins, because vitamin A is not synthesized in the body and must be derived from carotenoids in the diet. On the other hand, retinoids are also hormones - with intracrine activity - because retinol is transformed in the cells into molecules that bind to and activate specific nuclear receptors, exhibit their function, and are subsequently inactivated. The mechanisms of action of natural vitamin A metabolites on human skin are based on the time- and dose-dependent influence of morphogenesis, epithelial cell proliferation and differentiation, epithelial and mesenchymal synthetic performance, immune modulation, stimulation of angiogenesis and inhibition of carcinogenesis. As drugs, vitamin A and its natural metabolites have been approved for the topical and systemic treatment of mild to moderate and severe, recalcitrant acne, photoaging and biologic skin aging, acute promyelocytic leukaemia and Kaposi's sarcoma. On the other hand, the critical importance of the skin for the human body's vitamin D endocrine

  5. Genotoxic potential of nonsteroidal hormones

    Directory of Open Access Journals (Sweden)

    Topalović Dijana

    2015-01-01

    Full Text Available Hormones are cellular products involved in the regulation of a large number of processes in living systems, and which by their actions affect the growth, function and metabolism of cells. Considering that hormones are compounds normally present in the organism, it is important to determine if they can, under certain circumstances, lead to genetic changes in the hereditary material. Numerous experimental studies in vitro and in vivo in different systems, from bacteria to mammals, dealt with the mutagenic and genotoxic effects of hormones. This work presents an overview of the research on genotoxic effects of non­steroidal hormones, although possible changes of genetic material under their influence have not still been known enough, and moreover, investigations on their genotoxic influence have given conflicting results. The study results show that mechanisms of genotoxic effect of nonsteroidal hormones are manifested through the increase of oxidative stress by arising reactive oxygen species. A common mechanism of ROS occurence in thyroid hormones and catecholamines is through metabolic oxidation of their phenolic groups. Manifestation of insulin genotoxic effect is based on production of ROS by activation of NADPH isophorms, while testing oxytocin showed absence of genotoxic effect. Considering that the investigations on genotoxicity of nonsteroidal hormones demonstrated both positive and negative results, the explanation of this discordance involve limitations of test systems themselves, different cell types or biological species used in the experiments, different level of reactivity in vitro and in vivo, as well as possible variations in a tissue-specific expression. Integrated, the provided data contribute to better understanding of genotoxic effect of nonsteroidal hormones and point out to the role and mode of action of these hormones in the process of occurring of effects caused by oxidative stress. [Projekat Ministarstva nauke Republike

  6. Black Pleural Effusion: A Unique Presentation of Metastatic Melanoma

    Directory of Open Access Journals (Sweden)

    Akansha Chhabra

    2015-05-01

    Full Text Available Metastatic melanoma is a rare form of skin cancer, but one that comes with a high mortality rate. Pulmonary involvement is frequently seen in metastatic melanoma with only 2% of malignant melanoma patients with thorax metastasis presenting with pleural effusions. Herein, we report an extremely rare case of black pleural effusion from thoracic metastasis of cutaneous malignant melanoma. A 74-year-old man with known metastatic melanoma presented with a 1-month history of worsening lower back and hip pain and was found to have extensive osseous metastatic disease and multiple compression fractures. The patient underwent an uneventful kyphoplasty; however, the following day, he became acutely hypoxic and tachypneic with increased oxygen requirements. Radiographic evaluation revealed new bilateral pleural effusions. Bedside thoracentesis revealed a densely exudative, lymphocyte-predominant black effusion. Cytological examination showed numerous neoplastic cells with melanin deposition. A diagnosis of thoracic metastasis of malignant melanoma was established based on the gross and microscopic appearance of the pleural fluid. To the best of our knowledge, this is the first reported case of black pleural effusions secondary to metastatic melanoma in the United States. Despite the rarity of this presentation, it is important to determine the etiology of the black pleural effusion and to keep metastatic melanoma as a differential diagnosis.

  7. Association between contralateral prophylactic mastectomy and breast cancer outcomes by hormone receptor status.

    Science.gov (United States)

    Brewster, Abenaa M; Bedrosian, Isabelle; Parker, Patricia A; Dong, Wenli; Peterson, Susan K; Cantor, Scott B; Crosby, Melissa; Shen, Yu

    2012-11-15

    The effect of contralateral prophylactic mastectomy (CPM) on the survival of patients with early-stage breast cancer remains controversial. The objective of this study was to evaluate the benefits of CPM using a propensity scoring approach that reduces selection bias from the nonrandom assignment of patients in observational studies. A total of 3889 female patients with stage I to III breast cancer were identified who were treated at The University of Texas MD Anderson Cancer Center from 1997 to 2009. We assessed the association between CPM and disease-free (DFS) and overall survival (OS), by using Cox proportional hazards models to estimate hazard ratios (HRs), and by matching patients in the CPM and no-CPM groups using propensity scores (n = 497 pairs). With a median follow-up time of 4.5 years, CPM was associated with improved DFS (HR, 0.75; 95% confidence interval [CI], 0.59-0.97) and OS (HR, 0.74; 95% CI, 0.56-0.99), adjusted for prognostic factors. The improved DFS was seen predominantly among hormone receptor-negative (HR, 0.60; 95% CI, 0.38-0.95) compared with hormone receptor-positive patients (HR, 0.80; 95% CI, 0.58-1.10). For the matched patient cohort, stratified survival analysis also showed an improvement in DFS with CPM (HR, 0.48; 95% CI, 0.22-1.01) in hormone receptor-negative patients that was nearly statistically significant. CPM was associated with improved DFS for some patients with hormone receptor-negative breast cancer, after reducing selection bias. Identifying subsets of patients most likely to benefit from CPM may have important implications for a more personalized approach to treatment decisions about CPM. Copyright © 2012 American Cancer Society.

  8. Melanoma Therapy with Rhenium-Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs

    Energy Technology Data Exchange (ETDEWEB)

    Thomas P Quinn

    2005-11-22

    Malignant melanoma is the 6th most commonly diagnosed cancer with increasing incidence in the United States. It is estimated that 54,200 cases of malignant melanoma will be newly diagnosed and 7,600 cases of death will occur in the United States in the year 2003 (1). At the present time, more than 1.3% of Americans will develop malignant melanoma during their lifetime (2). The average survival for patients with metastatic melanoma is about 6-9 months (3). Moreover, metastatic melanoma deposits are resistant to conventional chemotherapy and external beam radiation therapy (3). Systematic chemotherapy is the primary therapeutic approach to treat patients with metastatic melanoma. Dacarbazine is the only single chemotherapy agent approved by FDA for metastatic melanoma treatment (5). However, the response rate to Dacarbazine is only approximately 20% (6). Therefore, there is a great need to develop novel treatment approaches for metastatic melanoma. The global goal of this research program is the rational design, characterization and validation of melanoma imaging and therapeutic radiopharmaceuticals. Significant progress has been made in the design and characterization of metal-cyclized radiolabeled alpha-melanocyte stimulating hormone peptides. Therapy studies with {sup 188}Re-CCMSH demonstrated the therapeutic efficacy of the receptor-targeted treatment in murine and human melanoma bearing mice (previous progress report). Dosimetry calculations, based on biodistribution data, indicated that a significant dose was delivered to the tumor. However, {sup 188}Re is a very energetic beta-particle emitter. The longer-range beta-particles theoretically would be better for larger tumors. In the treatment of melanoma, the larger primary tumor is usually surgically removed leaving metastatic disease as the focus of targeted radiotherapy. Isotopes with lower beta-energies and/or shorter particle lengths should be better suited for targeting metastases. The {sup 177}Lu

  9. Right Atrial Metastatic Melanoma with Unknown Primaries

    Directory of Open Access Journals (Sweden)

    Robin Kuriakose

    2015-01-01

    Full Text Available A 54-year-old male with history of anemia and rheumatoid arthritis presented with a three-month history of dyspnea on exertion and lower extremity edema. Patient was referred for a transthoracic echocardiogram that revealed a large right atrial mass with reduced ejection fraction of 40% and an incidental large liver mass. Subsequent cardiac MRI revealed a lobulated right atrial mass measuring 5.4 cm × 5.3 cm with inferior vena cava compression and adjacent multiple large liver lesions confirmed to be malignant melanoma through biopsy. Interestingly, no primaries were found in the patient. PET/CT imaging displayed hypermetabolic masses within the right atrium and liver that likely represent metastases, as well as bilateral pleural effusions, most likely due to heart failure. Preoperative coronary angiogram demonstrated perfusion to the mass by a dense network of neovasculature arising from the mid right coronary artery. The cardiac melanoma was surgically removed, and the right atrium was reconstructed with a pericardial patch. After surgery, all cardiac chambers appeared normal in size and function with associated moderate tricuspid regurgitation. The patient is currently being administered ipilimumab for systemic therapy of metastatic melanoma.

  10. Benign Sacral Metastatic Meningioma: A Rare Entity.

    Science.gov (United States)

    Strong, Michael J; Garces, Juanita; Tang, Wendell; Ware, Marcus L

    2015-01-01

    Meningiomas are common intracranial tumors with a low metastatic rate. Those that do metastasize often show histopathologic signs of malignancy. In rare cases, the primary and secondary tumors are histologically benign. We report the case of a 57-year-old female with a histologically benign intracranial meningioma that metastasized to the sacrum. The patient had a long history of intracranial meningioma with multiple recurrences. At each recurrence, histopathologic examination of the resected tumor showed no signs of malignancy. The sacral meningioma was biopsied and found to be histologically benign. The patient was treated with radiotherapy (54 Gy in 30 fractions), and her symptoms resolved. Six months later, the patient developed left leg weakness. Magnetic resonance imaging showed growth of her intracranial mass for which she underwent a craniotomy for tumor resection. Pathologic evaluation showed evidence of benign meningioma without atypical features. She recovered well from this procedure and returned to her baseline in several weeks. After treatment, the patient had no signs of radiographic progression in either location.

  11. Intraventricular metastatic clear cell renal carcinoma.

    Science.gov (United States)

    Sava, I; Sava, Anca; Şapte, Elena; Mihailov, Claudia; Dumitrescu, Gabriela; Poeată, I; Sava, Florina; Haba, Danisia

    2013-01-01

    Intraventricular tumors represent a diagnostic problem, due to a wide range of differential diagnosis, with an important variability of tumoral histological types in adult and pediatric population. Patient, Our case is represented by a patient, aged 48 years, without any history of significant personal pathology, accusing nausea, vomiting, and intensive headache. In the morning, he became confused, having hallucinations for a short period of time, and has accused drowsiness for several weeks. Imaging (CT and MRI) shows a neoformation in the third ventricle, accompanied by bilateral lateral ventricles dilatation, with predominantly annular enhancement. During surgery, through the middle third transcallosal interhemispheric approach, it was revealed a reddish, well-demarcated intraventricular mass, well vascularized and with a firm consistency. Final pathologic diagnosis was metastatic clear cell renal carcinoma. Initial postoperative evolution was good, and then neurological and respiratory condition worsened as a bronchopneumonia lead to patient's death in 12 days after surgery. Clear cell carcinoma metastasis located in the third ventricle should be taken into consideration for patients presenting a single intraventricular lesion even they have no documented primary malignancy.

  12. Metastatic undifferentiated pleomorphic sarcoma causing intraoperative stroke.

    Science.gov (United States)

    Spaulding, Reed; Koumoundouros, Theodoros; Parker, Joseph C

    2013-01-01

    Malignant Fibrous Histiocytoma was historically the most commonly diagnosed soft tissue sarcoma of adults. In 2002, the World Health Organization declassified malignant fibrous histiocytoma as a formal diagnostic entity. They recommended renaming the disease "Pleomorphic Undifferentiated Sarcoma". Current thoughts about the origin of this tumor are being debated. We report a case of a dedifferentiated liposarcoma that metastasized to the lung within one year. The histologic morphology of the metastasis was more aggressive than the primary lesion, and was consistent with a pleomorphic undifferentiated sarcoma. Following surgical resection of the metastatic pulmonary lesion, the patient never fully regained consciousness. He expired the day following his surgery. At autopsy, the patient was found to have died from a massive hemorrhagic stroke involving almost the entire left cerebrum. Tumor emboli from the pulmonary metastasis were seen in the left middle cerebral artery, causing the cerebral infarct. The embolic lesion was consistent with a pleomorphic undifferentiated sarcoma. This case illustrates the evolution that soft tissue sarcomas can undergo as they metastasize and become increasingly undifferentiated, and confirms the surgical risk of resecting such lesions.

  13. Advancing Immunotherapy in Metastatic Breast Cancer.

    Science.gov (United States)

    Mansour, Mariam; Teo, Zhi Ling; Luen, Stephen J; Loi, Sherene

    2017-06-01

    Despite many advances in the treatment of breast cancer, the development of metastatic disease remains an incurable and frequent cause of cancer death for women worldwide. An improved understanding of the role of host immunosurveillance in modulating breast cancer disease biology, as well as impressive survival benefits seen to checkpoint blockade in other malignancies have provided great hope for an expanding role of immunotherapies in breast cancer management. While these novel therapies are currently being investigated in clinical trials, signals of efficacy, and tolerability in early phase studies suggest these will eventually make their way into standard practice algorithms. Ongoing research has highlighted a high degree of intertumoural heterogeneity in tumour lymphocytic infiltrates, suggesting some tumours or subtypes are more immunogenic than others. Furthermore, tumour intrinsic mechanisms of immune evasion are beginning to be uncovered, potentially representing key therapeutic targets to use in combination with checkpoint blockade, exemplifying the emerging concept of personalised medicine approaches to immune therapies. Subsequently, different immunotherapeutic strategies may be required based on stratification by these factors-for the minority of tumours with a high level of pre-existing immunity, immune checkpoint blockade monotherapy may be sufficient. However, for the majority of tumours with lower levels of pre-existing immunity, combination approaches will likely be required to achieve maximal therapeutic effect. Results of ongoing clinical trials including combinations with chemotherapy, radiation therapy, and targeted therapies are eagerly awaited.

  14. Subcutaneous Angiomatoid Fibrous Histiocytoma Mimicking Metastatic Melanoma

    Directory of Open Access Journals (Sweden)

    E. Sparreboom

    2012-01-01

    Full Text Available Angiomatoid fibrous histiocytoma is an uncommon soft-tissue tumor of intermediate malignancy that is often misdiagnosed initially. As there is not one immunohistochemical marker that consequently stains positive or negative for angiomatoid fibrous histiocytoma, molecular diagnostics are becoming more widely used. So far three translocations have been reported to arise in angiomatoid fibrous histiocytoma: FUS-ATF1, EWSR1-CREB1, or EWSR1-ATF1. We present a case of angiomatoid fibrous histiocytoma on the upper arm of a 40-year-old female, which was initially misdiagnosed as metastatic melanoma in a lymph node. Revision of the pathology revealed an angiomatoid fibrous histiocytoma, which was later confirmed by a EWSR1-CREB1 translocation with molecular diagnostics. Furthermore, we review the relevant literature and provide an overview of all available case reports in the past ten years. This case report illustrates the importance for pathologists of knowing the typical pathology features of AFH and integrating immunohistochemical and molecular findings in order to prevent overdiagnosis of lymph node metastasis of a malignancy.

  15. Cost effectiveness of a 21-gene recurrence score assay versus Canadian clinical practice in post-menopausal women with early-stage estrogen or progesterone-receptor-positive, axillary lymph-node positive breast cancer.

    Science.gov (United States)

    Hannouf, Malek B; Xie, Bin; Brackstone, Muriel; Zaric, Gregory S

    2014-02-01

    A 21-gene recurrence score (RS) assay provides a method of guiding treatment decisions in women with early-stage breast cancer (ESBC). We investigated the cost effectiveness of using the RS assay versus current clinical practice (CCP) in post-menopausal women with estrogen- or progesterone-receptor-positive, one to three positive axillary lymph-node ESBC from the perspective of the Canadian public healthcare system. We developed a decision analytic model to project the lifetime clinical and economic consequences of ESBC. We assumed that the RS assay would classify patients among risk levels (low, intermediate and high) and corresponding adjuvant treatment regimens. The model was parameterized using 7-year follow-up data from the Manitoba Cancer Registry, cost data from Manitoba Health administrative databases and secondary sources. Costs are presented in 2012 Canadian dollars, and future costs and benefits were discounted at 5 %. In the base case analysis, the RS assay compared with CCP led to an increase of 0.08 quality-adjusted life-year (QALY) and an increase in cost of Can$36.2 per person, resulting in an incremental cost-effectiveness ratio (ICER) of Can$464/QALY gained. The ICER was most sensitive to the proportion of women classified to intermediate risk by the RS assay who received adjuvant chemotherapy, and absolute risk of relapse among patients receiving the RS assay. The RS assay is likely to be cost effective in the Canadian healthcare system. Field evaluations of the assay in this patient population will help reduce uncertainty in clinical guidelines for intermediate-range RS-assay values and specific disease outcomes by the RS assay, which are important drivers of ICER.

  16. Synthesis, development and preclinical comparison of two new peptide based freeze-dried kit formulation 99mTc-EDDA-Tricine-HYNIC-TOC and 99mTc-EDDA-Tricine-HYNIC-TATE for somatostatin receptor positive tumor scintigraphy

    Directory of Open Access Journals (Sweden)

    Gandomkar M.

    2006-07-01

    Full Text Available Somatostatin receptor (sstr scintigraphy with [111In diethylenetriaminepentaacetic acid]-octreotide ([111In-DTPA]-OC has became a routine diagnostic procedure in oncology. However, it suffers from some drawbacks concerning the limited availability, suboptimal imaging properties and elevated radiation burden of 111In. In this study synthesis, conjugation and preclinical evaluation of two new freeze-dried kit formulation based on somatostatin analogues, Tyr3-Octreotide (TOC and Tyr3-octreotate (TATE, designed for the labeling with 99mTc are described. After cleavage from the resin and preparation of the cyclized peptides, these compounds were conjugated with 6-hydrazinopyridine-3-carboxylic acid (HYNIC in solution. Radiolabeling of HYNIC peptide conjugates was performed at high specific activity using one-step kits formulation based on tricine and ethylenediamine-N,N′ -diacetic acid (EDDA as co-ligands. Both, 6-hydrazinopyridine-3-carboxylic acid0-Tyr3-Octreotide (HYNIC-TOC and 6-hydrazinopyridine-3-carboxylic acid0-Tyr3-Octreotate (HYNIC-TATE, showed a specific and high rate of internalization after 4 h in AR4-2J rat pancreatic tumor cells, (11.2±0.8 and 18.1±1.2 respectively. Biodistribution studies in AR4-2J tumor-bearing rats showed rapid clearance of both analogues from all sstr-negative tissues except the kidneys. The specific uptake in tumor and sstr-positive tissues especially pituitary, pancreas and adrenals were observed. After 4 h the adrenals to pancreas uptake ratio for HYNIC-TOC was higher than that of HYNIC-TATE. Although both compounds had high kidney and low liver excretion, for HYNIC-TATE, it was lower. The results suggest these two new peptide based freeze-dried kits might be of great promise for clinical application in imaging of somatostatin receptor-positive tumors.

  17. NeoPalAna: Neoadjuvant Palbociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor, and Anastrozole for Clinical Stage 2 or 3 Estrogen Receptor-Positive Breast Cancer.

    Science.gov (United States)

    Ma, Cynthia X; Gao, Feng; Luo, Jingqin; Northfelt, Donald W; Goetz, Matthew; Forero, Andres; Hoog, Jeremy; Naughton, Michael; Ademuyiwa, Foluso; Suresh, Rama; Anderson, Karen S; Margenthaler, Julie; Aft, Rebecca; Hobday, Timothy; Moynihan, Timothy; Gillanders, William; Cyr, Amy; Eberlein, Timothy J; Hieken, Tina; Krontiras, Helen; Guo, Zhanfang; Lee, Michelle V; Spies, Nicholas C; Skidmore, Zachary L; Griffith, Obi L; Griffith, Malachi; Thomas, Shana; Bumb, Caroline; Vij, Kiran; Bartlett, Cynthia Huang; Koehler, Maria; Al-Kateb, Hussam; Sanati, Souzan; Ellis, Matthew J

    2017-08-01

    Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor-positive (ER(+)) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the antiproliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies.Experimental Design: Eligible patients with clinical stage II/III ER(+)/HER2(-) breast cancer received anastrozole 1 mg daily for 4 weeks (cycle 0; with goserelin if premenopausal), followed by adding palbociclib (125 mg daily on days 1-21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67 > 10%, in which case patients went off study due to inadequate response. Anastrozole was continued until surgery, which occurred 3 to 5 weeks after palbociclib exposure. Later patients received additional 10 to 12 days of palbociclib (Cycle 5) immediately before surgery. Serial biopsies at baseline, C1D1, C1D15, and surgery were analyzed for Ki67, gene expression, and mutation profiles. The primary endpoint was complete cell cycle arrest (CCCA: central Ki67 ≤ 2.7%).Results: Fifty patients enrolled. The CCCA rate was significantly higher after adding palbociclib to anastrozole (C1D15 87% vs. C1D1 26%, P Palbociclib enhanced cell-cycle control over anastrozole monotherapy regardless of luminal subtype (A vs. B) and PIK3CA status with activity observed across a broad range of clinicopathologic and mutation profiles. Ki67 recovery at surgery following palbociclib washout was suppressed by cycle 5 palbociclib. Resistance was associated with nonluminal subtypes and persistent E2F-target gene expression.Conclusions: Palbociclib is an active antiproliferative agent for early-stage breast cancer resistant to anastrozole; however, prolonged administration may be necessary to maintain its effect. Clin Cancer Res; 23(15); 4055-65. ©2017 AACR. ©2017 American Association for Cancer Research.

  18. Impact of palbociclib plus letrozole on pain severity and pain interference with daily activities in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer as first-line treatment.

    Science.gov (United States)

    Bell, T; Crown, J P; Lang, I; Bhattacharyya, H; Zanotti, G; Randolph, S; Kim, S; Huang, X; Huang Bartlett, C; Finn, R S; Slamon, D

    2016-05-01

    Background Palbociclib is a recently approved drug for use in combination with letrozole as initial endocrine-based therapy for the treatment of postmenopausal women with advanced estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer. This report assesses the impact of palbociclib in combination with letrozole versus letrozole alone on patient-reported outcomes of pain. Methods Palbociclib was evaluated in an open-label, randomized, phase II study (PALOMA-1/TRIO-18) among postmenopausal women with advanced ER+/HER2- breast cancer who had not received prior systemic treatment for their advanced disease. Patients received continuous oral letrozole 2.5 mg daily alone or the same letrozole dose and schedule plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over repeated 28-day cycles. The primary study endpoint was investigator-assessed progression-free survival in the intent-to-treat population, and these results have recently been published (Finn et al., Lancet Oncol 2015;16:25-35). One of the key secondary endpoints was the evaluation of pain, as measured using the Brief Pain Inventory (BPI) patient-reported outcome tool. The BPI was administered at baseline and on day 1 of every cycle thereafter until disease progression and/or treatment discontinuation. Clinical trial registration This study is registered with ClinicalTrials.gov (NCT00721409). Results There were no statistically significant differences in Pain Severity or Pain Interference scores of the BPI between the two treatment groups for the overall population or among those with any bone disease at baseline. A limitation of the study is that results were not adjusted for the concomitant use of opioids or other medications used to control pain. Conclusions The addition of palbociclib to letrozole was associated with increased efficacy without negatively impacting pain severity or pain interference with daily activities.

  19. Correlation between tumour characteristics, SUV measurements, metabolic tumour volume, TLG and textural features assessed with {sup 18}F-FDG PET in a large cohort of oestrogen receptor-positive breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Lemarignier, Charles; Groheux, David [Saint-Louis Hospital, Assistance Publique - Hopitaux de Paris, Department of Nuclear Medicine, Paris (France); University Sorbonne Paris Cite, INSERM/CNRS UMR944/7212, Paris (France); Martineau, Antoine; Vercellino, Laetitia; Merlet, Pascal [Saint-Louis Hospital, Assistance Publique - Hopitaux de Paris, Department of Nuclear Medicine, Paris (France); Teixeira, Luis; Espie, Marc [Saint-Louis Hospital, Breast Diseases Unit, Paris (France); University Sorbonne Paris Cite, INSERM/CNRS UMR944/7212, Paris (France)

    2017-07-15

    The study was designed to evaluate 1) the relationship between PET image textural features (TFs) and SUVs, metabolic tumour volume (MTV), total lesion glycolysis (TLG) and tumour characteristics in a large prospective and homogenous cohort of oestrogen receptor-positive (ER+) breast cancer (BC) patients, and 2) the capability of those parameters to predict response to neoadjuvant chemotherapy (NAC). 171 consecutive patients with large or locally advanced ER+ BC without distant metastases underwent an {sup 18}F-FDG PET examination before NAC. The primary tumour was delineated with an adaptive threshold segmentation method. Parameters of volume, intensity and texture (entropy, homogeneity, contrast and energy) were measured and compared with tumour characteristics determined on pre-treatment breast biopsy (Wilcoxon rank-sum test). The correlation between PET-derived parameters was determined using Spearman's coefficient. The relationship between PET features and pathological findings was determined using the Wilcoxon rank-sum test. Spearman's coefficients between SUV{sub max} and TFs were 0.43, 0.24, -0.43 and -0.15 respectively for entropy, homogeneity, energy and contrast; they were higher between MTV and TFs: 0.99, 0.86, -0.99 and -0.87. All TFs showed a significant association with the histological type (IDC vs. ILC; 0.02 < P < 0.03) but didn't with immunohistochemical characteristics. SUV{sub max} and TLG predicted the pathological response (P = 0.0021 and P = 0.02 respectively); TFs didn't (P: 0.27, 0.19, 0.94, 0.19 respectively for entropy, homogeneity, energy and contrast). The correlation of TFs was poor with SUV parameters and high with MTV. TFs showed a significant association with the histological type. Finally, while SUV{sub max} and TLG were able to predict response to NAC, TFs failed. (orig.)

  20. Clinicopathologic Characteristics of Oestrogen Receptor-Positive/Progesterone Receptor-Negative/Her2-Negative Breast Cancer According to a Novel Definition of Negative Progesterone Receptor Status: A Large Population-Based Study from China.

    Directory of Open Access Journals (Sweden)

    An-qi Li

    Full Text Available A lack of progesterone receptor (PgR expression in oestrogen receptor-positive (ER+ tumours is associated with worse survival. PgR status is usually defined as positive or negative using 1% positive nuclei as a cut-off point. In this study, we aimed to assess the clinicopathologic characteristics of ER+/PgR-/HER2- tumours by comparing them with ER+/PgR+/HER2- tumours using a PgR cut-off point of 20% as a divisive criterion.We analysed 1,522 patients with primary breast cancer who had undergone surgery at the Cancer Center of Fudan University between 2012 and 2014. Age, grade, tumour size, lymph node status and lymphovascular invasion were assessed. Multinomial logistic regression, linear regression and chi-square test models were applied to assess associations between ER, PR and clinical features.ER+/PgR-/HER2- tumours showed poorer clinicopathologic characteristics relative to ER+/PgR+/HER2- tumours using a PgR threshold of 20% instead of 1%. The clinicopathologic characteristics did not differ between tumours with purely negative PgR expression and tumours with a PgR percentage ranging from 1% to 19%. The prognostic significance of PR expression appeared more pronounced in patients under a high Ki-67 status than those under a low Ki-67 status.Based on these findings, we propose the use of a novel threshold of 20% to define PgR status. Nevertheless, the impact of this new criterion on patient management and clinical treatment requires additional study.

  1. Glucocorticoid receptor knockdown decreases the antioxidant protection of B16 melanoma cells: an endocrine system-related mechanism that compromises metastatic cell resistance to vascular endothelium-induced tumor cytotoxicity.

    Science.gov (United States)

    Obrador, Elena; Valles, Soraya L; Benlloch, María; Sirerol, J Antoni; Pellicer, José A; Alcácer, Javier; Coronado, Javier Alcácer-F; Estrela, José M

    2014-01-01

    We previously reported an interorgan system in which stress-related hormones (corticosterone and noradrenaline), interleukin-6, and glutathione (GSH) coordinately regulate metastatic growth of highly aggressive B16-F10 melanoma cells. Corticosterone, at levels measured in tumor-bearing mice, also induces apoptotic cell death in metastatic cells with low GSH content. In the present study we explored the potential role of glucocorticoids in the regulation of metastatic cell death/survival during the early stages of organ invasion. Glucocorticoid receptor (GCR) knockdown decreased the expression and activity of γ-glutamylcysteine synthetase (γ-GCS), the rate-limiting step in GSH synthesis, in metastatic cells in vivo independent of the tumor location (liver, lung, or subcutaneous). The decrease in γ-GCS activity was associated with lower intracellular GSH levels. Nrf2- and p53-dependent down-regulation of γ-GCS was associated with a decrease in the activities of superoxide dismutase 1 and 2, catalase, glutathione peroxidase, and glutathione reductase, but not of the O2--generating NADPH oxidase. The GCR knockdown-induced decrease in antioxidant protection caused a drastic decrease in the survival of metastatic cells during their interaction with endothelial cells, both in vitro and in vivo; only 10% of cancer cells attached to the endothelium survived compared to 90% survival observed in the controls. This very low rate of metastatic cell survival was partially increased (up to 52%) in vivo by inoculating B16-F10 cells preloaded with GSH ester, which enters the cell and delivers free GSH. Taken together, our results indicate that glucocorticoid signaling influences the survival of metastatic cells during their interaction with the vascular endothelium.

  2. Functional and molecular characterisation of EO771.LMB tumours, a new C57BL/6-mouse-derived model of spontaneously metastatic mammary cancer

    Directory of Open Access Journals (Sweden)

    Cameron N. Johnstone

    2015-03-01

    Full Text Available The translation of basic research into improved therapies for breast cancer patients requires relevant preclinical models that incorporate spontaneous metastasis. We have completed a functional and molecular characterisation of a new isogenic C57BL/6 mouse model of breast cancer metastasis, comparing and contrasting it with the established BALB/c 4T1 model. Metastatic EO771.LMB tumours were derived from poorly metastatic parental EO771 mammary tumours. Functional differences were evaluated using both in vitro assays and spontaneous metastasis assays in mice. Results were compared to non-metastatic 67NR and metastatic 4T1.2 tumours of the 4T1 model. Protein and transcript levels of markers of human breast cancer molecular subtypes were measured in the four tumour lines, as well as p53 (Tp53 tumour-suppressor gene status and responses to tamoxifen in vivo and in vitro. Array-based expression profiling of whole tumours identified genes and pathways that were deregulated in metastatic tumours. EO771.LMB cells metastasised spontaneously to lung in C57BL/6 mice and displayed increased invasive capacity compared with parental EO771. By immunohistochemical assessment, EO771 and EO771.LMB were basal-like, as was the 4T1.2 tumour, whereas 67NR had a luminal phenotype. Primary tumours from all lines were negative for progesterone receptor, Erb-b2/Neu and cytokeratin 5/6, but positive for epidermal growth factor receptor (EGFR. Only 67NR displayed nuclear estrogen receptor alpha (ERα positivity. EO771 and EO771.LMB expressed mutant p53, whereas 67NR and 4T1.2 were p53-null. Integrated molecular analysis of both the EO771/EO771.LMB and 67NR/4T1.2 pairs indicated that upregulation of matrix metalloproteinase-3 (MMP-3, parathyroid hormone-like hormone (Pthlh and S100 calcium binding protein A8 (S100a8 and downregulation of the thrombospondin receptor (Cd36 might be causally involved in metastatic dissemination of breast cancer.

  3. Added Value of Serum Hormone Measurements in Risk Prediction Models for Breast Cancer for Women Not Using Exogenous Hormones: Results from the EPIC Cohort.

    Science.gov (United States)

    Hüsing, Anika; Fortner, Renée T; Kühn, Tilman; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Fournier, Agnes; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vassiliki; Orfanos, Philippos; Masala, Giovanna; Pala, Valeria; Tumino, Rosario; Fasanelli, Francesca; Panico, Salvatore; Bueno de Mesquita, H Bas; Peeters, Petra H; van Gills, Carla H; Quirós, J Ramón; Agudo, Antonio; Sánchez, Maria-Jose; Chirlaque, Maria-Dolores; Barricarte, Aurelio; Amiano, Pilar; Khaw, Kay-Tee; Travis, Ruth C; Dossus, Laure; Li, Kuanrong; Ferrari, Pietro; Merritt, Melissa A; Tzoulaki, Ioanna; Riboli, Elio; Kaaks, Rudolf

    2017-08-01

    Purpose: Circulating hormone concentrations are associated with breast cancer risk, with well-established associations for postmenopausal women. Biomarkers may represent minimally invasive measures to improve risk prediction models.Experimental Design: We evaluated improvements in discrimination gained by adding serum biomarker concentrations to risk estimates derived from risk prediction models developed by Gail and colleagues and Pfeiffer and colleagues using a nested case-control study within the EPIC cohort, including 1,217 breast cancer cases and 1,976 matched controls. Participants were pre- or postmenopausal at blood collection. Circulating sex steroids, prolactin, insulin-like growth factor (IGF) I, IGF-binding protein 3, and sex hormone-binding globulin (SHBG) were evaluated using backward elimination separately in women pre- and postmenopausal at blood collection. Improvement in discrimination was evaluated as the change in concordance statistic (C-statistic) from a modified Gail or Pfeiffer risk score alone versus models, including the biomarkers and risk score. Internal validation with bootstrapping (1,000-fold) was used to adjust for overfitting.Results: Among women postmenopausal at blood collection, estradiol, testosterone, and SHBG were selected into the prediction models. For breast cancer overall, model discrimination after including biomarkers was 5.3 percentage points higher than the modified Gail model alone, and 3.4 percentage points higher than the Pfeiffer model alone, after accounting for overfitting. Discrimination was more markedly improved for estrogen receptor-positive disease (percentage point change in C-statistic: 7.2, Gail; 4.8, Pfeiffer). We observed no improvement in discrimination among women premenopausal at blood collection.Conclusions: Integration of hormone measurements in clinical risk prediction models may represent a strategy to improve breast cancer risk stratification. Clin Cancer Res; 23(15); 4181-9. ©2017 AACR. ©2017

  4. Adrenal gland hormone secretion (image)

    Science.gov (United States)

    The adrenal gland secretes steroid hormones such as cortisol and aldosterone. It also makes precursors that can be converted ... steroids (androgen, estrogen). A different part of the adrenal gland makes adrenaline (epinephrine). When the glands produce ...

  5. Hormonal modulation of plant immunity

    NARCIS (Netherlands)

    Pieterse, C.M.J.; Does, D. van der; Zamioudis, C.; Leon-Reyes, A.; Wees, A.C.M. van

    2012-01-01

    Plant hormones have pivotal roles in the regulation of plant growth, development, and reproduction. Additionally, they emerged as cellular signal molecules with key functions in the regulation of immune responses to microbial pathogens, insect herbivores, and beneficial microbes. Their signaling

  6. Controversies in hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    A. Baziad

    2001-09-01

    Full Text Available Deficiency of estrogen hormone will result in either long-term or short-term health problems which may reduce the quality of life. There are numerous methods by which the quality of female life can be achieved. Since the problems occuring are due to the deficiency of estrogen hormone, the appropriate method to tackle the problem is by administration of estrogen hormone. The administration of hormone replacement therapy (HRT with estrogen may eliminate climacteric complaints, prevent osteoporosis, coronary heart disease, dementia, and colon cancer. Although HRT has a great deal of advantage, its use is still low and may result in controversies. These controversies are due to fact that both doctor and patient still hold on to the old, outmoded views which are not supported by numerous studies. Currently, the use of HRT is not only based on experience, or temporary observation, but more on evidence based medicine. (Med J Indones 2001; 10: 182-6Keywords: controversies, HRT

  7. Hormone replacement therapy in menopause

    National Research Council Canada - National Science Library

    Pardini, Dolores

    2014-01-01

    Although estrogen has been clinically available for more than six decades, women have been confused by different opinions regarding the risks and benefits of menopausal hormone therapy (HT), estrogen therapy (ET...

  8. Parathyroid hormone (PTH) blood test

    Science.gov (United States)

    ... gov/ency/article/003690.htm Parathyroid hormone (PTH) blood test To use the sharing features on this page, ... to measure the amount of PTH in your blood. How the Test is Performed A blood sample is needed. How ...

  9. Symptomatic meningioma induced by cross-sex hormone treatment in a male-to-female transsexual.

    Science.gov (United States)

    Bergoglio, Marina T; Gómez-Balaguer, Marcelino; Almonacid Folch, Elena; Hurtado Murillo, Felipe; Hernández-Mijares, Antonio

    2013-05-01

    Transsexualism is defined as a strong conviction of belonging to the opposite sex in individuals without any physical intersex condition. Cross-sex hormone therapy is an important component of medical treatment of transexuals but it is not exempt from adverse effects. We report a case of a meningioma in a male-to-female transsexual patient treated with estrogens and cyproterone acetate for the past 4 years. He claimed recently severe headache and visual impairment. Blood tests showed normal results. A contrast-enhanced magnetic resonance imaging (MRI) scan revealed a mass in the tuberculum sellae consistent with a meningioma. Treatment was discontinued and tumor resection was performed. Histologic diagnosis confirmed strongly progesterone receptor-positive and estrogen negative meningioma. After surgery, the patient rejected the possibility of continuing with the treatment of estrogens and cyproterone, and so triptorelin (GnRH agonist) was initiated. At 1-year follow-up the patient's symptoms had ameliorated and a MRI scan revealed no recurrence of the tumor. This is the third case reported in the literature of a meningioma after treatment with estrogens and cyproterone acetate. We consider extremely important a long-term follow-up observation of male-to-female transsexual undergoing cross-sex hormone therapy in order to detect as soon as possible the adverse effects that can be derived from this therapy. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  10. Thyroid hormone receptors in health and disease

    NARCIS (Netherlands)

    Boelen, A.; Kwakkel, J.; Fliers, E.

    2012-01-01

    Thyroid hormones (TH) play a key role in energy homeostasis throughout life. Thyroid hormone production and secretion by the thyroid gland is regulated via the hypothalamus-pituitary-thyroid (HPT)-axis. Thyroid hormone has to be transported into the cell, where it can bind to the thyroid hormone

  11. Hormone therapy and ovarian borderline tumors

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2012-01-01

    Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk.......Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk....

  12. Ghrelin: much more than a hunger hormone

    Science.gov (United States)

    Ghrelin is a multifaceted gut hormone that activates its receptor, growth hormone secretagogue receptor (GHS-R). Ghrelin's hallmark functions are its stimulatory effects on growth hormone release, food intake and fat deposition. Ghrelin is famously known as the 'hunger hormone'. However, ample recen...

  13. KRAS mutational concordance between primary and metastatic colorectal adenocarcinoma

    Science.gov (United States)

    PALIOGIANNIS, PANAGIOTIS; COSSU, ANTONIO; TANDA, FRANCESCO; PALMIERI, GIUSEPPE; PALOMBA, GRAZIA

    2014-01-01

    KRAS mutation analysis is commonly performed on tissue samples obtained from primary colorectal cancers (CRCs). The metastatic lesions of CRC are usually considered as qualitatively similar or even identical to the primary tumors. The aim of this study was to evaluate the spectrum and distribution of KRAS mutations in a large collection of CRCs, while also evaluating the concordance of primary and metastatic lesions among available paired specimens from the same patients. A total of 729 patients with histologically confirmed advanced CRC at the University Hospital and Local Health Unit (Sassari, Italy) were included. Clinical and pathological features were obtained from medical records and/or pathology reports. Formalin-fixed, paraffin-embedded tissue samples were used for mutation analysis. Genomic DNA was isolated using a standard protocol; the coding sequence and splice junctions of exons 2 and 3 in the KRAS gene were screened by direct automated sequencing. Overall, 219 (30%) KRAS mutations were found; 208 (30.1%) were identified in the 690 primary tumors and 11 (28.2%) in the 39 metastatic tissue samples. Among the 31 (4.3%) patients who had paired samples of primary CRC and synchronous or asynchronous metastases, 28 (90.3%) showed consistent mutation patterns between the primary tumors and metastatic lesions. In one case, an additive mutation (Q61L) was found in the metastatic tissue, while two other discrepant cases exhibited a different mutation distribution; Q61H in the primitive lesion and G13V in the metastatic lesion in one case, and a mutated primary tumor (Q61L) and wild-type metastasis in another case. The results of this study confirm that a high concordance exists between the results of KRAS mutation analysis performed in primitive and metastatic CRCs; independent subclones may be generated in a limited amount of patients. PMID:25202344

  14. Gender-related survival differences associated with EGFR polymorphisms in metastatic colon cancer.

    Science.gov (United States)

    Press, Oliver A; Zhang, Wu; Gordon, Michael A; Yang, Dongyun; Lurje, Georg; Iqbal, Syma; El-Khoueiry, Anthony; Lenz, Heinz-Josef

    2008-04-15

    Evidence is accumulating supporting gender-related differences in the development of colonic carcinomas. Sex steroid hormone receptors are expressed in the colon and interact with epidermal growth factor receptor (EGFR), a gene widely expressed in colonic tissue. Increased EGFR expression is linked with poor prognosis in colon cancer. Within the EGFR gene there are two functional polymorphisms of interest: a polymorphism located at codon 497 (HER-1 R497K) and a dinucleotide (CA)(n) repeat polymorphism located within intron 1. These germ-line polymorphisms of EGFR were analyzed in genomic DNA from 318 metastatic colon cancer patients, 177 males and 141 females, collected from 1992 to 2003. Gender-related survival differences were associated with the HER-1 R497K polymorphism (P(interaction) = 0.003). Females with the HER-1 497 Arg/Arg variant had better overall survival (OS) when compared with the Lys/Lys and/or Lys/Arg variants. In males the opposite was true. The EGFR dinucleotide (CA)(n) repeat also trended with a gender-related OS difference (P(interaction) = 0.11). Females with both short or=20 (CA)(n) repeats. In males the opposite was true. Combination analysis of the two polymorphisms taken together also revealed the same gender-related survival difference (P(interaction) = 0.002). These associations were observed using multivariable analysis. The two polymorphisms were not in linkage disequilibrium and are independent of one another. This study supports the role of functional EGFR polymorphisms as independent prognostic markers in metastatic colon cancer. As a prognostic factor, these variants had opposite prognostic implications based on gender.

  15. Prostate-specific antigen and hormone receptor expression in male and female breast carcinoma

    Directory of Open Access Journals (Sweden)

    Cohen Cynthia

    2010-09-01

    Full Text Available Abstract Background Prostate carcinoma is among the most common solid tumors to secondarily involve the male breast. Prostate specific antigen (PSA and prostate-specific acid phosphatase (PSAP are expressed in benign and malignant prostatic tissue, and immunohistochemical staining for these markers is often used to confirm the prostatic origin of metastatic carcinoma. PSA expression has been reported in male and female breast carcinoma and in gynecomastia, raising concerns about the utility of PSA for differentiating prostate carcinoma metastasis to the male breast from primary breast carcinoma. This study examined the frequency of PSA, PSAP, and hormone receptor expression in male breast carcinoma (MBC, female breast carcinoma (FBC, and gynecomastia. Methods Immunohistochemical staining for PSA, PSAP, AR, ER, and PR was performed on tissue microarrays representing six cases of gynecomastia, thirty MBC, and fifty-six FBC. Results PSA was positive in two of fifty-six FBC (3.7%, focally positive in one of thirty MBC (3.3%, and negative in the five examined cases of gynecomastia. PSAP expression was absent in MBC, FBC, and gynecomastia. Hormone receptor expression was similar in males and females (AR 74.1% in MBC vs. 67.9% in FBC, p = 0.62; ER 85.2% vs. 68.5%, p = 0.18; and PR 51.9% vs. 48.2%, p = 0.82. Conclusions PSA and PSAP are useful markers to distinguish primary breast carcinoma from prostate carcinoma metastatic to the male breast. Although PSA expression appeared to correlate with hormone receptor expression, the incidence of PSA expression in our population was too low to draw significant conclusions about an association between PSA expression and hormone receptor status in breast lesions.

  16. Neratinib Efficacy and Circulating Tumor DNA Detection of HER2 Mutations in HER2 Nonamplified Metastatic Breast Cancer.

    Science.gov (United States)

    Ma, Cynthia X; Bose, Ron; Gao, Feng; Freedman, Rachel A; Telli, Melinda L; Kimmick, Gretchen; Winer, Eric; Naughton, Michael; Goetz, Matthew P; Russell, Christy; Tripathy, Debu; Cobleigh, Melody; Forero, Andres; Pluard, Timothy J; Anders, Carey; Niravath, Polly Ann; Thomas, Shana; Anderson, Jill; Bumb, Caroline; Banks, Kimberly C; Lanman, Richard B; Bryce, Richard; Lalani, Alshad S; Pfeifer, John; Hayes, Daniel F; Pegram, Mark; Blackwell, Kimberly; Bedard, Philippe L; Al-Kateb, Hussam; Ellis, Matthew J C

    2017-10-01

    Purpose: Based on promising preclinical data, we conducted a single-arm phase II trial to assess the clinical benefit rate (CBR) of neratinib, defined as complete/partial response (CR/PR) or stable disease (SD) ≥24 weeks, in HER2mut nonamplified metastatic breast cancer (MBC). Secondary endpoints included progression-free survival (PFS), toxicity, and circulating tumor DNA (ctDNA) HER2mut detection.Experimental Design: Tumor tissue positive for HER2mut was required for eligibility. Neratinib was administered 240 mg daily with prophylactic loperamide. ctDNA sequencing was performed retrospectively for 54 patients (14 positive and 40 negative for tumor HER2mut).Results: Nine of 381 tumors (2.4%) sequenced centrally harbored HER2mut (lobular 7.8% vs. ductal 1.6%; P = 0.026). Thirteen additional HER2mut cases were identified locally. Twenty-one of these 22 HER2mut cases were estrogen receptor positive. Sixteen patients [median age 58 (31-74) years and three (2-10) prior metastatic regimens] received neratinib. The CBR was 31% [90% confidence interval (CI), 13%-55%], including one CR, one PR, and three SD ≥24 weeks. Median PFS was 16 (90% CI, 8-31) weeks. Diarrhea (grade 2, 44%; grade 3, 25%) was the most common adverse event. Baseline ctDNA sequencing identified the same HER2mut in 11 of 14 tumor-positive cases (sensitivity, 79%; 90% CI, 53%-94%) and correctly assigned 32 of 32 informative negative cases (specificity, 100%; 90% CI, 91%-100%). In addition, ctDNA HER2mut variant allele frequency decreased in nine of 11 paired samples at week 4, followed by an increase upon progression.Conclusions: Neratinib is active in HER2mut, nonamplified MBC. ctDNA sequencing offers a noninvasive strategy to identify patients with HER2mut cancers for clinical trial participation. Clin Cancer Res; 23(19); 5687-95. ©2017 AACR. ©2017 American Association for Cancer Research.

  17. Endocrine control of canine mammary neoplasms: serum reproductive hormone levels and tissue expression of steroid hormone, prolactin and growth hormone receptors.

    Science.gov (United States)

    Spoerri, Michèle; Guscetti, Franco; Hartnack, Sonja; Boos, Alois; Oei, Christine; Balogh, Orsolya; Nowaczyk, Renata M; Michel, Erika; Reichler, Iris M; Kowalewski, Mariusz P

    2015-09-15

    Neoplasms of the mammary gland are among the most common diseases in female domestic dogs (Canis familiaris). It is assumed that reproductive hormones influence tumorigenesis in this species, although the precise role of the endocrine milieu and reproductive state is subject to continuing discussion. In line with this, a recent systematic review of available data on the development of mammary neoplasms revealed weak evidence for risk reduction after neutering and an effect of age at neutering. Investigation of several hormone receptors has revealed decreased expression of estrogen receptor-alpha (ERα, ESR1), progesterone (P4) receptor (PGR), prolactin (PRL) receptor (PRLR) and growth hormone receptor (GHR) associated with neoplastic differentiation of mammary tissues. In other studies, increased levels of estrogens, progesterone and prolactin were found in serum and/or tissue homogenates of dogs with malignant neoplasms. However, the association between these entities within one animal population was never previously examined. Therefore, this study investigated the association between circulating serum concentrations of estradiol-17β, progesterone and prolactin, and gene expression of ERα (ESR1), ERβ (ESR2), PGR, PRLR, PRL and GHR, with respect to reproductive state (spayed vs. intact) and cycle stage (anestrus vs. diestrus). Additionally, the expression of E-cadherin (CDH-1) was evaluated as a possible indicator of metastatic potential. For all receptors, the lowest gene expression was found in malignant tumors compared to normal tissues of affected dogs. Steroid levels were not influenced by their corresponding receptor expression in mammary neoplasms, but increased PRL levels were negatively associated with low PRLR gene expression in malignant tumors. The expression of CDH-1 was influenced by tumor malignancy and cycle stage, i.e., the highest gene expression was found in benign mammary tumors in diestrous dogs compared to normal and malignant mammary

  18. Biology of Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Michele Milella, Alessandra Felici

    2011-01-01

    Full Text Available In the past ten years we have made exceptional progresses in the understanding of RCC biology, particularly by recognizing the crucial pathogenetic role of activation of the HIF/VEGF and mTOR pathways. This has resulted in the successful clinical development of anti-angiogenic and mTOR-targeted drugs, which have profoundly impacted on the natural history of the disease and have improved the duration and quality of RCC patient lives. However, further improvements are still greatly needed: 1 even in patients who obtain striking clinical responses early in the course of treatment, disease will ultimately escape control and progress to a treatment-resistant state, leading to therapeutic failure; 2 prolonged disease control usually requires 'continuous' treatment, even across different treatment lines, making the impact of chronic, low-grade, toxicities on quality of life greater and precluding, for most patients, the possibility of experiencing 'drug-free holidays'; 3 although we have successfully identified classes of drugs (or molecular mechanisms of action that are effective in a substantial proportion of patients, we still fall short of molecular predictive factors that identify individual patients who will (or will not benefit from a specific intervention and still proceed on a trial-and-error basis, far from a truly 'personalized' therapeutic approach; 4 finally (and perhaps most importantly, even in the best case scenario, currently available treatments inevitably fail to definitively 'cure' metastatic RCC patients. In this review we briefly summarize recent developments in the understanding of the molecular pathogenesis of RCC, the development of resistance/escape mechanisms, the rationale for sequencing agents with different mechanisms of action, and the importance of host-related factors. Unraveling the complex mechanisms by which RCC shapes host microenvironment and immune response and therapeutic treatments, in turn, shape both cancer

  19. Indirect costs associated with metastatic breast cancer.

    Science.gov (United States)

    Wan, Yin; Gao, Xin; Mehta, Sonam; Wang, Zhixiao; Faria, Claudio; Schwartzberg, Lee

    2013-10-01

    To compare the indirect costs of productivity loss between metastatic breast cancer (MBC) and early stage breast cancer (EBC) patients, as well as their respective family members. The MarketScan Health and Productivity Management database (2005-2009) was used. Adult BC patients eligible for employee benefits of sick leave and/or short-term disability were identified with ICD-9 codes. Difference in sick leave and short-term disability days was calculated between MBC patients and their propensity score matched EBC cohort and general population (controls) during a 12-month follow-up period. Generalized linear models were used to examine the impact of MBC on indirect costs to patients and their families. A total of 139 MBC, 432 EBC, and 820 controls were eligible for sick leave and 432 MBC, 1552 EBC, and 4682 controls were eligible for short-term disability (not mutually exclusive). After matching, no statistical difference was found in sick leave days and the associated costs between MBC and EBC cohorts. However, MBC patients had significantly higher short-term disability costs than EBC patients and controls (MBC: $6166 ± $9194 vs. EBC: $3690 ± $6673 vs. $558 ± $2487, both p indirect costs compared to EBC patients' families after controlling for key covariates. Productivity loss and associated costs in MBC patients are substantially higher than EBC patients or the general population. These findings underscore the economic burden of MBC from a US societal perspective. Various treatment regimens should be evaluated to identify opportunities to reduce the disease burden from the societal perspective.

  20. Dyadic Coping in Metastatic Breast Cancer

    Science.gov (United States)

    Badr, Hoda; Carmack, Cindy L.; Kashy, Deborah A.; Cristofanilli, Massimo; Revenson, Tracey A.

    2011-01-01

    Objective Couples facing metastatic breast cancer (MBC) must learn to cope with stressors that can affect both partners' quality of life as well as the quality of their relationship. Common dyadic coping involves taking a “we” approach, whereby partners work together to maintain their relationship while jointly managing their shared stress. This study prospectively evaluated whether common dyadic coping was associated with less cancer-related distress and greater dyadic adjustment for female MBC patients and their male partners. Design Couples (N = 191) completed surveys at the start of treatment for MBC (baseline), and 3 and 6 months later. Main Outcome Measures Cancer-related distress was assessed with the Impact of Events Scale; dyadic adjustment was assessed using the short-form of the Dyadic Adjustment Scale. Results Multilevel models using the couple as the unit of analysis showed that the effects of common positive dyadic coping on cancer-related distress significantly differed for patients and their partners. Whereas partners experienced slightly lower levels of distress, patients experienced slightly higher levels of distress. Although patients and partners who used more common negative dyadic coping experienced significantly greater distress at all times, the association was stronger for patients. Finally, using more common positive dyadic coping and less common negative dyadic coping was mutually beneficial for patients and partners in terms of greater dyadic adjustment. Conclusion Our findings underscore the importance of couples working together to manage the stress associated with MBC. Future research may benefit from greater focus on the interactions between patients and their partners to address ways that couples can adaptively cope together. PMID:20230090