Radiation therapy for unresectable locally advanced breast cancer

International Nuclear Information System (INIS)

Horikawa, Noriko; Inoue, Masayoshi; Uehara, Tomoko; Miyasaka, T.; Miyasaka, M.; Tabata, Yoji; Sakamoto, Nobuyuki; Nakagawa, Y.

2013-01-01

Thirteen cases of inoperable advanced breast cancer were treated with radiotherapy between 2002 to 2012 at Nara Prefectural Hospital. All cases were treated by radiotherapy and chemo-endocrine therapy. Patients received 60-81 Gy (median 60 Gy) to the primary breast tumor. Response of the breast tumors were complete response in 3 cases (23%), partial response in 8 cases (62%) and stable disease in 2 cases (15%) (response rate: 85%). All breast tumors had been controlled and skin troubles were reduced. Radiotherapy for breast cancer is useful for primary tumor control and improved quality of life (QOL). Radiotherapy should be considered to be useful modality in the treatment of advanced breast cancer. (author)

Routine use of standard breast MRI compared to axillary ultrasound for differentiating between no, limited and advanced axillary nodal disease in newly diagnosed breast cancer patients

Energy Technology Data Exchange (ETDEWEB)

Nijnatten, T.J.A. van, E-mail: Thiemovn@gmail.com [Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, Maastricht (Netherlands); Department of Surgery, Maastricht University Medical Center+, Maastricht (Netherlands); GROW – School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht (Netherlands); Ploumen, E.H. [Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, Maastricht (Netherlands); Department of Surgery, Maastricht University Medical Center+, Maastricht (Netherlands); Schipper, RJ. [Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, Maastricht (Netherlands); Department of Surgery, Maastricht University Medical Center+, Maastricht (Netherlands); GROW – School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht (Netherlands); Department of Surgery, Catharina Hospital, Eindhoven (Netherlands); Goorts, B. [Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, Maastricht (Netherlands); Department of Surgery, Maastricht University Medical Center+, Maastricht (Netherlands); GROW – School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht (Netherlands); Andriessen, E.H. [Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, Maastricht (Netherlands); Department of Surgery, Maastricht University Medical Center+, Maastricht (Netherlands); Vanwetswinkel, S.; Schavemaker, M. [Department of Radiology and Nuclear Medicine, Maastricht University Medical Center+, Maastricht (Netherlands); Nelemans, P. [Department of Epidemiology, Maastricht University Medical Center+, Maastricht (Netherlands); Vries, B. de [Department of Pathology, Zuyderland Hospital, Heerlen (Netherlands); and others

2016-12-15

Objectives: To compare standard breast MRI to dedicated axillary ultrasound (with or without tissue sampling) for differentiating between no, limited and advanced axillary nodal disease in breast cancer patients. Methods: All patients who underwent breast MRI and dedicated axillary ultrasound between 2009 and 2014 were eligible. Exclusion criteria were recurrent disease, neoadjuvant systemic therapy and not receiving completion axillary lymph node dissection after positive sentinel lymph node biopsy (SLNB). Two radiologists independently reassessed all MRI exams. Axillary ultrasound findings were retrospectively collected. Probability of advanced axillary nodal disease (pN2-3) given clinically node negative (cN0) or limited (cN1) findings was calculated, with corresponding negative predictive value (NPV) to exclude pN2-3 and positive predictive value (PPV) to identify axillary nodal disease. Histopathology served as gold standard. Results: A total of 377 cases resulted in 81.4% no, 14.4% limited and 4.2% advanced axillary nodal disease at final histopathology. Probability of pN2-3 given cN0 for breast MRI and axillary ultrasound was 0.7–0.9% versus 1.5% and probability of pN2-3 given cN1 was 11.6–15.4% versus 29.0%. When cN1 on breast MRI was observed, PPV to identify positive axillary nodal disease was 50.7% and 59.0%. Conclusions: Evaluation of axillary nodal status on standard breast MRI is comparable to dedicated axillary ultrasound in breast cancer patients. In patients who underwent preoperative standard breast MRI, axillary ultrasound is only required in case of suspicious nodal findings on MRI.

A systematic review of dual targeting in HER2-positive breast cancer

DEFF Research Database (Denmark)

Kümler, Iben; Tuxen, Malgorzata K; Nielsen, Dorte Lisbet

2014-01-01

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is overexpresed in 15-20% of all breast cancers. Treatment with trastuzumab has led to an improved outcome and prolonged survival of HER2-positive breast cancer patients and today the drug is established as standard of care in both...... the adjuvant and metastatic settings. However, trastuzumab resistance is common and a major focus in the treatment of HER2-positive breast cancer has been developing therapeutic agents to either potentiate the effect of trastuzumab or to target cells which have become resistant to trastuzumab. The present...... of lapatinib, pertuzumab or trastuzumab-DM1 in combination with trastuzumab in the (neo)adjuvant and metastatic settings. Furthermore, combinations of trastuzumab and drugs targeting the downstream pathway are described. CONCLUSION: Dual blockade is likely to represent a substantial advance for patients...

Neoadjuvant letrozole for postmenopausal estrogen receptor-positive, HER2-negative breast cancer patients, a study from the Danish Breast Cancer Cooperative Group (DBCG)

DEFF Research Database (Denmark)

Skriver, Signe Korsgaard; Laenkholm, Anne-Vibeke; Rasmussen, Birgitte Bruun

2018-01-01

response and 55% of patients had partial pathological response. ER at 100%, ductal subtype, tumor size below 2 cm and lymph node-negative status was significantly associated with a better response to NET and malignancy grade 3 with a poorer response to NET. One patient progressed during treatment......INTRODUCTION: Neoadjuvant endocrine treatment (NET) is a low-toxicity approach to achieve operability in locally advanced breast cancer, and to facilitate breast conservation in early breast cancer, particular in patients with highly estrogen receptor (ER) positive and HER2-negative disease. Here......, we report the results obtained by neoadjuvant letrozole in patients with early breast cancer in a phase-II design. MATERIAL AND METHODS: A total of 119 postmenopausal women with ER-positive, HER2-negative operable breast cancer were assigned to four months of neoadjuvant letrozole before definitive...

Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer.

Science.gov (United States)

Burstein, Harold J; Sun, Yan; Dirix, Luc Y; Jiang, Zefei; Paridaens, Robert; Tan, Antoinette R; Awada, Ahmad; Ranade, Anantbhushan; Jiao, Shunchang; Schwartz, Gary; Abbas, Richat; Powell, Christine; Turnbull, Kathleen; Vermette, Jennifer; Zacharchuk, Charles; Badwe, Rajendra

2010-03-10

Neratinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor. The efficacy and safety of neratinib were evaluated in two cohorts of patients with advanced ErbB2-positive breast cancer-those with and those without prior trastuzumab treatment-in an open-label, multicenter, phase II trial. Patients in the two cohorts (prior trastuzumab, n = 66; no prior trastuzumab, n = 70) received oral neratinib 240 mg once daily. The primary end point was the 16-week progression-free survival (PFS) rate for the evaluable population (prior trastuzumab, n = 63; no prior trastuzumab, n = 64), as assessed by independent review. The 16-week PFS rates were 59% for patients with prior trastuzumab treatment and 78% for patients with no prior trastuzumab treatment. Median PFS was 22.3 and 39.6 weeks, respectively. Objective response rates were 24% among patients with prior trastuzumab treatment and 56% in the trastuzumab-naïve cohort. The most common adverse events were diarrhea, nausea, vomiting, and fatigue. Diarrhea was the most frequent grades 3 to 4 adverse event, occurring in 30% of patients with prior trastuzumab treatment and in 13% of patients with no prior trastuzumab treatment, which prompted dose reductions in 29% and 4% of patients, respectively, but treatment discontinuation in only one patient. No neratinib-related, grades 3 or 4 cardiotoxicity was reported. Oral neratinib showed substantial clinical activity and was reasonably well tolerated among both heavily pretreated and trastuzumab-naïve patients who had advanced, ErbB2-positive breast cancer. Diarrhea was the most common adverse effect but was manageable with antidiarrheal agents and dose modification.

Cardiac autonomic modulation impairments in advanced breast cancer patients.

Science.gov (United States)

Arab, Claudia; Vanderlei, Luiz Carlos Marques; da Silva Paiva, Laércio; Fulghum, Kyle Levi; Fristachi, Carlos Elias; Nazario, Afonso Celso Pinto; Elias, Simone; Gebrim, Luiz Henrique; Ferreira Filho, Celso; Gidron, Yori; Ferreira, Celso

2018-05-02

To compare cardiac autonomic modulation in early- versus advanced-stage breast cancer patients before any type of cancer treatment and investigate associated factors. This cross-sectional study included women (30-69 years old) with primary diagnosis of breast cancer and women with benign breast tumors. We evaluated cardiac modulation by heart rate variability and assessed factors of anxiety, depression, physical activity, and other relevant medical variables. Patients were divided into three groups based on TNM staging of cancer severity: early-stage cancer (n = 42), advanced-stage cancer (n = 37), or benign breast tumors to serve as a control (n = 37). We analyzed heart rate variability in time and frequency domains. The advanced-stage cancer group had lower vagal modulation than early-stage and benign groups; also, the advance-stage group had lower overall heart rate variability when compared to benign conditions. Heart rate variability was influenced by age, menopausal status, and BMI. Heart rate variability seems to be a promising, non-invasive tool for early diagnosis of autonomic dysfunction in breast cancer and detection of cardiovascular impairments at cancer diagnosis. Cardiac autonomic modulation is inversely associated with breast cancer staging.

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

Advanced Breast Cancer as Indicator of Quality Mammography

International Nuclear Information System (INIS)

Gaona, Enrique

2003-01-01

Breast cancer is the most frequently diagnosed cancer and is the second leading cause of cancer death among women in the Mexican Republic. Mammography is the more important screening tool for detecting early breast cancer. Screening mammography involves taking x-rays from two views from each breast, typically from above (cranial-caudal view, CC) and from an oblique or angled view (mediolateral-oblique, MLO). The purpose of this study was to carry out an exploratory survey of the issue of patients with advanced breast cancer who have had a screening mammography. A general result of the survey is that 22.5% of all patients (102) with advanced breast cancer that participated in the study had previous screening mammography. But we should consider that 10% of breast cancers are not detected by mammography. Only 70% of the family doctors prescribed a diagnostic mammography when the first symptoms were diagnosed

Improved detection of breast cancer on FDG-PET cancer screening using breast positioning device

International Nuclear Information System (INIS)

Kaida, Hayato; Ishibashi, Masatoshi; Fujii, Teruhiko; Kurata, Seiji; Ogo, Etsuyo; Hayabuchi, Naofumi; Tanaka, Maki

2008-01-01

The aim of this study was to investigate the detection rate of breast cancer by positron emission tomography cancer screening using a breast positioning device. Between January 2004 and January 2006, 1,498 healthy asymptomatic individuals underwent cancer screening by fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) at our institution; 660 of 1498 asymptomatic healthy women underwent breast PET imaging in the prone position using the breast positioning device to examine the mammary glands in addition to whole-body PET imaging. All subjects that showed abnormal 18 F-FDG uptake in the mammary glands were referred for further examination or surgery at our institution or a local hospital. Our data were compared with the histopathological findings or findings of other imaging modalities in our institution and replies from the doctors at another hospital. Of the 660 participants, 7 (1.06%) were found to have breast cancers at a curable stage. All the seven cancers were detected by breast PET imaging, but only five of these were detected by whole-body PET imaging; the other two were detected by breast PET imaging using the breast positioning device. In cancer screening, prone breast imaging using a positioning device may help to improve the detection rate of breast cancer. However, overall cancer including mammography and ultrasonography screening should be performed to investigate the false-negative cases and reduce false-positive cases. The effectiveness of prone breast PET imaging in cancer screening should be investigated using a much larger number of cases in the near future. (author)

Breast Gangrene in an HIV-Positive Patient

Science.gov (United States)

Venkatramani, V; Pillai, S; Marathe, S; Rege, SA; Hardikar, JV

2009-01-01

Introduction Breast gangrene has been reported as a complication following puerperal sepsis, breast surgery, nipple piercings, warfarin toxicity, etc. We report a case of primary breast gangrene in an HIV-positive individual which, to the best of our knowledge, is the first of its kind. Case report A 40-year-old previously healthy woman presented with fulminating left breast gangrene. She was detected to be HIV positive. Mastectomy was performed. The detailed management of the condition is discussed. Conclusion Severe necrotising infections may be initial manifestations of HIV infection and patients with such infections should be screened for HIV. PMID:19622255

CPT-11/bevacizumab for the treatment of refractory brain metastases in patients with HER2-neu-positive breast cancer.

Science.gov (United States)

Sengupta, S; Rojas, R; Mahadevan, A; Kasper, E; Jeyapalan, S

2015-04-01

Nervous system relapse of patients with advanced HER2-neu-positive breast cancer is an increasing problem, with one-third of women developing brain metastases. Standard therapies using steroids, surgery and radiotherapy do not provide a lasting response. We evaluated CPT-11 and bevacizumab, which can both cross the blood-brain barrier, as combination therapy to treat HER2-neu-positive breast cancer with brain metastases.

Treatment of locally advanced/locally recurrent breast cancer and inflammatory breast cancer

International Nuclear Information System (INIS)

Murakami, Masao

2000-01-01

This paper summarizes the treatment of locally advanced breast cancer, inflammatory breast cancer, and locally recurrent breast cancer. A multidisciplinary approach considering subclinical distant metastases is needed to treat these types of breast cancer. Subclinical distant metastasis is observed in about 80% of case of locally advanced cancer, and treatment of subclinical distant metastases, e.g., by endocrinotherapy and chemotherapy, is therefore essential to improving the prognosis. The standard therapy for unresectable locally advanced breast cancer consists of induction chemotherapy with anthracyclines and local treatment with mastectomy or irradiation. Previous reports have stated that induction chemotherapy was effective in 60-80% of the primary lesions or lymph node metastasis, and the CR rates were in the 10-20% range. Combination therapy with induction chemotherapy clearly improved the outcome over local treatment alone. The usual irradiation dose is 50 to 60 Gy/5 to 7 weeks to the whole breast or the thoracic wall. Boost irradiation at a dose of 10 to 25 Gy is performed in unresectable cases. The boost irradiation dose to the lymph node area is usually 45 to 50 Gy/5 to 6 weeks in cases without gross lesions and 10 to 15 Gy in cases with gross lesions. Combination therapy consisting of conservative pectoral mastectomy and postoperative adjuvant chemo- endocrino-therapy (i.e., adjuvant therapy) has become the standard regimen for treating resectable locally advanced breast cancer, because it significantly improves the recurrence rate and survival rate compared to local treatment alone. Some clinical have studies indicated that neoadjuvant therapy (i.e., induction chemotherapy + surgery/radiation therapy) is comparable or superior to adjuvant therapy in terms of improving the prognosis. However, the efficacy and most appropriate method of breast-conserving therapy after induction chemotherapy are still unclear. More clinical trials are needed. It has been

The role of magnetotherapy in combined treatment of advanced cancer of the breast

International Nuclear Information System (INIS)

Letyagin, V.P.; Dobrynin, Ya.V.; Rybakov, Yu.L.; Ermilova, V.D.; Protchenko, N.V.

1996-01-01

The effects of conventional treatment of advanced breast cancer (radiotherapy + chemotherapy) and its use in combination with magnetotherapy (regimen 1 and 2, respectively) have been compared. The effects on the primary breast tumors were almost similar (68 and 69 %, respectively). Positive changes in lymph nodes in response to regimens 1 and 2 occurred in 22 and 88 % of cases, respectively. Marked pathomorphosis in the tumor was observed in 48 and 56 % of patients on regimen 1 and 2, respectively. Pilot experience of magnetotherapy as an adjuvant in combined therapy of breast cancer suggests the validity of further studies of relevant effectiveness in different cancer stage and long-term administration

TIMP-1 and responsiveness to gemcitabine in advanced breast cancer

DEFF Research Database (Denmark)

Jørgensen, Charlotte Levin Tykjær; Bjerre, Christina Annette; Ejlertsen, Bent Laursen

2014-01-01

receiving GD. CONCLUSIONS: TIMP-1 status was an independent prognostic factor for OS but not TTP in patients with advanced breast cancer receiving either D or GD. There was no statistically significant interaction between TIMP-1 status and treatment, but a trend towards an incremental OS from the addition...... and predictive marker in advanced breast cancer patients receiving docetaxel (D) or gemcitabine plus docetaxel (GD). METHODS: Patients with locally advanced or metastatic breast cancer who were assigned to D or GD by participation in a randomized phase III trial were included in the study. Assessment of TIMP-1...

Positive psychology interventions in breast cancer. A systematic review.

Science.gov (United States)

Casellas-Grau, Anna; Font, Antoni; Vives, Jaume

2014-01-01

Positive psychology is an emerging area of empirical study, not only in clinical, but also in health psychology. The present systematic review aims to synthesize the evidence about the positive psychology interventions utilized in breast cancer. Relevant studies were identified via Pubmed, PsycINFO, Web of Science, Scopus, Cochrane, CINAHL, Wiley Online Library, TDX, and DIALNET databases (up to April 2013). Only those papers focused on interventions related to positive psychology and carried out on breast cancer patients were included. Of the 7266 articles found through databases, 16 studies were finally included in this review. Five groups of therapies were found: mindfulness-based approaches, expression of positive emotions, spiritual interventions, hope therapy, and meaning-making interventions. These specific interventions promoted positive changes in breast cancer participants, such as enhanced quality of life, well-being, hope, benefit finding, or optimism. However, the disparity of the interventions and some methodological issues limit the outcomes. Some studies provided relevant evidence about the clear development of positive aspects from the breast cancer experience. Positive interventions applied to patients and survivors of breast cancer were found to be able to promote positive aspects. A global consensus of a positive therapies classification is needed to take one more step in structuring positive psychology. Copyright © 2013 John Wiley & Sons, Ltd.

Factors influencing diagnosis delay of advanced breast cancer in Moroccan women

OpenAIRE

Maghous, A.; Rais, F.; Ahid, S.; Benhmidou, N.; Bellahamou, K.; Loughlimi, H.; Marnouche, E.; Elmajjaoui, S.; Elkacemi, H.; Kebdani, T.; Benjaafar, N.

2016-01-01

Background Delay in the diagnosis of breast cancer in symptomatic women of 3?months or more is associated with advanced stage and low survival. We conducted this study to learn more about the extent and reasons behind diagnosis delay of advanced breast cancer in Moroccan women. Methods A group of patients with advanced breast cancer were interviewed at the National Institute of Oncology in Rabat during the period from February to December 2014. Diagnosis delay was devised into patient delay a...

CPT-11/bevacizumab for the treatment of refractory brain metastases in patients with HER2–neu-positive breast cancer

Science.gov (United States)

Sengupta, S.; Rojas, R.; Mahadevan, A.; Kasper, E.; Jeyapalan, S.

2015-01-01

Nervous system relapse of patients with advanced HER2–neu-positive breast cancer is an increasing problem, with one-third of women developing brain metastases. Standard therapies using steroids, surgery and radiotherapy do not provide a lasting response. We evaluated CPT-11 and bevacizumab, which can both cross the blood–brain barrier, as combination therapy to treat HER2–neu-positive breast cancer with brain metastases. PMID:26634139

Three-dimensional conformal breast irradiation in the prone position

Directory of Open Access Journals (Sweden)

C. Kurtman

2003-10-01

Full Text Available The prone position can be used for the planning of adjuvant radiotherapy after conservative breast surgery in order to deliver less irradiation to lung and cardiac tissue. In the present study, we compared the results of three-dimensional conformal radiotherapy planning for five patients irradiated in the supine and prone position. Tumor stage was T1N0M0 in four patients and T1N1M0 in one. All patients had been previously submitted to conservative breast surgery. Breast size was large in three patients and moderate in the other two. Irradiation in the prone position was performed using an immobilization foam pad with a hole cut into it to accommodate the breast so that it would hang down away from the chest wall. Dose-volume histograms showed that mean irradiation doses reaching the ipsilateral lung were 8.3 ± 3.6 Gy with the patient in the supine position and 1.4 ± 1.0 Gy with the patient in the prone position (P = 0.043. The values for the contralateral lung were 1.3 ± 0.7 and 0.3 ± 0.1 Gy (P = 0.043 and the values for cardiac tissue were 4.6 ± 1.6 and 3.0 ± 1.7 Gy (P = 0.079, respectively. Thus, the dose-volume histograms demonstrated that lung tissue irradiation was significantly lower with the patient in the prone position than in the supine position. Large-breasted women appeared to benefit most from irradiation in the prone position. Prone position breast irradiation appears to be a simple and effective alternative to the conventional supine position for patients with large breasts, since they are subjected to lower pulmonary doses which may cause less pulmonary side effects in the future.

Socioeconomic position and breast reconstruction in Danish women

DEFF Research Database (Denmark)

Hvilsom, Gitte B; Hölmich, Lisbet R; Frederiksen, Kirsten Skovsgaard

2011-01-01

Few studies have been conducted on the socioeconomic position of women undergoing breast reconstruction, and none have been conducted in the Danish population. We investigated the association between educational level and breast reconstruction in a nationwide cohort of Danish women with breast...

Women with inoperable or locally advanced breast cancer -- what characterizes them?

DEFF Research Database (Denmark)

El-Charnoubi, Waseem Asim Ghulam; Svendsen, Jesper Brink; Tange, Ulla Brix

2012-01-01

Breast cancer is the most common cancer among Danish women. Locally advanced breast cancer occurs in a relatively large proportion of all new primary breast cancer diagnoses and for unexplained reasons 20-30% of women with breast cancer wait more than eight weeks from the initial breast cancer...

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.

Interventional therapy of advanced and/or recurrent breast cancer

International Nuclear Information System (INIS)

Wang Zhiliang; Fan Ye; Cao Jun; Yan Liping; Yang Ya

2004-01-01

Objective: To evaluate the clinical efficacy of intraarterial infusion chemotherapy in patients with advanced and/or recurrent breast cancer. Methods: From February 2000 to March 2003, 18 patients with advanced and/or recurrent breast cancer were treated with interaarterial chemotherapy (IAC). The Seldinger's technique was used in all patients. IAC was administered for 2-3 courses every 3-4 weeks for each patient. Results: The procedure was successfully performed in all 18 patients including one with a complete response, 12 of a partial response, none in 3, and with progression in 2. The overall response rate was 72.2%. The frequent adverse effects were fever, leukopenia, nausea, and vomiting but no severe complication occurred. Conclusion: Intraarterial infusion chemotherapy is a safe, simple, complication-free and effective in the patients with advanced and/or recurrent breast cancer. (authors)

Follow-up of patients with localized breast cancer and first indicators of advanced breast cancer recurrence: A retrospective study.

Science.gov (United States)

Viot, Julien; Bachour, Martin; Meurisse, Aurélia; Pivot, Xavier; Fiteni, Frédéric

2017-08-01

We conducted a retrospective study to assess the follow-up of patients with localized breast cancer and the first indicators of advanced breast cancer recurrence. All patients with advanced breast cancer recurrence treated between January 2010 and June 2016 in our institution were registered. Among these patients, 303 patients initially treated for early breast cancer with curative intent were identified. After initial curative treatment, follow-up involved the oncologist, the general practitioner and the gynecologist in 68.0%, 48.9% and 19.1% of cases, respectively. The median DFI was 4 years for luminal A, 3.8 years for luminal B, 3.7 years for HER2-positive and 1.5 years for TNBC (p = 0.07). Breast cancer tumor marker was prescribed for 164 patients (54.1%). No difference in terms of follow-up was observed according to the molecular subtype. Symptoms were the primary indicator of relapse for 143 patients (47.2%). Breast cancer recurrence was discovered by CA 15.3 elevation in 57 patients (18.8%) and by CAE elevation in 3 patients (1%). The rate of relapse diagnosed by elevation of CA 15.3 or CAE was not statistically associated with the molecular subtype (p = 0.65). Luminal A cases showed a significantly higher rate of bone metastases (p = 0.0003). TNBC cases showed a significantly higher rate of local recurrence (p = 0.002) and a borderline statistical significant higher rate of lung/pleural metastases (p = 0.07). Follow-up recommendations could be adapted in clinical practice according to the molecular subtype. General practitioners should be more involved by the specialists in breast cancer follow-up. Copyright © 2017 Elsevier Ltd. All rights reserved.

Radiotherapy Boost Following Conservative Surgery for Locally Advanced Breast Cancer

International Nuclear Information System (INIS)

Cendales, Ricardo; Ospino, Rosalba; Torres, Felipe; Cotes, Martha

2009-01-01

Nearly half of breast cancer patients in developing countries present with a locally advanced cancer. Treatment is centered on a multimodal approach based on chemotherapy, surgery and radiotherapy. The growing use of neoadjuvant chemotherapy has led to a more conservative surgical approach; nonetheless, it is not yet considered as a standard. There are no clear recommendations on the use of a radiotherapy boost in such situation. A Medline search was developed. Most articles are retrospective series. Survival free of locoregional relapse in patients treated with neoadjuvant chemotherapy, breast conserving surgery and radiotherapy is good. All articles described a boost administered to nearly all patients without regard to their prognostic factors, given that a locally advanced tumor is already considered as a poor prognostic factor. Even tough the poor level of evidence, a recommendation can be made: radiotherapy boost should be administered to all patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and breast conserving surgery.

The influence of patient positioning in breast CT on breast tissue coverage and patient comfort

Energy Technology Data Exchange (ETDEWEB)

Roessler, A.C.; Althoff, F.; Kalender, W. [Erlangen Univ. (Germany). Inst. of Medical Physics; Wenkel, E. [University Hospital of Erlangen (Germany). Radiological Inst.

2015-02-15

The presented study aimed at optimizing a patient table design for breast CT (BCT) systems with respect to breast tissue coverage and patient comfort. Additionally, the benefits and acceptance of an immobilization device for BCT using underpressure were evaluated. Three different study parts were carried out. In a positioning study women were investigated on an MRI tabletop with exchangeable inserts (flat and cone-shaped with different opening diameters) to evaluate their influence on breast coverage and patient comfort in various positioning alternatives. Breast length and volume were calculated to compare positioning modalities including various opening diameters and forms. In the second study part, an underpressure system was tested for its functionality and comfort on a stereotactic biopsy table mimicking a future CT scanner table. In the last study part, this system was tested regarding breast tissue coverage. Best results for breast tissue coverage were shown for cone-shaped table inserts with an opening of 180 mm. Flat inserts did not provide complete coverage of breast tissue. The underpressure system showed robust function and tended to pull more breast tissue into the field of view. Patient comfort was rated good for all table inserts, with highest ratings for cone-shaped inserts. Cone-shaped tabletops appeared to be adequate for BCT systems and to allow imaging of almost the complete breast. An underpressure system proved promising for the fixation of the breast during imaging and increased coverage. Patient comfort appears to be adequate.

An approach to the management of locally advanced breast cancer ...

African Journals Online (AJOL)

Locally advanced breast cancer (LABC) comprises a heterogeneous group of diseases. It incorporates a subset of stage IIB (T3N0) disease, stage III disease and inflammatory breast cancer. In the developed world, 7% of breast cancer patients have stage III disease at diagnosis. In developing countries, LABC constitutes ...

Treatment of advanced breast cancer. An experience

Energy Technology Data Exchange (ETDEWEB)

Magnoni, G; Corcione, S; Api, P

1984-01-01

The Authors report their experience about the efficacy of the association surgery-radiotherapy-polichemotherapy, in the treatment of advanced breast cancer, emphasizing the importance of this association in the survival rate.

HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer

International Nuclear Information System (INIS)

Miller, Kathy; Cortes, Javier; Hurvitz, Sara A.; Krop, Ian E.; Tripathy, Debu; Verma, Sunil; Riahi, Kaveh; Reynolds, Joseph G.; Wickham, Thomas J.; Molnar, Istvan; Yardley, Denise A.

2016-01-01

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a particularly aggressive form of the disease, and ultimately progresses in patients with metastases on standard therapies. Anthracyclines, such as doxorubicin, are an effective treatment for HER2-positive breast cancer, particularly when administered in combination with trastuzumab – however, doxorubicin-related cardiotoxicity has limited its use. Many patients are therefore never treated with anthracyclines, even upon disease progression, despite the potential for benefit. MM-302 is a novel, HER2-targeted antibody–liposomal doxorubicin conjugate that specifically targets HER2-overexpressing cells. Preclinical and Phase 1 data suggest that MM-302, as a monotherapy or in combination with trastuzumab, could be effective for managing previously treated, anthracycline-naïve, HER2-positive breast cancer, without the cardiotoxicity observed with free doxorubicin formulations. HERMIONE is an open-label, multicenter, randomized (1:1) Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice (gemcitabine, capecitabine, or vinorelbine) plus trastuzumab planned to enroll 250 anthracycline-naïve patients with locally advanced/metastatic HER2-positive breast cancer. Key inclusion criteria are: previous treatment with trastuzumab (with or without pertuzumab) in any setting; refractory or intolerant to pertuzumab (refractory to pertuzumab defined as progression in the locally advanced or metastatic setting, or disease recurrence during or within 12 months of completing pertuzumab-containing neoadjuvant and/or adjuvant therapy); and disease progression on, or intolerant to, ado-trastuzumab emtansine for locally advanced or metastatic disease. The trial is currently being conducted at sites in the USA, Canada, and Western Europe. Treatment will be administered in 21-day cycles, and will be continued until disease progression or unacceptable toxicity. The primary endpoint is

Radiotherapy for advanced breast cancer. Immediate results

Energy Technology Data Exchange (ETDEWEB)

Lederman, M V; Silveira Filho, L; Martorelli Filho, B [Sao Paulo Univ. (Brazil). Faculdade de Medicina

1976-01-01

Seventy-four patients with advanced breast cancer were submited to local radiotherapy of the affected regions. The response of 155 metastatic lesions are recorded. Early results are good, with objective and functional clinical improvement.

Radiotherapy for advanced breast cancer. Immediate results

International Nuclear Information System (INIS)

Lederman, M.V.; Silveira Filho, L.; Martorelli Filho, B.

1976-01-01

Seventy-four patients with advanced breast cancer were submited to local radiotherapy of the affected regions. The response of 155 metastatic lesions are recorded. Early results are good, with objective and functional clinical improvement [pt

Advance Care Planning: Experience of Women With Breast Cancer

Science.gov (United States)

2006-07-01

recorded along with other characteristics. Inclusion criteria for the primary studies required that women with breast cancer be at least 21 years of age; cog ...W81XWH-04-1-0469 TITLE: Advance Care Planning: Experience of Women with Breast Cancer PRINCIPAL INVESTIGATOR: Ardith Z. Doorenbos...with Breast Cancer 5b. GRANT NUMBER W81XWH-04-1-0469 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Ardith Z. Doorenbos, Ph.D

Review of hormone-based treatments in postmenopausal patients with advanced breast cancer focusing on aromatase inhibitors and fulvestrant

DEFF Research Database (Denmark)

Kümler, Iben; Knoop, Ann S; Jessing, Christina A R

2016-01-01

. However, overall survival was not significantly increased. CONCLUSION: Conventional treatment with an aromatase inhibitor or fulvestrant may be an adequate treatment option for most patients with hormone receptor-positive advanced breast cancer. Mammalian target of rapamycin (mTOR) inhibition and cyclin...

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.

The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model.

Science.gov (United States)

Birnbaum, Jeanette; Gadi, Vijayakrishna K; Markowitz, Elan; Etzioni, Ruth

2016-02-16

Mammography trials, which are the primary sources of evidence for screening benefit, were conducted decades ago. Whether advances in systemic therapies have rendered previously observed benefits of screening less significant is unknown. To compare the outcomes of breast cancer screening trials had they been conducted using contemporary systemic treatments with outcomes of trials conducted with previously used treatments. Computer simulation model of 3 virtual screening trials with similar reductions in advanced-stage cancer cases but reflecting treatment patterns in 1975 (prechemotherapy era), 1999, or 2015 (treatment according to receptor status). Meta-analyses of screening and treatment trials; study of dissemination of primary systemic treatments; SEER (Surveillance, Epidemiology, and End Results) registry. U.S. women aged 50 to 74 years. 10 and 25 years. Population. Mammography, chemotherapy, tamoxifen, aromatase inhibitors, and trastuzumab. Breast cancer mortality rate ratio (MRR) and absolute risk reduction (ARR) obtained by the difference in cumulative breast cancer mortality between control and screening groups. At 10 years, screening in a 1975 trial yielded an MRR of 90% and an ARR of 5 deaths per 10,000 women. A 2015 screening trial yielded a 10-year MRR of 90% and an ARR of 3 deaths per 10,000 women. Greater reductions in advanced-stage disease yielded a greater screening effect, but MRRs remained similar across trials. However, ARRs were consistently lower under contemporary treatments. When contemporary treatments were available only for early-stage cases, the MRR was 88%. Disease models simplify reality and cannot capture all breast cancer subtypes. Advances in systemic therapies for breast cancer have not substantively reduced the relative benefits of screening but have likely reduced the absolute benefits because of their positive effect on breast cancer survival. University of Washington and National Cancer Institute.

Preoperative axillary lymph node evaluation in breast cancer patients by breast magnetic resonance imaging (MRI): Can breast MRI exclude advanced nodal disease?

International Nuclear Information System (INIS)

Hyun, Su Jeong; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Kim, Min Jung

2016-01-01

To evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in preoperative evaluation of axillary lymph node metastasis (ALNM) in breast cancer patients and to assess whether breast MRI can be used to exclude advanced nodal disease. A total of 425 patients were included in this study and breast MRI findings were retrospectively reviewed. The diagnostic performance of breast MRI for diagnosis of ALNM was evaluated in all patients, patients with neoadjuvant chemotherapy (NAC), and those without NAC (no-NAC). We evaluated whether negative MRI findings (cN0) can exclude advanced nodal disease (pN2-pN3) using the negative predictive value (NPV) in each group. The sensitivity and NPV of breast MRI in evaluation of ALNM was 51.3 % (60/117) and 83.3 % (284/341), respectively. For cN0 cases on MRI, pN2-pN3 manifested in 1.8 % (6/341) of the overall patients, 0.4 % (1/257) of the no-NAC group, and 6 % (5/84) of the NAC group. The NPV of negative MRI findings for exclusion of pN2-pN3 was higher for the no-NAC group than for the NAC group (99.6 % vs. 94.0 %, p = 0.039). Negative MRI findings (cN0) can exclude the presence of advanced nodal disease with an NPV of 99.6 % in the no-NAC group. (orig.)

Preoperative axillary lymph node evaluation in breast cancer patients by breast magnetic resonance imaging (MRI): Can breast MRI exclude advanced nodal disease?

Energy Technology Data Exchange (ETDEWEB)

Hyun, Su Jeong [Yonsei University College of Medicine, Department of Radiology, Breast Cancer Clinic, Severance Hospital, Research Institute of Radiological Science, Seoul (Korea, Republic of); Hallym University Medical Center, Department of Radiology, Kangnam Sacred Heart Hospital, Seoul (Korea, Republic of); Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Kim, Min Jung [Yonsei University College of Medicine, Department of Radiology, Breast Cancer Clinic, Severance Hospital, Research Institute of Radiological Science, Seoul (Korea, Republic of)

2016-11-15

To evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in preoperative evaluation of axillary lymph node metastasis (ALNM) in breast cancer patients and to assess whether breast MRI can be used to exclude advanced nodal disease. A total of 425 patients were included in this study and breast MRI findings were retrospectively reviewed. The diagnostic performance of breast MRI for diagnosis of ALNM was evaluated in all patients, patients with neoadjuvant chemotherapy (NAC), and those without NAC (no-NAC). We evaluated whether negative MRI findings (cN0) can exclude advanced nodal disease (pN2-pN3) using the negative predictive value (NPV) in each group. The sensitivity and NPV of breast MRI in evaluation of ALNM was 51.3 % (60/117) and 83.3 % (284/341), respectively. For cN0 cases on MRI, pN2-pN3 manifested in 1.8 % (6/341) of the overall patients, 0.4 % (1/257) of the no-NAC group, and 6 % (5/84) of the NAC group. The NPV of negative MRI findings for exclusion of pN2-pN3 was higher for the no-NAC group than for the NAC group (99.6 % vs. 94.0 %, p = 0.039). Negative MRI findings (cN0) can exclude the presence of advanced nodal disease with an NPV of 99.6 % in the no-NAC group. (orig.)

Patterns of resource utilization and cost for postmenopausal women with hormone-receptor–positive, human epidermal growth factor receptor-2–negative advanced breast cancer in Europe

International Nuclear Information System (INIS)

Jerusalem, Guy; Neven, Patrick; Marinsek, Nina; Zhang, Jie; Degun, Ravi; Benelli, Giancarlo; Saletan, Stephen; Ricci, Jean-François; Andre, Fabrice

2015-01-01

Healthcare resource utilization in breast cancer varies by disease characteristics and treatment choices. However, lack of clarity in guidelines can result in varied interpretation and heterogeneous treatment management and costs. In Europe, the extent of this variability is unclear. Therefore, evaluation of chemotherapy use and costs versus hormone therapy across Europe is needed. This retrospective chart review (N = 355) examined primarily direct costs for chemotherapy versus hormone therapy in postmenopausal women with hormone-receptor–positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer across 5 European countries (France, Germany, The Netherlands, Belgium, and Sweden). Total direct costs across the first 3 treatment lines were approximately €10 000 to €14 000 lower for an additional line of hormone therapy-based treatment versus switching to chemotherapy-based treatment. Direct cost difference between chemotherapy-based and hormone therapy-based regimens was approximately €1900 to €2500 per month. Chemotherapy-based regimens were associated with increased resource utilization (managing side effects; concomitant targeted therapy use; and increased frequencies of hospitalizations, provider visits, and monitoring tests). The proportion of patients taking sick leave doubled after switching from hormone therapy to chemotherapy. These results suggest chemotherapy is associated with increased direct costs and potentially with increased indirect costs (lower productivity of working patients) versus hormone therapy in HR+, HER2– advanced breast cancer. The online version of this article (doi:10.1186/s12885-015-1762-3) contains supplementary material, which is available to authorized users

TU-EF-207-00: Advances in Breast Imaging

Energy Technology Data Exchange (ETDEWEB)

NONE

2015-06-15

Breast imaging technology is advancing on several fronts. In digital mammography, the major technological trend has been on optimization of approaches for performing combined mammography and tomosynthesis using the same system. In parallel, photon-counting slot-scan mammography is now in clinical use and more efforts are directed towards further development of this approach for spectral imaging. Spectral imaging refers to simultaneous acquisition of two or more energy-windowed images. Depending on the detector and associated electronics, there are a number of ways this can be accomplished. Spectral mammography using photon-counting detectors can suppress electronic noise and importantly, it enables decomposition of the image into various material compositions of interest facilitating quantitative imaging. Spectral imaging can be particularly important in intravenously injected contrast mammography and eventually tomosynthesis. The various approaches and applications of spectral mammography are discussed. Digital breast tomosynthesis relies on the mechanical movement of the x-ray tube to acquire a number of projections in a predefined arc, typically from 9 to 25 projections over a scan angle of +/−7.5 to 25 degrees depending on the particular system. The mechanical x-ray tube motion requires relatively long acquisition time, typically between 3.7 to 25 seconds depending on the system. Moreover, mechanical scanning may have an effect on the spatial resolution due to internal x-ray filament or external mechanical vibrations. New x-ray source arrays have been developed and they are aimed at replacing the scanned x-ray tube for improved acquisition time and potentially for higher spatial resolution. The potential advantages and challenges of this approach are described. Combination of digital mammography and tomosynthesis in a single system places increased demands on certain functional aspects of the detector and overall performance, particularly in the tomosynthesis

A phase II study of combined ridaforolimus and dalotuzumab compared with exemestane in patients with estrogen receptor-positive breast cancer

DEFF Research Database (Denmark)

Baselga, José; Morales, Serafin M.; Awada, Ahmad

2017-01-01

Purpose: Combining the mTOR inhibitor ridaforolimus and the anti-IGFR antibody dalotuzumab demonstrated antitumor activity, including partial responses, in estrogen receptor (ER)-positive advanced breast cancer, especially in high proliferation tumors (Ki67 > 15%). Methods: This randomized...

Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

Directory of Open Access Journals (Sweden)

Guilherme Freire Angotti Carrara

Full Text Available OBJECTIVE: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04. A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01. CONCLUSIONS: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.

Experience about the treatment of advanced breast cancer

Energy Technology Data Exchange (ETDEWEB)

Api, P; Corcione, S; Magnoni, G

1985-01-01

The authors report their experience about the efficacy of the association surgery-radiotherapy-polichemotheraphy, in the treatment of advanced breast cancer, emphasizing the importance of this association in the survival rate.

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.

Factors influencing diagnosis delay of advanced breast cancer in Moroccan women.

Science.gov (United States)

Maghous, A; Rais, F; Ahid, S; Benhmidou, N; Bellahamou, K; Loughlimi, H; Marnouche, E; Elmajjaoui, S; Elkacemi, H; Kebdani, T; Benjaafar, N

2016-06-07

Delay in the diagnosis of breast cancer in symptomatic women of 3 months or more is associated with advanced stage and low survival. We conducted this study to learn more about the extent and reasons behind diagnosis delay of advanced breast cancer in Moroccan women. A group of patients with advanced breast cancer were interviewed at the National Institute of Oncology in Rabat during the period from February to December 2014. Diagnosis delay was devised into patient delay and system delay. Patient delay was defined as time from first symptoms until first medical consultation. System delay was defined as time from first presentation to a health care provider until definite diagnosis or treatment. Prospective information and clinical data were collected on a form during an interview with each patient and from medical records. In all, 137 patients were interviewed. The mean age of women was 48.3 ± 10.4 years. The median of consultation time was 6[4,12] months and the median of diagnosis time was 1[1,3] months. Diagnosis delay was associated to a personal reason in 96 (70.1 %) patients and to a medical reason in 19 (13.9 %) patients. A number of factors predicted diagnosis delay: symptoms were not considered serious in 66 (55.9 %) patients; traditional therapy was applied in 15 (12.7 %) patients and fear of cancer diagnosis and/or treatment in 14 (11.9 %) patients. A use of traditional methods was significantly associated with rural residence and far away from basic health center (p = 0.000). Paradoxically, a family history of breast cancer was significantly higher in who report a fear of cancer diagnosis and/or treatment to diagnosis delay (p Diagnosis delay is very serious problem in Morocco. Diagnosis delay was associated with complex interactions between several factors and with advanced stages. There is a need for improving breast cancer information in our populations and training of general practitioners to reduce advanced breast cancer by

TU-AB-204-04: Advances in CBCT for Breast Imaging

International Nuclear Information System (INIS)

Boone, J.

2015-01-01

assessment of novel therapies. Finally, Dr. J. Boone (UC Davis) will present on the topic: Advances in CBCT for Breast Imaging. Breast CT has been studied as an imaging tool for diagnostic breast evaluation and for potential breast cancer screening. The breast CT application lends itself to CBCT because of the small dimensions of the breast, the tapered shape of the breast towards higher cone angle, and the fact that there are no bones in the breast. The performance of various generations of breast CT scanners developed in recent years will be discussed, focusing on advances in spatial resolution and image noise characteristics. The results will also demonstrate the results of clinical trials using both computer and human observers. Learning Objectives: Understand the challenges, key technological advances, and emerging opportunities of CBCT in: Brain perfusion imaging, including assessment of ischemic stroke Cardiac imaging for functional assessment in cardiac interventions Orthopedics imaging for evaluation of musculoskeletal trauma, arthritis, and osteoporosis Breast imaging for screening and diagnosis of breast cancer. Work presented in this symposium includes research support by: Siemens Healthcare (Dr. Chen); NIH and Siemens Healthcare (Dr. Fahrig); NIH and Carestream Health (Dr. Zbijewski); and NIH (Dr. Boone)

TU-AB-204-04: Advances in CBCT for Breast Imaging

Energy Technology Data Exchange (ETDEWEB)

Boone, J. [University of California Davis School of Medicine (United States)

2015-06-15

assessment of novel therapies. Finally, Dr. J. Boone (UC Davis) will present on the topic: Advances in CBCT for Breast Imaging. Breast CT has been studied as an imaging tool for diagnostic breast evaluation and for potential breast cancer screening. The breast CT application lends itself to CBCT because of the small dimensions of the breast, the tapered shape of the breast towards higher cone angle, and the fact that there are no bones in the breast. The performance of various generations of breast CT scanners developed in recent years will be discussed, focusing on advances in spatial resolution and image noise characteristics. The results will also demonstrate the results of clinical trials using both computer and human observers. Learning Objectives: Understand the challenges, key technological advances, and emerging opportunities of CBCT in: Brain perfusion imaging, including assessment of ischemic stroke Cardiac imaging for functional assessment in cardiac interventions Orthopedics imaging for evaluation of musculoskeletal trauma, arthritis, and osteoporosis Breast imaging for screening and diagnosis of breast cancer. Work presented in this symposium includes research support by: Siemens Healthcare (Dr. Chen); NIH and Siemens Healthcare (Dr. Fahrig); NIH and Carestream Health (Dr. Zbijewski); and NIH (Dr. Boone)

Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline.

Science.gov (United States)

Ramakrishna, Naren; Temin, Sarah; Chandarlapaty, Sarat; Crews, Jennie R; Davidson, Nancy E; Esteva, Francisco J; Giordano, Sharon H; Gonzalez-Angulo, Ana M; Kirshner, Jeffrey J; Krop, Ian; Levinson, Jennifer; Modi, Shanu; Patt, Debra A; Perez, Edith A; Perlmutter, Jane; Winer, Eric P; Lin, Nancy U

2014-07-01

To provide formal expert consensus-based recommendations to practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer. The American Society of Clinical Oncology (ASCO) convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic review of the literature. When that failed to yield sufficiently strong quality evidence, the Expert Panel undertook a formal expert consensus-based process to produce these recommendations. ASCO used a modified Delphi process. The panel members drafted recommendations, and a group of other experts joined them for two rounds of formal ratings of the recommendations. No studies or existing guidelines met the systematic review criteria; therefore, ASCO conducted a formal expert consensus-based process. Patients with brain metastases should receive appropriate local therapy and systemic therapy, if indicated. Local therapies include surgery, whole-brain radiotherapy, and stereotactic radiosurgery. Treatments depend on factors such as patient prognosis, presence of symptoms, resectability, number and size of metastases, prior therapy, and whether metastases are diffuse. Other options include systemic therapy, best supportive care, enrollment onto a clinical trial, and/or palliative care. Clinicians should not perform routine magnetic resonance imaging (MRI) to screen for brain metastases, but rather should have a low threshold for MRI of the brain because of the high incidence of brain metastases among patients with HER2-positive advanced breast cancer. © 2014 by American Society of Clinical Oncology.

Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Older Patients With Locally Advanced or Metastatic Breast Cancer

Science.gov (United States)

2018-03-05

Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

The Aesthetically Ideal Position of the Nipple-Areola Complex on the Breast.

Science.gov (United States)

Lewin, Richard; Amoroso, Matteo; Plate, Nikolina; Trogen, Clara; Selvaggi, Gennaro

2016-10-01

Several studies have attempted to identify an objective description of the aesthetically ideal breast, but they have all suffered in their reliability because of having several intrinsic limitations. It is therefore essential to design a template of ideal breast features in order to predict and evaluate aesthetic outcomes in both reconstructive and cosmetic breast surgery. The aim of this study was to determine the aesthetically preferred position of the nipple-areola complex on the breast. A questionnaire was sent by regular mail to 1000 men and 1000 women aged between 16 and 74 years. They were asked to rank the attractiveness of a series of breasts of women in images with different NAC positions. The images showed breasts from two different angles: 12 frontal-view images with both breasts shown, and five side-view images with only one breast shown. All of the breasts had equal dimensions and proportions, with the same areola size but different NAC positions. Statistical analysis of data was carried out. Eight hundred and thirteen of 2000 participants completed the questionnaire. The NAC placement preferred by both genders had a ratio of 40:60 x and 50:50 y, which means that it was best situated in the middle of the breast gland vertically and slightly lateral to the midpoint horizontally. Significant differences were found between the age and gender subgroup preferences. This study identified the preferred position of the nipple-areola complex on the female breast in the general population. This is an important information when planning breast reconstructive and cosmetic surgery. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Serum soluble ST2 is associated with ER-positive breast cancer

International Nuclear Information System (INIS)

Lu, Da-peng; Zhou, Xiang-yu; Yao, Lu-tian; Liu, Cai-gang; Ma, Wei; Jin, Feng; Wu, Yun-fei

2014-01-01

ST2, a member of the interleukin (IL)-1receptor family, regulates Th1/Th2 immune responses in autoimmune and inflammatory conditions. However, the role of ST2 signaling in tumor growth and metastasis of breast cancers has not been investigated. This study investigated the possible role of soluble ST2 (sST2) in breast cancer. The serum levels of IL-33, sST2, and vascular endothelial growth factor (VEGF) in 150 breast cancer patients and 90 healthy women were measured by enzyme-linked immunosorbent assay. Estrogen receptor(ER), progesterone receptor, human epithelial receptor (HER)-2, and cell cycle regulated protein Ki-67 were measured. Clinical stage, tumor size, lymph node metastasis, and histological type were also recorded. The serum levels of sST2, IL-33, and VEGF were significantly higher in breast cancer patients than in the control group (P < 0.05, each). Serum sST2 levels in ER-positive breast cancer patients were significantly associated with age, histological type, clinical stage, tumor size, and Ki-67 status (P < 0.05, each). Moreover, the serum levels of IL-33 and sST2 in breast cancers significantly correlated with VEGF levels (IL-33: r = 0.375, P < 0.0001; sST2: r = 0.164, P = 0.045). Serum levels of sST2, IL-33, and VEGF decreased after modified radical mastectomy in ER-positive breast cancers. Serum levels of IL-33, sST2, and VEGF and clinicopathological factors were not significantly correlated with disease-free survival and overall survival of ER-positive breast cancer women during follow-up. Serum sST2 levels in ER-positive breast cancer patients are significantly associated with factors that indicate poor prognosis

Adjuvant neutron therapy in complex treatment of patients with locally advanced breast cancer

Science.gov (United States)

Lisin, V. A.; Velikaya, V. V.; Startseva, Zh. A.; Popova, N. O.; Goldberg, V. E.

2017-09-01

The study included 128 patients with stage T2-4N0-3M0 locally advanced breast cancer. All patients were divided into two groups. Group I (study group) consisted of 68 patients, who received neutron therapy, and group II (control group) comprised 60 patients, who received electron beam therapy. Neutron therapy was well tolerated by the patients and 1-2 grade radiation skin reactions were the most common. Neutron therapy was shown to be effective in multimodality treatment of the patients with locally advanced breast cancer. The 8-year recurrence-free survival rate in the patients with locally advanced breast cancer was 94.5 ± 4.1% after neutron therapy and 81.4 ± 5.9% after electron beam therapy (p = 0.05).

Preliminary Results on Setup Precision of Prone-Lateral Patient Positioning for Whole Breast Irradiation

International Nuclear Information System (INIS)

Veldeman, Liv; Speleers, Bruno; Bakker, Marlies; Jacobs, Filip; Coghe, Marc; De Gersem, Werner; Impens, Aline; Nechelput, Sarah; De Wagter, Carlos

2010-01-01

Purpose: The aim of this study was to develop a rapid and reproducible technique for prone positioning and to compare dose-volume indices in prone and supine positions. Methods and Materials: Eighteen patients underwent computed tomography imaging for radiotherapy planning in prone and supine position. Experience was gained in the first eight patients, which lead to modifications of the Horizon prone breast board (Civco Medical Solutions, Orange City, Iowa, USA) and the patient setup technique. A unilateral breast holder (U-BH) was developed (Van de Velde, Schellebelle, Belgium) to retract the contralateral breast away from the treated breast. The technique was then applied to an additional 10 patients. The setup precision was evaluated using daily cone-beam CT. Results: Modifications to the breast board were made to secure a prone-lateral rather then a pure prone position. We evolved from a classical setup using laser marks on the patients' body to a direct breast setup using marks on the breast only. The setup precision of the direct positioning procedure with the modified breast board and the U-BH is comparable to supine setup data in the literature. Dose-volume indices for heart and lung show significantly better results for prone than for supine position, and dose homogeneity within the treated breast did not differ according to the treatment position. Conclusions: The setup precision of our prone-lateral positioning technique is comparable to supine data in literature. Our data show the advantage of prone radiotherapy to spare the lung and heart. Further research is necessary to reduce the duration of prone setup.

Lapatinib for treatment of advanced or metastasized breast cancer: systematic review.

Science.gov (United States)

Riera, Rachel; Soárez, Patrícia Coelho de; Puga, Maria Eduarda Dos Santos; Ferraz, Marcos Bosi

2009-09-01

Around 16% to 20% of women with breast cancer have advanced, metastasized breast cancer. At this stage, the disease is treatable, but not curable. The objective here was to assess the effectiveness of lapatinib for treating patients with advanced or metastasized breast cancer. Systematic review of the literature, developed at Centro Paulista de Economia da Saúde (CPES), Universidade Federal de São Paulo (Unifesp). Systematic review with searches in virtual databases (PubMed, Lilacs [Literatura Latino-Americana e do Caribe em Ciências da Saúde], Cochrane Library, Scirus and Web of Science) and manual search. Only one clinical trial that met the selection criteria was found. This study showed that lapatinib in association with capecitabine reduced the risk of cancer progression by 51% (95% confidence interval, CI: 0.34-0.71; P < 0.001), compared with capecitabine alone, without any increase in severe adverse effects. The combination of lapatinib plus capecitabine was more effective than capecitabine alone for reducing the risk of cancer progression. Further randomized clinical trials need to be carried out with the aim of assessing the effectiveness of lapatinib as monotherapy or in association for first-line or second-line treatment of advanced breast cancer.

Prospective study of postoperative whole breast radiotherapy for Japanese large-breasted women: a clinical and dosimetric comparisons between supine and prone positions and a dose measurement using a breast phantom

International Nuclear Information System (INIS)

Takahashi, Kana; Morota, Madoka; Kagami, Yoshikazu; Okamoto, Hiroyuki; Sekii, Shuhei; Inaba, Koji; Murakami, Naoya; Igaki, Hiroshi; Ito, Yoshinori; Uno, Takashi; Itami, Jun

2016-01-01

This prospective study aimed to compare dose volume histograms (DVH) of the breasts and organs at risk (OARs) of whole breast radiotherapy in the supine and prone positions, and frequency and severity of acute and late toxicities were analyzed. Early-stage breast cancer patients with large breasts (Japanese bra size C or larger, or the widest measurements of the bust ≥ 95 cm) undergoing partial mastectomy participated in this study. CT-based treatment plans were made in each position, and various dosimetric parameters for the breast and OARs were calculated to compare the supine and prone radiotherapy plans. The actual treatment was delivered in the position regarded as better. From 2009 to 2010, 22 patients were prospectively accrued. Median follow-up period was 58 months. The homogeneity index and lung doses were significantly lower in the prone position (P = 0.008, P < 0.0001 and P < 0.0001, respectively). Cardiac dose showed no significant differences between two positions. By comparing two plans, the prone position was chosen in 77 % of the patients. In the prone position, ≥ grade 2 acute dermatitis were seen in 47 % of patients treated, whereas 20 % of the patients treated in the supine position had grade 2 and no cases of grade 3, although without a statistical significance of the rates of ≥ grade 2 acute dermatitis between the two positions (P = 0.28). The actual dose measurement using a breast phantom revealed significantly higher surface dose of the breast treated in the prone position than that in the supine position. Breast irradiation in the prone position improves PTV homogeneity and lowers doses to the OARs in the Japanese large-breast patients. However meticulous positioning of the breast in the prone board avoiding the bolus effect is necessary to prevent acute dermatitis

Advanced breast cancer and its prevention by screening

NARCIS (Netherlands)

de Koning, H. J.; van Ineveld, B. M.; de Haes, J. C.; van Oortmarssen, G. J.; Klijn, J. G.; van der Maas, P. J.

1992-01-01

In discussions on breast cancer screening, much attention has been focussed on the possible morbidity generated by screening. Favourable effects like the prevention of advanced disease seem underestimated, probably because quantification is that difficult. To analyse the amount of care and treatment

PAM50 breast cancer intrinsic subtypes and effect of gemcitabine in advanced breast cancer patients

DEFF Research Database (Denmark)

Jørgensen, Charlotte Levin Tykjær; Nielsen, Torsten O; Bjerre, Karsten D

2014-01-01

BACKGROUND: In vitro studies suggest basal breast cancers are more sensitive to gemcitabine relative to other intrinsic subtypes. The main objective of this study was to use specimens from a randomized clinical trial to evaluate whether the basal-like subtype identifies patients with advanced...... breast cancer who benefit from gemcitabine plus docetaxel (GD) compared to single agent docetaxel (D). MATERIAL AND METHODS: From patients randomly assigned to GD or D, RNA was isolated from archival formalin-fixed, paraffin-embedded primary breast tumor tissue and used for PAM50 intrinsic subtyping...... chemotherapy were analyzed by the Kaplan-Meier method, and Cox proportional hazards regression models. Data analysis was performed independently by the Danish Breast Cancer Cooperative Group (DBCG) statistical core and all statistical tests were two-sided. RESULTS: RNA from 270 patients was evaluable; 84...

New developments in the treatment of HER2-positive breast cancer

Directory of Open Access Journals (Sweden)

Nahta R

2012-05-01

Full Text Available Rita NahtaDepartments of Pharmacology and Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USAAbstract: Approximately 20%–30% of metastatic breast cancers show increased expression of the human epidermal growth factor receptor-2 (HER2 tyrosine kinase. Two HER2-specific therapies are currently approved for clinical treatment of patients with HER2-overexpressing metastatic breast cancer. Trastuzumab is a monoclonal antibody against HER2 and is approved for first-line treatment of HER2-positive metastatic breast cancer. Lapatinib is a small molecule dual inhibitor of epidermal growth factor receptor and HER2 tyrosine kinases, and is approved for trastuzumab-refractory disease. Although trastuzumab is a highly effective therapy for patients with HER2-overexpressing metastatic breast cancer, a significant number of patients in the initial clinical trials of trastuzumab monotherapy showed resistance to trastuzumab-based therapy. Further, among those who did respond, the initial trials indicated that the median time to progression was less than 1 year. Similarly, lapatinib is effective in a subset of trastuzumab-refractory cases, but the majority of patients display resistance. This review discusses the multiple molecular mechanisms of resistance that have been proposed in the literature. In addition, novel agents that are being tested for efficacy against HER2-positive breast cancer, including the antibodies pertuzumab and trastuzumab-DM1 and the immunotoxin affitoxin, are reviewed. The introduction of trastuzumab has revolutionized the clinical care of patients with HER2-positive metastatic breast cancer and has resulted in dramatic reductions in recurrences of early-stage HER2-positive breast cancer. The development and implementation of gene- and protein-based assays that measure potential molecular predictors of trastuzumab resistance will allow individualization of HER2-targeted therapeutic approaches

Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma

International Nuclear Information System (INIS)

Ma, Ji; Zhang, Jian; Liu, Wenchao; Guo, Yan; Chen, Suning; Zhong, Cuiping; Xue, Yan; Zhang, Yuan; Lai, Xiaofeng; Wei, Yifang; Yu, Shentong

2014-01-01

Tamoxifen, an endocrine therapy drug used to treat breast cancer, is designed to interrupt estrogen signaling by blocking the estrogen receptor (ER). However, many ER-positive patients are low reactive or resistant to tamoxifen. Metformin is a widely used anti-diabetic drug with noteworthy anti-cancer effects. We investigated whether metformin has the additive effects with tamoxifen in ER-positive breast cancer therapy. The efficacy of metformin alone and in combination with tamoxifen against ER-positive breast cancer was analyzed by cell survival, DNA replication activity, plate colony formation, soft-agar, flow cytometry, immunohistochemistry, and nude mice model assays. The involved signaling pathways were detected by western blot assay. When metformin was combined with tamoxifen, the concentration of tamoxifen required for growth inhibition was substantially reduced. Moreover, metformin enhanced tamoxifen-mediated inhibition of proliferation, DNA replication activity, colony formation, soft-agar colony formation, and induction of apoptosis in ER-positive breast cancer cells. In addition, these tamoxifen-induced effects that were enhanced by metformin may be involved in the bax/bcl-2 apoptotic pathway and the AMPK/mTOR/p70S6 growth pathway. Finally, two-drug combination therapy significantly inhibited tumor growth in vivo. The present work shows that metformin and tamoxifen additively inhibited the growth and augmented the apoptosis of ER-positive breast cancer cells. It provides leads for future research on this drug combination for the treatment of ER-positive breast cancer

Survival of women with locally advanced breast cancer at a teaching hospital in Lahore

International Nuclear Information System (INIS)

Iqbal, J.; Bano, K.; Saeed, A.; Akram, M.; Aziz, Z.

2010-01-01

To correlate the clinical features of women presenting with locally advanced breast cancer with event-free survival (EFS) and overall survival (OS) and to evaluate the patterns of relapse. Methods: A total of 200 patients presenting consecutively over 9 years with Stage III breast cancer were evaluated for age, socio-economic status (SES), tumour size and grade, number of involved lymph nodes, stage III sub-categories, estrogen and progesterone receptor (ER/PR) status, treatment profiles and responses, and sites of relapse. EFS and OS at 5 and 10 years were calculated. Results: Median age was 45 years. Poorly differentiated tumours were found in 127 patients, while 128 had larger tumours (T3 and T4). Eighty women had extensive nodal involvement (N2 and N3), and 86 had Stage IIIA tumours. Chemotherapy was given to 44 patients before surgery and one of these patients achieved pathological complete response. At 5 and 10 years, EFS was 25% and 7%, and OS was 52% and 31%, respectively. By Cox regression analysis, significant predictors of EFS included tumour size (95% CI 1.14-1.72), nodal involvement (95% CI 1.06-1.59) and ER/PR positive tumours (95% CI 1.08-2.29). Predictors of OS included nodal involvement (95% CI 0.98-3.3) and ER/PR positive tumours (95% CI 1.08-2.29). No patient in stage IIIC was alive at 10 years. Loco-regional disease was the most common site of relapse (28.5%). Conclusions: Locally advance breast cancer at our centre is associated with poor survival, and most patients relapsed by 5 years. (author)

cAMP-response-element-binding protein positively regulates breast cancer metastasis and subsequent bone destruction

Energy Technology Data Exchange (ETDEWEB)

Son, Jieun; Lee, Jong-Ho; Kim, Ha-Neui; Ha, Hyunil, E-mail: hyunil74@hotmail.com; Lee, Zang Hee, E-mail: zang1959@snu.ac.kr

2010-07-23

Research highlights: {yields} CREB is highly expressed in advanced breast cancer cells. {yields} Tumor-related factors such as TGF-{beta} further elevate CREB expression. {yields} CREB upregulation stimulates metastatic potential of breast cancer cells. {yields} CREB signaling is required for breast cancer-induced bone destruction. -- Abstract: cAMP-response-element-binding protein (CREB) signaling has been reported to be associated with cancer development and poor clinical outcome in various types of cancer. However, it remains to be elucidated whether CREB is involved in breast cancer development and osteotropism. Here, we found that metastatic MDA-MB-231 breast cancer cells exhibited higher CREB expression than did non-metastatic MCF-7 cells and that CREB expression was further increased by several soluble factors linked to cancer progression, such as IL-1, IGF-1, and TGF-{beta}. Using wild-type CREB and a dominant-negative form (K-CREB), we found that CREB signaling positively regulated the proliferation, migration, and invasion of MDA-MB-231 cells. In addition, K-CREB prevented MDA-MB-231 cell-induced osteolytic lesions in a mouse model of cancer metastasis. Furthermore, CREB signaling in cancer cells regulated the gene expression of PTHrP, MMPs, and OPG, which are closely involved in cancer metastasis and bone destruction. These results indicate that breast cancer cells acquire CREB overexpression during their development and that this CREB upregulation plays an important role in multiple steps of breast cancer bone metastasis.

Palliative systemic therapy and overall survival of 1,395 patients with advanced breast cancer - Results from the prospective German TMK cohort study.

Science.gov (United States)

Fietz, Thomas; Tesch, Hans; Rauh, Jacqueline; Boller, Emil; Kruggel, Lisa; Jänicke, Martina; Marschner, Norbert

2017-08-01

Data on treatment and outcome of advanced breast cancer in routine practice are rare, especially concerning recurrent disease, but important to complement the results from clinical trials and to improve the standard of care. We present data on choice of systemic first-line treatment, number of treatment lines, and survival of patients treated by medical oncologists in Germany. 1395 patients recruited by 124 sites at start of first-line therapy into the ongoing, prospective German clinical cohort study TMK (Tumour Registry Breast Cancer) between February 2007 and October 2015 were analysed. The median OS was 33.8 months (95% CI 30.2-40.2) for HR-positive/HER2-negative, 38.2 months (95% CI 31.3-43.0) for HER2-positive and 16.8 months (95% CI 11.5-22.0) for triple negative breast cancer. Patients with triple negative tumours more often died before start of a third-line therapy than patients with HR-positive or HER2-positive tumours (44% vs. 25%). Use of taxane-based chemotherapies has increased since 2007, with 65% of all first-line chemotherapy-treatments containing taxanes in 2013-15 (60% HR-positive/HER2-negative, 75% HER2-positive, 56% triple negative). 52% of the patients with HR-positive/HER2-negative tumours received first-line endocrine therapy in 2013-15; when restricted to patients with only non-visceral metastases this percentage increased to 63%. To our knowledge, this is the first cohort study showing systemic first-line therapy for all subtypes of advanced breast cancer. Overall survival in the TMK is comparable to that reported by clinical trials despite the inclusion of older and comorbid patients. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Advancement of mass spectrometry-based proteomics technologies to explore triple negative breast cancer.

Science.gov (United States)

Miah, Sayem; Banks, Charles A S; Adams, Mark K; Florens, Laurence; Lukong, Kiven E; Washburn, Michael P

2016-12-20

Understanding the complexity of cancer biology requires extensive information about the cancer proteome over the course of the disease. The recent advances in mass spectrometry-based proteomics technologies have led to the accumulation of an incredible amount of such proteomic information. This information allows us to identify protein signatures or protein biomarkers, which can be used to improve cancer diagnosis, prognosis and treatment. For example, mass spectrometry-based proteomics has been used in breast cancer research for over two decades to elucidate protein function. Breast cancer is a heterogeneous group of diseases with distinct molecular features that are reflected in tumour characteristics and clinical outcomes. Compared with all other subtypes of breast cancer, triple-negative breast cancer is perhaps the most distinct in nature and heterogeneity. In this review, we provide an introductory overview of the application of advanced proteomic technologies to triple-negative breast cancer research.

Supporting women with advanced breast cancer: the impact of altered functional status on their social roles.

Science.gov (United States)

Chen, Bai Qi Peggy; Parmar, Monica P; Gartshore, Kimberley

2014-01-01

Despite early detection of breast cancer and the progress of treatment modalities, metastasis-specific symptoms continue to impact women's functional status and daily living. The aim of this study was to explore the experience of altered functional status and social roles of women with advanced breast cancer. Using qualitative descriptive methodology, semi-structured interviews were conducted with 10 women diagnosed with advanced breast cancer and altered functional status attending a tertiary care cancer centre. Results illustrated the adaptive experience of women living with their illness as they reshaped their social roles to fit with their altered functional status and advanced disease. These findings highlight the opportunity for supportive care nursing interventions to facilitate the behavioural and cognitive transitions that are experienced by women with advanced breast cancer and altered functional status. These results may have implications for women with other advanced chronic diseases, though more research is required.

CT breast dose reduction with the use of breast positioning and organ-based tube current modulation.

Science.gov (United States)

Fu, Wanyi; Tian, Xiaoyu; Sturgeon, Gregory M; Agasthya, Greeshma; Segars, William Paul; Goodsitt, Mitchell M; Kazerooni, Ella A; Samei, Ehsan

2017-02-01

This study aimed to investigate the breast dose reduction potential of a breast-positioning (BP) technique for thoracic CT examinations with organ-based tube current modulation (OTCM). This study included 13 female anthropomorphic computational phantoms (XCAT, age range: 27-65 y.o., weight range: 52-105.8 kg). Each phantom was modified to simulate three breast sizes in standard supine geometry. The modeled breasts were then morphed to emulate BP that constrained the majority of the breast tissue inside the 120° anterior tube current (mA) reduction zone. The OTCM mA value was modeled using a ray-tracing program, which reduced the mA to 20% in the anterior region with a corresponding increase to the posterior region. The organ doses were estimated by a validated Monte Carlo program for a typical clinical CT system (SOMATOM Definition Flash, Siemens Healthcare). The simulated organ doses and organ doses normalized by CTDI vol were used to compare three CT protocols: attenuation-based tube current modulation (ATCM), OTCM, and OTCM with BP (OTCM BP ). On average, compared to ATCM, OTCM reduced breast dose by 19.3 ± 4.5%, whereas OTCM BP reduced breast dose by 38.6 ± 8.1% (an additional 23.8 ± 9.4%). The dose saving of OTCM BP was more significant for larger breasts (on average 33, 38, and 44% reduction for 0.5, 1, and 2 kg breasts, respectively). Compared to ATCM, OTCM BP also reduced thymus and heart dose by 15.1 ± 7.4% and 15.9 ± 6.2% respectively. In thoracic CT examinations, OTCM with a breast-positioning technique can markedly reduce unnecessary exposure to radiosensitive organs in anterior chest wall, specifically breast tissue. The breast dose reduction is more notable for women with larger breasts. © 2016 American Association of Physicists in Medicine.

Novel approaches to target HER2-positive breast cancer: trastuzumab emtansine

International Nuclear Information System (INIS)

Recondo, Gonzalo Jr; Vega, Maximo de la; Galanternik, Fernando; Díaz-Cantón, Enrique; Leone, Bernardo Amadeo; Leone, José Pablo

2016-01-01

The human epidermal growth factor receptor 2 (HER2) is overexpressed in 20% of breast carcinomas. Prior to the development of targeted therapies, HER2-positive breast cancer was associated with more aggressive disease and poor prognosis. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that results from the combination of trastuzumab and DM1, a derivative of the antimicrotubule agent maytansine. This molecule has the ability to enhance cytotoxic drug delivery to specifically targeted cells that overexpress HER2, therefore, maximizing efficacy while sparing toxicity. In recent years, T-DM1 has shown to improve outcomes in metastatic HER2-positive breast cancer that is resistant to trastuzumab. In addition, T-DM1 is currently being tested in the neoadjuvant and adjuvant settings to identify patients who may benefit from this therapy. This review focuses on the mechanism of action, early and late-phase clinical trials, and ongoing studies of T-DM1 in HER2-positive breast cancer

Subsets of Women With Close or Positive Margins After Breast-Conserving Surgery With High Local Recurrence Risk Despite Breast Plus Boost Radiotherapy

International Nuclear Information System (INIS)

Lupe, Krystine; Truong, Pauline T.; Alexander, Cheryl; Lesperance, Mary; Speers, Caroline; Tyldesley, Scott

2011-01-01

Purpose: (1) To examine the effect of surgical margin status on local recurrence (LR) and survival following breast-conserving therapy; (2) To identify subsets with close or positive margins with high LR risk despite whole breast radiotherapy (RT) plus boost. Methods and Materials: Subjects were 2,264 women with pT1–3, any N, M0 invasive breast cancer, treated with breast-conserving surgery and whole breast ± boost RT. Five-year Kaplan-Meier (KM) LR, breast cancer–specific and overall survival (BCSS and OS) were compared between cohorts with negative (n = 1,980), close (n = 222), and positive (n = 62) margins. LR rates were analyzed according to clinicopathologic characteristics. Multivariable Cox regression modeling and matched analysis of close/positive margin cases and negative margin controls were performed. Results: Median follow-up was 5.2 years. Boost RT was used in 92% of patients with close or positive margins. Five-year KM LR rates in the negative, close and positive margin cohorts were 1.3%, 4.0%, and 5.2%, respectively (p = 0.001). BCSS and OS were similar in the three margin subgroups. In the close/positive margin cohort, LR rates were 10.2% with age 10% despite whole breast plus boost RT. These patients should be considered for more definitive surgery.

Quantitative ultrasound characterization of locally advanced breast cancer by estimation of its scatterer properties

Energy Technology Data Exchange (ETDEWEB)

Tadayyon, Hadi [Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Sadeghi-Naini, Ali; Czarnota, Gregory, E-mail: Gregory.Czarnota@sunnybrook.ca [Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5T 1P5 (Canada); Wirtzfeld, Lauren [Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada); Wright, Frances C. [Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada)

2014-01-15

Purpose: Tumor grading is an important part of breast cancer diagnosis and currently requires biopsy as its standard. Here, the authors investigate quantitative ultrasound parameters in locally advanced breast cancers that can potentially separate tumors from normal breast tissue and differentiate tumor grades. Methods: Ultrasound images and radiofrequency data from 42 locally advanced breast cancer patients were acquired and analyzed. Parameters related to the linear regression of the power spectrum—midband fit, slope, and 0-MHz-intercept—were determined from breast tumors and normal breast tissues. Mean scatterer spacing was estimated from the spectral autocorrelation, and the effective scatterer diameter and effective acoustic concentration were estimated from the Gaussian form factor. Parametric maps of each quantitative ultrasound parameter were constructed from the gated radiofrequency segments in tumor and normal tissue regions of interest. In addition to the mean values of the parametric maps, higher order statistical features, computed from gray-level co-occurrence matrices were also determined and used for characterization. Finally, linear and quadratic discriminant analyses were performed using combinations of quantitative ultrasound parameters to classify breast tissues. Results: Quantitative ultrasound parameters were found to be statistically different between tumor and normal tissue (p < 0.05). The combination of effective acoustic concentration and mean scatterer spacing could separate tumor from normal tissue with 82% accuracy, while the addition of effective scatterer diameter to the combination did not provide significant improvement (83% accuracy). Furthermore, the two advanced parameters, including effective scatterer diameter and mean scatterer spacing, were found to be statistically differentiating among grade I, II, and III tumors (p = 0.014 for scatterer spacing, p = 0.035 for effective scatterer diameter). The separation of the tumor

Quantitative ultrasound characterization of locally advanced breast cancer by estimation of its scatterer properties

International Nuclear Information System (INIS)

Tadayyon, Hadi; Sadeghi-Naini, Ali; Czarnota, Gregory; Wirtzfeld, Lauren; Wright, Frances C.

2014-01-01

Purpose: Tumor grading is an important part of breast cancer diagnosis and currently requires biopsy as its standard. Here, the authors investigate quantitative ultrasound parameters in locally advanced breast cancers that can potentially separate tumors from normal breast tissue and differentiate tumor grades. Methods: Ultrasound images and radiofrequency data from 42 locally advanced breast cancer patients were acquired and analyzed. Parameters related to the linear regression of the power spectrum—midband fit, slope, and 0-MHz-intercept—were determined from breast tumors and normal breast tissues. Mean scatterer spacing was estimated from the spectral autocorrelation, and the effective scatterer diameter and effective acoustic concentration were estimated from the Gaussian form factor. Parametric maps of each quantitative ultrasound parameter were constructed from the gated radiofrequency segments in tumor and normal tissue regions of interest. In addition to the mean values of the parametric maps, higher order statistical features, computed from gray-level co-occurrence matrices were also determined and used for characterization. Finally, linear and quadratic discriminant analyses were performed using combinations of quantitative ultrasound parameters to classify breast tissues. Results: Quantitative ultrasound parameters were found to be statistically different between tumor and normal tissue (p < 0.05). The combination of effective acoustic concentration and mean scatterer spacing could separate tumor from normal tissue with 82% accuracy, while the addition of effective scatterer diameter to the combination did not provide significant improvement (83% accuracy). Furthermore, the two advanced parameters, including effective scatterer diameter and mean scatterer spacing, were found to be statistically differentiating among grade I, II, and III tumors (p = 0.014 for scatterer spacing, p = 0.035 for effective scatterer diameter). The separation of the tumor

Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer

DEFF Research Database (Denmark)

von Minckwitz, Gunter; Procter, Marion; de Azambuja, Evandro

2017-01-01

BACKGROUND: Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2......)-positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer. METHODS: We randomly assigned patients with node-positive or high-risk node-negative HER2-positive......, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab. We assumed a 3-year invasive-disease-free survival rate of 91.8% with pertuzumab and 89.2% with placebo. RESULTS: In the trial population, 63% of the patients...

Radiation binary targeted therapy for HER-2 positive breast cancers: assumptions, theoretical assessment and future directions

Energy Technology Data Exchange (ETDEWEB)

Mundy, Daniel W [School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47909 (United States); Harb, Wael [Horizon Oncology, The Care Group, Unity Medical Center, Lafayette, IN 47901 (United States); Jevremovic, Tatjana [School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47909 (United States)

2006-03-21

A novel radiation targeted therapy is investigated for HER-2 positive breast cancers. The proposed concept combines two known approaches, but never used together for the treatment of advanced, relapsed or metastasized HER-2 positive breast cancers. The proposed radiation binary targeted concept is based on the anti HER-2 monoclonal antibodies (MABs) that would be used as vehicles to transport the nontoxic agent to cancer cells. The anti HER-2 MABs have been successful in targeting HER-2 positive breast cancers with high affinity. The proposed concept would utilize a neutral nontoxic boron-10 predicting that anti HER-2 MABs would assure its selective delivery to cancer cells. MABs against HER-2 have been a widely researched strategy in the clinical setting. The most promising antibody is Trastuzumab (Herceptin (registered) ). Targeting HER-2 with the MAB Trastuzumab has been proven to be a successful strategy in inducing tumour regression and improving patient survival. Unfortunately, these tumours become resistant and afflicted women succumb to breast cancer. In the proposed concept, when the tumour region is loaded with boron-10 it is irradiated with neutrons (treatment used for head and neck cancers, melanoma and glioblastoma for over 40 years in Japan and Europe). The irradiation process takes less than an hour producing minimal side effects. This paper summarizes our recent theoretical assessments of radiation binary targeted therapy for HER-2 positive breast cancers on: the effective drug delivery mechanism, the numerical model to evaluate the targeted radiation delivery and the survey study to find the neutron facility in the world that might be capable of producing the radiation effect as needed. A novel method of drug delivery utilizing Trastuzumab is described, followed by the description of a computational Monte Carlo based breast model used to determine radiation dose distributions. The total flux and neutron energy spectra of five currently available

Awareness and current knowledge of breast cancer.

Science.gov (United States)

Akram, Muhammad; Iqbal, Mehwish; Daniyal, Muhammad; Khan, Asmat Ullah

2017-10-02

Breast cancer remains a worldwide public health dilemma and is currently the most common tumour in the globe. Awareness of breast cancer, public attentiveness, and advancement in breast imaging has made a positive impact on recognition and screening of breast cancer. Breast cancer is life-threatening disease in females and the leading cause of mortality among women population. For the previous two decades, studies related to the breast cancer has guided to astonishing advancement in our understanding of the breast cancer, resulting in further proficient treatments. Amongst all the malignant diseases, breast cancer is considered as one of the leading cause of death in post menopausal women accounting for 23% of all cancer deaths. It is a global issue now, but still it is diagnosed in their advanced stages due to the negligence of women regarding the self inspection and clinical examination of the breast. This review addresses anatomy of the breast, risk factors, epidemiology of breast cancer, pathogenesis of breast cancer, stages of breast cancer, diagnostic investigations and treatment including chemotherapy, surgery, targeted therapies, hormone replacement therapy, radiation therapy, complementary therapies, gene therapy and stem-cell therapy etc for breast cancer.

A national survey exploring UK trainees' perceptions, core training experience, and decisions to pursue advanced training in breast radiology.

Science.gov (United States)

Lowes, S; Bydder, M; Sinnatamby, R

2017-11-01

To investigate UK radiology trainees' perceptions of breast radiology and the factors that influenced their decision whether or not to choose breast radiology as an area of special interest. An online survey was compiled and distributed to all UK specialty trainees in clinical radiology via the Royal College of Radiologists Junior Radiologists' Forum (JRF) regional representatives. There were 275 respondents, representing 22% of all UK radiology trainees. Responses were received from all regions. A significant factor identified in influencing whether or not trainees decide to pursue advanced training in breast radiology is the timing and quality of their initial core training experience. Specific positive aspects of breast radiology that were repeatedly identified included the high level of patient contact and frequent use of interventional procedures. Recurring negative aspects of breast radiology included isolation from general radiology and finding the subject matter boring. Breast radiology faces a significant workforce shortfall that is predicted to worsen in the coming years. There has never been a greater need to recruit specialty trainees into this field, and action is urgently needed to help ensure the sustainability of breast services and drive further improvements to patient care. The findings from this survey should be regarded as a challenge to all breast radiologists to engage with trainees from an early stage in their training and to enthuse them with the many positive aspects of a career in breast radiology. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

[Clinical relevance of ESR1 circulating mutations detection in hormone receptor positive metastatic breast cancer].

Science.gov (United States)

Clatot, Florian; Perdrix, Anne; Sefrioui, David; Sarafan-Vasseur, Nasrin; Di Fiore, Frédéric

2018-01-01

If hormone therapy is a key treatment for hormone receptor positive advanced breast cancers, secondary resistance occurs as a rule. Recently, acquired alterations of the ESR1 gene have been identified as a mechanism of resistance on aromatase inhibitor (AI) treatment. The selective pressure by AI exposure during the metastatic setting triggers the emergence of ESR1 activating mutations. In that context, the "liquid biopsy" concept has been used to detect this molecular resistance before progression. Thus, the ESR1 circulating mutation detection will soon be used in daily practice to help monitoring patients on AI treatment and provide an early change for specific therapies that still have to be determined in prospective clinical trials. This review will present the acquired ESR1 mutations, as well as the methods used for their detection in blood and the potential clinical impact of this approach for hormone receptor positive breast cancer management. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Galectin-7 Expression Potentiates HER-2-Positive Phenotype in Breast Cancer.

Directory of Open Access Journals (Sweden)

Andrée-Anne Grosset

Full Text Available HER-2 positive tumors are among the most aggressive subtypes of breast cancer and are frequently associated with metastasis and poor outcome. As with other aggressive subtypes of breast cancer, these tumors are associated with abnormally high expression of galectin-7 (gal-7, which confers metastatic breast tumor cells with increased invasive behavior. Although previous studies in the rat model of breast tumorigenesis have shown that gal-7 is also increased in primary breast tumor, its contribution to the development of the primary breast tumors remains unclear. In the present work, we have used genetically-engineered gal-7-deficient mice to examine the role of gal-7 in the development of the mammary gland and of breast cancer. Using histological and immunohistological analysis of whole mammary glands at different stages of development, we detected no significant changes between normal and gal-7-deficient mice. To test the involvement of gal-7 in breast cancer, we next examined the effects of loss of gal-7 on mammary tumor development by crossing gal-7-deficient mice with the mammary tumor transgenic mouse strain FVB-Tg(MMTV-Erbb2NK1Mul/J. Finally, assessment of mice survival and tumor volume showed a delay of mammary tumor growth in the absence of systemic gal-7. These data suggest that gal-7 could potentiate the phenotype of HER-2 positive primary breast cancer.

Clinical efficacy of breast-conserving surgery combined with neoadjuvant chemotherapy for locally advanced breast cancer: a report of 81 cases

Directory of Open Access Journals (Sweden)

Zhi-yu CAO

2015-07-01

Full Text Available Objective　To investigate the clinical efficacy of neoadjuvant chemotherapy combined with breast-conserving surgery for locally advanced breast cancer. Methods　Eighty-one patients with locally advanced breast cancer were selected from those who were admitted into 309 Hospital of PLA from January 2009 to October 2013, consisting of 65 patients in stage Ⅲa and 16 in stage Ⅲb, and they were treated with neoadjuvant chemotherapy combined with breast-conserving surgery. The clinical efficacy [complete response (CR, partial response (PR, stable disease (SD and progress disease (PD] was observed during follow-up. Results　All the patients were followed-up for 12-60 months with a median of 34 months. There were 12 CR patients (14.8%, including 4 with pathological complete response (4.9%, and 52 PR patients (64.2%, 17 SD patients (21.0%. No PD was observed. The overall response rate(ORR was 79.0%(64/81. After follow-up for 12-60 months (median 34 months, distant metastasis to the lung, liver, meninges and bone occurred in 3 patients (3.7%, 3/81 and 1 of them died. Forty-eight patients received breastconserving surgery. The local recurrence rate was 6.3% (3/48. Assessment of cosmetic result was carried out in 48 patients who received breast-conserving surgery and comprehensive treatment for one year, and excellent results were obtained in 14.6% (7/48, good in 43.8% (21/48, and poor in 41.7% (20/48. Conclusions　The therapeutic efficacy of locally advanced breast cancer is satisfactory by neoadjuvant chemotherapy and breast-conserving surgery. Standardization of excision and postoperative radiotherapy, systemic comprehensive treatment is the key to the success of the treatment. DOI: 10.11855/j.issn.0577-7402.2015.06.14

Evaluation Of Oxidative Stress And Apoptosis In Breast Cancer ...

African Journals Online (AJOL)

were positively correlated with positive progesterone receptor. In Conclusion; oxidative stress, NO and apoptosis are highly detected in breast cancer tissues especially with advanced grade and stage. Key words: Breast cancer, Reactive Oxygen Species (ROS), malondialdehyde (MDA), Nitric Oxide (NO), Total Antioxidants

The use of a standardized positioning support cushion during daily routine of breast irradiation

International Nuclear Information System (INIS)

Thilmann, Christoph; Adamietz, Irenaeus A.; Saran, Frank; Mose, Stefan; Kostka, A.; Boettcher, H.D.

1998-01-01

Purpose: The use of positioning and immobilization techniques during external beam irradiation of the female breast is time consuming and expensive. The currently available standardized positioning devices are insufficient. For this reason, we designed a new and generally useable hard foam positioning support cushion for the use during breast irradiation, and tested its clinical usefulness in a prospective study. Methods and Materials: Fifty-five female breast cancer patients receiving adjuvant radiotherapy following breast-conservative surgery were irradiated either without immobilization (n = 27) or with the positioning support cushion (n = 28). The time necessary for patient setup, the lying subjective comfort and --comparing portal images with simulator images--the reproducibility of the set up were determined. Results: Irradiation reproducibility was significantly improved (average deviation without positioning support cushion: 8.4 mm, with positioning support cushion: 6.1 mm, p < 0.001). The time required for the positioning of the patient with positioning support cushion was in average 73 s, without cushion it was 55 s. A significantly higher proportion of patients (72%) found the position with the positioning support cushion as pleasant, whereas only 46% of patients were pleased with the position without cushion. Conclusion: The positioning support cushion designed in our department makes a substantial contribution to quality assurance in breast irradiation. It significantly increases the patients' comfort in a supine position. In contrast to conventional positioning and fixation aids it may be quickly and easily applied at low costs. Therefore, its use can be recommended

HER2-positive male breast cancer with thyroid cancer: an institutional report and review of literature.

Science.gov (United States)

Bardhan, Pooja; Bui, Marilyn M; Minton, Susan; Loftus, Loretta; Carter, W Bradford; Laronga, Christine; Ismail-Khan, Roohi

2012-01-01

We report a rare finding of two male breast cancer patients with HER2-positive breast cancer who also developed thyroid cancer. We reviewed 45 male breast cancer patients treated in our institution from 2003 to 2008. Only five male breast cancer patients were HER2-positive. In reviewing the published data, we found no cases of thyroid cancer and concurrent breast cancer in men. However, breast cancer and thyroid cancer have shown close association in women. This finding therefore provokes speculation as to whether we should investigate whether women with HER2-positive breast cancer are at a higher risk for thyroid cancer. Although this observation seems to be clinically prevalent, publications are sparse in clinical research areas linking thyroid cancer to breast cancer.

Gestalt Breastfeeding: Helping Mothers and Infants Optimize Positional Stability and Intraoral Breast Tissue Volume for Effective, Pain-Free Milk Transfer.

Science.gov (United States)

Douglas, Pamela; Keogh, Renee

2017-08-01

In the past decade, biological nurturing and activation of maternal and infant instincts after birth have constituted a major advance in clinical breastfeeding support. Yet, physiologic breastfeeding initiation is not enough to ensure ongoing pain-free and effective breastfeeding for many pairs. Current interventions, including "hands-off" mammalian approaches, do not improve breastfeeding outcomes, including in randomized controlled trials. Back-arching, difficulty latching or staying on the breast, and fussing at the breast are common signs of infant positional instability during breastfeeding. These cues are, however, often misdiagnosed as signs of medical conditions or oral connective tissue abnormalities, and underlying positional instability is not addressed. New clinical approaches are urgently required. This article offers a clinical approach to fit and hold (or latch and positioning)- gestalt breastfeeding, which aims to optimize positional stability and intraoral breast tissue volumes for pain-free effective breastfeeding. The word gestalt (pronounced "ger-shtolt") means a whole that is more than the sum of its parts. Gestalt breastfeeding builds on the theoretical foundations of complexity science, physiologic breastfeeding initiation, and new understandings of the biomechanics of infant suck elucidated in ultrasound studies. It also integrates simple psychological strategies from applied functional contextualism, popularly known as Acceptance and Commitment Therapy, empowering women to attend mindfully to breast sensations and their infant's cues. Gestalt breastfeeding can be reproduced for research purposes, including in comparison studies with oral surgery, and has the potential to improve breastfeeding outcomes.

The impact of a focally positive resection margin on the local control in patients treated with breast-conserving therapy

International Nuclear Information System (INIS)

Park, Seho; Park, Hyung-Seok; Kim, Seung-ll; Koo, Ja-Seung; Park, Byeong-Woo; Lee, Kyong-Sik

2011-01-01

The aim of the study was to investigate the parameters affecting positive margin and the impact of positive margin on outcomes after breast-conserving therapy in patients with breast cancer. Characteristics and survival of 705 patients attempted breast-conserving therapy between January 1994 and December 2004 were retrospectively analyzed using χ 2 tests, the Kaplan-Meier methods and multivariate analyses. Ninety-five (13.5%) showed positive margins at initial resection. Among them, 28 (4.0%) had negative margin on the initial frozen section; however, they finally turned out a focally positive margin with intraductal carcinoma on the permanent pathology. Positive margin at initial resection was significantly associated with lobular histology (P=0.001), four or more involved lymph nodes (P=0.015) and the presence of extensive intraductal component (P<0.001). A focally positive margin did not influence local (P=0.250; 95% confidence interval, 0.612-6.592) or regional failure (P=0.756; 95% confidence interval, 0.297-5.311). Patients with a focally positive margin showed an advanced nodal stage and received a higher dose of irradiation and more systemic therapy. Nodal involvements were the most significant factor for locoregional failure. Although the achievement of negative margins is the best way to reduce local failure, patients with a focally positive margin and favorable risk factors such as node negativity and older age could have an option of close follow-up with adequate boost irradiation and adjuvant therapy instead of conversion to total mastectomy. (author)

Concurrent chemo-radiotherapy following neoadjuvant chemotherapy in locally advanced breast cancer

Directory of Open Access Journals (Sweden)

Zinser-Sierra Juan

2009-07-01

Full Text Available Abstract Background Despite broad advances in multimodal treatment of locally advanced breast cancer (LABC, 30 to 40% of patients develop loco-regional relapse. The aim of this study was to analyze in a retrospective manner the effectiveness of concurrent chemo-radiotherapy (CCRTh after neoadjuvant chemotherapy (NCT in patients with LABC. Methods One hundred twelve patients with LABC (stage IIB-IIIB were treated with NCT (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FAC, or doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (AC IV in four 21-day courses followed by CCRTh (60 Gy breast irradiation and weekly mitomycin 5 mg/m2, 5-fluorouracil 500 mg/m2, and dexamethasone 16 mg, or cisplatin 30 mg/m2, gemcitabine 100 mg/m2 and dexamethasone 16 mg, and 6–8 weeks later, surgery and two additional courses of FAC, AC, or paclitaxel 90 mg/m2 weekly for 12 weeks, and in case of estrogen-receptor positive patients, hormonal therapy. Results Stages IIB, IIIA and -B were 21.4, 42.9, and 35.7%, respectively. Pathological complete response (pCR in the breast was 42% (95% CI, 33.2–50.5% and, 29.5% (95% CI, 21.4–37.5% if including both the breast and the axillary nodes. Multivariate analysis showed that the main determinant of pCR was negative estrogen-receptor status (HR = 3.8; 95% CI, 1.5–9; p = 0.016. The 5-year disease-free survival (DFS was 76.9% (95% CI, 68.2–84.7%. No relationship between pCR and DFS was found. Multivariate analysis demonstrated that the main DFS determinant was clinical stage (IIB and IIIA vs. IIIB, HR = 3.1; 95% CI, 1.02–9.74; p = 0.04. Only one patient had local recurrence. Five-year overall survival was 84.2% (95% CI, 75–93.2%. The toxicity profile was acceptable. Conclusion This non-conventional multimodal treatment has good loco-regional control for LABC. Randomized clinical trials of preoperative CCRTh following chemotherapy, in patients with LABC are warranted.

The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor positive early stage breast cancer

International Nuclear Information System (INIS)

Fowble, B.; Fein, D.A.; Hanlon, A.L.; Eisenberg, B.L.; Hoffman, J.P.; Sigurdson, E.R.; Daly, M.B.; Goldstein, L.J.

1995-01-01

Purpose: In the NSABP B14 trial evaluating tamoxifen (tam) in axillary node negative, estrogen receptor positive tumors fewer breast recurrences were observed in patients treated with conservative surgery and radiation who received tam compared to the observation arm. An additional series, however, has suggested that tam adversely impacts on the cosmetic result. To further address these issues we compared the outcome of estrogen receptor positive tumors treated with conservative surgery and radiation with or without tam. Materials and Methods: From 1982 to 1991, 491 women with estrogen receptor positive stage I-II breast cancer underwent excisional biopsy, axillary dissection and radiation. The median age of the patient population was 60 years (range 39-85). The median followup was 5.3 years (range .1-12.8). 69% had T1 tumors and 83% had histologically negative axillary nodes. Reexcision was performed in 49%. The final margin of resection was negative in 64%, unknown in 18%, and close or positive in 19%. None of the patients received adjuvant chemotherapy. 154 patients received tam and 337 received no adjuvant therapy. Patients who received tam were more often axillary node positive (44% tam vs 5% no tam) and less often had unknown margins (9% tam vs 22% no tam). There were no significant differences for the 2 groups for median age, primary tumor size, histology, race, or use of reexcision. Results: The 5 yr act rate of breast recurrence was 4% for the tam patients compared to 7% for patients not receiving tam (p=.21). At 8 yrs, the breast recurrence rates were 4% for the tam patients compared to 11% for the no tam patients (p=.05). However, at 9 years the rates were 17% tam vs 14% no tam (p=.21). The benefit from tam in terms of a decreased 5 year actuarial breast recurrence rate was most evident for patients who did not have a reexcision (3% tam vs 10% no tam, p=.15), had unknown margins (7% tam vs 13% no tam, p=.37) or close margins (0% tam vs 11% no tam, p=.34

The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor positive early stage breast cancer

Energy Technology Data Exchange (ETDEWEB)

Fowble, B; Fein, D A; Hanlon, A L; Eisenberg, B L; Hoffman, J P; Sigurdson, E R; Daly, M B; Goldstein, L J

1995-07-01

Purpose: In the NSABP B14 trial evaluating tamoxifen (tam) in axillary node negative, estrogen receptor positive tumors fewer breast recurrences were observed in patients treated with conservative surgery and radiation who received tam compared to the observation arm. An additional series, however, has suggested that tam adversely impacts on the cosmetic result. To further address these issues we compared the outcome of estrogen receptor positive tumors treated with conservative surgery and radiation with or without tam. Materials and Methods: From 1982 to 1991, 491 women with estrogen receptor positive stage I-II breast cancer underwent excisional biopsy, axillary dissection and radiation. The median age of the patient population was 60 years (range 39-85). The median followup was 5.3 years (range .1-12.8). 69% had T1 tumors and 83% had histologically negative axillary nodes. Reexcision was performed in 49%. The final margin of resection was negative in 64%, unknown in 18%, and close or positive in 19%. None of the patients received adjuvant chemotherapy. 154 patients received tam and 337 received no adjuvant therapy. Patients who received tam were more often axillary node positive (44% tam vs 5% no tam) and less often had unknown margins (9% tam vs 22% no tam). There were no significant differences for the 2 groups for median age, primary tumor size, histology, race, or use of reexcision. Results: The 5 yr act rate of breast recurrence was 4% for the tam patients compared to 7% for patients not receiving tam (p=.21). At 8 yrs, the breast recurrence rates were 4% for the tam patients compared to 11% for the no tam patients (p=.05). However, at 9 years the rates were 17% tam vs 14% no tam (p=.21). The benefit from tam in terms of a decreased 5 year actuarial breast recurrence rate was most evident for patients who did not have a reexcision (3% tam vs 10% no tam, p=.15), had unknown margins (7% tam vs 13% no tam, p=.37) or close margins (0% tam vs 11% no tam, p=.34

Breast-Conservative Surgery With Close or Positive Margins: Can the Breast Be Preserved With High-Dose-Rate Brachytherapy Boost?

International Nuclear Information System (INIS)

Guinot, Jose Luis; Roldan, Susana; Maronas, Maria; Tortajada, Isabel; Carrascosa, Maria; Chust, Maria Luisa; Estornell, Marian; Mengual, Jose Luis; Arribas, Leoncio

2007-01-01

Purpose: To evaluate the likelihood of preserving the breast in women who show close or positive margins after conservative surgery for early breast carcinoma. Methods and Materials: Since 1996, 125 women with less than 5 mm or positive margins and positive separate cavity margin sampling were entered in a prospective trial with high-dose radiotherapy. A standard dose of 50 Gy to the whole breast was followed by a high-dose-rate brachytherapy application delivering 3 fractions of 4.4 Gy in 24 hours. The median follow-up was 84 months. Results: There were only seven local recurrences, with an actuarial local control rate of 95.8% at 5 years and 91.1% at 9 years. Actuarial overall and cause-specific survival rates were 92.6% and 95% at 5 years and 86.7% and 90.4% at 9 years, respectively. Late fibrosis was the most common complication, in 30% of patients, with good or excellent cosmetic results in 77%. The final result was that 95.2% of breasts were preserved. Conclusions: Close or positive-margin breast cancer can be well managed with a high-dose boost in a wide tumor bed by means of high-dose-rate brachytherapy. This technique can avoid mastectomy or poor cosmetic resection, with minimal risk of local or general failure

Pharmacodynamics, pharmacokinetics and clinical efficacy of neratinib in HER2-positive breast cancer and breast cancer with HER2 mutations.

Science.gov (United States)

Kourie, Hampig Raphael; Chaix, Marie; Gombos, Andrea; Aftimos, Phillippe; Awada, Ahmad

2016-08-01

Despite the availability of several potent HER2-directed targeted agents, primary and acquired resistance continues to influence patient outcomes in HER2-positive breast cancer. Neratinib is an irreversible pan-HER tyrosine kinase inhibitor in late-phase clinical development. This review article focuses on neratinib in the treatment of HER2-positive breast cancer - early and metastatic stage - and HER2-mutant breast cancer, with particular emphasis on the pharmacokinetics and pharmacodynamics of the drug. The phase III ExteNET trial shows that neratinib improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in early-stage HER2-positive breast cancer, and in particular HER2+/HR+ tumors. Survival data are awaited. The investigational role of neratinib in high-risk patients or conversely in de-escalation dual regimens with other anti-HER2 therapies and without chemotherapy are of interest. Phase II trials show that neratinib has efficacy, either as monotherapy or in combination with other chemotherapeutic or endocrine agents, in patients with HER2-positive metastatic breast cancer and in tumors harboring HER2 mutations. The role of neratinib in therapeutic algorithms of HER2-positive patients, as well as delaying CNS events, awaits the results of ongoing trials such as NALA. Diarrhea, the main toxicity of neratinib, can be effectively managed with early loperamide prophylaxis.

Helical Tomotherapy Planning for Left-Sided Breast Cancer Patients With Positive Lymph Nodes: Comparison to Conventional Multiport Breast Technique

International Nuclear Information System (INIS)

Goddu, S. Murty; Chaudhari, Summer; Mamalui-Hunter, Maria; Pechenaya, Olga L.; Pratt, David; Mutic, Sasa; Zoberi, Imran; Jeswani, Sam; Powell, Simon N.; Low, Daniel A.

2009-01-01

Purpose: To evaluate the feasibility of using helical tomotherapy for locally advanced left-sided breast cancer. Methods and Materials: Treatment plans were generated for 10 left-sided breast cancer patients with positive lymph nodes comparing a multiport breast (three-dimensional) technique with the tomotherapy treatment planning system. The planning target volumes, including the chest wall/breast, supraclavicular, axillary, and internal mammary lymph nodes, were contoured. The treatment plans were generated on the tomotherapy treatment planning system to deliver 50.4 Gy to the planning target volume. To spare the contralateral tissues, directional blocking was applied to the right breast and right lung. The optimization goals were to protect the lungs, heart, and right breast. Results: The tomotherapy plans increased the minimal dose to the planning target volume (minimal dose received by 99% of target volume = 46.2 ± 1.3 Gy vs. 27.9 ± 17.1 Gy) while improving the dose homogeneity (dose difference between the minimal dose received by 5% and 95% of the planning target volume = 7.5 ± 1.8 Gy vs. 37.5 ± 26.9 Gy). The mean percentage of the left lung volume receiving ≥20 Gy in the tomotherapy plans decreased from 32.6% ± 4.1% to 17.6% ± 3.5%, while restricting the right-lung mean dose to <5 Gy. However, the mean percentage of volume receiving ≥5 Gy for the total lung increased from 25.2% ± 4.2% for the three-dimensional technique to 46.9% ± 8.4% for the tomotherapy plan. The mean volume receiving ≥35 Gy for the heart decreased from 5.6% ± 4.8% to 2.2% ± 1.5% in the tomotherapy plans. However, the mean heart dose for tomotherapy delivery increased from 7.5 ± 3.4 Gy to 12.2 ± 1.8 Gy. Conclusion: The tomotherapy plans provided better dose conformity and homogeneity than did the three-dimensional plans for treatment of left-sided breast tumors with regional lymph node involvement, while allowing greater sparing of the heart and left lung from doses

Capecitabine and its role in the treatment of advanced HER2 positive breast cancer

International Nuclear Information System (INIS)

Barilla, R.; Sycova-Mila, Z.; Andrasina, I.

2011-01-01

Metastatic breast cancer is the leading cause of death from cancer among women worldwide. Approximately 20 % women with breast cancer that over express HER2, considered to be strong predictor for disease progression and death, are at greater risk than women whose tumors do not over express HER2. It represents an important therapeutic target in this population. We currently have 2 registered targeted drugs in this setting (trastuzumab and lapatinib) and others are being investigated in clinical trials (pertuzumab, neratinib etc.). (5, 6) The treatment of intensively pretreated breast cancer is essentially palliative with the aim of providing antitumor activity and prolonging survival but without significant deterioration in quality of life. Despite the era of targeted therapies in several cancer types with certainty we cannot omit cytotoxic chemotherapy in these patients. (author)

Neoadjuvant radiotherapy for primary advanced or locally recurrent breast cancer

Energy Technology Data Exchange (ETDEWEB)

Watanabe, Hiroaki; Nio, Yoshinori; Inoue, Yasushi; Teramoto, Mutsumi; Nagami, Haruhiko; Yano, Seiji; Sumi, Shoichiro; Tamura, Katsuhiro; Kushima, Takeyuki [Shimane Medical Univ., Izumo (Japan)

1998-03-01

Neoadjuvant radiotherapy for breast cancer has rarely been reported. In the present study, we investigated the objective response and histopathological effects of neoadjuvant radiotherapy in patients with primary advanced or locally recurrent breast cancer. Between 1992 and 1997, a total of 11 patients with primary or recurrent breast cancer (5 primary advanced and 6 locally recurrent breast cancers) were treated with neoadjuvant radiotherapy before surgery. Six patients received radiotherapy alone and 5 received radiotherapy in combination with chemotherapy, and the objective response was assessed according to the criteria of the Japanese Society of Cancer Therapy. After neoadjuvant radiotherapy or radiochemotherapy, all patients underwent surgery or biopsy, and histopathological effects were assessed according to the criteria of the Japanese Research Society for Gastric Cancer Study. The overall objective response was 27% (3PR/11; 2PR in 5 primary cancers and 1PR in 6 recurrent cancers), and histopathological effects included 5 grade-3 or -2 responses (45%; 2 grade-3 and 1 grade-2 in primary cancers and 2 grade-2 in recurrent cancers). There were no correlations between total radiation dose and objective response or histopathological effects. The objective response rates were 40% (2/5) in the radiochemotherapy group and 17% (1/6) in the radiotherapy alone group, histopathological effects higher than grade-2 were seen in 60% (3/5) in the radiochemotherapy group and 33% (2/6) in the radiotherapy alone group, and a grade-3 response was seen only in the radiochemotherapy group. Neoadjuvant radiotherapy for breast cancer resulted in a high response rate and was more effective against primary cancer than recurrent cancer. Furthermore, chemotherapy may be beneficial in improving the efficacy of radiotherapy. (author)

Neoadjuvant radiotherapy for primary advanced or locally recurrent breast cancer

International Nuclear Information System (INIS)

Watanabe, Hiroaki; Nio, Yoshinori; Inoue, Yasushi; Teramoto, Mutsumi; Nagami, Haruhiko; Yano, Seiji; Sumi, Shoichiro; Tamura, Katsuhiro; Kushima, Takeyuki

1998-01-01

Neoadjuvant radiotherapy for breast cancer has rarely been reported. In the present study, we investigated the objective response and histopathological effects of neoadjuvant radiotherapy in patients with primary advanced or locally recurrent breast cancer. Between 1992 and 1997, a total of 11 patients with primary or recurrent breast cancer (5 primary advanced and 6 locally recurrent breast cancers) were treated with neoadjuvant radiotherapy before surgery. Six patients received radiotherapy alone and 5 received radiotherapy in combination with chemotherapy, and the objective response was assessed according to the criteria of the Japanese Society of Cancer Therapy. After neoadjuvant radiotherapy or radiochemotherapy, all patients underwent surgery or biopsy, and histopathological effects were assessed according to the criteria of the Japanese Research Society for Gastric Cancer Study. The overall objective response was 27% (3PR/11; 2PR in 5 primary cancers and 1PR in 6 recurrent cancers), and histopathological effects included 5 grade-3 or -2 responses (45%; 2 grade-3 and 1 grade-2 in primary cancers and 2 grade-2 in recurrent cancers). There were no correlations between total radiation dose and objective response or histopathological effects. The objective response rates were 40% (2/5) in the radiochemotherapy group and 17% (1/6) in the radiotherapy alone group, histopathological effects higher than grade-2 were seen in 60% (3/5) in the radiochemotherapy group and 33% (2/6) in the radiotherapy alone group, and a grade-3 response was seen only in the radiochemotherapy group. Neoadjuvant radiotherapy for breast cancer resulted in a high response rate and was more effective against primary cancer than recurrent cancer. Furthermore, chemotherapy may be beneficial in improving the efficacy of radiotherapy. (author)

Prognostic outcomes in advanced breast cancer: the metastasis-free interval is important.

Science.gov (United States)

Shen, Tiansheng; Gao, Cheng; Zhang, Kui; Siegal, Gene P; Wei, Shi

2017-12-01

Metastatic breast cancer is a heterogeneous disease with a diverse clinical course. There have been limited studies regarding prognostic outcomes in patients with de novo metastatic breast cancer versus those with metastatic recurrence, with controversial observations. In this study, we sought to examine the difference in survival outcomes among patients with advanced breast cancer stratified based on metastasis-free interval (MFI) and to further explore the role of systemic therapy in these patient groups. Of 569 consecutive patients with stage IV breast cancer between 1998 and 2013, 201 had de novo metastatic disease (metastasis at diagnosis) and 368 developed metastatic recurrence, including 168 with an MFI≤24 months and 200 with an MFI>24 months. In the 492 patients who received systemic therapy, de novo metastasis was an independent favorable prognostic factor for overall survival after metastasis when compared with metastatic recurrence irrespective of MFI. Compared with the patients with metastatic recurrence with an MFI≤24 months, those with an MFI>24 months had a superior survival outcome, although it did not reach statistical significance by multivariate analysis. In contrast, de novo metastatic breast cancer was associated with a worse prognosis when compared with recurring metastasis in the patients who did not receive systemic treatment. These findings provide more insight into the natural history of advanced breast cancer, thus necessitating further investigation into the molecular mechanism of drug resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Risk of breast cancer after false-positive results in mammographic screening.

Science.gov (United States)

Román, Marta; Castells, Xavier; Hofvind, Solveig; von Euler-Chelpin, My

2016-06-01

Women with false-positive results are commonly referred back to routine screening. Questions remain regarding their long-term outcome of breast cancer. We assessed the risk of screen-detected breast cancer in women with false-positive results. We conducted a joint analysis using individual level data from the population-based screening programs in Copenhagen and Funen in Denmark, Norway, and Spain. Overall, 150,383 screened women from Denmark (1991-2008), 612,138 from Norway (1996-2010), and 1,172,572 from Spain (1990-2006) were included. Poisson regression was used to estimate the relative risk (RR) of screen-detected cancer for women with false-positive versus negative results. We analyzed information from 1,935,093 women 50-69 years who underwent 6,094,515 screening exams. During an average 5.8 years of follow-up, 230,609 (11.9%) women received a false-positive result and 27,849 (1.4%) were diagnosed with screen-detected cancer. The adjusted RR of screen-detected cancer after a false-positive result was 2.01 (95% CI: 1.93-2.09). Women who tested false-positive at first screen had a RR of 1.86 (95% CI: 1.77-1.96), whereas those who tested false-positive at third screening had a RR of 2.42 (95% CI: 2.21-2.64). The RR of breast cancer at the screening test after the false-positive result was 3.95 (95% CI: 3.71-4.21), whereas it decreased to 1.25 (95% CI: 1.17-1.34) three or more screens after the false-positive result. Women with false-positive results had a twofold risk of screen-detected breast cancer compared to women with negative tests. The risk remained significantly higher three or more screens after the false-positive result. The increased risk should be considered when discussing stratified screening strategies. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

ADAM10 mediates trastuzumab resistance and is correlated with survival in HER2 positive breast cancer

Science.gov (United States)

Feldinger, Katharina; Generali, Daniele; Kramer-Marek, Gabriela; Gijsen, Merel; Ng, Tzi Bun; Wong, Jack Ho; Strina, Carla; Cappelletti, Mariarosa; Andreis, Daniele; Li, Ji-Liang; Bridges, Esther; Turley, Helen; Leek, Russell; Roxanis, Ioannis; Capala, Jacek; Murphy, Gillian; Harris, Adrian L.; Kong, Anthony

2014-01-01

Trastuzumab prolongs survival in HER2 positive breast cancer patients. However, resistance remains a challenge. We have previously shown that ADAM17 plays a key role in maintaining HER2 phosphorylation during trastuzumab treatment. Beside ADAM17, ADAM10 is the other well characterized ADAM protease responsible for HER ligand shedding. Therefore, we studied the role of ADAM10 in relation to trastuzumab treatment and resistance in HER2 positive breast cancer. ADAM10 expression was assessed in HER2 positive breast cancer cell lines and xenograft mice treated with trastuzumab. Trastuzumab treatment increased ADAM10 levels in HER2 positive breast cancer cells (p≤0.001 in BT474; p≤0.01 in SKBR3) and in vivo (p≤0.0001) compared to control, correlating with a decrease in PKB phosphorylation. ADAM10 inhibition or knockdown enhanced trastuzumab response in naïve and trastuzumab resistant breast cancer cells. Trastuzumab monotherapy upregulated ADAM10 (p≤0.05); and higher pre-treatment ADAM10 levels correlated with decreased clinical response (p≤0.05) at day 21 in HER2 positive breast cancer patients undergoing a trastuzumab treatment window study. Higher ADAM10 levels correlated with poorer relapse-free survival (p≤0.01) in a cohort of HER2 positive breast cancer patients. Our studies implicate a role of ADAM10 in acquired resistance to trastuzumab and establish ADAM10 as a therapeutic target and a potential biomarker for HER2 positive breast cancer patients. PMID:24952873

Risk factors for positive margins in conservative surgery for breast cancer after neoadjuvant chemotherapy.

Science.gov (United States)

Bouzón, Alberto; Acea, Benigno; García, Alejandra; Iglesias, Ángela; Mosquera, Joaquín; Santiago, Paz; Seoane, Teresa

2016-01-01

Breast conservative surgery after neoadjuvant chemotherapy intends to remove any residual tumor with negative margins. The purpose of this study was to analyze the preoperative clinical-pathological factors influencing the margin status after conservative surgery in breast cancer patients receiving neoadjuvant chemotherapy. A retrospective study of 91 breast cancer patients undergoing neoadjuvant chemotherapy (92 breast lesions) during the period 2006 to 2013. A Cox regression analysis to identify baseline tumor characteristics associated with positive margins after breast conservative surgery was performed. Of all cases, 71 tumors were initially treated with conservative surgery after neoadjuvant chemotherapy. Pathologic exam revealed positive margins in 16 of the 71 cases (22.5%). The incidence of positive margins was significantly higher in cancers with initial size >5cm (P=.021), in cancers with low tumor grade (P=.031), and in patients with hormone receptor-positive cancer (P=.006). After a median follow-up of 45.2 months, 7 patients of the 71 treated with conservative surgery had disease recurrence (9.8%). There was no significant difference in terms of disease-free survival according to the margin status (P=.596). A baseline tumor size >5cm, low tumor grade and hormone receptor-positive status increase the risk for surgical margin involvement in breast conservative surgery after neoadjuvant chemotherapy. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

TU-EF-207-04: Advances in Detector Technology for Breast Tomosynthesis

Energy Technology Data Exchange (ETDEWEB)

Zhao, W. [SUNY Stony Brook (United States)

2015-06-15

Breast imaging technology is advancing on several fronts. In digital mammography, the major technological trend has been on optimization of approaches for performing combined mammography and tomosynthesis using the same system. In parallel, photon-counting slot-scan mammography is now in clinical use and more efforts are directed towards further development of this approach for spectral imaging. Spectral imaging refers to simultaneous acquisition of two or more energy-windowed images. Depending on the detector and associated electronics, there are a number of ways this can be accomplished. Spectral mammography using photon-counting detectors can suppress electronic noise and importantly, it enables decomposition of the image into various material compositions of interest facilitating quantitative imaging. Spectral imaging can be particularly important in intravenously injected contrast mammography and eventually tomosynthesis. The various approaches and applications of spectral mammography are discussed. Digital breast tomosynthesis relies on the mechanical movement of the x-ray tube to acquire a number of projections in a predefined arc, typically from 9 to 25 projections over a scan angle of +/−7.5 to 25 degrees depending on the particular system. The mechanical x-ray tube motion requires relatively long acquisition time, typically between 3.7 to 25 seconds depending on the system. Moreover, mechanical scanning may have an effect on the spatial resolution due to internal x-ray filament or external mechanical vibrations. New x-ray source arrays have been developed and they are aimed at replacing the scanned x-ray tube for improved acquisition time and potentially for higher spatial resolution. The potential advantages and challenges of this approach are described. Combination of digital mammography and tomosynthesis in a single system places increased demands on certain functional aspects of the detector and overall performance, particularly in the tomosynthesis

TU-EF-207-04: Advances in Detector Technology for Breast Tomosynthesis

International Nuclear Information System (INIS)

Zhao, W.

2015-01-01

Breast imaging technology is advancing on several fronts. In digital mammography, the major technological trend has been on optimization of approaches for performing combined mammography and tomosynthesis using the same system. In parallel, photon-counting slot-scan mammography is now in clinical use and more efforts are directed towards further development of this approach for spectral imaging. Spectral imaging refers to simultaneous acquisition of two or more energy-windowed images. Depending on the detector and associated electronics, there are a number of ways this can be accomplished. Spectral mammography using photon-counting detectors can suppress electronic noise and importantly, it enables decomposition of the image into various material compositions of interest facilitating quantitative imaging. Spectral imaging can be particularly important in intravenously injected contrast mammography and eventually tomosynthesis. The various approaches and applications of spectral mammography are discussed. Digital breast tomosynthesis relies on the mechanical movement of the x-ray tube to acquire a number of projections in a predefined arc, typically from 9 to 25 projections over a scan angle of +/−7.5 to 25 degrees depending on the particular system. The mechanical x-ray tube motion requires relatively long acquisition time, typically between 3.7 to 25 seconds depending on the system. Moreover, mechanical scanning may have an effect on the spatial resolution due to internal x-ray filament or external mechanical vibrations. New x-ray source arrays have been developed and they are aimed at replacing the scanned x-ray tube for improved acquisition time and potentially for higher spatial resolution. The potential advantages and challenges of this approach are described. Combination of digital mammography and tomosynthesis in a single system places increased demands on certain functional aspects of the detector and overall performance, particularly in the tomosynthesis

Retrospective Analysis of Locally Advanced Noninflammatory Breast Cancer From Chennai, South India, 1990-1999

International Nuclear Information System (INIS)

Shanta, Viswanathan; Swaminathan, Rajaraman; Rama, Ranganathan M.Sc.; Radhika, Ramachandran M.S.

2008-01-01

Purpose: This was a retrospective observational study to elicit the outcome of the therapeutic strategy of concurrent neoadjuvant chemoradiotherapy protocol for locally advanced breast cancer. Methods and Materials: A large series of 1,117 consecutive cases of locally advanced breast cancer treated at the Cancer Institute (WIA), in Chennai, South India, between 1990 and 1999 and followed through 2004 formed the basis for this study. Disease-free survival was the main outcome, and nodal and tumor downstaging were the intermediate outcome measures studied. Results: Primary tumor downstaging was observed in 45% and nodal downstaging in 57.5%. The disease-free survival rate of nodal downstaged patients at 5, 10, and 15 years was 75%, 65%, and 58%, respectively. The corresponding rates for pre- and postoperative node-negative patients were 70%, 60%, and 59%. The best survival was seen among those who were tumor and node negative postoperatively. Nodal downstaging halved the risk of disease recurrence and death compared with node positivity, irrespective of tumor sterility. Conclusions: A randomized trial using cyclophosphamide, methotrexate, and 5-fluorouracil vs. an anthracycline-based regimen in the setting of concurrent chemoradiotherapy appears indicated. Additional preoperative chemotherapy to maximize nodal and tumor downstaging should be investigated. A change in postoperative chemotherapy according to nodal status could also be explored

The value of imaging in standing position in preoperative breast lymphoscintigraphy.

Science.gov (United States)

Anagnostou, Christos; Baiocco, Cinzia; Arnulfo, Alberto; Liberatore, Mauro; Baccheschi, Anna Maria; Inglese, Eugenio

2011-08-01

Breast lymphoscintigraphy is an accurate technique, but in a minority of cases the sentinel node (SN) visualization cannot be achieved or can be very difficult. We evaluated the potential clinical advantages and limitations of performing imaging in the standing position. The aim was to establish if this examination modality is quicker and helpful in the presence of "hidden" SN, checking also for any influence of SN skin landmarking in the upright position on the correct intraoperative SN identification. The overall objective was to verify if the standing position can be routinely used in breast lymphoscintigraphy. A total of 144 patients underwent lymphoscintigraphy in both standing and supine positions. In both modalities, a skin landmark was set coincident with the SN orthogonal projections. The acquisition times of 2 groups (each consisting of 45 patients) examined with the standing or supine acquisition modality, were compared. In 6 cases with hidden SN and in 34 cases with difficult or partial visualization in one of the supine views, the standing protocol was effective and led to better and quicker visualization of lymph nodes (median examination time: 25.5 minutes standing, 35.5 minutes supine). Significant differences in skin landmark position between the 2 modalities were present only in overweight patients and in large breasts. This, however, did not have a negative impact on successful intraoperative localization of SN with the gamma probe. Standing acquisition resulted to be a faster, easier, and more accurate examination protocol and can be used as the routine method for SN detection in breast lymphoscintigraphy.

Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-1-0268 TITLE: Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer PRINCIPAL INVESTIGATOR...Eric Winer CONTRACTING ORGANIZATION: Dana-Farber Cancer Institute Boston, MA 02215 REPORT DATE: OCTOBER 2017 TYPE OF REPORT: ANNUAL PREPARED FOR...CONTRACT NUMBER Randomized Trial of Asprin as Adjuvant Therapy for Node- Positive Breast Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

Locally advanced breast cancer (stage III and stage IV)

International Nuclear Information System (INIS)

Baracat, F.F.; Grabert, H.; Lima, G.R. de; Pontes, M.; Ferraro, O.; Santana, A.; Brook, E.S.

1987-01-01

The results concerning to the treatment of 193 patients with locally advanced breast cancer-stage III and stage IV are analysed. All the patients were treated with radical radiotherapy plus total mastectomy about 6 weeks later; 53 pacients received also chemotherapy (CMF - 12 courses) and 52 were oophorectomized. (M.A.C) [pt

Advances in the Molecular Analysis of Breast Cancer: Pathway Toward Personalized Medicine.

Science.gov (United States)

Rosa, Marilin

2015-04-01

Breast cancer is a heterogeneous disease that encompasses a wide range of clinical behaviors and histological and molecular variants. It is the most common type of cancer affecting women worldwide and is the second leading cause of cancer death. A comprehensive literature search was performed to explore the advances in molecular medicine related to the diagnosis and treatment of breast cancer. During the last few decades, advances in molecular medicine have changed the landscape of cancer treatment as new molecular tests complement and, in many instances, exceed traditional methods for determining patient prognosis and response to treatment options. Personalized medicine is becoming the standard of care around the world. Developments in molecular profiling, genomic analysis, and the discovery of targeted drug therapies have significantly improved patient survival rates and quality of life. This review highlights what pathologists need to know about current molecular tests for classification and prognostic/ predictive assessment of breast carcinoma as well as their role as part of the medical team.

Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer

Directory of Open Access Journals (Sweden)

Rottenfusser Andrea

2009-10-01

Full Text Available Abstract Background In Her2-positive advanced breast cancer, the upfront use of trastuzumab is well established. Upon progression on first-line therapy, patients may be switched to lapatinib. Others however remain candidates for continued antibody treatment (treatment beyond progression. Here, we aimed to identify factors predicting for activity of second-line trastuzumab-based therapy. Methods Ninety-seven patients treated with > 1 line of trastuzumab-containing therapy were available for this analysis. Her2-status was determined by immunohistochemistry and re-analyzed by FISH if a score of 2+ was gained. Time to progression (TTP on second-line therapy was defined as primary study endpoint. TTP and overall survival (OS were estimated using the Kaplan-Meier product limit method. Multivariate analyses (Cox proportional hazards model, multinomial logistic regression were applied in order to identify factors associated with TTP, response, OS, and incidence of brain metastases. p values Results Median TTP on second-line trastuzumab-based therapy was 7 months (95% CI 5.74-8.26, and 8 months (95% CI 6.25-9.74 on first-line, respectively (n.s.. In the multivariate models, none of the clinical or histopthological features could reliably predict for activity of second-line trastuzumab-based treatment. OS was 43 months suggesting improved survival in patients treated with trastuzumab in multiple-lines. A significant deterioration of cardiac function was observed in three patients; 40.2% developed brain metastases while on second-line trastuzumab or thereafter. Conclusion Trastuzumab beyond progression showed considerable activity. None of the variables investigated correlated with activity of second-line therapy. In order to predict for activity of second-line trastuzumab, it appears necessary to evaluate factors known to confer trastuzumab-resistance.

Clinical significance of circulating tumor cells (CTCs) with respect to optimal cut-off value and tumor markers in advanced/metastatic breast cancer.

Science.gov (United States)

Shiomi-Mouri, Yukako; Kousaka, Junko; Ando, Takahito; Tetsuka, Rie; Nakano, Shogo; Yoshida, Miwa; Fujii, Kimihito; Akizuki, Miwa; Imai, Tsuneo; Fukutomi, Takashi; Kobayashi, Katsumasa

2016-01-01

Although carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are useful tumor markers (TMs) in metastatic breast cancer (MBC), circulating tumor cells (CTCs) are also detected in patients with advanced or metastatic breast cancer. We analyzed CTCs in MBC patients in order to establish the optimal cut-off value, to evaluate the prognostic utility of CTC count, and to clarify whether CTC count could provide information in addition to CEA and CA15-3. We studied 98 MBC patients enrolled between June 2007 and March 2013. To quantify CTCs, 7.5 ml of blood was collected and CEA and CA15-3 were measured simultaneously. CTCs were counted using the CellSearch™ System. The CTC count was dichotomized as 0 (CTC-negative) or ≥1 (CTC-positive). The clinical significance of CTCs was evaluated in terms of its relationship with levels of CEA and CA15-3. Associations between qualitative variables were evaluated using the chi-square test. In order to evaluate the predictive value of CTCs for advanced or metastatic breast cancer, multivariate Cox proportional hazards modeling was used to calculate hazard ratios. With a CTC cut-off value of 1, there were 53 (54.1 %) CTC-negative patients and 45 (45.9 %) CTC-positive patients. Patients in the CTC-positive group had worse survival than those in the CTC-negative group (p CEA and CA15-3.

Risk of breast cancer after false-positive results in mammographic screening

DEFF Research Database (Denmark)

Roman, Marta; Castells, Xavier; Hofvind, Solveig

2016-01-01

risk (RR) of screen-detected cancer for women with false-positive versus negative results. We analyzed information from 1,935,093 women 50–69 years who underwent 6,094,515 screening exams. During an average 5.8 years of follow-up, 230,609 (11.9%) women received a false-positive result and 27,849 (1......Women with false-positive results are commonly referred back to routine screening. Questions remain regarding their long-term outcome of breast cancer. We assessed the risk of screen-detected breast cancer in women with false-positive results. We conducted a joint analysis using individual level.......4%) were diagnosed with screen-detected cancer. The adjusted RR of screen-detected cancer after a false-positive result was 2.01 (95% CI: 1.93–2.09). Women who tested false-positive at first screen had a RR of 1.86 (95% CI: 1.77–1.96), whereas those who tested false-positive at third screening had a RR...

Steroid induction of therapy-resistant cytokeratin-5-positive cells in estrogen receptor-positive breast cancer through a BCL6-dependent mechanism

Science.gov (United States)

Goodman, C R; Sato, T; Peck, A R; Girondo, M A; Yang, N; Liu, C; Yanac, A F; Kovatich, A J; Hooke, J A; Shriver, C D; Mitchell, E P; Hyslop, T; Rui, H

2016-01-01

Therapy resistance remains a major problem in estrogen receptor-α (ERα)-positive breast cancer. A subgroup of ERα-positive breast cancer is characterized by mosaic presence of a minor population of ERα-negative cancer cells expressing the basal cytokeratin-5 (CK5). These CK5-positive cells are therapy resistant and have increased tumor-initiating potential. Although a series of reports document induction of the CK5-positive cells by progestins, it is unknown if other 3-ketosteroids share this ability. We now report that glucocorticoids and mineralocorticoids effectively expand the CK5-positive cell population. CK5-positive cells induced by 3-ketosteroids lacked ERα and progesterone receptors, expressed stem cell marker, CD44, and displayed increased clonogenicity in soft agar and broad drug-resistance in vitro and in vivo. Upregulation of CK5-positive cells by 3-ketosteroids required induction of the transcriptional repressor BCL6 based on suppression of BCL6 by two independent BCL6 small hairpin RNAs or by prolactin. Prolactin also suppressed 3-ketosteroid induction of CK5+ cells in T47D xenografts in vivo. Survival analysis with recursive partitioning in node-negative ERα-positive breast cancer using quantitative CK5 and BCL6 mRNA or protein expression data identified patients at high or low risk for tumor recurrence in two independent patient cohorts. The data provide a mechanism by which common pathophysiological or pharmacologic elevations in glucocorticoids or other 3-ketosteroids may adversely affect patients with mixed ERα+/CK5+ breast cancer. The observations further suggest a cooperative diagnostic utility of CK5 and BCL6 expression levels and justify exploring efficacy of inhibitors of BCL6 and 3-ketosteroid receptors for a subset of ERα-positive breast cancers. PMID:26096934

Treatment of locally advanced breast carcinoma with high-dose external beam supervoltage radiotherapy

International Nuclear Information System (INIS)

Brufman, G.; Weshler, Z.; Prosnitz, L.R.; Fuks, Z.

1981-01-01

Between 1960 and 1978, 87 patients with locally advanced Tsub(3-4)Nsub(0-3)M 0 carcinoma of the breast were treated with 5,000 to 8,000 rad of external beam supervoltage radiotherapy. Initial clinical eradication of the tumour was observed in 76 of 87 cases (87%), but the actuarial probability of local control at 5 yr was only 53%. Furthermore, the actuarial probability of disease-free survival was 25% at 5 yr and 13% at 10 yr. Most of the patients eventually succumbed to metastatic breast carcinoma and the actuarial survival at 5 yr was 43% and at 10 yr, 16%. The addition of adjuvant low-dose chemotherapy, given to 13 patients, did not affect the rates of local control, survival or disease-free survival. The most common long-term complication was extensive and deforming radiation-induced fibrosis of the treated breast. The actuarial probability of 10-yr survival without a local recurrence and without severe fibrosis of the treated breast was only 17.5%. The role of adjuvant high-dose chemotherapy in the treatment of locally advanced breast carcinoma and the possible use of improved radiotherapy techniques to achieve a more effective long-term local control and a more desirable cosmetic end result are discussed. (author)

6.3 MeV fast neutrons in the treatment of patients with locally advanced and locally recurrent breast cancer

Energy Technology Data Exchange (ETDEWEB)

Velikaya, V. V., E-mail: viktoria.v.v@inbox.ru; Startseva, Zh. A., E-mail: zhanna.alex@rambler.ru [Tomsk Cancer Research Institute, Kooperativny Street 5, Tomsk, 634050 (Russian Federation); National Research Tomsk Polytechnic University, Lenin Avenue 30, Tomsk, 634050 (Russian Federation); Musabaeva, L. I., E-mail: musabaevaLI@oncology.tomsk.ru; Lisin, V. A., E-mail: Lisin@oncology.tomsk.ru [Tomsk Cancer Research Institute, Kooperativny Street 5, Tomsk, 634050 (Russian Federation)

2016-08-02

The study included 135 breast cancer patients (70 patients with locally recurrent breast cancer and 65 patients with locally advanced breast cancer with unfavorable prognostic factors) who received the neutron therapy alone or in combination with the photon therapy. The neutron therapy was shown to be effective in multimodality treatment of patients with locally advanced and locally recurrent breast cancer. The 8-year survival rate in patients without repeated breast cancer recurrence was 87.6 ± 8.7% after the neutron and neutron-photon therapy and 54.3 ± 9.2% after the electron beam therapy.

The Role of Doppler Ultrasound in Assessing the Therapeutic Response in Advanced Breast Cancer

Directory of Open Access Journals (Sweden)

Jamal Eyvazi-Ziaei

2018-01-01

Full Text Available Background and Objectives: Breast cancer is one of the most common cancers in Iran, which neo-adjuvant chemotherapy used to treat in advanced types to reduce tumor burden. The aim of this study was to evaluate the ultrasound scales of patients with advanced disease, using two common treatment methods include TACs (Taxotere, Adriamycin, and Cyclophosphamide and AC (Adriamycin, Cyclophosphamide. Material and Methods: Clinical examination and Doppler ultrasound were performed before and after treatment. Before and after the treatment, the size of the primary tumor and tumor vascularization, and the ultrasound Resistivity Index (RI, Pulsality Index (PI, Peak Systolic Velocity (PSV and the condition of the anterior lymph nodes, and the effect of two different therapies were investigated in response to treatment. The SPSS statistical software 17.0 was used to evaluate the relationship between the variables with 95% confidence interval, and P≤ 0.05. Results: The mean age of the patients was 48.90 (±10.58 SD years. From these, 8 were postmenopausal and 9 were menopausal, and in 3 cases the situation was unknown. There was significant difference between the PSV levels of the main breast mass, pre and post chemotherapy (P=0.004. Changes in other indexes of breast mass and axillary mass were not statistical significant. Conclusion: Color Doppler ultrasonography seems to be a promising alternative as an independent and complementary tool, to assess the response to treatment of breast masses to primary medical treatment in advanced breast cancers.

Palmitate-induced ER stress increases trastuzumab sensitivity in HER2/neu-positive breast cancer cells

International Nuclear Information System (INIS)

Baumann, Jan; Wong, Jason; Sun, Yan; Conklin, Douglas S.

2016-01-01

HER2/neu-positive breast cancer cells have recently been shown to use a unique Warburg-like metabolism for survival and aggressive behavior. These cells exhibit increased fatty acid synthesis and storage compared to normal breast cells or other tumor cells. Disruption of this synthetic process results in apoptosis. Since the addition of physiological doses of exogenous palmitate induces cell death in HER2/neu-positive breast cancer cells, the pathway is likely operating at its limits in these cells. We have studied the response of HER2/neu-positive breast cancer cells to physiological concentrations of exogenous palmitate to identify lipotoxicity-associated consequences of this physiology. Since epidemiological data show that a diet rich in saturated fatty acids is negatively associated with the development of HER2/neu-positive cancer, this cellular physiology may be relevant to the etiology and treatment of the disease. We sought to identify signaling pathways that are regulated by physiological concentrations of exogenous palmitate specifically in HER2/neu-positive breast cancer cells and gain insights into the molecular mechanism and its relevance to disease prevention and treatment. Transcriptional profiling was performed to assess programs that are regulated in HER2-normal MCF7 and HER2/neu-positive SKBR3 breast cancer cells in response to exogenous palmitate. Computational analyses were used to define and predict functional relationships and identify networks that are differentially regulated in the two cell lines. These predictions were tested using reporter assays, fluorescence-based high content microscopy, flow cytometry and immunoblotting. Physiological effects were confirmed in HER2/neu-positive BT474 and HCC1569 breast cancer cell lines. Exogenous palmitate induces functionally distinct transcriptional programs in HER2/neu-positive breast cancer cells. In the lipogenic HER2/neu-positive SKBR3 cell line, palmitate induces a G2 phase cell cycle delay and

The impact of tamoxifen on breast recurrence, cosmesis, complications, and survival in estrogen receptor-positive early-stage breast cancer

International Nuclear Information System (INIS)

Fowble, Barbara; Fein, Douglas A.; Hanlon, Alexandra L.; Eisenberg, Burton L.; Hoffman, John P.; Sigurdson, Elin R.; Daly, Mary B.; Goldstein, Lori J.

1996-01-01

Purpose: To evaluate the impact of tamoxifen on breast recurrence, cosmesis, complications, overall and cause-specific survival in women with Stage I-II breast cancer and estrogen receptor positive tumors undergoing conservative surgery and radiation. Methods and Materials: From 1982 to 1991, 491 women with estrogen receptor positive Stage I-II breast cancer underwent excisional biopsy, axillary dissection, and radiation. The median age of the patient population was 60 years with 21% < 50 years of age. The median follow-up was 5.3 years (range 0.1 to 12.8). Sixty-nine percent had T1 tumors and 83% had histologically negative axillary nodes. Reexcision was performed in 49% and the final margin of resection was negative in 64%. One hundred fifty-four patients received tamoxifen and 337 patients received no adjuvant therapy. None of the patients received adjuvant chemotherapy. Results: There were no significant differences between the two groups for age, race, clinical tumor size, histology, the use of reexcision, or median total dose to the primary. Patients who received tamoxifen were more often axillary node positive (44% tamoxifen vs. 5% no tamoxifen), and, therefore, a greater percentage received treatment to the breast and regional nodes. The tamoxifen patients less often had unknown margins of resection (9% tamoxifen vs. 22% no tamoxifen). The 5-year actuarial breast recurrence rate was 4% for the tamoxifen patients compared to 7% for patients not receiving tamoxifen (p 0.21). Tamoxifen resulted in a modest decrease in the 5-year actuarial risk of a breast recurrence in axillary node-negative patients, in those with unknown or close margins of resection, and in those who underwent a single excision. Axillary node-positive patients had a clinically significant decrease in the 5-year actuarial breast recurrence rate (21 vs. 4%; p 0.08). The 5-year actuarial rate of distant metastasis was not significantly decreased by the addition of adjuvant tamoxifen in all

TU-EF-207-01: Introductory Remarks on Recent Advances in Breast Imaging

Energy Technology Data Exchange (ETDEWEB)

Karellas, A. [University of Massachusetts Medical School (United States)

2015-06-15

Breast imaging technology is advancing on several fronts. In digital mammography, the major technological trend has been on optimization of approaches for performing combined mammography and tomosynthesis using the same system. In parallel, photon-counting slot-scan mammography is now in clinical use and more efforts are directed towards further development of this approach for spectral imaging. Spectral imaging refers to simultaneous acquisition of two or more energy-windowed images. Depending on the detector and associated electronics, there are a number of ways this can be accomplished. Spectral mammography using photon-counting detectors can suppress electronic noise and importantly, it enables decomposition of the image into various material compositions of interest facilitating quantitative imaging. Spectral imaging can be particularly important in intravenously injected contrast mammography and eventually tomosynthesis. The various approaches and applications of spectral mammography are discussed. Digital breast tomosynthesis relies on the mechanical movement of the x-ray tube to acquire a number of projections in a predefined arc, typically from 9 to 25 projections over a scan angle of +/−7.5 to 25 degrees depending on the particular system. The mechanical x-ray tube motion requires relatively long acquisition time, typically between 3.7 to 25 seconds depending on the system. Moreover, mechanical scanning may have an effect on the spatial resolution due to internal x-ray filament or external mechanical vibrations. New x-ray source arrays have been developed and they are aimed at replacing the scanned x-ray tube for improved acquisition time and potentially for higher spatial resolution. The potential advantages and challenges of this approach are described. Combination of digital mammography and tomosynthesis in a single system places increased demands on certain functional aspects of the detector and overall performance, particularly in the tomosynthesis

TU-EF-207-01: Introductory Remarks on Recent Advances in Breast Imaging

International Nuclear Information System (INIS)

Karellas, A.

2015-01-01

Breast imaging technology is advancing on several fronts. In digital mammography, the major technological trend has been on optimization of approaches for performing combined mammography and tomosynthesis using the same system. In parallel, photon-counting slot-scan mammography is now in clinical use and more efforts are directed towards further development of this approach for spectral imaging. Spectral imaging refers to simultaneous acquisition of two or more energy-windowed images. Depending on the detector and associated electronics, there are a number of ways this can be accomplished. Spectral mammography using photon-counting detectors can suppress electronic noise and importantly, it enables decomposition of the image into various material compositions of interest facilitating quantitative imaging. Spectral imaging can be particularly important in intravenously injected contrast mammography and eventually tomosynthesis. The various approaches and applications of spectral mammography are discussed. Digital breast tomosynthesis relies on the mechanical movement of the x-ray tube to acquire a number of projections in a predefined arc, typically from 9 to 25 projections over a scan angle of +/−7.5 to 25 degrees depending on the particular system. The mechanical x-ray tube motion requires relatively long acquisition time, typically between 3.7 to 25 seconds depending on the system. Moreover, mechanical scanning may have an effect on the spatial resolution due to internal x-ray filament or external mechanical vibrations. New x-ray source arrays have been developed and they are aimed at replacing the scanned x-ray tube for improved acquisition time and potentially for higher spatial resolution. The potential advantages and challenges of this approach are described. Combination of digital mammography and tomosynthesis in a single system places increased demands on certain functional aspects of the detector and overall performance, particularly in the tomosynthesis

Prone versus supine positioning for whole and partial-breast radiotherapy: A comparison of non-target tissue dosimetry

International Nuclear Information System (INIS)

Kirby, Anna M.; Evans, Philip M.; Donovan, Ellen M.; Convery, Helen M.; Haviland, Joanna S.; Yarnold, John R.

2010-01-01

Purpose: To compare non-target tissue (including left-anterior-descending coronary-artery (LAD)) dosimetry of prone versus supine whole (WBI) and partial-breast irradiation (PBI). Methods and materials: Sixty-five post-lumpectomy breast cancer patients underwent CT-imaging supine and prone. On each dataset, the whole-breast clinical-target-volume (WB-CTV), partial-breast CTV (tumour-bed + 15 mm), ipsilateral-lung and chest-wall were outlined. Heart and LAD were outlined in left-sided cases (n = 30). Tangential-field WBI and PBI plans were generated for each position. Mean LAD, heart, and ipsilateral-lung doses (x mean ), maximum LAD (LAD max ) doses, and the volume of chest-wall receiving 50 Gy (V 50Gy ) were compared. Results: Two-hundred and sixty plans were generated. Prone positioning reduced heart and LAD doses in 19/30 WBI cases (median reduction in LAD mean = 6.2 Gy) and 7/30 PBI cases (median reduction in LAD max = 29.3 Gy) (no difference in 4/30 cases). However, prone positioning increased cardiac doses in 8/30 WBI (median increase in LAD mean = 9.5 Gy) and 19/30 PBI cases (median increase in LAD max = 22.9 Gy) (no difference in 3/30 cases). WB-CTV > 1000cm 3 was associated with improved cardiac dosimetry in the prone position for WBI (p = 0.04) and PBI (p = 0.04). Prone positioning reduced ipsilateral-lung mean in 65/65 WBI and 61/65 PBI cases, and chest-wall V 50Gy in all WBI cases. PBI reduced normal-tissue doses compared to WBI in all cases, regardless of the treatment position. Conclusions: In the context of tangential-field WBI and PBI, prone positioning is likely to benefit left-breast-affected women of larger breast volume, but to be detrimental in left-breast-affected women of smaller breast volume. Right-breast-affected women are likely to benefit from prone positioning regardless of breast volume.

Carcinoembryonic antigen: an invaluable marker for advanced breast cancer.

Directory of Open Access Journals (Sweden)

Pathak K

1996-07-01

Full Text Available Serial serum Carcinoembryonic antigen (CEA levels were measured in 150 individuals (50 patients with breast cancer, 50 benign breast diseases and 50 other controls. These levels were correlated with clinicopathological parameters and follow-up information. Serum CEA levels were independent of the primary tumor status, their histology, lymphoreticular response and the patients′ characteristics as well as the age, sex and the menstrual status. However, the nodal status, number of involved nodes and the grade of the tumors had significant influence on the level of serum CEA. Breast cancer patients especially those with metastasis had significantly higher serum CEA levels as compared to the controls and those with localised disease, irrespective of the site of metastasis. These levels were lowered appreciably by the disease regression and were raised or stable during the disease progression. Receiver operating characteristic (ROC curve showed metastasis to be more frequent in patients with pretreatment serum CEA levels above 25 ng/ml and persistent post treatment CEA levels above 15 ng/ml. Serum CEA level was found to be a valuable prognostic indicator for advanced breast cancer and serial serum CEA levels provided an average lead time of about 3.9 months before the clinical appearance of metastasis.

Prognostic value of the 99mTc-Isonitrile washout rate in neoadjuvant chemotherapy in patients with locally advanced breast cancer

International Nuclear Information System (INIS)

Silva, N. Jr.; Anselmi, C.E.; Foppa, M.; Batista, L.; Grobocopatel, D.; Hunsche, A.; Fernandes, D.; Berdichevski, E.; Madke, R.; Baptista, I.; Martini, J.; Obando, A.

2004-01-01

Full text: Neoadjuvant chemotherapy is the pre-surgical treatment of choice in patients with locally advanced breast tumor for better disease control and breast conservation. Resistance to chemotherapy may be seen in about 18%-51% of the cancers. The term multi drug resistance (MDR) is commonly used to indicate the expression of the transmembrane glycoprotein (P-glycoprotein). This protein removes some very important chemotherapeutic drugs from inside the cell and is responsible for the clinical manifestation of the MDR. The knowledge of MDR before the initiation of chemotherapy can help choosing the best treatment. 99mTc-Isonitrile is a radiotracer largely used in nuclear medicine. It enters cells, is identified by the P-glycoprotein as a substrate and is, therefore, expelled from the neoplastic cell. Various studies have demonstrated direct correlation between the 99mTc-Isonitrile efflux, P-glycoprotein expression and MDR. On the other hand, 99mTc-Isonitrile retention in the tumor suggests chemosensitivity. The objective of this study was to monitor the response to neoadjuvant chemotherapy in breast cancer by the use of 99mTc-Sestamibi scintimammography and its washout rate in a pilot study. Five patients with locally advanced breast cancer were subjected to neoadjuvant chemotherapy. Inclusion criteria were locally advanced tumor, biopsy results, no distant metastasis, and completion of the whole chemotherapy protocol. Exclusion criteria were any previous cancer treatment or other primary tumor. All the patients underwent 99mTc-Sestamibi scintimammography before and after completion of the chemotherapy protocol. For scintimammography, 740MBq of radiotracer was injected in the arm contra lateral to the side of lesion. Planar images were acquired at 10 and 240 minutes, in anterior supine position as well as in both lateral projections in prone position. Regions of interest of same size were drawn over the tumor and in the contra lateral breast to correct for

Comparative study on mammography between triple negative and triple positive breast cancer

International Nuclear Information System (INIS)

Cui Chunxiao; Lin Qing; Yang Qing; Zhang Chuanyu; Wang Shaohua; Yu Hualong; Duan Feng; Liu Shihe

2012-01-01

Objective: To analyze the mammographic findings of triple-negative breast cancer [TNBC, which is estrogen receptor (ER) negative, progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) negative] and triple-positive breast cancer (TPBC, which is ER positive, PR positive, and HER2 positive), and to evaluate the relationship of immunohistochemologic receptor status and mammographic findings. Methods: The immunohistochemistry results of 631 cases with breast cancers were reviewed, including 117 cases of TNBC and 44 cases of TPBC. All of the patients took mammography at initial diagnosis. We retrospectively evaluated the visibility, morphology, distribution and size of the lesion (masses and calcifications) and breast density on mammography of TNBC, and compared them with those of TPBC. The age onset and tumor sizes of TNBC and TPBC were compared by using Chi-square test and t test. Results: The visibility rate of TNBC and TPBC on mammography were 88.0%(103/117) and 90.9% (40/44), and the difference between them was insignificant (χ 2 =0.055, P >0.05). TNBC was more frequently associated with merely a mass (56/103) than TPBC (12/40) (χ 2 =6.860, P<0.01), and the mean diameter of the mass of TNBC [(2.6 ± 1.4) cm] was larger than that of TPBC [(2.0 ± 0.6) cm] (t=2.087, P<0.05). TNBC were less frequently associated with microcalcifications (37/103) than TPBC (24/40) (χ 2 =7.423, P<0.01). Mammographic density and lesion visibility were similar between the two different immunophenotypes of breast cancers. The mean age of TNBC (52±9) was more than that of TPBC (48 ±8) (t=2.759, P<0.01). Infiltrating ductal carcinoma was the main pathologic type of both groups. Basal-like breast cancer accounted for 49% (57/117) of TNBC while none happened in TPBC. Conclusions: TNBC shows merely a mass with indistinct margins,lager size and is less associated with microcalcifications. These mammographic features might be useful in diagnosing triple

Role of mammography in evaluating residual cancer of locally advanced breast carcinoma after neo-adjuvant chemotherapy : compared with clinical examination

International Nuclear Information System (INIS)

Choi, Byoung Wook; Kim, Eun Kyung; Oh, Ki Keun; Cho, Jae Min; Chung, Hyun Cheol; Lee, Byung Chan; Lee, Kyong Sik; Lee, Yong Hee

1997-01-01

To compare the usefulness of mammography and clinical examination in the evaluation of residual cancer of locally-advanced breast carcinoma treated with neoadjuvant chemotherapy. Among 67 patients with locally advanced breast carcinoma who were treated with neoadjuvant chemotherapy, 18, aged 35-67 (mean, 48) years, underwent mammography before and after this therapy. The 18 sets of mammographs were analyzed retrospectively and compared with the results of clinical examination based on histologic diagnosis. On histologic examinations, 16 of 18 patients (89%) were found to have residual cancer, but in one of these 16, mammography did not show this same result. On mammography, residual cancer was found in 16 patients, but in one of this group, histologic examination did not reveal the same finding. Clinically, a complete response was shown by four patients, and a partial response by 11 ; three showed no response. On histolgogic examination, three of the four patients with complete clinical response were found to have residual cancer. Post-treatment mammographic findings showed that 11 patients had measurable mass ; all of these had residual cancer (positive predictive value : 100%). However, five of seven patients in whom no measurable mass was evident also had residual cancer. Seven of 8 patients in whom microcalcifications were seen on mammography were found to have residual cancer (positive predictive value : 88%). The sensitivity of mammography in predicting residual cancer was greater than that of clinical examination (94% vs 81%), even when microscopic residual cancer was considered as a complete response (92% vs 77%). The specificity of mammography was the same as that of clinical examination(50% vs 50%, 20% vs 20%). In evaluating residual cancer of locally-advanced breast carcinoma after neoadjuvant chemotheragy, mammography is more accurate and informative than clincal examination. In predicting residual cancer, however, it is not accurate enough to replace

Systemic therapy for HER2-positive early-stage breast cancer.

Science.gov (United States)

Mathew, Aju; Romond, Edward H

The advent of the targeted monoclonal antbody trastuzumab for treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer marked a revolution in the understanding and management of mammary carcinoma and, in practice, separated this subtype from other kinds of primary breast malignancy. Long term follow-up from the initial large adjuvant trials continue to show remarkably positive results. Currently, at least four additional agents targeting this receptor, using different and complementary mechanisms of action compared with trastuzumab, have been incorporated into clinical trials. The small molecule tyrosine kinase inhibitors lapatinib and neratinib, in addition to the antibody pertuzumab and the antibody-drug conjugate trastuzumab-ematansine, have shown efficacy in metastatic breast cancer and are being evaluated both in neoadjuvant and adjuvant trials for early stage disease. The cytotoxic chemotherapy regimens used in combination with these agents also are evolving and different therapeutic approaches are emerging for patients depending on their relative level of risk from their cancers, thus moving clinical management toward individualized therapy. Much has been learned about managing the toxicities of treatment and pre-operative approaches have provided a means of assessing the sensitivity of individual patients' cancers to specific treatment regimens. This review traces the development of these studies and focuses on improvements in adjuvant and neoadjuvant therapy for patients with HER2-positive disease whose prognosis has changed in the last decade from dire to favorable. A path forward has been set by which the goal of cure is attainable for almost all patients faced with this aggressive form of breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Characteristics and treatment of human epidermal growth factor receptor 2 positive breast cancer: 43,485 cases from the National Cancer Database treated in 2010 and 2011.

Science.gov (United States)

Killelea, Brigid K; Chagpar, Anees B; Horowitz, Nina R; Lannin, Donald R

2017-02-01

Although identification of human epidermal growth factor receptor 2 (Her2) positive breast cancer represents one of the greatest advances over the past 3 decades, it has not been studied extensively on a national level. The National Cancer Database is a joint project of the American Cancer Society and the American College of Surgeons and contains data on about 70% of the cancer cases in the United States. Data on Her2 have been collected since 2010 and was used for this study. Of 298,937 cases of invasive breast cancer with known Her2 status diagnosed in 2010 and 2011, 43,485 (14.5%) were Her2 positive. Her2 positivity was greatest in Asian/Pacific Islanders and least in non-Hispanic Whites and was markedly more common in younger women. The incidence of Her2 positive tumors ranged from a low of 13.9% in the Mountain West region to a high of 16.0% in the West South Central region (P breast preservation (odds ratio = .78, confidence interval = .76 to .80). Her2 positive tumors have distinct epidemiologic, clinical, and treatment characteristics. Copyright © 2016 Elsevier Inc. All rights reserved.

Endocrine therapy for postmenopausal women with hormone receptor-positive her2-negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement.

Science.gov (United States)

Pritchard, K I; Gelmon, K A; Rayson, D; Provencher, L; Webster, M; McLeod, D; Verma, S

2013-02-01

Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2-) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients-efect, sofea, confirm, and bolero-2-have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2- advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient's age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged.

Bazedoxifene exhibits antiestrogenic activity in animal models of tamoxifen-resistant breast cancer: implications for treatment of advanced disease.

Science.gov (United States)

Wardell, Suzanne E; Nelson, Erik R; Chao, Christina A; McDonnell, Donald P

2013-05-01

There is compelling evidence to suggest that drugs that function as pure estrogen receptor (ER-α) antagonists, or that downregulate the expression of ER-α, would have clinical use in the treatment of advanced tamoxifen- and aromatase-resistant breast cancer. Although such compounds are currently in development, we reasoned, based on our understanding of ER-α pharmacology, that there may already exist among the most recently developed selective estrogen receptor modulators (SERM) compounds that would have usage as breast cancer therapeutics. Thus, our objective was to identify among available SERMs those with unique pharmacologic activities and to evaluate their potential clinical use with predictive models of advanced breast cancer. A validated molecular profiling technology was used to classify clinically relevant SERMs based on their impact on ER-α conformation. The functional consequences of these observed mechanistic differences on (i) gene expression, (ii) receptor stability, and (iii) activity in cellular and animal models of advanced endocrine-resistant breast cancer were assessed. The high-affinity SERM bazedoxifene was shown to function as a pure ER-α antagonist in cellular models of breast cancer and effectively inhibited the growth of both tamoxifen-sensitive and -resistant breast tumor xenografts. Interestingly, bazedoxifene induced a unique conformational change in ER-α that resulted in its proteasomal degradation, although the latter activity was dispensable for its antagonist efficacy. Bazedoxifene was recently approved for use in the European Union for the treatment of osteoporosis and thus may represent a near-term therapeutic option for patients with advanced breast cancer. ©2013 AACR.

Detection of breast cancer using advanced techniques of data mining with neural networks

International Nuclear Information System (INIS)

Ortiz M, J. A.; Celaya P, J. M.; Martinez B, M. R.; Solis S, L. O.; Castaneda M, R.; Garza V, I.; Martinez F, M.; Lopez H, Y.; Ortiz R, J. M.

2016-10-01

The breast cancer is one of the biggest health problems worldwide, is the most diagnosed cancer in women and prevention seems impossible since its cause is unknown, due to this; the early detection has a key role in the patient prognosis. In developing countries such as Mexico, where access to specialized health services is minimal, the regular clinical review is infrequent and there are not enough radiologists; the most common form of detection of breast cancer is through self-exploration, but this is only detected in later stages, when is already palpable. For these reasons, the objective of the present work is the creation of a system of computer assisted diagnosis (CAD x) using information analysis techniques such as data mining and advanced techniques of artificial intelligence, seeking to offer a previous medical diagnosis or a second opinion, as if it was a second radiologist in order to reduce the rate of mortality from breast cancer. In this paper, advances in the design of computational algorithms using computer vision techniques for the extraction of features derived from mammograms are presented. Using data mining techniques of data mining is possible to identify patients with a high risk of breast cancer. With the information obtained from the mammography analysis, the objective in the next stage will be to establish a methodology for the generation of imaging bio-markers to establish a breast cancer risk index for Mexican patients. In this first stage we present results of the classification of patients with high and low risk of suffering from breast cancer using neural networks. (Author)

Breast Cancer Immunotherapy

Institute of Scientific and Technical Information of China (English)

Juhua Zhou; Yin Zhong

2004-01-01

Breast cancer is a leading cause of cancer-related deaths in women worldwide. Although tumorectomy,radiotherapy, chemotherapy and hormone replacement therapy have been used for the treatment of breast cancer, there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. Breast cancer immunotherapy includes antibody based immunotherapy, cancer vaccine immunotherapy, adoptive T cell transfer immunotherapy and T cell receptor gene transfer immunotherapy. Antibody based immunotherapy such as the monoclonal antibody against HER-2/neu (trastuzumab) is successfully used in the treatment of breast cancer patients with over-expressed HER-2/neu, however, HER-2/neu is over-expressed only in 25-30% of breast cancer patients. Cancer vaccine immunotherapy is a promising method to treat cancer patients. Cancer vaccines can be used to induce specific anti-tumor immunity in breast cancer patients, but cannot induce objective tumor regression. Adoptive T cell transfer immunotherapy is an effective method in the treatment of melanoma patients. Recent advances in anti-tumor T cell generation ex vivo and limited clinical trial data have made the feasibility of adoptive T cell transfer immunotherapy in the treatment of breast cancer patients. T cell receptor gene transfer can redirect the specificity of T cells. Chimeric receptor, scFv(anti-HER-2/neu)/zeta receptor, was successfully used to redirect cytotoxic T lymphocyte hybridoma cells to obtain anti-HER-2/neu positive tumor cells, suggesting the feasibility of treatment of breast cancer patients with T cell receptor gene transfer immunotherapy. Clinical trials will approve that immunotherapy is an effective method to cure breast cancer disease in the near future.

Breast Cancer Immunotherapy

Institute of Scientific and Technical Information of China (English)

JuhuaZhou; YinZhong

2004-01-01

Breast cancer is a leading cause of cancer-related deaths in women worldwide. Although tumorectomy, radiotherapy, chemotherapy and hormone replacement therapy have been used for the treatment of breast cancer, there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. Breast cancer immunotherapy includes antibody based immunotherapy, cancer vaccine immunotherapy, adoptive T cell transfer immunotherapy and T cell receptor gene transfer immunotherapy. Antibody based immunotherapy such as the monoclonal antibody against HER-2/neu (trastuzumab) is successfully used in the treatment of breast cancer patients with over-expressed HER-2/neu, however, HER-2/neu is over-expressed only in 25-30% of breast cancer patients. Cancer vaccine immunotherapy is a promising method to treat cancer patients. Cancer vaccines can be used to induce specific anti-tumor immunity in breast cancer patients, but cannot induce objective tumor regression. Adoptive T cell transfer immunotherapy is an effective method in the treatment of melanoma patients. Recent advances in anti-tumor T cell generation ex vivo and limited clinical trial data have made the feasibility of adoptive T cell transfer immunotherapy in the treatment of breast cancer patients. T cell receptor gene transfer can redirect the specificity of T cells. Chimeric receptor, scFv(anti-HER-2/neu)/zeta receptor, was successfully used to redirect cytotoxic T lymphocyte hybridoma cells to obtain anti-HER-2/neu positive tumor cells, suggesting the feasibility of treatment of breast cancer patients with T cell receptor gene transfer immunotherapy. Clinical trials will approve that immunotherapy is an effective method to cure breast cancer disease in the near future. Cellular & Molecular Immunology.

Combination Immunotherapy for the Treatment of High-Risk HER2-Positive Breast Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-14-1-0109 TITLE: Combination Immunotherapy for the Treatment of High-Risk HER2-Positive Breast Cancer PRINCIPAL INVESTIGATOR...Elizabeth A. Mittendorf, MD, PhD CONTRACTING ORGANIZATION: University of Texas MD Anderson Cancer Center Houston, TX 77030 REPORT DATE: October...CONTRACT NUMBER Combination Immunotherapy for the Treatment of High-Risk HER2-Positive Breast Cancer 5b. GRANT NUMBER W81XWH-14-1-0109 5c. PROGRAM

Comparison of prone versus supine 18F-FDG-PET of locally advanced breast cancer: Phantom and preliminary clinical studies

International Nuclear Information System (INIS)

Williams, Jason M.; Rani, Sudheer D.; Li, Xia; Whisenant, Jennifer G.; Abramson, Richard G.; Arlinghaus, Lori R.; Lee, Tzu-Cheng; MacDonald, Lawrence R.; Partridge, Savannah C.; Kang, Hakmook; Linden, Hannah M.; Kinahan, Paul E.; Yankeelov, Thomas E.

2015-01-01

Purpose: Previous studies have demonstrated how imaging of the breast with patients lying prone using a supportive positioning device markedly facilitates longitudinal and/or multimodal image registration. In this contribution, the authors’ primary objective was to determine if there are differences in the standardized uptake value (SUV) derived from [ 18 F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in breast tumors imaged in the standard supine position and in the prone position using a specialized positioning device. Methods: A custom positioning device was constructed to allow for breast scanning in the prone position. Rigid and nonrigid phantom studies evaluated differences in prone and supine PET. Clinical studies comprised 18F-FDG-PET of 34 patients with locally advanced breast cancer imaged in the prone position (with the custom support) followed by imaging in the supine position (without the support). Mean and maximum values (SUV peak and SUV max , respectively) were obtained from tumor regions-of-interest for both positions. Prone and supine SUV were linearly corrected to account for the differences in 18F-FDG uptake time. Correlation, Bland–Altman, and nonparametric analyses were performed on uptake time-corrected and uncorrected data. Results: SUV from the rigid PET breast phantom imaged in the prone position with the support device was 1.9% lower than without the support device. In the nonrigid PET breast phantom, prone SUV with the support device was 5.0% lower than supine SUV without the support device. In patients, the median (range) difference in uptake time between prone and supine scans was 16.4 min (13.4–30.9 min), which was significantly—but not completely—reduced by the linear correction method. SUV peak and SUV max from prone versus supine scans were highly correlated, with concordance correlation coefficients of 0.91 and 0.90, respectively. Prone SUV peak and SUV max were significantly lower than supine in both

Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

Directory of Open Access Journals (Sweden)

John F. Flynn

2009-01-01

Full Text Available This review will focus on recent advances in the application of antiepidermal growth factor receptor (anti-EGFR for the treatment of breast cancer. The choice of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from evidence pinpointing its role in various anti-EGFR therapies. Therefore, an increase in our understanding of EGFR mechanism and signaling might reveal novel targets amenable to intervention in the clinic. This knowledge base might also improve existing medical treatment options and identify research gaps in the design of new therapeutic agents. While the approved use of drugs like the dual kinase inhibitor Lapatinib represents significant advances in the clinical management of breast cancer, confirmatory studies must be considered to foster the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical efficacy.

Recent Advances in the Treatment of Breast Cancer

Directory of Open Access Journals (Sweden)

Christy W. S. Tong

2018-06-01

Full Text Available Breast cancer (BC is the most common malignancy in women. It is classified into a few major molecular subtypes according to hormone and growth factor receptor expression. Over the past few years, substantial advances have been made in the discovery of new drugs for treating BC. Improved understanding of the biologic heterogeneity of BC has allowed the development of more effective and individualized approach to treatment. In this review, we provide an update about the current treatment strategy and discuss the various emerging novel therapies for the major molecular subtypes of BC. A brief account of the clinical development of inhibitors of poly(ADP-ribose polymerase, cyclin-dependent kinases 4 and 6, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway, histone deacetylation, multi-targeting tyrosine kinases, and immune checkpoints for personalized treatment of BC is included. However, no targeted drug has been approved for the most aggressive subtype—triple negative breast cancer (TNBC. Thus, we discuss the heterogeneity of TNBC and how molecular subtyping of TNBC may help drug discovery for this deadly disease. The emergence of drug resistance also poses threat to the successful development of targeted therapy in various molecular subtypes of BC. New clinical trials should incorporate advanced methods to identify changes induced by drug treatment, which may be associated with the upregulation of compensatory signaling pathways in drug resistant cancer cells.

Risk of breast cancer after false-positive test results in screening mammography

DEFF Research Database (Denmark)

von Euler-Chelpin, My Catarina; Risør, Louise Madeleine; Thorsted, Brian Larsen

2012-01-01

Screening for disease in healthy people inevitably leads to some false-positive tests in disease-free individuals. Normally, women with false-positive screening tests for breast cancer are referred back to routine screening. However, the long-term outcome for women with false-positive tests...

Locally advanced (neglected) breast cancer: the reality? relevance of two cases and reflection how to optimise the multidisciplinary approach

International Nuclear Information System (INIS)

Monnier, L.; Even, C.; Kirova, Y.M.; Even, C.; Cottu, P.H.

2009-01-01

The standard treatment for breast cancer patients with untreated locally advanced breast cancer is neo-adjuvant chemotherapy or hormonal treatment. In some cases, this treatment is followed by surgery and/or radiotherapy when the multidisciplinary approach is present. In some cases of patients presenting metastatic diseases, the radiotherapy is forgotten or proposed late when the local disease is extremely advanced with symptoms and decreased quality of life. Two cases of extremely advanced non operable T4 stage breast cancer are reported and the importance of multidisciplinary approach is discussed. The place and the right time of radiotherapy in this multidisciplinary strategy is reported. (authors)

Long-term Clinical Outcomes of Whole-Breast Irradiation Delivered in the Prone Position

International Nuclear Information System (INIS)

Stegman, Lauren D.; Beal, Katherine P.; Hunt, Margie A.; Fornier, Monica N.; McCormick, Beryl

2007-01-01

Purpose: The aim of this study was to evaluate retrospectively the effectiveness and toxicity of post-lumpectomy whole-breast radiation therapy delivered with prone positioning. Methods and Materials: Between September 1992 and August 2004, 245 women with 248 early-stage invasive or in situ breast cancers were treated using a prone breast board. Photon fields treated the whole breast to 46 to 50.4 Gy with standard fractionation. The target volume was clinically palpable breast tissue; no attempt was made to irradiate chest wall lymphatics. Tumor bed boosts were delivered in 85% of cases. Adjuvant chemotherapy and hormonal therapy were administered to 42% and 62% of patients, respectively. Results: After a median follow-up of 4.9 years, the 5 year actuarial true local and elsewhere ipsilateral breast tumor recurrence rates were 4.8% and 1.3%, respectively. The 5-year actuarial rates of regional nodal recurrence and distant metastases were 1.6% and 7.4%. Actuarial disease-free, disease-specific, and overall survival rates at 5 years were 89.4%, 97.3%, and 93%, respectively. Treatment breaks were required by 2.4% of patients. Grade 3 acute dermatitis and edema were each limited to 2% of patients. Only 4.9% of patients complained of acute chest wall discomfort. Chronic Grade 2 to 3 skin and subcutaneous tissue toxicities were reported in 4.4% and 13.7% of patients, respectively. Conclusions: Prone position breast radiation results in similar long-term disease control with a favorable toxicity profile compared with standard supine tangents. The anatomic advantages of prone positioning may contribute to improving the therapeutic ratio of post-lumpectomy radiation by improving dose homogeneity and minimizing incidental cardiac and lung dose

Epirubicin With Cyclophosphamide Followed by Docetaxel With Trastuzumab and Bevacizumab as Neoadjuvant Therapy for HER2-Positive Locally Advanced Breast Cancer or as Adjuvant Therapy for HER2-Positive Pathologic Stage III Breast Cancer: A Phase II Trial of the NSABP Foundation Research Group, FB-5.

Science.gov (United States)

Smith, John W; Buyse, Marc E; Rastogi, Priya; Geyer, Charles E; Jacobs, Samuel A; Patocskai, Erica J; Robidoux, André; Conlin, Alison K; Ansari, Bilal; Keogh, George P; Stella, Philip J; Gross, Howard M; Lord, Raymond S; Polikoff, Jonathan A; Mauquoi, Celine; Mamounas, Eleftherios P; Swain, Sandra M; Wolmark, Norman

2017-02-01

The purpose of this study was to determine the cardiac safety and clinical activity of trastuzumab and bevacizumab with docetaxel after epirubicin with cyclophosphamide (EC) in patients with HER2-positive locally advanced breast cancer (LABC) or pathologic stage 3 breast cancer (PS3BC). Patients received every 3 week treatment with 4 cycles of EC (90/600 mg/m 2 ) followed by 4 cycles of docetaxel (100 mg/m 2 ). Targeted therapy with standard-dose trastuzumab with bevacizumab 15 mg/kg was given for a total of 1 year. Coprimary end points were (1) rate of cardiac events (CEs) in all patients defined as clinical congestive heart failure with a significant decrease in left ventricular ejection fraction or cardiac deaths; and (2) pathologic complete response (pCR) in breast and nodes in the neoadjuvant cohort. An independent cardiac review panel determined whether criteria for a CE were met. A total of 105 patients were accrued, 76 with LABC treated with neoadjuvant therapy and 29 with PS3BC treated with adjuvant therapy. Median follow-up was 59.2 months. Among 99 evaluable patients for cardiac safety, 4 (4%; 95% confidence interval [CI], 1.1%-10.0%) met CE criteria. The pCR percentage in LABC patients was 46% (95% CI, 34%-59%). Five-year recurrence-free survival (RFS) and overall survival (OS) for all patients was 79.9% and 90.8%, respectively. The regimen met predefined criteria for activity of interest with an acceptable rate of CEs. Although the pCR percentage was comparable with chemotherapy regimens with trastuzumab alone the high RFS and OS are of interest in these high-risk populations. Copyright © 2016 Elsevier Inc. All rights reserved.

GATA3 expression in advanced breast cancer: prognostic value and organ-specific relapse.

Science.gov (United States)

McCleskey, Brandi C; Penedo, Thuy L; Zhang, Kui; Hameed, Omar; Siegal, Gene P; Wei, Shi

2015-11-01

GATA3 is a transcription factor regulating luminal cell differentiation in the mammary glands and has been implicated in the luminal types of breast carcinoma. The prognostic significance of GATA3 in breast cancer remains controversial. In this study, we assessed the prognostic value of the molecule in a subset of 62 advanced breast cancers and 10 control breast cancers (no metastasis after follow-up). GATA3 expression levels in luminal tumors of advanced stage were significantly higher than that of the human epidermal growth factor receptor 2 (HER2) subtype and triple-negative carcinomas, as expected, but were similar to those of the luminal controls. Furthermore, 88% of nonluminal tumors showed variable GATA3 expression, for which the HER2 subtype had significantly higher GATA3 expression than that of the triple-negative carcinomas. Interestingly, GATA3 levels were significantly lower in carcinomas with lung relapse compared to those with metastatic recurrence to other organs, thus reflecting the findings in animal models. No significant difference was observed between tumors with bone relapse and those metastasized to nonskeletal sites. Moreover, high GATA3 expression was significantly associated with favorable relapse-free survival and overall survival. These findings suggest that GATA3 may not act solely as a luminal differentiation marker, and further uncovering the molecular pathways by which GATA3 regulates the downstream targets will be crucial to our understanding of breast cancer dissemination. Copyright© by the American Society for Clinical Pathology.

Advanced Imaging and Receipt of Guideline Concordant Care in Women with Early Stage Breast Cancer

Directory of Open Access Journals (Sweden)

Elizabeth Trice Loggers

2016-01-01

Full Text Available Objective. It is unknown whether advanced imaging (AI is associated with higher quality breast cancer (BC care. Materials and Methods. Claims and Surveillance Epidemiology and End Results data were linked for women diagnosed with incident stage I-III BC between 2002 and 2008 in western Washington State. We examined receipt of preoperative breast magnetic resonance imaging (MRI or AI (defined as computed tomography [CT]/positron emission tomography [PET]/PET/CT versus mammogram and/or ultrasound (M-US alone and receipt of guideline concordant care (GCC using multivariable logistic regression. Results. Of 5247 women, 67% received M-US, 23% MRI, 8% CT, and 3% PET/PET-CT. In 2002, 5% received MRI and 5% AI compared to 45% and 12%, respectively, in 2008. 79% received GCC, but GCC declined over time and was associated with younger age, urban residence, less comorbidity, shorter time from diagnosis to surgery, and earlier year of diagnosis. Breast MRI was associated with GCC for lumpectomy plus radiation therapy (RT (OR 1.55, 95% CI 1.08–2.26, and p=0.02 and AI was associated with GCC for adjuvant chemotherapy for estrogen-receptor positive (ER+ BC (OR 1.74, 95% CI 1.17–2.59, and p=0.01. Conclusion. GCC was associated with prior receipt of breast MRI and AI for lumpectomy plus RT and adjuvant chemotherapy for ER+ BC, respectively.

[Axillary pathologic response after neoadjuvant chemotherapy in locally advanced breast cancer with axillary involvement].

Science.gov (United States)

Jiménez-Ballvé, A; Serrano-Palacio, A; García-Sáenz, J A; Ortega Candil, A; Salsidua-Arroyo, O; Román-Santamaría, J M; Pelayo Alarcón, A; Fuentes Ferrer, M E; Carreras-Delgado, J L

2015-01-01

To compare axillary involvement (N+) at initial staging in locally advanced breast cancer (LABC) with axillary lymphadenectomy histologic results after neoadjuvant chemotherapy treatment (NeoChemo). Retrospective study between November 2011 and September 2013 of LABC cases treated with neoadjuvant chemotherapy based on docetaxel (associated with trastuzumab in HER2 positive cases and carboplatin/adriamycin in HER2 negative cases). Those clinically or radiologically suspected cases of axillary involvement were histologically confirmed. When there was no suspicion of axillary involvement, sentinel lymph node radioguided biopsy (SLNRB) was performed using intradermal injection of (99m)Tc-nanocolloid albumin prior to neoadjuvant treatment. Axillary lymphadenectomy after NeoChemo was undertaken in all cases with positive axilla. Final pathologic response was classified as complete (pCR) when there was no evidence of tumoral disease and as non-pathologic complete response (no pCR) in the opposite case. A total of 346 patients treated with docetaxel were reviewed, identifying 105 LABC. Axillary involvement at initial staging was detected in 70 (67%) before starting NeoChemo. From these 70, 73% (n=51) were N+ (fine needle biopsy and/or biopsy) and the remaining 19 (27%) were occult N+ detected by SLNRB. Axillary lymphadenectomy detected pCR in 56% (39/70), increasing up to 84% pCR when initial N+ status was reached using SNLB. On the other hand, when N+ was detected using fine needle biopsy/lymph biopsy, pCR was only 45%. More than 50% of women affected by locally advanced breast cancer with tumoral axillary involvement at initial diagnosis present free metastatic axilla after therapeutic neoadjuvant chemotherapy effect. This increases up to almost 90% in case of occult metastatic axilla detected with sentinel node biopsy prior starting neoadjuvant chemotherapy. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

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

Science.gov (United States)

Mori, Ryutaro; Nagao, Yasuko

2014-01-01

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. Patients who received chemotherapy after hormone therapy for metastatic breast cancer between 2006 and 2013 at our institution were investigated. 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. The efficacy of chemotherapy for metastatic breast cancer cannot be predicted based on the efficacy of prior hormone therapy or tumor subtype, and clinicians should administer chemotherapy in all cases of

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

Accelerated Intensity-Modulated Radiotherapy to Breast in Prone Position: Dosimetric Results

International Nuclear Information System (INIS)

De Wyngaert, J. Keith; Jozsef, Gabor; Mitchell, James; Rosenstein, Barry; Formenti, Silvia C.

2007-01-01

Purpose: To report the physics and dosimetry results of a trial of accelerated intensity-modulated radiotherapy to the whole breast with a concomitant boost to the tumor bed in patients treated in the prone position. Methods and Materials: Patients underwent computed tomography planning and treatment in the prone position on a dedicated treatment platform. The platform has an open aperture on the side to allow for the index breast to fall away from the chest wall. Noncontrast computed tomography images were acquired at 2.5- or 3.75-mm-thick intervals, from the level of the mandible to below the diaphragm. A dose of 40.5 Gy was delivered to the entire breast at 2.7-Gy fractions in 15 fractions. An additional dose of 0.5 Gy was delivered as a concomitant boost to the lumpectomy site, with a 1-cm margin, using inverse planning, for a total dose of 48 Gy in 15 fractions. No more than 10% of the heart and lung volume was allowed to receive >18 and >20 Gy, respectively. Results: Between September 2003 and August 2005, 91 patients were enrolled in the study. The median volume of heart that received ≥18 Gy was 0.5%, with a maximal value of 4.7%. The median volume of ipsilateral lung that received ≥20 Gy was 0.8%, with a maximum of 7.2%. Conclusion: This technique for whole breast radiotherapy is feasible and enables an accelerated regimen in the prone position while sparing the lung and heart

Trastuzumab Emtansine in Treating Older Patients With Human Epidermal Growth Factor Receptor 2-Positive Stage I-III Breast Cancer

Science.gov (United States)

2018-02-01

Estrogen Receptor Status; HER2 Positive Breast Carcinoma; Progesterone Receptor Status; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Predicting the Toxicity of Adjuvant Breast Cancer Drug Combination Therapy

Science.gov (United States)

2013-03-01

Neratinib Versus Lapatinib Plus Capecitabine For ErbB2 Positive Advanced Breast Cancer Active, not recruiting No Results Available YES neratinib -9...Drug: Neratinib |Drug: Lapatinib|Drug: Capecitabine Efficacy and Safety of BMS-690514 in Combination With Letrozole to Treat Metastatic Breast Cancer

Endocrine therapy for postmenopausal women with hormone receptor–positive her2–negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement

Science.gov (United States)

Pritchard, K.I.; Gelmon, K.A.; Rayson, D.; Provencher, L.; Webster, M.; McLeod, D.; Verma, S.

2013-01-01

Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2–) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients—efect, sofea, confirm, and bolero-2—have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2– advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient’s age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged. PMID:23443928

Radiation therapy in the management of locally advanced and disseminated breast cancer

International Nuclear Information System (INIS)

Chu, F.C.H.

1980-01-01

Radiation theraoy should be fully used in the management of advanced breast cancer. Locally advanced primary or recurrent carcinoma, with limited extent, should be treated aggressively, aimed at permanent control. Palliative treatment of incurable or metastatic lesions relieves symptoms and improves patient's quality of survival. Some metastatic lesions involving vital structures may create emergencies. Prompt institution of radiation therapy may reverse the serious complication and save the patient's life

Identification of the sentinel lymph node using hemosiderin in locally advanced breast cancer

Directory of Open Access Journals (Sweden)

PAULO HENRIQUE WALTER DE AGUIAR

Full Text Available ABSTRACT Objective: to verify the agreement rate in the identification of sentinel lymph node using an autologous marker rich in hemosiderin and 99 Technetium (Tc99 in patients with locally advanced breast cancer. Methods: clinical trial phase 1, prospective, non-randomized, of 18 patients with breast cancer and clinically negative axilla stages T2=4cm, T3 and T4. Patients were submitted to sub-areolar injection of hemosiderin 48 hours prior to sentinel biopsy surgery, and the identification rate was compared at intraoperative period to the gold standard marker Tc99. Agreement between methods was determined by Kappa index. Results: identification rate of sentinel lymph node was 88.9%, with a medium of two sentinel lymph nodes per patients. The study identified sentinel lymph nodes stained by hemosiderin in 83.3% patients (n=15, and, compared to Tc99 identification, the agreement rate was 94.4%. Conclusion: autologous marker rich in hemosiderin was effective to identify sentinel lymph nodes in locally advanced breast cancer patients.

Extra-nodal extension is a significant prognostic factor in lymph node positive breast cancer.

Directory of Open Access Journals (Sweden)

Sura Aziz

Full Text Available Presence of lymph node (LN metastasis is a strong prognostic factor in breast cancer, whereas the importance of extra-nodal extension and other nodal tumor features have not yet been fully recognized. Here, we examined microscopic features of lymph node metastases and their prognostic value in a population-based cohort of node positive breast cancer (n = 218, as part of the prospective Norwegian Breast Cancer Screening Program NBCSP (1996-2009. Sections were reviewed for the largest metastatic tumor diameter (TD-MET, nodal afferent and efferent vascular invasion (AVI and EVI, extra-nodal extension (ENE, number of ENE foci, as well as circumferential (CD-ENE and perpendicular (PD-ENE diameter of extra-nodal growth. Number of positive lymph nodes, EVI, and PD-ENE were significantly increased with larger primary tumor (PT diameter. Univariate survival analysis showed that several features of nodal metastases were associated with disease-free (DFS or breast cancer specific survival (BCSS. Multivariate analysis demonstrated an independent prognostic value of PD-ENE (with 3 mm as cut-off value in predicting DFS and BCSS, along with number of positive nodes and histologic grade of the primary tumor (for DFS: P = 0.01, P = 0.02, P = 0.01, respectively; for BCSS: P = 0.02, P = 0.008, P = 0.02, respectively. To conclude, the extent of ENE by its perpendicular diameter was independently prognostic and should be considered in line with nodal tumor burden in treatment decisions of node positive breast cancer.

Effective Treatment of Solitary Pituitary Metastasis with Panhypopituitarism in HER2-Positive Breast Cancer by Lapatinib.

Science.gov (United States)

Park, Youngmok; Kim, Hyemin; Kim, Eui-Hyun; Suh, Chang-Ok; Lee, Soohyeon

2016-01-01

Brain metastasis affects one third of patients with HER2-positive breast cancer after treatment with trastuzumab. Surgical resection and radiation therapy are often unsuccessful at accomplishing complete control of metastasis. Lapatinib is presumed to cross the blood-brain barrier, and exhibits clinical activities for treatment of HER2-positive breast cancer. A 43-year-old woman was treated for early breast carcinoma with total mastectomy, axillary lymph-node dissection, and adjuvant chemotherapy with cyclophosphamide plus doxorubicin. After the end of adjuvant trastuzumab therapy, she was diagnosed with panhypopituitarism due to pituitary metastasis. Surgical removal and whole brain radiation therapy were performed, but a portion of viable tumor remained. Only taking lapatinib, the size of the metastatic lesion began to shrink. Trastuzumab may have controlled the micro-metastasis of breast cancer, but it was unable to control its progression to the central nervous system. Lapatinib is a possible option for HER2-positive metastatic breast cancer patients with brain metastasis.

Breast calcifications. A standardized mammographic reporting and data system to improve positive predictive value

International Nuclear Information System (INIS)

Perugini, G.; Bonzanini, B.; Valentino, C.

1999-01-01

The purpose of this work is to investigate the usefulness of a standardized reporting and data system in improving the positive predictive value of mammography in breast calcifications. Using the Breast Imaging Reporting and Data System lexicon developed by the American College of Radiology, it is defined 5 descriptive categories of breast calcifications and classified diagnostic suspicion of malignancy on a 3-grade scale (low, intermediate and high). Two radiologists reviewed 117 mammographic studies selected from those of the patients submitted to surgical biopsy for mammographically detected calcifications from January 1993 to December 1997, and classified them according to the above criteria. The positive predictive value was calculated for all examinations and for the stratified groups. Defining a standardized system for assessing and describing breast calcifications helps improve the diagnostic accuracy of mammography in clinical practice [it

21-Gene Recurrence Score and Locoregional Recurrence in Node-Positive/ER-Positive Breast Cancer Treated With Chemo-Endocrine Therapy.

Science.gov (United States)

Mamounas, Eleftherios P; Liu, Qing; Paik, Soonmyung; Baehner, Frederick L; Tang, Gong; Jeong, Jong-Hyeon; Kim, S Rim; Butler, Steven M; Jamshidian, Farid; Cherbavaz, Diana B; Sing, Amy P; Shak, Steven; Julian, Thomas B; Lembersky, Barry C; Wickerham, D Lawrence; Costantino, Joseph P; Wolmark, Norman

2017-01-01

The 21-gene recurrence score (RS) predicts risk of locoregional recurrence (LRR) in node-negative, estrogen receptor (ER)-positive breast cancer. We evaluated the association between RS and LRR in node-positive, ER-positive patients treated with adjuvant chemotherapy plus tamoxifen in National Surgical Adjuvant Breast and Bowel Project B-28. B-28 compared doxorubicin/cyclophosphamide (AC X 4) with AC X 4 followed by paclitaxel X 4. Tamoxifen was given to patients age 50 years or older and those younger than age 50 years with ER-positive and/or progesterone receptor-positive tumors. Lumpectomy patients received breast radiotherapy. Mastectomy patients received no radiotherapy. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Cumulative incidence functions and subdistribution hazard regression models were used for LRR to account for competing risks including distant recurrence, second primary cancers, and death from other causes. Median follow-up was 11.2 years. All statistical tests were one-sided. There were 80 LRRs (7.5%) as first events (68% local/32% regional). RS was low: 36.2%; intermediate: 34.2%; and high: 29.6%. RS was a statistically significant predictor of LRR in univariate analyses (10-year cumulative incidence of LRR = 3.3%, 7.2%, and 12.2% for low, intermediate, and high RS, respectively, P < .001). In multivariable regression analysis, RS remained an independent predictor of LRR (hazard ratio [HR] = 2.59, 95% confidence interval [CI] = 1.28 to 5.26, for a 50-point difference, P = .008) along with pathologic nodal status (HR = 1.91, 95% CI = 1.20 to 3.03, for four or more vs one to three positive nodes, P = .006) and tumor size (HR = 1.28, 95% CI = 1.05 to 1.55, for a 1 cm difference, P = .02). RS statistically significantly predicts risk of LRR in node-positive, ER-positive breast cancer patients after adjuvant chemotherapy plus tamoxifen. These findings can help in the selection of

Comparison of prone versus supine 18F-FDG-PET of locally advanced breast cancer: Phantom and preliminary clinical studies

Energy Technology Data Exchange (ETDEWEB)

Williams, Jason M.; Rani, Sudheer D.; Li, Xia; Whisenant, Jennifer G.; Abramson, Richard G. [Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232 and Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee 37232 (United States); Arlinghaus, Lori R. [Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232 (United States); Lee, Tzu-Cheng [Department of Bioengineering, University of Washington, Seattle, Washington 98195 (United States); MacDonald, Lawrence R.; Partridge, Savannah C. [Department of Radiology, University of Washington, Seattle, Washington 98195 (United States); Kang, Hakmook [Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232 and Department of Biostatistics, Vanderbilt University, Nashville, Tennessee 37232 (United States); Linden, Hannah M. [Department of Medical Oncology, University of Washington, Seattle, Washington 98195 (United States); Kinahan, Paul E. [Department of Radiology, University of Washington, Seattle, Washington 98195 (United States); Department of Bioengineering, University of Washington, Seattle, Washington 98195 (United States); Department of Physics, University of Washington, Seattle, Washington 98195 (United States); Department of Electrical Engineering, University of Washington, Seattle, Washington 98195 (United States); Yankeelov, Thomas E., E-mail: thomas.yankeelov@vanderbilt.edu [Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232 (United States); Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee 37232 (United States); Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37232 (United States); Department of Physics, Vanderbilt University, Nashville, Tennessee 37232 (United States); Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee 37232 (United States)

2015-07-15

Purpose: Previous studies have demonstrated how imaging of the breast with patients lying prone using a supportive positioning device markedly facilitates longitudinal and/or multimodal image registration. In this contribution, the authors’ primary objective was to determine if there are differences in the standardized uptake value (SUV) derived from [{sup 18}F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in breast tumors imaged in the standard supine position and in the prone position using a specialized positioning device. Methods: A custom positioning device was constructed to allow for breast scanning in the prone position. Rigid and nonrigid phantom studies evaluated differences in prone and supine PET. Clinical studies comprised 18F-FDG-PET of 34 patients with locally advanced breast cancer imaged in the prone position (with the custom support) followed by imaging in the supine position (without the support). Mean and maximum values (SUV{sub peak} and SUV{sub max}, respectively) were obtained from tumor regions-of-interest for both positions. Prone and supine SUV were linearly corrected to account for the differences in 18F-FDG uptake time. Correlation, Bland–Altman, and nonparametric analyses were performed on uptake time-corrected and uncorrected data. Results: SUV from the rigid PET breast phantom imaged in the prone position with the support device was 1.9% lower than without the support device. In the nonrigid PET breast phantom, prone SUV with the support device was 5.0% lower than supine SUV without the support device. In patients, the median (range) difference in uptake time between prone and supine scans was 16.4 min (13.4–30.9 min), which was significantly—but not completely—reduced by the linear correction method. SUV{sub peak} and SUV{sub max} from prone versus supine scans were highly correlated, with concordance correlation coefficients of 0.91 and 0.90, respectively. Prone SUV{sub peak} and SUV{sub max} were

Vinorelbine as first-line or second-line therapy for advanced breast cancer

DEFF Research Database (Denmark)

Langkjer, Sven T; Ejlertsen, Bent; Mouridsen, Henning

2008-01-01

INTRODUCTION: This study was conducted to establish the maximum tolerated dose (MTD) of intravenous vinorelbine and on the determined dose to assess efficacy and safety in patients with metastatic breast cancer previously treated with epirubicin. PATIENTS AND METHODS: Patients had histologically...... proven breast cancer and had received a prior epirubicin based regimen either adjuvant or as first line therapy for advanced disease. Vinorelbine was administered intravenously day 1 and 8 in a 3 weeks' schedule. Subsequently 48 additional patients were treated at one dose-level below MTD. RESULTS: Fifty...

Breast radiotherapy in the lateral decubitus position: A technique to prevent lung and heart irradiation

International Nuclear Information System (INIS)

Campana, Francois; Kirova, Youlia M.; Rosenwald, Jean-Claude; Dendale, Remi; Vilcoq, Jacques R.; Dreyfus, Helene; Fourquet, Alain

2005-01-01

Purpose: To present an original technique for breast radiotherapy, with the aim of limiting lung and heart irradiation, satisfying quality assurance criteria. Methods and Material: An original radiotherapy technique for breast irradiation has been developed at the Institute Curie in January 1996. It consists of isocentric breast irradiation in the lateral decubitus position (isocentric lateral decubitus [ILD]). This technique is indicated for voluminous or pendulous breasts needing breast irradiation only. Thin carbon fiber supports and special patient positioning devices have been developed especially for this technique. In vivo measurements were performed to check the dose distribution before the routine use of the technique. Results: ILD has been successfully implemented in routine practice, and 500 patients have been already treated. Breast radiotherapy is performed using a dose of 50 Gy at ICRU point in 25 fractions. ILD shows good homogeneity of the dose in breast treatment volume, treatment fields are perpendicular to the skin ensuring its protection, and extremely low dose is delivered to the underlying lung and heart. Conclusion: In cases of voluminous breasts or patients with a history of lung and heart disease, our technique provides several advantages over the conventional technique with opposing tangential fields. This technique improves the dose homogeneity according to the ICRU recommendations

Health-related quality-of-life outcomes: a reflexology trial with patients with advanced-stage breast cancer.

Science.gov (United States)

Wyatt, Gwen; Sikorskii, Alla; Rahbar, Mohammad Hossein; Victorson, David; You, Mei

2012-11-01

To evaluate the safety and efficacy of reflexology, a complementary therapy that applies pressure to specific areas of the feet. Longitudinal, randomized clinical trial. Thirteen community-based medical oncology clinics across the midwestern United States. A convenience sample of 385 predominantly Caucasian women with advanced-stage breast cancer receiving chemotherapy and/or hormonal therapy. Following the baseline interview, women were randomized into three primary groups: reflexology (n = 95), lay foot manipulation (LFM) (n = 95), or conventional care (n = 96). Two preliminary reflexology (n = 51) and LFM (n = 48) test groups were used to establish the protocols. Participants were interviewed again postintervention at study weeks 5 and 11. Breast cancer-specific health-related quality of life (HRQOL), physical functioning, and symptoms. No adverse events were reported. A longitudinal comparison revealed significant improvements in physical functioning for the reflexology group compared to the control group (p = 0.04). Severity of dyspnea was reduced in the reflexology group compared to the control group (p Reflexology may be added to existing evidence-based supportive care to improve HRQOL for patients with advanced-stage breast cancer during chemotherapy and/or hormonal therapy. Reflexology can be recommended for safety and usefulness in relieving dyspnea and enhancing functional status among women with advanced-stage breast cancer.

An Unusual Case of Locally Advanced Glycogen-Rich Clear Cell Carcinoma of the Breast

Directory of Open Access Journals (Sweden)

Beatriz Martín-Martín

2011-09-01

Full Text Available Glycogen-rich clear cell (GRCC is a rare subtype of breast carcinoma characterized by carcinoma cells containing an optically clear cytoplasm and intracytoplasmic glycogen. We present the case of a 55-year-old woman with a palpable mass in the right breast and clinical signs of locally advanced breast cancer (LABC. The diagnosis of GRCC carcinoma was based on certain histopathological characteristics of the tumor and immunohistochemical analysis. To our knowledge, this is the first case of GRCC LABC with intratumoral calcifications. There is no evidence of recurrence or metastatic disease after 14 months’ follow-up.

TNFα-Induced Mucin 4 Expression Elicits Trastuzumab Resistance in HER2-Positive Breast Cancer.

Science.gov (United States)

Mercogliano, María F; De Martino, Mara; Venturutti, Leandro; Rivas, Martín A; Proietti, Cecilia J; Inurrigarro, Gloria; Frahm, Isabel; Allemand, Daniel H; Deza, Ernesto Gil; Ares, Sandra; Gercovich, Felipe G; Guzmán, Pablo; Roa, Juan C; Elizalde, Patricia V; Schillaci, Roxana

2017-02-01

Although trastuzumab administration improved the outcome of HER2-positive breast cancer patients, resistance events hamper its clinical benefits. We demonstrated that TNFα stimulation in vitro induces trastuzumab resistance in HER2-positive breast cancer cell lines. Here, we explored the mechanism of TNFα-induced trastuzumab resistance and the therapeutic strategies to overcome it. Trastuzumab-sensitive breast cancer cells, genetically engineered to stably overexpress TNFα, and de novo trastuzumab-resistant tumors, were used to evaluate trastuzumab response and TNFα-blocking antibodies effectiveness respectively. Immunohistochemistry and antibody-dependent cell cytotoxicity (ADCC), together with siRNA strategy, were used to explore TNFα influence on the expression and function of its downstream target, mucin 4 (MUC4). The clinical relevance of MUC4 expression was studied in a cohort of 78 HER2-positive breast cancer patients treated with adjuvant trastuzumab. TNFα overexpression turned trastuzumab-sensitive cells and tumors into resistant ones. Histopathologic findings revealed mucin foci in TNFα-producing tumors. TNFα induced upregulation of MUC4 that reduced trastuzumab binding to its epitope and impaired ADCC. Silencing MUC4 enhanced trastuzumab binding, increased ADCC, and overcame trastuzumab and trastuzumab-emtansine antiproliferative effects in TNFα-overexpressing cells. Accordingly, administration of TNFα-blocking antibodies downregulated MUC4 and sensitized de novo trastuzumab-resistant breast cancer cells and tumors to trastuzumab. In HER2-positive breast cancer samples, MUC4 expression was found to be an independent predictor of poor disease-free survival (P = 0.008). We identified TNFα-induced MUC4 expression as a novel trastuzumab resistance mechanism. We propose MUC4 expression as a predictive biomarker of trastuzumab efficacy and a guide to combination therapy of TNFα-blocking antibodies with trastuzumab. Clin Cancer Res; 23(3); 636-48. �

Tryptase-positive mast cells correlate with angiogenesis in early breast cancer patients.

Science.gov (United States)

Ranieri, Girolamo; Ammendola, Michele; Patruno, Rosa; Celano, Giuseppe; Zito, Francesco Alfredo; Montemurro, Severino; Rella, Addolorata; Di Lecce, Valentina; Gadaleta, Cosmo Damiano; Battista De Sarro, Giovanni; Ribatti, Domenico

2009-07-01

Literature data indicate that mast cells (MCs) are involved in tumor angiogenesis due to the release of several pro-angiogenetic factors among which tryptase, a serine protease stored in MCs granules, is one of the most active. However, no data are available concerning the role of MCs in angiogenesis in primary human breast cancer. In this study, we have evaluated the correlations between the number of MCs positive to tryptase (MCDPT), the area occupied by MCs positive to tryptase (MCAPT) and microvascular density (MVD) and endothelial area (EA) in a series of 88 primary T1-3, N0-2 M0 female breast cancer, by means of immunohistochemistry and image analysis methods. Data demonstrated a significant (r = from 0.78 to 0.89; p-value from 0.001 to 0.002 by Pearson's analysis respectively) correlation between MCDPT, MCAPT, MVD, EA to each other. No correlation concerning MCDPT, MCAPT, MVD, EA and the main clinicopathological features was found. Our results suggest that tryptase-positive MCs play a role in breast cancer angiogenesis. In this context several tryptase inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated in clinical trials as a new anti-angiogenetic approach.

The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer

Science.gov (United States)

Magnani, Luca; Patten, Darren K.; Nguyen, Van T.M.; Hong, Sung-Pil; Steel, Jennifer H.; Patel, Naina; Lombardo, Ylenia; Faronato, Monica; Gomes, Ana R.; Woodley, Laura; Page, Karen; Guttery, David; Primrose, Lindsay; Garcia, Daniel Fernandez; Shaw, Jacqui; Viola, Patrizia; Green, Andrew; Nolan, Christopher; Ellis, Ian O.; Rakha, Emad A.; Shousha, Sami; Lam, Eric W.-F.; Győrffy, Balázs; Lupien, Mathieu; Coombes, R. Charles

2015-01-01

Over 30% of ERα breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ERα binding. Here we demonstrate that PBX1 plays a central role in regulating the ERα transcriptional response to epidermal growth factor (EGF) signaling. PBX1 regulates a subset of EGF-ERα genes highly expressed in aggressive breast tumours. Retrospective stratification of luminal patients using PBX1 protein levels in primary cancer further demonstrates that elevated PBX1 protein levels correlate with earlier metastatic progression. In agreement, PBX1 protein levels are significantly upregulated during metastatic progression in ERα-positive breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive tumours is partly mediated by genomic amplification of the PBX1 locus. Correspondingly, ERα-positive breast cancer patients carrying PBX1 amplification are characterized by poor survival. Notably, we demonstrate that PBX1 amplification can be identified in tumor derived-circulating free DNA of ERα-positive metastatic patients. Metastatic patients with PBX1 amplification are also characterized by shorter relapse-free survival. Our data identifies PBX1 amplification as a functional hallmark of aggressive ERα-positive breast cancers. Mechanistically, PBX1 amplification impinges on several critical pathways associated with aggressive ERα-positive breast cancer. PMID:26215677

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib

Directory of Open Access Journals (Sweden)

Kourie HR

2017-07-01

Full Text Available Hampig Raphael Kourie,1 Elie El Rassy,1 Florian Clatot,2,3 Evandro de Azambuja,4 Matteo Lambertini3,4 1Department of Oncology, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon; 2Department of Medical Oncology and IRON/U1245, Centre Henri Becquerel, Rouen, France; 3Breast Cancer Translational Research Laboratory, 4Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium Abstract: Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2 by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib. Keywords: breast cancer, HER2-positive, neratinib, early-stage, targeted

Osteoporosis management in patients with breast cancer : EMAS position statement

NARCIS (Netherlands)

Trémollieres, Florence A; Ceausu, Iuliana; Depypere, Herman; Lambrinoudaki, Irene; Mueck, Alfred; Pérez-López, Faustino R; van der Schouw, Yvonne T; Senturk, Levent M; Simoncini, Tommaso; Stevenson, John C; Stute, Petra; Rees, Margaret

Aromatase inhibitors (AIs) are the first-line recommended standard of care for postmenopausal estrogen receptor-positive breast cancer. Because they cause a profound suppression of estrogen levels, concerns regarding their potential to increase the risk of fracture were rapidly raised. There is

Regional Nodal Irradiation After Breast Conserving Surgery for Early HER2-Positive Breast Cancer: Results of a Subanalysis From the ALTTO Trial.

Science.gov (United States)

Gingras, Isabelle; Holmes, Eileen; De Azambuja, Evandro; Nguyen, David H A; Izquierdo, Miguel; Anne Zujewski, Jo; Inbar, Moshe; Naume, Bjorn; Tomasello, Gianluca; Gralow, Julie R; Wolff, Antonio C; Harris, Lyndsay; Gnant, Michael; Moreno-Aspitia, Alvaro; Piccart, Martine J; Azim, Hatem A

2017-08-01

Two randomized trials recently demonstrated that regional nodal irradiation (RNI) could reduce the risk of recurrence in early breast cancer; however, these trials were conducted in the pretrastuzumab era. Whether these results are applicable to human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with anti-HER2-targeted therapy is unknown. This retrospective analysis was performed on patients with node-positive breast cancer who were enrolled in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization phase III adjuvant trial and subjected to BCS. The primary objective of the present study was to examine the effect of RNI on disease-free survival (DFS). A multivariable cox regression analysis adjusted for number of positive lymph nodes, tumor size, grade, age, hormone receptors status, presence of macrometastatis, treatment arm, and chemotherapy timing was carried out to investigate the relationship between RNI and DFS. One thousand six hundred sixty-four HER2-positive breast cancer patients were included, of whom 878 (52.8%) had received RNI to the axillary, supraclavicular, and/or internal mammary lymph nodes. Patients in the RNI group had higher nodal burden and more frequently had tumors larger than 2 cm. At a median follow-up of 4.5 years, DFS was 84.3% in the RNI group and 88.3% in the non-RNI group. No differences in regional recurrence (0.9 % vs 0.6 %) or in overall survival (93.6% vs 95.3%) were observed between the two groups. After adjustment in multivariable analysis, there was no statistically significant association between RNI and DFS (hazard ratio = 0.96, 95% confidence interval = 0.71 to 1.29). Our analysis did not demonstrate a DFS benefit of RNI in HER2-positive, node-positive patients treated with adjuvant HER2-targeted therapy. The benefit of RNI in HER2-positive breast cancer needs further testing within randomized clinical trials. © The Author 2017. Published by Oxford University Press. All

HER-2-positive metastatic breast cancer: new possibilities for therapy

Directory of Open Access Journals (Sweden)

E. V. Artamonova

2013-01-01

Full Text Available This article is devoted to modern approaches in HER-2-positive metastatic breast cancer therapy. Recently treatment algorithm for this type of cancer included trastuzumab plus cytostatic in first line, continuation of trastuzumab with another chemotherapy regimen in second line, further switch to lapatinib and eventual return to trastuzumab after progression. Nowadays our options are broader owing to new anti-HER-2 agents which are pertruzumab and T-DM1. Now the most effective therapy regimen in first line is double HER-2 blockade (trastuzumab + pertuzumab in combination with docetaxel. Benefit of new agent T-DM1 versus combination of lapatinib and capecitabin is proved in patients progressed on trastuzumab and taxanes. T-DM1 also showed high efficacy as salvage therapy in intensively pretreated patients with meta- static HER-2-positive breast cancer who progressed on taxanes, trastuzumab and lapatinib.

A Phase I/Ib Study of Enzalutamide Alone and in Combination with Endocrine Therapies in Women with Advanced Breast Cancer.

Science.gov (United States)

Schwartzberg, Lee S; Yardley, Denise A; Elias, Anthony D; Patel, Manish; LoRusso, Patricia; Burris, Howard A; Gucalp, Ayca; Peterson, Amy C; Blaney, Martha E; Steinberg, Joyce L; Gibbons, Jacqueline A; Traina, Tiffany A

2017-08-01

Purpose: Several lines of evidence support targeting the androgen signaling pathway in breast cancer. Enzalutamide is a potent inhibitor of androgen receptor signaling. Preclinical data in estrogen-expressing breast cancer models demonstrated activity of enzalutamide monotherapy and enhanced activity when combined with various endocrine therapies (ET). Enzalutamide is a strong cytochrome P450 3A4 (CYP3A4) inducer, and ETs are commonly metabolized by CYP3A4. The pharmacokinetic (PK) interactions, safety, and tolerability of enzalutamide monotherapy and in combination with ETs were assessed in this phase I/Ib study. Experimental Design: Enzalutamide monotherapy was assessed in dose-escalation and dose-expansion cohorts of patients with advanced breast cancer. Additional cohorts examined effects of enzalutamide on anastrozole, exemestane, and fulvestrant PK in patients with estrogen receptor-positive/progesterone receptor-positive (ER + /PgR + ) breast cancer. Results: Enzalutamide monotherapy ( n = 29) or in combination with ETs ( n = 70) was generally well tolerated. Enzalutamide PK in women was similar to prior data on PK in men with prostate cancer. Enzalutamide decreased plasma exposure to anastrozole by approximately 90% and exemestane by approximately 50%. Enzalutamide did not significantly affect fulvestrant PK. Exposure of exemestane 50 mg/day given with enzalutamide was similar to exemestane 25 mg/day alone. Conclusions: These results support a 160 mg/day enzalutamide dose in women with breast cancer. Enzalutamide can be given in combination with fulvestrant without dose modifications. Exemestane should be doubled from 25 mg/day to 50 mg/day when given in combination with enzalutamide; this combination is being investigated in a randomized phase II study in patients with ER + /PgR + breast cancer. Clin Cancer Res; 23(15); 4046-54. ©2017 AACR . ©2017 American Association for Cancer Research.

The integrative epigenomic-transcriptomic landscape of ER positive breast cancer.

Science.gov (United States)

Gao, Yang; Jones, Allison; Fasching, Peter A; Ruebner, Matthias; Beckmann, Matthias W; Widschwendter, Martin; Teschendorff, Andrew E

2015-01-01

While recent integrative analyses of copy number and gene expression data in breast cancer have revealed a complex molecular landscape with multiple subtypes and many oncogenic/tumour suppressor driver events, much less is known about the role of DNA methylation in shaping breast cancer taxonomy and defining driver events. Here, we applied a powerful integrative network algorithm to matched DNA methylation and RNA-Seq data for 724 estrogen receptor (ER)-positive (ER+) breast cancers and 111 normal adjacent tissue specimens from The Cancer Genome Atlas (TCGA) project, in order to identify putative epigenetic driver events and to explore the resulting molecular taxonomy. This revealed the existence of nine functionally deregulated epigenetic hotspots encompassing a total of 146 genes, which we were able to validate in independent data sets encompassing over 1000 ER+ breast cancers. Integrative clustering of the matched messenger RNA (mRNA) and DNA methylation data over these genes resulted in only two clusters, which correlated very strongly with the luminal-A and luminal B subtypes. Overall, luminal-A and luminal-B breast cancers shared the same epigenetically deregulated hotspots but with luminal-B cancers exhibiting increased aberrant DNA methylation patterns relative to normal tissue. We show that increased levels of DNA methylation and mRNA expression deviation from the normal state define a marker of poor prognosis. Our data further implicates epigenetic silencing of WNT signalling antagonists and bone morphogenetic proteins (BMP) as key events underlying both luminal subtypes but specially of luminal-B breast cancer. Finally, we show that DNA methylation changes within the identified epigenetic interactome hotspots do not exhibit mutually exclusive patterns within the same cancer sample, instead exhibiting coordinated changes within the sample. Our results indicate that the integrative DNA methylation and transcriptomic landscape of ER+ breast cancer is

A gene expression signature of retinoblastoma loss-of-function is a predictive biomarker of resistance to palbociclib in breast cancer cell lines and is prognostic in patients with ER positive early breast cancer.

Science.gov (United States)

Malorni, Luca; Piazza, Silvano; Ciani, Yari; Guarducci, Cristina; Bonechi, Martina; Biagioni, Chiara; Hart, Christopher D; Verardo, Roberto; Di Leo, Angelo; Migliaccio, Ilenia

2016-09-13

Palbociclib is a CDK4/6 inhibitor that received FDA approval for treatment of hormone receptor positive (HR+) HER2 negative (HER2neg) advanced breast cancer. To better personalize patients treatment it is critical to identify subgroups that would mostly benefit from it. We hypothesize that complex alterations of the Retinoblastoma (Rb) pathway might be implicated in resistance to CDK4/6 inhibitors and aim to investigate whether signatures of Rb loss-of-function would identify breast cancer cell lines resistant to palbociclib. We established a gene expression signature of Rb loss-of-function (RBsig) by identifying genes correlated with E2F1 and E2F2 expression in breast cancers within The Cancer Genome Atlas. We assessed the RBsig prognostic role in the METABRIC and in a comprehensive breast cancer meta-dataset. Finally, we analyzed whether RBsig would discriminate palbociclib-sensitive and -resistant breast cancer cells in a large RNA sequencing-based dataset. The RBsig was associated with RB1 genetic status in all tumors (p <7e-32) and in luminal or basal subtypes (p < 7e-11 and p < 0.002, respectively). The RBsig was prognostic in the METABRIC dataset (discovery: HR = 1.93 [1.5-2.4] p = 1.4e-08; validation: HR = 2.01 [1.6-2.5] p = 1.3e-09). Untreated and endocrine treated patients with estrogen receptor positive breast cancer expressing high RBsig had significantly worse recurrence free survival compared to those with low RBsig (HR = 2.37 [1.8 - 3.2] p = 1.87e-08 and HR = 2.62 [1.9- 3.5] p = 8.6e-11, respectively). The RBsig was able to identify palbociclib resistant and sensitive breast cancer cells (ROC AUC = 0,7778). Signatures of RB loss might be helpful in personalizing treatment of patients with HR+/HER2neg breast cancer. Further validation in patients receiving palbociclib is warranted.

Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer

Science.gov (United States)

2018-04-09

Estrogen Receptor Positive; Postmenopausal; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7

Lapatinib for the treatment of breast cancer in the People’s Republic of China

Directory of Open Access Journals (Sweden)

Wang HJ

2014-07-01

Full Text Available Hongjiang Wang Department of Breast Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China Abstract: Lapatinib is an oral, small-molecule, reversible inhibitor of both epidermal growth factor receptor and human epidermal growth factor receptor–2 (HER2 tyrosine kinases. In March 2007, the US Food and Drug Administration approved lapatinib for use in combination with capecitabine for the treatment of women with HER2-overexpressing, advanced or metastatic breast cancer. This review discusses the available information of lapatinib in Chinese breast cancer patients, focusing on its effectiveness and clinical application against advanced or metastatic breast cancer. In pivotal phase III trials, a combination of lapatinib and capecitabine significantly decreased the risk of disease progression compared to capecitabine alone in women with HER2-positive advanced or metastatic breast cancer. Other trials were used to evaluate lapatinib in combination with hormone therapy, in combination with trastuzumab, and as an adjunct to adjuvant therapy for early-stage disease. Preclinical data have revealed that lapatinib is active in trastuzumab-resistant cell lines as well as synergistic with trastuzumab. In clinical trials, lapatinib has not been associated with serious or symptomatic cardiotoxicity. Further, it can cross the blood–brain barrier and may therefore have a role in preventing cancer progression in the central nervous system. Thus, lapatinib warrants further evaluation in HER2-positive metastatic and early-stage breast cancer patients. Keywords: lapatinib, HER2 positive, breast cancer, molecular targeting therapy

Phase II study of neoadjuvant gemcitabine, pegylated liposomal doxorubicin, and docetaxel in locally advanced breast cancer.

Science.gov (United States)

Artioli, Grazia; Grazia, Artioli; Mocellin, Simone; Simone, Mocellin; Borgato, Lucia; Lucia, Borgato; Cappetta, Alessandro; Alessandro, Cappetta; Bozza, Fernando; Fernando, Bozza; Zavagno, Giorgio; Giorgio, Zavagno; Zovato, Stefania; Stefania, Zovato; Marchet, Alberto; Alberto, Marchet; Pastorelli, Davide; Davide, Pastorelli

2010-09-01

This was a phase II study to assess the activity of a novel neoadjuvant regimen in locally-advanced breast cancer. Fifty patients with histological confirmation of locally advanced breast cancer received treatment with gemcitabine 1000 mg/m(2) (day 1) followed by gemcitabine 800 mg/m(2) plus docetaxel 75 mg/m(2) plus pegylated liposomal doxorubicin (PLD) 30 mg/m(2) (day 8) every 3 weeks for at least 4 cycles, plus a final 2 additional cycles. Tumour size was T1 (n=2), T2 (n=32), T3 (n=14), T4 (n=2). All 50 patients underwent surgery. Clinical complete, partial and no response were observed in 13 (26%), 24 (48%) and 11 (22%) patients, respectively (overall response rate: 74%). The number of chemotherapy cycles was found to be an independent predictor of a pathologic complete response. The combination of gemcitabine-docetaxel-PLD can yield high tumour response rates in patients with locally-advanced breast cancer who undergo a full treatment of 6 cycles.

Supportive care needs in Hong Kong Chinese women confronting advanced breast cancer.

Science.gov (United States)

Au, Angel; Lam, Wendy; Tsang, Janice; Yau, Tsz-kok; Soong, Inda; Yeo, Winnie; Suen, Joyce; Ho, Wing M; Wong, Ka-yan; Kwong, Ava; Suen, Dacita; Sze, Wing-Kin; Ng, Alice; Girgis, Afaf; Fielding, Richard

2013-05-01

Women with advanced breast cancer (ABC) are living longer, so understanding their needs becomes important. This cross-sectional study investigated the type and extent of unmet supportive care needs in Hong Kong Chinese women with advanced breast cancer. Face-to-face interviews were conducted among women with stage III or stage IV disease mostly awaiting chemotherapy (76%) to identify unmet needs using the Supportive Care Needs Survey Short Form, psychological morbidity using the Hospital Anxiety and Depression Scale, symptom distress using the Memorial Symptom Assessment Scale, and satisfaction with care using the Patient satisfaction questionnaire (PSQ-9). About 27-72% of 198/220 (90%) women (mean age = 53.4 ± 9.74 (standard deviation) years) identified needs from the health system, information, and patient support (HSIPS) domain as the top 15 most prevalent unmet needs. 'having one member of hospital staff with whom you can talk to about all aspect of your condition, treatment, and follow-up' was most cited by 72% of the patients, with remaining unmet needs addressing mostly desire for information. Unmet need strength did not differ between women with stage III and stage IV disease, whereas women with first time diagnosis reported greater health system and information unmet needs compared with women with recurrent disease. Stepwise multiple regression analyses revealed that symptom distress was consistently positively associated with all but sexuality need domains, whereas low satisfaction with care was associated with HSIPS (β = 3.270, p living (β = 2.810, p < 0.01) domains. Chinese women with ABC expressed need for continuity of care and improved information provision. High symptom distress was associated with lower levels of satisfaction with care. These unmet needs appear to reflect current care services shortcomings. Copyright © 2012 John Wiley & Sons, Ltd.

Positive predictive value of additional synchronous breast lesions in whole-breast ultrasonography at the diagnosis of breast cancer: clinical and imaging factors

International Nuclear Information System (INIS)

Kim, Ah Hyun; Kim, Min Jung; Kim, Eun Kyung; Moon, Hee Jung; Park, Hee Jung

2014-01-01

To evaluate the positive predictive value (PPV) of bilateral whole-breast ultrasonography (BWBU) for detection of synchronous breast lesions on initial diagnosis of breast cancer and evaluate factors affecting the PPV of BWBU according to varying clinicoimaging factors. A total of 75 patients who had synchronous lesions with pathologic confirmation at the initial diagnosis of breast cancer during January 2007 and December 2007 were included. The clinical factors of the patients were evaluated. One observer retrospectively reviewed the imaging studies of the index breast cancer lesion and the synchronous lesion. The PPV for additional biopsy was calculated for BWBU and various clinical and imaging factors affecting the PPV for BWBU were evaluated. The overall PPV for additional biopsy was 25.7% (18 of 70). The PPV for synchronous lesions detected both on mammography and BWBU, and detected only on BWBU, was 76.9% (10 of 13) and 14.3% (7 of 49), respectively. There was no clinical factor affecting the PPV for BWBU. Among the imaging factors, ipsilateral location of the synchronous lesion to the index lesion (P=0.06) showed a marginal statistically significant correlation with malignancy in the synchronous breast lesion. A mass with calcification on mammography presentation (P<0.01), presence of calcification among the ultrasonography findings (P<0.01), and high Breast Imaging Reporting and Data System final assessment (P<0.01) were imaging factors that were associated with malignancy in the additional synchronous lesion. BWBU can detect additional synchronous malignancy at the diagnosis of breast cancer with a relatively high PPV, especially when mammography findings are correlated with ultrasonographic findings.

Bone Metastasis in Advanced Breast Cancer: Analysis of Gene Expression Microarray.

Science.gov (United States)

Cosphiadi, Irawan; Atmakusumah, Tubagus D; Siregar, Nurjati C; Muthalib, Abdul; Harahap, Alida; Mansyur, Muchtarruddin

2018-03-08

Approximately 30% to 40% of breast cancer recurrences involve bone metastasis (BM). Certain genes have been linked to BM; however, none have been able to predict bone involvement. In this study, we analyzed gene expression profiles in advanced breast cancer patients to elucidate genes that can be used to predict BM. A total of 92 advanced breast cancer patients, including 46 patients with BM and 46 patients without BM, were identified for this study. Immunohistochemistry and gene expression analysis was performed on 81 formalin-fixed paraffin-embedded samples. Data were collected through medical records, and gene expression of 200 selected genes compiled from 6 previous studies was performed using NanoString nCounter. Genetic expression profiles showed that 22 genes were significantly differentially expressed between breast cancer patients with metastasis in bone and other organs (BM+) and non-BM, whereas subjects with only BM showed 17 significantly differentially expressed genes. The following genes were associated with an increasing incidence of BM in the BM+ group: estrogen receptor 1 (ESR1), GATA binding protein 3 (GATA3), and melanophilin with an area under the curve (AUC) of 0.804. In the BM group, the following genes were associated with an increasing incidence of BM: ESR1, progesterone receptor, B-cell lymphoma 2, Rab escort protein, N-acetyltransferase 1, GATA3, annexin A9, and chromosome 9 open reading frame 116. ESR1 and GATA3 showed an increased strength of association with an AUC of 0.928. A combination of the identified 3 genes in BM+ and 8 genes in BM showed better prediction than did each individual gene, and this combination can be used as a training set. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Safety and efficacy of neratinib in combination with capecitabine in patients with metastatic human epidermal growth factor receptor 2-positive breast cancer.

Science.gov (United States)

Saura, Cristina; Garcia-Saenz, Jose A; Xu, Binghe; Harb, Wael; Moroose, Rebecca; Pluard, Timothy; Cortés, Javier; Kiger, Corinne; Germa, Caroline; Wang, Kongming; Martin, Miguel; Baselga, José; Kim, Sung-Bae

2014-11-10

Neratinib is a potent irreversible pan-tyrosine kinase inhibitor with antitumor activity and acceptable tolerability in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer. A multinational, open-label, phase I/II trial was conducted to determine the maximum-tolerated dose (MTD) of neratinib plus capecitabine in patients with solid tumors (part one) and to evaluate the safety and efficacy of neratinib plus capecitabine in patients with HER2-positive metastatic breast cancer (part two). Part one was a 3 + 3 dose-escalation study in which patients with advanced solid tumors received oral neratinib once per day continuously plus capecitabine twice per day on days 1 to 14 of a 21-day cycle at predefined dose levels. In part two, patients with trastuzumab-pretreated HER2-positive metastatic breast cancer received neratinib plus capecitabine at the MTD. The primary end point in part two was objective response rate (ORR). In part one (n = 33), the combination of neratinib 240 mg per day plus capecitabine 1,500 mg/m(2) per day was defined as the MTD, which was further evaluated in part 2 (n = 72). The most common drug-related adverse events were diarrhea (88%) and palmar-plantar erythrodysesthesia syndrome (48%). In part two, the ORR was 64% (n = 39 of 61) in patients with no prior lapatinib exposure and 57% (n = 4 of 7) in patients previously treated with lapatinib. Median progression-free survival was 40.3 and 35.9 weeks, respectively. Neratinib in combination with capecitabine had a manageable toxicity profile and showed promising antitumor activity in patients with HER2-positive metastatic breast cancer pretreated with trastuzumab and lapatinib. © 2014 by American Society of Clinical Oncology.

VMAT techniques for lymph node-positive left sided breast cancer

International Nuclear Information System (INIS)

Pasler, Marlies; Lutterbach, Johannes; Bjoernsgard, Mari; Reichmann, Ursula; Bartelt, Susanne; Georg, Dietmar; Medical Univ. Vienna

2015-01-01

To investigate the plan quality of two different volumetric modulated arc therapy (VMAT) techniques for lymph node-positive left-sided breast cancer. Two VMAT plans were generated for 10 lymph node-positive left-sided breast cancer patients: one plan using one single segment of a full rotation, typically an arc segment of 230 (1s-VMAT); and a second plan consisting of 2 small tangential arc segments of about 50 (2s-VMAT). For plan comparison, various dose and dose volume metrics (D mean , D 98% , D 2% for target volumes, D 2% , D mean and V x% for organs at risk (OAR)) were evaluated. Both techniques fulfilled both clinical target dose and OAR goals. 1s-VMAT achieved a slightly better homogeneity and better target coverage (D 2% = 54.2 ± 0.7 Gy, D 98% = 30.3 ± 1.8 Gy) compared to 2s-VMAT (D 2% = 55.0 ± 1.1 Gy, D 98% = 29.9 ± 1.7 Gy). For geometrical reasons, OAR sparing was noticeable but not significant better using 2s-VMAT, particularly heart and contralateral breast. The heart received a mean dose of 4.4 ± 0.8 Gy using 1s-VMAT and 3.3 ± 1.0 Gy using 2s-VMAT; the contralateral breast received 1.5 ± 0.3 Gy and 0.9 ± 0.3 Gy, respectively. A VMAT technique based on two small tangential arc segments enables improved OAR sparing; the differences between the two techniques in target coverage and homogeneity are minor. Patient age and -anatomy must be considered for each individual case when deciding which technique to be used.

TU-EF-207-03: Advances in Stationary Breast Tomosynthesis Using Distributed X-Ray Sources

Energy Technology Data Exchange (ETDEWEB)

Zhou, O. [The University of North Carolina at Chapel Hill (United States)

2015-06-15

Breast imaging technology is advancing on several fronts. In digital mammography, the major technological trend has been on optimization of approaches for performing combined mammography and tomosynthesis using the same system. In parallel, photon-counting slot-scan mammography is now in clinical use and more efforts are directed towards further development of this approach for spectral imaging. Spectral imaging refers to simultaneous acquisition of two or more energy-windowed images. Depending on the detector and associated electronics, there are a number of ways this can be accomplished. Spectral mammography using photon-counting detectors can suppress electronic noise and importantly, it enables decomposition of the image into various material compositions of interest facilitating quantitative imaging. Spectral imaging can be particularly important in intravenously injected contrast mammography and eventually tomosynthesis. The various approaches and applications of spectral mammography are discussed. Digital breast tomosynthesis relies on the mechanical movement of the x-ray tube to acquire a number of projections in a predefined arc, typically from 9 to 25 projections over a scan angle of +/−7.5 to 25 degrees depending on the particular system. The mechanical x-ray tube motion requires relatively long acquisition time, typically between 3.7 to 25 seconds depending on the system. Moreover, mechanical scanning may have an effect on the spatial resolution due to internal x-ray filament or external mechanical vibrations. New x-ray source arrays have been developed and they are aimed at replacing the scanned x-ray tube for improved acquisition time and potentially for higher spatial resolution. The potential advantages and challenges of this approach are described. Combination of digital mammography and tomosynthesis in a single system places increased demands on certain functional aspects of the detector and overall performance, particularly in the tomosynthesis

TU-EF-207-03: Advances in Stationary Breast Tomosynthesis Using Distributed X-Ray Sources

International Nuclear Information System (INIS)

Zhou, O.

2015-01-01

Breast imaging technology is advancing on several fronts. In digital mammography, the major technological trend has been on optimization of approaches for performing combined mammography and tomosynthesis using the same system. In parallel, photon-counting slot-scan mammography is now in clinical use and more efforts are directed towards further development of this approach for spectral imaging. Spectral imaging refers to simultaneous acquisition of two or more energy-windowed images. Depending on the detector and associated electronics, there are a number of ways this can be accomplished. Spectral mammography using photon-counting detectors can suppress electronic noise and importantly, it enables decomposition of the image into various material compositions of interest facilitating quantitative imaging. Spectral imaging can be particularly important in intravenously injected contrast mammography and eventually tomosynthesis. The various approaches and applications of spectral mammography are discussed. Digital breast tomosynthesis relies on the mechanical movement of the x-ray tube to acquire a number of projections in a predefined arc, typically from 9 to 25 projections over a scan angle of +/−7.5 to 25 degrees depending on the particular system. The mechanical x-ray tube motion requires relatively long acquisition time, typically between 3.7 to 25 seconds depending on the system. Moreover, mechanical scanning may have an effect on the spatial resolution due to internal x-ray filament or external mechanical vibrations. New x-ray source arrays have been developed and they are aimed at replacing the scanned x-ray tube for improved acquisition time and potentially for higher spatial resolution. The potential advantages and challenges of this approach are described. Combination of digital mammography and tomosynthesis in a single system places increased demands on certain functional aspects of the detector and overall performance, particularly in the tomosynthesis

Glutathione S-transferase M1 null genotype: lack of association with tumour characteristics and survival in advanced breast cancer

International Nuclear Information System (INIS)

Lizard-Nacol, Sarab; Coudert, Bruno; Colosetti, Pascal; Riedinger, Jean-Marc; Fargeot, Pierre; Brunet-Lecomte, Patrick

1999-01-01

Glutathione S-transferase (GST)M1, a member of the μ class GST gene family, has been shown to be polymorphic because of a partial gene deletion. This results in a failure to express the GSTM1 gene in 50-60% of individuals. Several studies have demonstrated a possible link with the GSTM1-null genotype and susceptibility to cancer. Furthermore, a GSTM1 isoenzyme has been positively associated with protective effect against mutagenic drugs, such as alkylating agents and anthracyclines. To determine whether GSTM1 polymorphisms are associated with tumour characteristics and survival in advanced breast cancer patients, and whether it may constitute a prognostic factor. We genotyped 92 patients receiving primary chemotherapy, which included cyclophosphamide, doxorubicine and 5-fluorouracil. The relationships between allelism at GSTM1 and clinicopathological parameters including age, menopausal status, tumour size, grade hormone receptors, involved nodes and p53 gene mutations were analysed. Of the patients with GSTM1-positive genotype, tissue samples obtained before and after treatment were available from 28 cases, allowing RNA extraction and GSTM1 expression by reverse transcription polymerase chain reaction. Relationships with clinical response to chemotherapy, and disease-free and overall survival were also evaluated. The data obtained was analysed using logistic regression to estimate the odds ratio and 95% confidence interval. Of 92 patients, 57.6% (n = 53) were classified as heritably GSTM1-deficient, and 42.4% (n = 39) were of the GSTM1-positive genotype. There were no statistically significant relationships between GSTM1-null genotype and the clinicopathological parameters analysed. No relationship was observed between GSTM1 RNA expression and objective clinical response to chemotherapy. Objective clinical response to chemotherapy was related only to clinical tumour size (P = 0.0177) and to the absence of intraductal carcinoma (P = 0.0013). GSTM1-null genotype

Risk Factors for Regional Nodal Relapse in Breast Cancer Patients With One to Three Positive Axillary Nodes

Energy Technology Data Exchange (ETDEWEB)

Yates, Lucy, E-mail: lucy.yates@gstt.nhs.uk [Guy' s, King' s, St Thomas' Cancer Centre, Guy' s Hospital, London (United Kingdom); Kirby, Anna [Guy' s, King' s, St Thomas' Cancer Centre, Guy' s Hospital, London (United Kingdom); Department of Clinical Oncology, Royal Marsden Hospital, Sutton (United Kingdom); Crichton, Siobhan [Department of Statistics, Kings College London (United Kingdom); Gillett, Cheryl [Breast Pathology, Kings College London (United Kingdom); Cane, Paul [Department of Histopathology, Guy' s and St Thomas' Foundation Trust, London (United Kingdom); Fentiman, Ian; Sawyer, Elinor [Guy' s, King' s, St Thomas' Cancer Centre, Guy' s Hospital, London (United Kingdom)

2012-04-01

Purpose: In many centers, supraclavicular fossa radiotherapy (SCF RT) is not routinely offered to breast cancer patients with one to three positive lymph nodes. We aimed to identify a subgroup of these patients who are at high risk of supra or infraclavicular fossa relapse (SCFR) such that they can be offered SCFRT at the time of diagnosis to improve long term locoregional control. Methods and Materials: We performed a retrospective analysis of the pathological features of 1,065 cases of invasive breast cancer with one to three positive axillary lymph nodes. Patients underwent radical breast conserving surgery or mastectomy. A total of 45% of patients received adjuvant chest wall/breast RT. No patients received adjuvant SCFRT. The primary outcome was SCFR. Secondary outcomes were chest wall/breast recurrence, distant metastasis, all death, and breast-cancer specific death. Kaplan-Meier estimates were used to calculate actuarial event rates and survival functions compared using log-rank tests. Multivariate analyses (MVA) of factors associated with outcome were conducted using Cox proportional hazards models. Results: Median follow-up was 9.7 years. SCFR rate was 9.2%. Median time from primary diagnosis to SCFR was 3.4 years (range, 0.7-14.4 years). SCFR was associated with significantly lower 10-year survival (18% vs. 65%; p < 0.001). Higher grade and number of positive lymph nodes were the most significant predictors of SCFR on MVA (p < 0.001). 10 year SCFR rates were less than 1% in all patients with Grade 1 cancers compared with 30% in those having Grade 3 cancers with three positive lymph nodes. Additional factors associated with SCFR on univariate analysis but not on MVA included larger nodal deposits (p = 0.002) and proportion of positive nodes (p = 0.003). Conclusions: Breast cancer patients with one to three positive lymph nodes have a heterogenous risk of SCFR. Patients with two to three positive axillary nodes and/or high-grade disease may warrant

Invasive micropapillary carcinoma of the breast overexpresses MUC4 and is associated with poor outcome to adjuvant trastuzumab in HER2-positive breast cancer.

Science.gov (United States)

Mercogliano, María F; Inurrigarro, Gloria; De Martino, Mara; Venturutti, Leandro; Rivas, Martín A; Cordo-Russo, Rosalía; Proietti, Cecilia J; Fernández, Elmer A; Frahm, Isabel; Barchuk, Sabrina; Allemand, Daniel H; Figurelli, Silvina; Deza, Ernesto Gil; Ares, Sandra; Gercovich, Felipe G; Cortese, Eduardo; Amasino, Matías; Guzmán, Pablo; Roa, Juan C; Elizalde, Patricia V; Schillaci, Roxana

2017-12-28

Invasive micropapillary carcinoma of the breast (IMPC) is a histological tumor variant that occurs with low frequency characterized by an inside-out formation of tumor clusters with a pseudopapillary arrangement. IMPC is an aggressive tumor with poor clinical outcome. In addition, this histological subtype usually expresses human epidermal growth factor receptor 2 (HER2) which also correlates with a more aggressive tumor. In this work we studied the clinical significance of IMPC in HER2-positive breast cancer patients treated with adjuvant trastuzumab. We also analyzed mucin 4 (MUC4) expression as a novel biomarker to identify IMPC. We retrospectively studied 86 HER2-positive breast cancer patients treated with trastuzumab and chemotherapy in the adjuvant setting. We explored the association of the IMPC component with clinicopathological parameters at diagnosis and its prognostic value. We compared MUC4 expression in IMPC with respect to other histological breast cancer subtypes by immunohistochemistry. IMPC, either as a pure entity or associated with invasive ductal carcinoma (IDC), was present in 18.6% of HER2-positive cases. It was positively correlated with estrogen receptor expression and tumor size and inversely correlated with patient's age. Disease-free survival was significantly lower in patients with IMPC (hazard ratio = 2.6; 95%, confidence interval 1.1-6.1, P = 0.0340). MUC4, a glycoprotein associated with metastasis, was strongly expressed in all IMPC cases tested. IMPC appeared as the histological breast cancer subtype with the highest MUC4 expression compared to IDC, lobular and mucinous carcinoma. In HER2-positive breast cancer, the presence of IMPC should be carefully examined. As it is often not informed, because it is relatively difficult to identify or altogether overlooked, we propose MUC4 expression as a useful biomarker to highlight IMPC presence. Patients with MUC4-positive tumors with IMPC component should be more frequently

A review of breast tomosynthesis. Part II. Image reconstruction, processing and analysis, and advanced applications

Science.gov (United States)

Sechopoulos, Ioannis

2013-01-01

Many important post-acquisition aspects of breast tomosynthesis imaging can impact its clinical performance. Chief among them is the reconstruction algorithm that generates the representation of the three-dimensional breast volume from the acquired projections. But even after reconstruction, additional processes, such as artifact reduction algorithms, computer aided detection and diagnosis, among others, can also impact the performance of breast tomosynthesis in the clinical realm. In this two part paper, a review of breast tomosynthesis research is performed, with an emphasis on its medical physics aspects. In the companion paper, the first part of this review, the research performed relevant to the image acquisition process is examined. This second part will review the research on the post-acquisition aspects, including reconstruction, image processing, and analysis, as well as the advanced applications being investigated for breast tomosynthesis. PMID:23298127

TNK2 Tyrosine Kinase as a Novel Therapeutic Target in Triple-Negative Breast Cancer

Science.gov (United States)

2017-10-01

Award Number: W81XWH-15-1-0311 TITLE: TNK2 Tyrosine Kinase as a Novel Therapeutic Target in Triple- Negative Breast Cancer PRINCIPAL...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Triple-negative breast cancers (TNBCs) represent only 10%-15% of all breast cancers ; however... cancers (TNBC) represent 10-15% of all breast cancers . While significant advances have been made for targeted therapy of ER and HER2-positive breast

Prognostic and predictive values of EGFR overexpression and EGFR copy number alteration in HER2-positive breast cancer.

Science.gov (United States)

Lee, H J; Seo, A N; Kim, E J; Jang, M H; Kim, Y J; Kim, J H; Kim, S-W; Ryu, H S; Park, I A; Im, S-A; Gong, G; Jung, K H; Kim, H J; Park, S Y

2015-01-06

Epidermal growth factor receptor (EGFR) is overexpressed in a subset of human epidermal growth factor receptor 2 (HER2)-positive breast cancers, and coexpression of HER2 and EGFR has been reported to be associated with poor clinical outcome. Moreover, interaction between HER2 and EGFR has been suggested to be a possible basis for trastuzumab resistance. We analysed the clinical significance of EGFR overexpression and EGFR gene copy number alterations in 242 HER2-positive primary breast cancers. In addition, we examined the correlations between EGFR overexpression, trastuzumab response and clinical outcome in 447 primary, and 112 metastatic HER2-positive breast cancer patients treated by trastuzumab. Of the 242 primary cases, the level of EGFR overexpression was 2+ in 12.7% and 3+ in 11.8%. High EGFR gene copy number was detected in 10.3%. Epidermal growth factor receptor overexpression was associated with hormone receptor negativity and high Ki-67 proliferation index. In survival analyses, EGFR overexpression, but not high EGFR copy number, was associated with poor disease-free survival in all patients, and in the subgroup not receiving adjuvant trastuzumab. In 447 HER2-positive primary breast cancer patients treated with adjuvant trastuzumab, EGFR overexpression was also an independent poor prognostic factor. However, EGFR overexpression was not associated with trastuzumab response, progression-free survival or overall survival in the metastatic setting. Epidermal growth factor receptor overexpression, but not high EGFR copy number, is a poor prognostic factor in HER2-positive primary breast cancer. Epidermal growth factor receptor overexpression is a predictive factor for trastuzumab response in HER2-positive primary breast cancer, but not in metastatic breast cancer.

Optimal utilization of a breast care advanced practice clinician.

Science.gov (United States)

Russell, Katie W; Mone, Mary C; Serpico, Victoria J; Ward, Cori; Lynch, Joanna; Neumayer, Leigh A; Nelson, Edward W

2014-12-01

Incorporation of "lean" business philosophy within health care has the goal of adding value by reducing cost and improving quality. Applying these principles to the role of Advance Practice Clinicians (APCs) is relevant because they have become essential members of the healthcare team. An independent surgical breast care clinic directed by an APC was created with measurements of success to include the following: time to obtain an appointment, financial viability, and patient/APC/MD satisfaction. During the study period, there was a trend toward a decreased median time to obtain an appointment. Monthly APC charges increased from $388 to $30,800. The mean provider satisfaction score by Press Ganey was 96% for the APC and 95.8% for the surgeon. Both clinicians expressed significant satisfaction with clinic development. Overall, initiation of an APC breast clinic met the proposed goals of success. The use of lean philosophy demonstrates that implementation of change can result in added value in patient care. Copyright © 2014 Elsevier Inc. All rights reserved.

Breast and gastrointestinal cancer updates from ASCO 2015.

Science.gov (United States)

Dawood, Shaheenah

2015-01-01

This review focuses on the updates presented at the ASCO 2015 symposium in breast and gastrointestinal malignancies. Some were practice changing while others gave us an exciting glimpse into what's to come in the very near future. Immunotherapy was the buzz word this year with data presented on every tumor site. Data on the efficacy of anti PD-1 agents in colorectal, hepatocellular and gastric cancer were presented. In breast cancer we saw data on a new and exciting therapeutic target in the form of androgen receptor among triple receptor negative breast tumors presented. Positive results of the PALOMA 3 trial were presented that has given women with hormone receptor positive metastatic breast cancer another therapeutic option. Furthermore data on strategies to further improve anti her2 therapy, optimizing of chemotherapy in the early and advanced stage and various strategies to improve endocrine therapy among patients with breast cancer were presented.

Self-transcendence and emotional well-being in women with advanced breast cancer.

Science.gov (United States)

Coward, D D

1991-07-01

Self-transcendence has been associated, in previous studies, with stressful life events and emotional well-being. This study examined the relationships among self-transcendence, emotional well-being, and illness-related distress in women with advanced breast cancer. The study employed a cross-sectional correlational design in a convenience sample (n = 107) of women with Stage IIIb and Stage IV breast cancer. Subjects completed a questionnaire that included Reed's Self-Transcendence Scale; Bradburn's Affect Balance Scale (ABS); a Cognitive Well-Being (CWB) Scale based on work by Campbell, Converse, and Rogers; McCorkle and Young's Symptom Distress Scale (SDS); and the Karnofsky Performance Scale (KPS). Data were analyzed using factor analytic structural equations modeling. Self-transcendence decreased illness distress (assessed by the SDS and the KPS) through the mediating effect of emotional well-being (assessed by the ABS and the CWB Scale). Self-transcendence directly affected emotional well-being (beta = 0.69), and emotional well-being had a strong negative effect on illness distress (beta = -0.84). A direct path from self-transcendence to illness distress (beta = -0.31) became nonsignificant (beta = -0.08) when controlling for emotional well-being. Further research using longitudinal data will seek to validate these relationships and to explain how nurses can promote self-transcendence in women with advanced breast cancer, as well as in others with life-threatening illnesses.

Trastuzumab after Chemotherapy Is Effective in HER2-Positive Breast Cancer

Science.gov (United States)

Treatment with trastuzumab for 1 year following standard chemotherapy improved disease-free survival in women with HER2-positive early breast cancer, according to 4-year follow-up results of the Herceptin Adjuvant (HERA) trial reported February 25, 2011,

The scaffold protein MEK Partner 1 is required for the survival of estrogen receptor positive breast cancer cells

Directory of Open Access Journals (Sweden)

Marina Mihaela

2012-07-01

Full Text Available Abstract MEK Partner 1 (MP1 or MAPKSP1 is a scaffold protein that has been reported to function in multiple signaling pathways, including the ERK, PAK and mTORC pathways. Several of these pathways influence the biology of breast cancer, but MP1’s functional significance in breast cancer cells has not been investigated. In this report, we demonstrate a requirement for MP1 expression in estrogen receptor (ER positive breast cancer cells. MP1 is widely expressed in both ER-positive and negative breast cancer cell lines, and in non-tumorigenic mammary epithelial cell lines. However, inhibition of its expression using siRNA duplexes resulted in detachment and apoptosis of several ER-positive breast cancer cell lines, but not ER-negative breast cancer cells or non-tumorigenic mammary epithelial cells. Inhibition of MP1 expression in ER-positive MCF-7 cells did not affect ERK activity, but resulted in reduced Akt1 activity and reduced ER expression and activity. Inhibition of ER expression did not result in cell death, suggesting that decreased ER expression is not the cause of cell death. In contrast, pharmacological inhibition of PI3K signaling did induce cell death in MCF-7 cells, and expression of a constitutively active form of Akt1 partially rescued the cell death observed when the MP1 gene was silenced in these cells. Together, these results suggest that MP1 is required for pro-survival signaling from the PI3K/Akt pathway in ER-positive breast cancer cells.

A phase I-II study of the histone deacetylase inhibitor vorinostat plus sequential weekly paclitaxel and doxorubicin-cyclophosphamide in locally advanced breast cancer.

Science.gov (United States)

Tu, Yifan; Hershman, Dawn L; Bhalla, Kapil; Fiskus, Warren; Pellegrino, Christine M; Andreopoulou, Eleni; Makower, Della; Kalinsky, Kevin; Fehn, Karen; Fineberg, Susan; Negassa, Abdissa; Montgomery, Leslie L; Wiechmann, Lisa S; Alpaugh, R Katherine; Huang, Min; Sparano, Joseph A

2014-07-01

Histone deacetylases (HDACs) are a family of enzymes that regulate chromatin remodeling and gene transcription. Vorinostat is a panHDAC inhibitor that sensitizes breast cancer cells to taxanes and trastuzumab by suppressing HDAC6 and Hsp90 client proteins. Fifty-five patients with clinical stage IIA-IIIC breast cancer received 12 weekly doses of paclitaxel (80 mg/m(2)) plus vorinostat (200-300 mg PO BID) on days 1-3 of each paclitaxel dose plus trastuzumab (for Her2/neu positive disease only), followed by doxorubicin/cyclophosphamide (60/600 mg/m(2) every 2 weeks plus pegfilgrastim). The primary study endpoint was pathologic complete response (pCR). pCR occurred in 13 of 24 evaluable patients with Her2-positive disease (54, 95 % confidence intervals [CI] 35-72 %), which met the prespecified study endpoint. pCR occurred in 4 of 15 patients with triple negative disease (27, 95 % CI 11-52 %) and none of 12 patients with ER-positive, Her2/neu negative disease (0, 95 % CI 0-24 %), which did not meet the prespecified endpoint. ER-positive tumors exhibited lower Ki67 and higher Hsp70 expression, and HDAC6, Hsp70, p21, and p27 expression were not predictive of response. Vorinostat increased acetylation of Hsp90 and alpha tubulin, and reduced expression of Hsp90 client proteins and HDAC6 in the primary tumor. Combination of vorinostat with weekly paclitaxel plus trastuzumab followed by doxorubicin-cyclophosphamide is associated with a high pCR rate in locally advanced Her2/neu positive breast cancer. Consistent with cell line and xenograft data, vorinostat increased acetylation of Hsp90 and alpha tubulin, and decreased Hsp90 client protein and HDAC6 expression in human breast cancers in vivo.

VMAT techniques for lymph node-positive left sided breast cancer

Energy Technology Data Exchange (ETDEWEB)

Pasler, Marlies; Lutterbach, Johannes; Bjoernsgard, Mari; Reichmann, Ursula; Bartelt, Susanne [Lake Constance Radiation Oncology Center Singen, Friedrichshafen (Germany); Georg, Dietmar [Medical Univ. Vienna/AKH Vienna (Austria). Dept. of Radiooncology; Medical Univ. Vienna (Austria). Christian Doppler Lab. for Medical Radiation Research for Radiation Oncology

2015-09-01

To investigate the plan quality of two different volumetric modulated arc therapy (VMAT) techniques for lymph node-positive left-sided breast cancer. Two VMAT plans were generated for 10 lymph node-positive left-sided breast cancer patients: one plan using one single segment of a full rotation, typically an arc segment of 230 (1s-VMAT); and a second plan consisting of 2 small tangential arc segments of about 50 (2s-VMAT). For plan comparison, various dose and dose volume metrics (D{sub mean}, D{sub 98%}, D{sub 2%} for target volumes, D{sub 2%}, D{sub mean} and V{sub x%} for organs at risk (OAR)) were evaluated. Both techniques fulfilled both clinical target dose and OAR goals. 1s-VMAT achieved a slightly better homogeneity and better target coverage (D{sub 2%} = 54.2 ± 0.7 Gy, D{sub 98%} = 30.3 ± 1.8 Gy) compared to 2s-VMAT (D{sub 2%} = 55.0 ± 1.1 Gy, D{sub 98%} = 29.9 ± 1.7 Gy). For geometrical reasons, OAR sparing was noticeable but not significant better using 2s-VMAT, particularly heart and contralateral breast. The heart received a mean dose of 4.4 ± 0.8 Gy using 1s-VMAT and 3.3 ± 1.0 Gy using 2s-VMAT; the contralateral breast received 1.5 ± 0.3 Gy and 0.9 ± 0.3 Gy, respectively. A VMAT technique based on two small tangential arc segments enables improved OAR sparing; the differences between the two techniques in target coverage and homogeneity are minor. Patient age and -anatomy must be considered for each individual case when deciding which technique to be used.

Alterations in mRNA profiles of trastuzumab‑resistant Her‑2‑positive breast cancer.

Science.gov (United States)

Zhao, Bin; Zhao, Yang; Sun, Yan; Niu, Haitao; Sheng, Long; Huang, Dongfang; Li, Li

2018-05-07

Breast cancer is one of the most common malignancies in women. Neoadjuvant trastuzumab therapy improves the prognosis of certain Her‑2‑positive breast cancer patients, however around two‑thirds of patients with Her‑2‑positive breast cancer do not benefit from Her‑2‑targeted therapy. To investigate the key mechanisms in trastuzumab resistance, potential biomarkers for neoadjuvant trastuzumab sensitivity were investigated using the gene expression omnibus (GEO) database for mRNA microarray data of Her‑2‑positive breast cancer patients who received neoadjuvant trastuzumab therapy. GEO profiles of 22 patients with a complete response and 48 patients with a partial response were identified in the GSE22358, GSE62327 and GSE66305 datasets. A total of 2,376, 1,000 and 1,152 differentially expressed genes in GSE22358, GSE62327 and GSE66305 datasets were demonstrated, respectively, utilizing GEO2R software. Furthermore, enriched gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed using the Database for Annotation, Visualization and Integrated Discovery software. Subsequently, a protein‑protein interaction network was established using STRING software. The results demonstrated that low sex‑determining region Y‑box 11 and high Bcl‑2 expression may be employed as markers for neoadjuvant trastuzumab therapy for Her‑2‑positive breast cancer. More importantly, phosphoinositide 3‑kinase/Akt and angiogenesis pathways, which are known to be the key targets of trastuzumab, were activated at a lower level in the partial response patients, while the Wnt and estrogen receptor signaling pathways were activated in these patients. Therefore, combination therapy of trastuzumab and anti‑Wnt or hormone therapy may be a promising treatment modality and should be tested in further studies.

Self-management and transitions in women with advanced breast cancer.

Science.gov (United States)

Schulman-Green, Dena; Bradley, Elizabeth H; Knobf, M Tish; Prigerson, Holly; DiGiovanna, Michael P; McCorkle, Ruth

2011-10-01

Self-management involves behaviors that individuals perform to handle health conditions. Self-management may be particularly challenging during transitions-shifts from one life phase or status to another, for example, from cure- to noncure-oriented care-because they can be disruptive and stressful. Little is known about individuals' experiences with self-management, especially during transitions. Our purpose was to describe experiences of self-management in the context of transitions among women with advanced breast cancer. We interviewed a purposive sample of 15 women with metastatic breast cancer about their self-management preferences, practices, and experiences, including how they managed transitions. Interviews were recorded and transcribed. The qualitative method of interpretive description was used to code and analyze the data. Participants' mean age was 52 years (range 37-91 years); most were White (80%), married (80%), and college educated (60%). Self-management practices related to womens' health and to communication with loved ones and providers. Participants expressed a range of preferences for participation in self-management. Self-management included developing skills, becoming empowered, and creating supportive networks. Barriers to self-management included symptom distress, difficulty obtaining information, and lack of knowledge about the cancer trajectory. Women identified transitions as shifts in physical, emotional, and social well-being, as when their cancer progressed and there was a need to change therapy. Transitions often prompted changes in how actively women self-managed and were experienced as positive, negative, and neutral. Self-management preferences can vary. Providers should explore and revisit patients' preferences and ability to self-manage over time, particularly during transitions. Copyright © 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2- advanced breast cancer in the randomized MONALEESA-2 trial.

Science.gov (United States)

O'Shaughnessy, Joyce; Petrakova, Katarina; Sonke, Gabe S; Conte, Pierfranco; Arteaga, Carlos L; Cameron, David A; Hart, Lowell L; Villanueva, Cristian; Jakobsen, Erik; Beck, Joseph T; Lindquist, Deborah; Souami, Farida; Mondal, Shoubhik; Germa, Caroline; Hortobagyi, Gabriel N

2018-02-01

Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. 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). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate. Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27-0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population. Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2- de novo advanced breast cancer.

Niclosamide inhibits epithelial-mesenchymal transition and tumor growth in lapatinib-resistant human epidermal growth factor receptor 2-positive breast cancer.

Science.gov (United States)

Liu, Junjun; Chen, Xiaosong; Ward, Toby; Mao, Yan; Bockhorn, Jessica; Liu, Xiaofei; Wang, Gen; Pegram, Mark; Shen, Kunwei

2016-02-01

Acquired resistance to lapatinib, a human epidermal growth factor receptor 2 kinase inhibitor, remains a clinical problem for women with human epidermal growth factor receptor 2-positive advanced breast cancer, as metastasis is commonly observed in these patients. Niclosamide, an anti-helminthic agent, has recently been shown to exhibit cytotoxicity to tumor cells with stem-like characteristics. This study was designed to identify the mechanisms underlying lapatinib resistance and to determine whether niclosamide inhibits lapatinib resistance by reversing epithelial-mesenchymal transition. Here, two human epidermal growth factor receptor 2-positive breast cancer cell lines, SKBR3 and BT474, were exposed to increasing concentrations of lapatinib to establish lapatinib-resistant cultures. Lapatinib-resistant SKBR3 and BT474 cells exhibited up-regulation of the phenotypic epithelial-mesenchymal transition markers Snail, vimentin and α-smooth muscle actin, accompanied by activation of nuclear factor-кB and Src and a concomitant increase in stem cell marker expression (CD44(high)/CD24(low)), compared to naive lapatinib-sensitive SKBR3 and BT474 cells, respectively. Interestingly, niclosamide reversed epithelial-mesenchymal transition, induced apoptosis and inhibited cell growth by perturbing aberrant signaling pathway activation in lapatinib-resistant human epidermal growth factor receptor 2-positive cells. The ability of niclosamide to alleviate stem-like phenotype development and invasion was confirmed. Collectively, our results demonstrate that lapatinib resistance correlates with epithelial-mesenchymal transition and that niclosamide inhibits lapatinib-resistant cell viability and epithelial-mesenchymal transition. These findings suggest a role of niclosamide or derivatives optimized for more favorable bioavailability not only in reversing lapatinib resistance but also in reducing metastatic potential during the treatment of human epidermal growth factor receptor

Significant difference in p53 and p21 protein immunoreactivity in HPV 16 positive and HPV negative breast carcinomas

International Nuclear Information System (INIS)

Hennig, E.M.; Norwegian Radium Hospital, Oslo; Kvinnsland, S.; Holm, R.; Nesland, J.M.

1999-01-01

Human papillomavirus (HPV) 16 has previously been found in 19/41 breast carcinomas (46%) in women with a history of HPV 16 positive CIN III lesions. There was no significant difference in distribution of histological subtypes, mean or median tumour diameter or number of regional lymph node metastases in the HPV positive and HPV negative breast carcinoma groups. P53, p21 and c-erbB-2 proteins were analyzed by immunohistochemistry in the HPV 16 positive and HPV negative breast carcinomas. There was a significant difference in p53 and p21 protein immunoreactivity between HPV 16 positive and HPV negative breast carcinomas (p=0.0091 and p=0.0040), with a significant less detectable p53 and p21 protein immunoreactivity in the HPV 16 positive cases. There was also a significant difference in the coexpression of p53/p21 between the HPV 16 positive and HPV 16 negative breast carcinomas (p=0.002). No significant difference in immunostaining for c-erbB-2 protein in the two groups was found (p=0.15), or for the coexpression of p53/c-erbB-2 (p=0.19). The significantly lower expression of p53 and p21 proteins in HPV 16 positive than in HPV 16 negative breast carcinomas supports the hypothesis of inactivation and degradation of wild-type p53 proteins by HPV 16 E6 and that p53 mutation is not necessary for transformation in the HPV 16 positive cases. (orig.)

Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial.

Science.gov (United States)

Johnston, Stephen Rd; Kilburn, Lucy S; Ellis, Paul; Dodwell, David; Cameron, David; Hayward, Larry; Im, Young-Hyuck; Braybrooke, Jeremy P; Brunt, A Murray; Cheung, Kwok-Leung; Jyothirmayi, Rema; Robinson, Anne; Wardley, Andrew M; Wheatley, Duncan; Howell, Anthony; Coombes, Gill; Sergenson, Nicole; Sin, Hui-Jung; Folkerd, Elizabeth; Dowsett, Mitch; Bliss, Judith M

2013-09-01

The optimum endocrine treatment for postmenopausal women with advanced hormone-receptor-positive breast cancer that has progressed on non-steroidal aromatase inhibitors (NSAIs) is unclear. The aim of the SoFEA trial was to assess a maximum double endocrine targeting approach with the steroidal anti-oestrogen fulvestrant in combination with continued oestrogen deprivation. In a composite, multicentre, phase 3 randomised controlled trial done in the UK and South Korea, postmenopausal women with hormone-receptor-positive breast cancer (oestrogen receptor [ER] positive, progesterone receptor [PR] positive, or both) were eligible if they had relapsed or progressed with locally advanced or metastatic disease on an NSAI (given as adjuvant for at least 12 months or as first-line treatment for at least 6 months). Additionally, patients had to have adequate organ function and a WHO performance status of 0-2. Participants were randomly assigned (1:1:1) to receive fulvestrant (500 mg intramuscular injection on day 1, followed by 250 mg doses on days 15 and 29, and then every 28 days) plus daily oral anastrozole (1 mg); fulvestrant plus anastrozole-matched placebo; or daily oral exemestane (25 mg). Randomisation was done with computer-generated permuted blocks, and stratification was by centre and previous use of an NSAI as adjuvant treatment or for locally advanced or metastatic disease. Participants and investigators were aware of assignment to fulvestrant or exemestane, but not of assignment to anastrozole or placebo. The primary endpoint was progression-free survival (PFS). Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, numbers NCT00253422 (UK) and NCT00944918 (South Korea). Between March 26, 2004, and Aug 6, 2010, 723 patients underwent randomisation: 243 were assigned to receive fulvestrant plus anastrozole, 231 to fulvestrant plus placebo, and 249 to exemestane. Median PFS was 4·4 months (95% CI 3·4-5·4) in patients assigned to

WE-FG-207A-00: Advances in Dedicated Breast CT

International Nuclear Information System (INIS)

2016-01-01

Mammography-based screening has been a valuable imaging tool for the early detection of non-palpable lesions and has contributed to significant reduction in breast cancer associated mortality. However, the breast imaging community recognizes that mammography is not ideal, and in particular is inferior for women with dense breasts. Also, the 2-D projection of a 3-D organ results in tissue superposition contributing to false-positives. The sensitivity of mammography is breast-density dependent. Its sensitivity, especially in dense breasts, is low due to overlapping tissue and the fact that normal breast tissue, benign lesions and breast cancers all have similar “densities”, making lesion detection more difficult. We ideally need 3-D imaging for imaging the 3-D breast. MRI is 3-D, whole breast ultrasound is 3-D, digital breast tomosynthesis is called 3-D but is really “pseudo 3-D” due to poor resolution along the depth-direction. Also, and importantly, we need to be able to administer intravenous contrast agents for optimal imaging, similar to other organ systems in the body. Dedicated breast CT allows for 3-D imaging of the uncompressed breast. In current designs, the patient is positioned prone on the table and the breast is pendant through an aperture and the scan takes approximately 10 seconds [O’Connell et al., AJR 195: 496–509, 2010]. Almost on the heels of the invention of CT itself, work began on the development of dedicated breast CT. These early breast CT systems were used in clinical trials and the results from comparative performance evaluation of breast CT and mammography for 1625 subjects were reported in 1980 [Chang et al., Cancer 46: 939–46, 1980]. However, the technological limitations at that time stymied clinical translation for decades. Subsequent to the landmark article in 2001 [Boone et al., Radiology 221: 657–67, 2001] that demonstrated the potential feasibility in terms of radiation dose, multiple research groups are actively

WE-FG-207A-00: Advances in Dedicated Breast CT

Energy Technology Data Exchange (ETDEWEB)

NONE

2016-06-15

Mammography-based screening has been a valuable imaging tool for the early detection of non-palpable lesions and has contributed to significant reduction in breast cancer associated mortality. However, the breast imaging community recognizes that mammography is not ideal, and in particular is inferior for women with dense breasts. Also, the 2-D projection of a 3-D organ results in tissue superposition contributing to false-positives. The sensitivity of mammography is breast-density dependent. Its sensitivity, especially in dense breasts, is low due to overlapping tissue and the fact that normal breast tissue, benign lesions and breast cancers all have similar “densities”, making lesion detection more difficult. We ideally need 3-D imaging for imaging the 3-D breast. MRI is 3-D, whole breast ultrasound is 3-D, digital breast tomosynthesis is called 3-D but is really “pseudo 3-D” due to poor resolution along the depth-direction. Also, and importantly, we need to be able to administer intravenous contrast agents for optimal imaging, similar to other organ systems in the body. Dedicated breast CT allows for 3-D imaging of the uncompressed breast. In current designs, the patient is positioned prone on the table and the breast is pendant through an aperture and the scan takes approximately 10 seconds [O’Connell et al., AJR 195: 496–509, 2010]. Almost on the heels of the invention of CT itself, work began on the development of dedicated breast CT. These early breast CT systems were used in clinical trials and the results from comparative performance evaluation of breast CT and mammography for 1625 subjects were reported in 1980 [Chang et al., Cancer 46: 939–46, 1980]. However, the technological limitations at that time stymied clinical translation for decades. Subsequent to the landmark article in 2001 [Boone et al., Radiology 221: 657–67, 2001] that demonstrated the potential feasibility in terms of radiation dose, multiple research groups are actively

Prognostic factors of HER2-positive breast cancer patients who develop brain metastasis: a multicenter retrospective analysis.

Science.gov (United States)

Hayashi, Naoki; Niikura, Naoki; Masuda, Norikazu; Takashima, Seiki; Nakamura, Rikiya; Watanabe, Ken-ichi; Kanbayashi, Chizuko; Ishida, Mayumi; Hozumi, Yasuo; Tsuneizumi, Michiko; Kondo, Naoto; Naito, Yoichi; Honda, Yayoi; Matsui, Akira; Fujisawa, Tomomi; Oshitanai, Risa; Yasojima, Hiroyuki; Yamauchi, Hideko; Saji, Shigehira; Iwata, Hiroji

2015-01-01

The clinical course and prognostic factors of HER2-positive breast cancer patients with brain metastases are not well known because of the relatively small population. The aim of this study was to determine prognostic factors associated with HER2-positive patients who develop brain metastases. This retrospective study assessed the largest dataset to date of 432 HER2-positive patients who were diagnosed with brain metastases from 24 institutions of the Japan Clinical Oncology Group, Breast Cancer Study Group. The median age of the 432 patients was 54 years (range, 20-86 years). Of the patients, 162 patients (37.5 %) had ER-positive/HER2-positive (ER+HER2+) breast cancer, and 270 (62.5 %) had ER-negative/HER2-positive (ER-HER2+) breast cancer. The median brain metastasis-free survival period from primary breast cancer was 33.5 months in both groups. The median survival after developing brain metastasis was 16.5 and 11.5 months in the ER+HER2+ and ER-HER2+ groups, respectively, (p = 0.117). Patients with >3 brain metastases had significantly shorter overall survival in both ER+HER2+ (p developing brain metastases was not associated with survival duration after developing brain metastases (p = 0.571). However, patients treated with both trastuzumab and lapatinib after developing metastasis had significantly longer survival than patients treated with trastuzumab alone, lapatinib alone, or no HER2-targeting agent (p brain metastases, regardless of the use of trastuzumab before developing brain metastasis, treatment with both trastuzumab and lapatinib might improve survival.

A deep learning based strategy for identifying and associating mitotic activity with gene expression derived risk categories in estrogen receptor positive breast cancers.

Science.gov (United States)

Romo-Bucheli, David; Janowczyk, Andrew; Gilmore, Hannah; Romero, Eduardo; Madabhushi, Anant

2017-06-01

The treatment and management of early stage estrogen receptor positive (ER+) breast cancer is hindered by the difficulty in identifying patients who require adjuvant chemotherapy in contrast to those that will respond to hormonal therapy. To distinguish between the more and less aggressive breast tumors, which is a fundamental criterion for the selection of an appropriate treatment plan, Oncotype DX (ODX) and other gene expression tests are typically employed. While informative, these gene expression tests are expensive, tissue destructive, and require specialized facilities. Bloom-Richardson (BR) grade, the common scheme employed in breast cancer grading, has been shown to be correlated with the Oncotype DX risk score. Unfortunately, studies have also shown that the BR grade determined experiences notable inter-observer variability. One of the constituent categories in BR grading is the mitotic index. The goal of this study was to develop a deep learning (DL) classifier to identify mitotic figures from whole slides images of ER+ breast cancer, the hypothesis being that the number of mitoses identified by the DL classifier would correlate with the corresponding Oncotype DX risk categories. The mitosis detector yielded an average F-score of 0.556 in the AMIDA mitosis dataset using a 6-fold validation setup. For a cohort of 174 whole slide images with early stage ER+ breast cancer for which the corresponding Oncotype DX score was available, the distributions of the number of mitoses identified by the DL classifier was found to be significantly different between the high vs low Oncotype DX risk groups (P machine classifier trained to separate low/high Oncotype DX risk categories using the mitotic count determined by the DL classifier yielded a 83.19% classification accuracy. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

Sentinel node biopsy performance after neoadjuvant chemotherapy in locally advanced breast cancer: A systematic review and meta-analysis.

Science.gov (United States)

Mocellin, Simone; Goldin, Elena; Marchet, Alberto; Nitti, Donato

2016-01-15

The use of sentinel node biopsy (SNB) after neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer is debated. Our aim was to quantitatively review the available evidence on the performance of SNB after NAC in patients with locally advanced breast cancer. We performed a systematic review (by searching the PubMed, Cochrane and Scopus databases) and random effects meta-analysis to investigate on the feasibility and accuracy of SNB in these patients. The two outcomes of interest were the sentinel node identification rate (SIR) and the false negative rate (FNR). Sensitivity analysis and meta-regression were used to investigate the potential sources of between-study heterogeneity. We retrieved 72 eligible studies enrolling 7,451 patients. Upon meta-analysis, summary SIR resulted 89.6% [95% confidence interval (CI): 87.8-91.2; heterogeneity I(2): 76.9%], which poorly compares with the 95% SIR observed in some recent series of early breast cancer. The summary FNR resulted 14.2% (CI: 12.5-16.0; heterogeneity I(2): 29.1%), which was significantly higher than the 8-10% reference value. Considering an average post-NAC lymph node positivity rate of 50%, the downstaging due to false negative SNB would occur in 7/100 patients (with an excess error rate of 2-3/100 as compared to the early-stage setting). No plausible source of between-study heterogeneity was found. Based on the largest series of studies ever meta-analyzed, our findings highlight the limits of SNB performance in this population, where the impact of SNB on patient survival is still to be defined. © 2015 UICC.

Shear-wave elastography in the diagnosis of solid breast masses: what leads to false-negative or false-positive results?

Science.gov (United States)

Yoon, Jung Hyun; Jung, Hae Kyoung; Lee, Jong Tae; Ko, Kyung Hee

2013-09-01

To investigate the factors that have an effect on false-positive or false-negative shear-wave elastography (SWE) results in solid breast masses. From June to December 2012, 222 breast lesions of 199 consecutive women (mean age: 45.3 ± 10.1 years; range, 21 to 88 years) who had been scheduled for biopsy or surgical excision were included. Greyscale ultrasound and SWE were performed in all women before biopsy. Final ultrasound assessments and SWE parameters (pattern classification and maximum elasticity) were recorded and compared with histopathology results. Patient and lesion factors in the 'true' and 'false' groups were compared. Of the 222 masses, 175 (78.8 %) were benign, and 47 (21.2 %) were malignant. False-positive rates of benign masses were significantly higher than false-negative rates of malignancy in SWE patterns, 36.6 % to 6.4 % (P masses, factors showing significance among false SWE features were lesion size, breast thickness and lesion depth (all P breast masses had SWE images of good quality. False SWE features were more significantly seen in benign masses. Lesion size, breast thickness and lesion depth have significance in producing false results, and this needs consideration in SWE image acquisition. • Shear-wave elastography (SWE) is widely used during breast imaging • At SWE, false-positive rates were significantly higher than false-negative rates • Larger size, breast thickness, depth and fair quality influences false-positive SWE features • Smaller size, larger breast thickness and depth influences false-negative SWE features.

Efficacy of intraarterial chemoinfusion therapy for locally advanced breast cancer patients: a retrospective analysis of 28 cases

Directory of Open Access Journals (Sweden)

Zhang W

2013-06-01

Full Text Available Wei Zhang,1,* Rong Liu,1,* Yingying Wang,1 Sheng Qian,1 Jianhua Wang,1 Zhiping Yan,1 Hongwei Zhang21Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China; 2Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China*These authors contributed equally to this workObjective: The objective of this study was to evaluate the outcome of image-guided delivery of intraarterially infused chemotherapeutic drugs for patients with locally advanced breast cancer.Methods: Twenty-eight patients with pathologically proven, locally advanced breast cancer received intraarterial chemoinfusion therapy (chemoinfusion with docetaxel 75 mg/m2 and epirubicin 50 mg/m2. Digital subtraction angiography was performed to determine tumor arterial blood supply and to guide chemotherapy infusion. Patients were evaluated for complete remission (CR and partial remission (PR.Results: Twenty-eight patients received a total of 64 intraarterial chemoinfusions, 20 patients (71.4% received two infusions, and eight patients (28.6% received three infusions. One patient (3.6% had CR and 23 (82.1% had PR. The total effectiveness rate (CR and PR was 85.7% (24/28. All stage 3 patients underwent Phase II surgical resection after chemoinfusion, and the surgical resection participation rate was 100% (26/26. The mean time from the first chemoinfusion to surgery was 2 ± 1.2 months. Two patients with stage 4 cancer died of distant metastasis and cachexia, and the remaining 26 patients were still alive.Conclusion: Intraarterial chemoinfusion is a safe and effective therapy, achieving down-staging in a relatively short period for locally advanced breast cancer.Keywords: advanced breast cancer, intraarterial infusion, chemotherapy, therapeutic effect

Impact of group psychotherapy in chemotherapy induced vomiting for treatment of advanced breast and lungs cancer

International Nuclear Information System (INIS)

Pervez, T.; Mein, F.D.; Alharbi, T.M.

2007-01-01

To assess the effect of group psychotherapy in the management of the side effects of chemotherapy treatment in advanced breast and lung cancer. One hundred patients treated with chemotherapy for advanced stage (IIIB and IV) breast and lung cancer were selected with ECOG performance status of 0 or 1. All patients received anti-emetic medications half an hour before chemotherapy. All those patients in this category who completed fist line chemotherapy with 6 cycles were included. Fifty were subjected to group discussions with other patients, family members and medical staff. This was labeled group A. The other 50 were not included in group discussion and were labeled group B. Both the group received similar standard chemotherapy and pre-medication for vomiting as per their disease and chemotherapy schedule. Breast and lung cancer patients were 29 and 21 in each arm respectively. At the end of the discharge, grade 2 and above of vomiting, according to common terminology criteria for adverse events (CTCAE) was counted for all patients in both the arms A and B, over full length of treatment for 6 cycles, and then were compared statistically. Mean with standard deviation for adverse event (vomiting) in group A and B was 6.2 + 2.6 and 13.4 + 3.8 respectively per cycle of treatment. It was observed that group psychotherapy had statistically significant effect (p-value <0.05) on the management of vomiting. Group psychotherapy can be used to reduce the incidence of vomiting in advanced breast and lung cancer patients treated with chemotherapy. (author)

Postmastectomy Radiotherapy for Locally Advanced Breast Cancer Receiving Neoadjuvant Chemotherapy

Directory of Open Access Journals (Sweden)

Icro Meattini

2014-01-01

Full Text Available Neoadjuvant chemotherapy (NAC is widely used in locally advanced breast cancer (BC treatment. The role of postmastectomy radiotherapy (PMRT after NAC is strongly debated. The aim of our analysis was to identify major prognostic factors in a single-center series, with emphasis on PMRT. From 1997 to 2011, 170 patients were treated with NAC and mastectomy at our center; 98 cases (57.6% underwent PMRT and 72 cases (42.4% did not receive radiation. At a median follow-up period of 7.7 years (range 2–16 for the whole cohort, median time to locoregional recurrence (LRR was 3.3 years (range 0.7–12.4. The 5-year and 10-year actuarial LRR rate were 14.5% and 15.9%, respectively. At the multivariate analysis the factors that significantly correlated with survival outcome were ≥4 positive nodes (HR 5.0, 1.51–16.52; P=0.035, extracapsular extension (HR 2.18, 1.37–3.46; P=0.009, and estrogen receptor positive disease (HR 0.57, 0.36–0.90; P=0.003. Concerning LRR according to use of radiation, PMRT reduced LRR for patient with clinical T3 staged disease (P=0.015. Our experience confirmed the impact of pathological nodal involvement on survival outcome. PMRT was found to improve local control in patients presenting with clinical T3 tumors, regardless of the response to chemotherapy.

Patient-reported Quality of Life and Treatment Satisfaction in Patients With HR+/HER2- Advanced/Metastatic Breast Cancer.

Science.gov (United States)

Wood, Robert; Mitra, Debanjali; de Courcy, Jonathan; Iyer, Shrividya

2017-08-01

Globally, around 1.67 million new cases of breast cancer are diagnosed each year, with advanced breast cancer (ABC-Stage III) and metastatic breast cancer (MBC-Stage IV) together accounting for up to 22% of incident cases. Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 - ) breast cancer comprises 66% of ABC/MBC. Understanding disease-specific health-related quality of life and patient satisfaction with treatments currently available for HR + /HER2 - ABC/MBC in clinical practice is essential for assessing potential unmet need in this patient population. Data on treatment patterns in patients with HR + /HER2 - ABC/MBC were collected from oncology practices across the United States and Europe in a cross-sectional study in a clinical practice setting, the Adelphi Real World Advanced Breast Cancer Disease Specific Programme. A subset of patients included in the study completed several self-reported tools, including the Functional Assessment of Cancer Therapy-Breast and the Cancer Therapy Satisfaction Questionnaire. Analyses were conducted using data from the overall cohort and stratified by current treatment, metastatic sites, and number of prior therapy lines. Overall, 739 patients were recruited by 173 oncologists; 83% of patients had MBC, with the balance having ABC. The majority of patients with MBC had visceral metastases without bone metastases, and similar percentages of the total study population (≈40%) were receiving chemotherapy and endocrine therapy. Patients receiving only endocrine therapy had significantly better cancer-specific quality of life than did those receiving chemotherapy. Endocrine therapy also associated with fewer concerns about side effects and higher treatment satisfaction than chemotherapy. Statistically lower scores, indicating poorer well-being, were observed in patients with both bone and visceral metastases compared with those with either bone-only or visceral-only metastases for all but the

Staging of breast cancer and the advanced applications of digital mammogram: what the physician needs to know?

Science.gov (United States)

Helal, Maha H; Mansour, Sahar M; Zaglol, Mai; Salaleldin, Lamia A; Nada, Omniya M; Haggag, Marwa A

2017-03-01

To study the role of advanced applications of digital mammogram, whether contrast-enhanced spectral mammography (CESM) or digital breast tomosynthesis (DBT), in the "T" staging of histologically proven breast cancer before planning for treatment management. In this prospective analysis, we evaluated 98 proved malignant breast masses regarding their size, multiplicity and the presence of associated clusters of microcalcifications. Evaluation methods included digital mammography (DM), 3D tomosynthesis and CESM. Traditional DM was first performed then in a period of 10-14-day interval; breast tomosynthesis and contrast-based mammography were performed for the involved breast only. Views at tomosynthesis were acquired in a "step-and-shoot" tube motion mode to produce multiple (11-15), low-dose images and in contrast-enhanced study, low-energy (22-33 kVp) and high-energy (44-49 kVp) exposures were taken after the i.v. injection of the contrast agent. Operative data were the gold standard reference. Breast tomosynthesis showed the highest accuracy in size assessment (n = 69, 70.4%) than contrast-enhanced (n = 49, 50%) and regular mammography (n = 59, 60.2%). Contrast-enhanced mammography presented the least performance in assessing calcifications, yet it was most sensitive in the detection of multiplicity (92.3%), followed by tomosynthesis (77%) and regular mammography (53.8%). The combined analysis of the three modalities provided an accuracy of 74% in the "T" staging of breast cancer. The combined application of tomosynthesis and contrast-enhanced digital mammogram enhanced the performance of the traditional DM and presented an informative method in the staging of breast cancer. Advances in knowledge: Staging and management planning of breast cancer can divert according to tumour size, multiplicity and the presence of microcalcifications. DBT shows sharp outlines of the tumour with no overlap tissue and spots microcalcifications. Contrast

Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative, hormone receptor-positive breast cancer in BOLERO-2.

Science.gov (United States)

Pritchard, Kathleen I; Burris, Howard A; Ito, Yoshinori; Rugo, Hope S; Dakhil, Shaker; Hortobagyi, Gabriel N; Campone, Mario; Csöszi, Tibor; Baselga, José; Puttawibul, Puttisak; Piccart, Martine; Heng, Daniel; Noguchi, Shinzaburo; Srimuninnimit, Vichien; Bourgeois, Hugues; Gonzalez Martin, Antonio; Osborne, Karen; Panneerselvam, Ashok; Taran, Tetiana; Sahmoud, Tarek; Gnant, Michael

2013-12-01

Postmenopausal women with hormone receptor-positive (HR(+)) breast cancer in whom disease progresses or there is recurrence while taking a nonsteroidal aromatase inhibitor (NSAI) are usually treated with exemestane (EXE), but no single standard of care exists in this setting. The BOLERO-2 trial demonstrated that adding everolimus (EVE) to EXE improved progression-free survival (PFS) while maintaining quality of life when compared with EXE alone. Because many women with HR(+) advanced breast cancer are elderly, the tolerability profile of EVE plus EXE in this population is of interest. BOLERO-2, a phase III randomized trial, compared EVE (10 mg/d) and placebo (PBO), both plus EXE (25 mg/d), in 724 postmenopausal women with HR(+) advanced breast cancer recurring/progressing after treatment with NSAIs. Safety and efficacy data in elderly patients are reported at 18-month median follow-up. Baseline disease characteristics and treatment histories among the elderly subsets (≥ 65 years, n = 275; ≥ 70 years, n = 164) were generally comparable with younger patients. The addition of EVE to EXE improved PFS regardless of age (hazard ratio, 0.59 [≥ 65 years] and 0.45 [≥ 70 years]). Adverse events (AEs) of special interest (all grades) that occurred more frequently with EVE than with PBO included stomatitis, infections, rash, pneumonitis, and hyperglycemia. Elderly EVE-treated patients had similar incidences of these AEs as did younger patients but had more on-treatment deaths. Adding EVE to EXE offers substantially improved PFS over EXE and was generally well tolerated in elderly patients with HR(+) advanced breast cancer. Careful monitoring and appropriate dose reductions or interruptions for AE management are recommended during treatment with EVE in this patient population. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Joint relative risks for estrogen receptor-positive breast cancer from a clinical model, polygenic risk score, and sex hormones.

Science.gov (United States)

Shieh, Yiwey; Hu, Donglei; Ma, Lin; Huntsman, Scott; Gard, Charlotte C; Leung, Jessica W T; Tice, Jeffrey A; Ziv, Elad; Kerlikowske, Karla; Cummings, Steven R

2017-11-01

Models that predict the risk of estrogen receptor (ER)-positive breast cancers may improve our ability to target chemoprevention. We investigated the contributions of sex hormones to the discrimination of the Breast Cancer Surveillance Consortium (BCSC) risk model and a polygenic risk score comprised of 83 single nucleotide polymorphisms. We conducted a nested case-control study of 110 women with ER-positive breast cancers and 214 matched controls within a mammography screening cohort. Participants were postmenopausal and not on hormonal therapy. The associations of estradiol, estrone, testosterone, and sex hormone binding globulin with ER-positive breast cancer were evaluated using conditional logistic regression. We assessed the individual and combined discrimination of estradiol, the BCSC risk score, and polygenic risk score using the area under the receiver operating characteristic curve (AUROC). Of the sex hormones assessed, estradiol (OR 3.64, 95% CI 1.64-8.06 for top vs bottom quartile), and to a lesser degree estrone, was most strongly associated with ER-positive breast cancer in unadjusted analysis. The BCSC risk score (OR 1.32, 95% CI 1.00-1.75 per 1% increase) and polygenic risk score (OR 1.58, 95% CI 1.06-2.36 per standard deviation) were also associated with ER-positive cancers. A model containing the BCSC risk score, polygenic risk score, and estradiol levels showed good discrimination for ER-positive cancers (AUROC 0.72, 95% CI 0.65-0.79), representing a significant improvement over the BCSC risk score (AUROC 0.58, 95% CI 0.50-0.65). Adding estradiol and a polygenic risk score to a clinical risk model improves discrimination for postmenopausal ER-positive breast cancers.

Identification of Insulin-Like Growth Factor-I Receptor (IGF-IR) Gene Promoter-Binding Proteins in Estrogen Receptor (ER)-Positive and ER-Depleted Breast Cancer Cells

International Nuclear Information System (INIS)

Sarfstein, Rive; Belfiore, Antonino; Werner, Haim

2010-01-01

The insulin-like growth factor I receptor (IGF-IR) has been implicated in the etiology of breast cancer. Overexpression of the IGF-IR gene is a typical feature of most primary breast cancers, whereas low IGF-IR levels are seen at advanced stages. Hence, evaluation of IGF-IR levels might be important for assessing prognosis. In the present study, we employed a proteomic approach based on DNA affinity chromatography followed either by mass spectroscopy (MS) or Western blot analysis to identify transcription factors that may associate with the IGF-IR promoter in estrogen receptor (ER)-positive and ER-depleted breast cancer cells. A biotinylated IGF-IR promoter fragment was bound to streptavidin magnetic beads and incubated with nuclear extracts of breast cancer cells. IGF-IR promoter-binding proteins were eluted with high salt and analyzed by MS and Western blots. Among the proteins that were found to bind to the IGF-IR promoter we identified zinc finger transcription factors Sp1 and KLF6, ER-α, p53, c-jun, and poly (ADP-ribosylation) polymerase. Furthermore, chromatin immune-precipitation (ChIP) analysis confirmed the direct in vivo binding of some of these transcription factors to IGF-IR promoter DNA. The functional relevance of binding data was assessed by cotransfection experiments with specific expression vectors along with an IGF-IR promoter reporter. In summary, we identified nuclear proteins that are potentially responsible for the differential expression of the IGF-IR gene in ER-positive and ER-depleted breast cancer cells

Identification of Insulin-Like Growth Factor-I Receptor (IGF-IR) Gene Promoter-Binding Proteins in Estrogen Receptor (ER)-Positive and ER-Depleted Breast Cancer Cells

Energy Technology Data Exchange (ETDEWEB)

Sarfstein, Rive [Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978 (Israel); Belfiore, Antonino [Department of Clinical and Experimental Medicine, University Magna Graecia of Catanzaro, Catanzaro 88100 (Italy); Werner, Haim, E-mail: hwerner@post.tau.ac.il [Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978 (Israel)

2010-03-25

The insulin-like growth factor I receptor (IGF-IR) has been implicated in the etiology of breast cancer. Overexpression of the IGF-IR gene is a typical feature of most primary breast cancers, whereas low IGF-IR levels are seen at advanced stages. Hence, evaluation of IGF-IR levels might be important for assessing prognosis. In the present study, we employed a proteomic approach based on DNA affinity chromatography followed either by mass spectroscopy (MS) or Western blot analysis to identify transcription factors that may associate with the IGF-IR promoter in estrogen receptor (ER)-positive and ER-depleted breast cancer cells. A biotinylated IGF-IR promoter fragment was bound to streptavidin magnetic beads and incubated with nuclear extracts of breast cancer cells. IGF-IR promoter-binding proteins were eluted with high salt and analyzed by MS and Western blots. Among the proteins that were found to bind to the IGF-IR promoter we identified zinc finger transcription factors Sp1 and KLF6, ER-α, p53, c-jun, and poly (ADP-ribosylation) polymerase. Furthermore, chromatin immune-precipitation (ChIP) analysis confirmed the direct in vivo binding of some of these transcription factors to IGF-IR promoter DNA. The functional relevance of binding data was assessed by cotransfection experiments with specific expression vectors along with an IGF-IR promoter reporter. In summary, we identified nuclear proteins that are potentially responsible for the differential expression of the IGF-IR gene in ER-positive and ER-depleted breast cancer cells.

Advanced breast cancer rates in the epoch of service screening: The 400,000 women cohort study from Italy.

Science.gov (United States)

Puliti, Donella; Bucchi, Lauro; Mancini, Silvia; Paci, Eugenio; Baracco, Susanna; Campari, Cinzia; Canuti, Debora; Cirilli, Claudia; Collina, Natalina; Conti, Giovanni Maria; Di Felice, Enza; Falcini, Fabio; Michiara, Maria; Negri, Rossella; Ravaioli, Alessandra; Sassoli De' Bianchi, Priscilla; Serafini, Monica; Zorzi, Manuel; Caldarella, Adele; Cataliotti, Luigi; Zappa, Marco

2017-04-01

The objective of this study was to evaluate if mammography screening attendance is associated with a reduction in late-stage breast cancer incidence. The cohort included over 400,000 Italian women who were first invited to participate in regional screening programmes during the 1990s and were followed for breast cancer incidence for 13 years. We obtained individual data on their exposure to screening and correlated this with total and stage-specific breast cancer incidence. Socio-economic status and pre-screening incidence data were used to assess the presence of self-selection bias. Overall, screening attendance was associated with a 10% excess risk of in situ and invasive breast cancer (IRR = 1.10; 95% confidence interval (CI): 1.06-1.14), which dropped to 5% for invasive cancers only (IRR = 1.05; 95% CI: 1.01-1.09). There were significant reductions among attenders for specific cancer stages; we observed a 39% reduction for T2 or larger (IRR = 0.61; 95% CI: 0.57-0.66), 19% for node positives (IRR = 0.81; 95% CI: 0.76-0.86) and 28% for stage II and higher (IRR = 0.72; 95% CI: 0.68-0.76). Our data suggest that the presence of self-selection bias is limited and, overall, invited women experienced a 17% reduction of advanced cancers compared with pre-screening rates. Comparing attenders' and non-attenders' stage-specific breast cancer incidence, we have estimated that screening attendance is associated with a reduction of nearly 30% for stages II+. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prospective Assessment of Optimal Individual Position (Prone Versus Supine) for Breast Radiotherapy: Volumetric and Dosimetric Correlations in 100 Patients

International Nuclear Information System (INIS)

Lymberis, Stella C.; Wyngaert, John Keith de; Parhar, Preeti; Chhabra, Arpit M.; Fenton-Kerimian, Maria; Chang Jengwha; Hochman, Tsivia; Guth, Amber; Roses, Daniel; Goldberg, Judith D.; Formenti, Silvia C.

2012-01-01

Purpose: Damage to heart and lung from breast radiotherapy is associated with increased cardiovascular mortality and lung cancer development. We conducted a prospective study to evaluate which position is best to spare lung and heart from radiotherapy exposure. Methods and Materials: One hundred consecutive Stage 0–IIA breast cancer patients consented to participate in a research trial that required two computed tomography simulation scans for planning both supine and prone positions. The optimal position was defined as that which best covered the contoured breast and tumor bed while it minimized critical organ irradiation, as quantified by the in-field heart and lung volume. The trial was designed to plan the first 100 patients in each position to study correlations between in-field volumes of organs at risk and dose. Results: Fifty-three left and 47 right breast cancer patients were consecutively accrued to the trial. In all patients, the prone position was optimal for sparing lung volume compared to the supine setup (mean lung volume reduction was 93.5 cc for right and 103.6 cc for left breast cancer patients). In 46/53 (87%) left breast cancer patients best treated prone, in-field heart volume was reduced by a mean of 12 cc and by 1.8 cc for the other 7/53 (13%) patients best treated supine. As predicted, supine-prone differences in in-field volume and mean dose of heart and lung were highly correlated (Spearman's correlation coefficient for left breast cancer patients was 0.90 for heart and 0.94 for lung and 0.92 for right breast cancer patients for lung). Conclusions: Prone setup reduced the amount of irradiated lung in all patients and reduced the amount of heart volume irradiated in 87% of left breast cancer patients. In-field organ volume is a valid surrogate for predicting dose; the trial continued to the planned target of 400.

Expression level of novel tumor suppressor gene FATS is associated with the outcome of node positive breast cancer

Institute of Scientific and Technical Information of China (English)

ZHANG Jun; GU Lin; ZHAO Lu-jun; ZHANG Xi-feng; QIU Li; LI Zheng

2011-01-01

Background Recently, we reported the identification of a previously uncharacterized and evolutionarily conserved gene, fragile-site associated tumor suppressor (FATS), at a frequently deleted region in irradiation (IR)-induced tumors.However, the role of FATS in breast cancer development and its clinical significance has not been defined. The aim of this study was to determine the role of FA7S in breast cancer development and to evaluate its clinical significance in breast cancer.Methods The expression level of FATS mRNA was determined in 106 breast carcinomas and 23 paired normal breast tissues using quantitative real time reverse transcription-polymerase chain reaction (RT-PCR). The relationship between FATS expression and clinicopathological parameters were also analyzed.Results The mRNA level of FATS was down-regulated in breast cancer compared with paired normal tissues. Low expression of FATS was correlated with high nuclear grade. There was a tendency to a favorable outcome for patients with high expression of FATS (P=0.346). However, low expression of FATS was associated with poor outcome of breast cancer patients with node positive (P=0.011). Furthermore, the mRNA level of FATS showed an independent value in predicting the outcome of breast cancer patients with positive lymph nodes.Conclusion FATS is involved in the carcinogenesis and development of breast cancer and could be a potential biomarker and prognostic factor for breast cancer therapy.

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib.

Science.gov (United States)

Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

2017-01-01

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib.

Efficacy and tolerability of high dose "ethinylestradiol" in post-menopausal advanced breast cancer patients heavily pre-treated with endocrine agents

OpenAIRE

Agrawal, Amit; Robertson, John FR; Cheung, KL

2006-01-01

Abstract Background High dose estrogens (HDEs) were frequently used as endocrine agents prior to the introduction of tamoxifen which carries fewer side effects. Due to the development of resistance to available endocrine agents in almost all women with metastatic breast cancer, interest has renewed in the use of HDEs as yet another endocrine option that may have activity. We report our experience with one of the HDEs ("ethinylestradiol" 1 mg daily) in advanced breast cancer (locally advanced ...

Breast cancer in Kumasi, Ghana

International Nuclear Information System (INIS)

Ohene-Yeboah, M.; Adjei, E.

2012-01-01

Breast cancer is the leading cause of cancer deaths in Ghanaian women.To describes the characteristics of breast cancer patients attending the Komfo Anokye Teaching Hospital in Kumasi, Ghana.The study was conducted at the Komfo Anokye Teaching Hospital. Between July 1st 2004 and June 30th 2009 patients presenting with breast lumps were assessed by clinical examination, imaging studies and pathological examination. Relevant clinical and pathological were recorded prospectively data on all patients with microscopically proven breast cancer. The cancers were graded according to the modified Bloom-Richardson system. Tissue immunoperoxidase stains for oestrogen, progesterone receptors and c-erb2 oncogene were performed with commercially prepared antigens and reagents.Nineteen thousand four hundred and twenty – three (19,423) patients were seen during the study period. There were 330 (1.7%) patients with histologically proven breast cancer. The mean age was 49.1 years. A palpable breast lump was detected in 248 patients (75.2%). Two hundred and eighty –one patients (85.2%) presented with Stages III and IV , 271 (82.1%) invasive and 230 ( 85.2%) high grade carcinomas. Oestrogen and progesterone receptors were positive in 32 and 9 cases respectively. Her2 protein was positive in 11 cases. In Kumasi, as in other parts of Ghana, breast cancer affects mostly young pre-menopausal who present with advanced disease. The cancers have unfavourable prognostic features and are unlikely to respond to hormonal therapy. (au)

Anti-metastasis activity of black rice anthocyanins against breast cancer: analyses using an ErbB2 positive breast cancer cell line and tumoral xenograft model.

Science.gov (United States)

Luo, Li-Ping; Han, Bin; Yu, Xiao-Ping; Chen, Xiang-Yan; Zhou, Jie; Chen, Wei; Zhu, Yan-Feng; Peng, Xiao-Li; Zou, Qiang; Li, Sui-Yan

2014-01-01

Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.

Novel HER2 Aptamer Selectively Delivers Cytotoxic Drug to HER2-positive Breast Cancer Cells in Vitro

Directory of Open Access Journals (Sweden)

Liu Zhe

2012-07-01

Full Text Available Abstract Background Aptamer-based tumor targeted drug delivery system is a promising approach that may increase the efficacy of chemotherapy and reduce the related toxicity. HER2 protein is an attractive target for tumor-specific drug delivery because of its overexpression in multiple malignancies, including breast, gastric, ovarian, and lung cancers. Methods In this paper, we developed a new HER2 aptamer (HB5 by using systematic evolution of ligands by exponential enrichment technology (SELEX and exploited its role as a targeting ligand for delivering doxorubicin (Dox to breast cancer cells in vitro. Results The selected aptamer was an 86-nucleotide DNA molecule that bound to an epitope peptide of HER2 with a Kd of 18.9 nM. The aptamer also bound to the extracellular domain (ECD of HER2 protein with a Kdof 316 nM, and had minimal cross reactivity to albumin or trypsin. In addition, the aptamer was found to preferentially bind to HER2-positive but not HER2-negative breast cancer cells. An aptamer-doxorubicin complex (Apt-Dox was formulated by intercalating Dox into the DNA structure of HB5. The Apt-Dox complex could selectively deliver Dox to HER2-positive breast cancer cells while reducing the drug intake by HER2-negative cells in vitro. Moreover, Apt-Dox retained the cytotoxicity of Dox against HER2-positive breast cancer cells, but reduced the cytotoxicity to HER2-negative cells. Conclusions The results suggest that the selected HER2 aptamer may have application potentials in targeted therapy against HER2-positive breast cancer cells.

Ifosfamide, mesna and epirubicin as second-line chemotherapy in advanced breast cancer.

Science.gov (United States)

Kiraz, S; Baltali, E; Güler, N; Barista, I; Benekli, M; Celik, I; Güllü, I H; Kars, A; Tekuzman, G; Firat, D

1996-08-01

The ifosfamide, mesna and epirubicin (IMEpi) combination is administered to 16 patients having advanced metastatic breast carcinoma as second-line chemotherapy. We observed complete response in 6%, partial response in 44% (total overall response rate of 50%), stable disease in 12% and progressive disease in the remaining 38% of the patients. The median remission duration in responders was calculated to be 9.6 months. IMEpi regimen had a tolerable toxicity profile including alopecia, nausea and vomiting, microscopic hematuria, leukopenia and neurotoxicity in which serious complications necessitating discontinuation of the chemotherapy were not encountered. It might be concluded that IMEpi chemotherapy combination is an effective alternative among schedules in the management of patients with stage IV breast carcinoma without serious side effects.

A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1).

Science.gov (United States)

Bonnefoi, H; Grellety, T; Tredan, O; Saghatchian, M; Dalenc, F; Mailliez, A; L'Haridon, T; Cottu, P; Abadie-Lacourtoisie, S; You, B; Mousseau, M; Dauba, J; Del Piano, F; Desmoulins, I; Coussy, F; Madranges, N; Grenier, J; Bidard, F C; Proudhon, C; MacGrogan, G; Orsini, C; Pulido, M; Gonçalves, A

2016-05-01

Several expression array studies identified molecular apocrine breast cancer (BC) as a subtype that expresses androgen receptor (AR) but not estrogen receptor α. We carried out a multicentre single-arm phase II trial in women with AR-positive, estrogen, progesterone receptor and HER2-negative (triple-negative) metastatic or inoperable locally advanced BC to assess the efficacy and safety of abiraterone acetate (AA) plus prednisone. Patients with a metastatic or locally advanced, centrally reviewed, triple-negative and AR-positive (≥10% by immunohistochemistry, IHC) BC were eligible. Any number of previous lines of chemotherapy was allowed. AA (1000 mg) was administered once a day with prednisone (5 mg) twice a day until disease progression or intolerance. The primary end point was clinical benefit rate (CBR) at 6 months defined as the proportion of patients presenting a complete response (CR), partial response (PR) or stable disease (SD) ≥6 months. Secondary end points were objective response rate (ORR), progression-free survival (PFS) and safety. One hundred and forty-six patients from 27 centres consented for IHC central review. Of the 138 patients with sufficient tissue available, 53 (37.6%) were AR-positive and triple-negative, and 34 of them were included from July 2013 to December 2014. Thirty patients were eligible and evaluable for the primary end point. The 6-month CBR was 20.0% [95% confidence interval (CI) 7.7%-38.6%], including 1 CR and 5 SD ≥6 months, 5 of them still being under treatment at the time of analysis (6.4+, 9.2+, 14.5+, 17.6+, 23.4+ months). The ORR was 6.7% (95% CI 0.8%-22.1%). The median PFS was 2.8 months (95% CI 1.7%-5.4%). Fatigue, hypertension, hypokalaemia and nausea were the most common drug-related adverse events; the majority of them being grade 1 or 2. AA plus prednisone treatment is beneficial for some patients with molecular apocrine tumours and five patients are still on treatment. NCT01842321. © The Author 2016

ABP 980: promising trastuzumab biosimilar for HER2-positive breast cancer.

Science.gov (United States)

Paplomata, Elisavet; Nahta, Rita

2018-03-01

Approval of the HER2-targeted antibody trastuzumab dramatically improved outcomes for patients with HER2-positive breast cancer. Multiple trastuzumab biosimilars, including ABP 980, are in clinical development. Biosimilars are not identical to the reference biologic, but exhibit equivalence and safety in analytical and clinical studies. Areas covered: A brief introduction to trastuzumab, overview of trastuzumab biosimilars, and detailed review of ABP 980 preclinical and clinical studies are included. We searched PubMed and 2016-2017 ASCO and ESMO conference proceedings for 'ABP 980' or 'trastuzumab biosimilar'. 'ABP 980 and breast cancer' or 'trastuzumab biosimilar and breast cancer' were used to search clinicaltrials.gov for phase III trials. Analytical studies of ABP 980 pharmacokinetics (PK) or pharmacodynamics (PD), phase I studies of ABP 980 safety and PK/PD, and phase III studies of clinical efficacy vs trastuzumab are included. Expert opinion: Questions remain regarding long-term impact of biosimilars on overall healthcare costs, insurance coverage of multiple approved biosimilars, and extensive clinical safety and efficacy follow-up. By producing a competitive market, trastuzumab biosimilars are anticipated to improve access to standard of care therapies, although real-world evidence remains to be obtained. Increased global access to HER2-targeted therapy may eventually alter the landscape of breast cancer and survival rates.

Timing of radiotherapy (RT) and chemotherapy (CT) following breast conserving surgery (BCS) for patients with node-positive breast cancer

Energy Technology Data Exchange (ETDEWEB)

Wallgren, A; Bernier, J; Gelber, RD; Roncadin, M; Joseph, D; Castiglione, M

1995-07-01

Purpose: To evaluate the effects of delaying RT until after different durations of initial courses of CT for pts with node-positive breast cancer. Methods and Materials: From 7/86-4/93, the IBCSG enrolled 1475 eligible node-positive pre- and perimenopausal pts in Trial 6 and 1212 eligible node-positive postmenopausal pts in Trial 7. Pts in Trial 6 were randomized to receive one of four treatments: (1) CMF x 6 cycles (1 cycle=28 days; cyclophosphamide 100 mg/m{sup 2} orally days 1-14; methotrexate 40 mg/m{sup 2} iv. days 1 and 8; 5-fluorouracil 600 mg/m{sup 2} iv days 1 and 8); (2) CMF x 6 cycles followed by single cycles at months 9, 12 and 15; (3) CMF x 3 cycles; (4) CMF x 3 followed by single cycles at months 6, 9 and 12. Pts in Trial 7 were randomized to receive one of four treatments: (5) tamoxifen (TAM: 20 mg daily) plus CMF x 3 cycles, months 1,2,3; (6) TAM plus CMF x 3 plus single cycles of CMF at months 9, 12 and 15; (7) TAM alone for five yrs; (8) TAM plus single cycles of CMF at months 9, 12 and 15. The randomizations were stratified according to type of surgery; 434 pts in Trial 6 (29%) and 285 pts in Trial 7 (24%) had breast conserving surgery and are the subjects of this report. Pts were randomized to receive RT to the conserved breast AFTER completing the initial block of CT if assigned; i.e. month 7 for arms 1 and 2; month 4 for arms 3 and 4; month 4 for arms 5 and 6; month 1 for arms 7 and 8. 24% of pts in Trial 6 and 27% of pts in Trial 7 had four or more axillary lymph nodes involved. Possible prognostic factors including age, estrogen receptor status, nodal status and tumor size were balanced across randomized groups. Four-year actuarial total failure rates (failure at any site), risks of developing distant metastases (DM) (at any time during observation), and overall survival (OS) were estimated using the Kaplan-Meier method. To avoid potential bias due to competing causes of failure, only patients who could be followed for at least 4 years

Nuclear HER4 mediates acquired resistance to trastuzumab and is associated with poor outcome in HER2 positive breast cancer

Science.gov (United States)

Nafi, Siti Norasikin Mohd; Generali, Daniele; Kramer-Marek, Gabriela; Gijsen, Merel; Strina, Carla; Cappelletti, Mariarosa; Andreis, Daniele; Haider, Syed; Li, Ji-Liang; Bridges, Esther; Capala, Jacek; Ioannis, Roxanis; Harris, Adrian L; Kong, Anthony

2014-01-01

The role of HER4 in breast cancer is controversial and its role in relation to trastuzumab resistance remains unclear. We showed that trastuzumab treatment and its acquired resistance induced HER4 upregulation, cleavage and nuclear translocation. However, knockdown of HER4 by specific siRNAs increased trastuzumab sensitivity and reversed its resistance in HER2 positive breast cancer cells. Preventing HER4 cleavage by a γ-secretase inhibitor and inhibiting HER4 tyrosine kinase activity by neratinib decreased trastuzumab-induced HER4 nuclear translocation and enhanced trastuzumab response. There was also increased nuclear HER4 staining in the tumours from BT474 xenograft mice and human patients treated with trastuzumab. Furthermore, nuclear HER4 predicted poor clinical response to trastuzumab monotherapy in patients undergoing a window study and was shown to be an independent poor prognostic factor in HER2 positive breast cancer. Our data suggest that HER4 plays a key role in relation to trastuzumab resistance in HER2 positive breast cancer. Therefore, our study provides novel findings that HER4 activation, cleavage and nuclear translocation influence trastuzumab sensitivity and resistance in HER2 positive breast cancer. Nuclear HER4 could be a potential prognostic and predictive biomarker and understanding the role of HER4 may provide strategies to overcome trastuzumab resistance in HER2 positive breast cancer. PMID:25153719

Familial risks and estrogen receptor-positive breast cancer in Hong Kong Chinese women.

Science.gov (United States)

Tse, Lap Ah; Li, Mengjie; Chan, Wing-cheong; Kwok, Chi-hei; Leung, Siu-lan; Wu, Cherry; Yu, Ignatius Tak-sun; Yu, Wai-cho; Lao, Xiangqian; Wang, Xiaorong; Wong, Carmen Ka-man; Lee, Priscilla Ming-yi; Wang, Feng; Yang, Xiaohong Rose

2015-01-01

The role of family history to the risk of breast cancer was analyzed by incorporating menopausal status in Hong Kong Chinese women, with a particular respect to the estrogen receptor-positive (ER+) type. Seven hundred and forty seven breast cancer incident cases and 781 hospital controls who had completed information on family cancer history in first-degree relatives (nature father, mother, and siblings) were recruited. Odds ratio for breast cancer were calculated by unconditional multiple logistic regression, stratified by menopausal status (a surrogate of endogenous female sex hormone level and age) and type of relative affected with the disease. Further subgroup analysis by tumor type according to ER status was investigated. Altogether 52 (6.96%) breast cancer cases and 23 (2.95%) controls was found that the patients' one or more first-degree relatives had a history of breast cancer, showing an adjusted odds ratio (OR) of 2.41 (95%CI: 1.45-4.02). An excess risk of breast cancer was restricted to the ER+ tumor (OR = 2.43, 95% CI: 1.38-4.28), with a relatively higher risk associated with an affected mother (OR = 3.97, 95%CI: 1.46-10.79) than an affected sister (OR = 2.06, 95%CI: 1.07-3.97), while the relative risk was more prominent in the subgroup of pre-menopausal women. Compared with the breast cancer overall, the familial risks to the ER+ tumor increased progressively with the number of affected first-degree relatives. This study provides new insights on a relationship between family breast cancer history, menopausal status, and the ER+ breast cancer. A separate risk prediction model for ER+ tumor in Asian population is desired.

The role of a prone setup in breast radiation therapy.

Science.gov (United States)

Huppert, Nelly; Jozsef, Gabor; Dewyngaert, Keith; Formenti, Silvia Chiara

2011-01-01

Most patients undergoing breast conservation therapy receive radiotherapy in the supine position. Historically, prone breast irradiation has been advocated for women with large pendulous breasts in order to decrease acute and late toxicities. With the advent of CT planning, the prone technique has become both feasible and reproducible. It was shown to be advantageous not only for women with larger breasts but in most patients since it consistently reduces, if not eliminates, the inclusion of heart and lung within the field. The prone setup has been accepted as the best localizing position for both MRI and stereotactic biopsy, but its adoption has been delayed in radiotherapy. New technological advances including image-modulated radiation therapy and image-guided radiation therapy have made possible the exploration of accelerated fractionation schemes with a concomitant boost to the tumor bed in the prone position, along with better imaging and verification of reproducibility of patient setup. This review describes some of the available techniques for prone breast radiotherapy and the available experience in their application. The NYU prone breast radiotherapy approach is discussed, including a summary of the results from several prospective trials.

The role of a prone setup in breast radiation therapy

Directory of Open Access Journals (Sweden)

Nelly eHuppert

2011-10-01

Full Text Available Most patients undergoing breast conservation therapy (BCT receive radiotherapy in the supine position. Historically, prone breast irradiation has been advocated for women with large pendulous breasts in order to decrease acute and late toxicities. With the advent of CT planning, the prone technique has become both feasible and reproducible. It was shown to be advantageous not only for women with larger breasts but in most patients since it consistently reduces, if not eliminates, the inclusion of heart and lung within the field. The prone setup has been accepted as the best localizing position for both MRI and stereotactic biopsy, but its adoption has been delayed in radiotherapy. New technological advances including image-modulated radiation therapy (IMRT and image-guided radiation therapy (IGRT have made possible the exploration of accelerated fractionation schemes with a concomitant boost to the tumor bed in the prone position, along with better imaging and verification of reproducibility of patient setup. This review describes some of the available techniques for prone breast radiotherapy and the available experience in their application. The NYU prone breast radiotherapy approach is discussed, including a summary of the results from several prospective trials.

The Role of a Prone Setup in Breast Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Huppert, Nelly; Jozsef, Gabor; DeWyngaert, Keith; Formenti, Silvia Chiara, E-mail: silvia.formenti@nyumc.org [Department of Radiation Oncology, New York University School of Medicine, New York University Langone Medical Center, New York, NY (United States)

2011-10-11

Most patients undergoing breast conservation therapy receive radiotherapy in the supine position. Historically, prone breast irradiation has been advocated for women with large pendulous breasts in order to decrease acute and late toxicities. With the advent of CT planning, the prone technique has become both feasible and reproducible. It was shown to be advantageous not only for women with larger breasts but in most patients since it consistently reduces, if not eliminates, the inclusion of heart and lung within the field. The prone setup has been accepted as the best localizing position for both MRI and stereotactic biopsy, but its adoption has been delayed in radiotherapy. New technological advances including image-modulated radiation therapy and image-guided radiation therapy have made possible the exploration of accelerated fractionation schemes with a concomitant boost to the tumor bed in the prone position, along with better imaging and verification of reproducibility of patient setup. This review describes some of the available techniques for prone breast radiotherapy and the available experience in their application. The NYU prone breast radiotherapy approach is discussed, including a summary of the results from several prospective trials.

Prolactin suppresses a progestin-induced CK5-positive cell population in luminal breast cancer through inhibition of progestin-driven BCL6 expression

Science.gov (United States)

Sato, Takahiro; Tran, Thai H.; Peck, Amy R.; Girondo, Melanie A.; Liu, Chengbao; Goodman, Chelain R.; Neilson, Lynn M.; Freydin, Boris; Chervoneva, Inna; Hyslop, Terry; Kovatich, Albert J.; Hooke, Jeffrey A.; Shriver, Craig D.; Fuchs, Serge Y.; Rui, Hallgeir

2014-01-01

Prolactin controls the development and function of milk-producing breast epithelia but also supports growth and differentiation of breast cancer, especially luminal subtypes. A principal signaling mediator of prolactin, Stat5, promotes cellular differentiation of breast cancer cells in vitro, and loss of active Stat5 in tumors is associated with anti-estrogen therapy failure in patients. In luminal breast cancer progesterone induces a cytokeratin-5 (CK5)-positive basal cell-like population. This population possesses characteristics of tumor stem cells including quiescence, therapy-resistance, and tumor-initiating capacity. Here we report that prolactin counteracts induction of the CK5-positive population by the synthetic progestin R5020 in luminal breast cancer cells both in vitro and in vivo. CK5-positive cells were chemoresistant as determined by four-fold reduced rate of apoptosis following docetaxel exposure. Progestin-induction of CK5 was preceded by marked up-regulation of BCL6, an oncogene and transcriptional repressor critical for the maintenance of leukemia-initiating cells. Knockdown of BCL6 prevented induction of CK5-positive cell population by progestin. Prolactin suppressed progestin-induced BCL6 through Jak2-Stat5 but not Erk- or Akt-dependent pathways. In premenopausal but not postmenopausal patients with hormone receptor-positive breast cancer, tumor protein levels of CK5 correlated positively with BCL6, and high BCL6 or CK5 protein levels were associated with unfavorable clinical outcome. Suppression of progestin-induction of CK5-positive cells represents a novel pro-differentiation effect of prolactin in breast cancer. The present progress may have direct implications for breast cancer progression and therapy since loss of prolactin receptor-Stat5 signaling occurs frequently and BCL6 inhibitors currently being evaluated for lymphomas may have value for breast cancer. PMID:23708665

[Chemical pollution and breast milk: Taking positions].

Science.gov (United States)

Díaz-Gómez, N M; Ares, S; Hernández-Aguilar, M T; Ortega-García, J A; Paricio-Talayero, J M; Landa-Rivera, L

2013-12-01

Chemical pollution affects all ecosystems of our planet. Human milk has been used as a biomarker of environmental pollution as, due to bioaccumulation processes in fat tissue, many chemical compounds reach measurable concentrations that can be readily tested in breast milk. Quite frequently information about the presence of contaminants in breast milk appears in the media, leading to misunderstanding among parents and health professionals, and in some cases breastfeeding the child is stopped. In this article, the Breastfeeding Committee of the Spanish Association of Paediatrics stresses the importance of promoting breastfeeding as the healthiest option, because its benefits clearly outweigh any health risks associated with chemical contaminants in breast milk. Breast milk contains protective factors that counteract the potential effects related to prenatal exposure to environmental pollutants. This article summarises the key recommendations to reduce the level of chemical contaminants in breast milk. It also highlights the importance of government involvement in the development of programs to eliminate or reduce chemical contamination of food and the environment. In this way, the negative effects on child health resulting from exposure to these toxic compounds through the placenta and breast milk may be prevented. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

CYBPET: a cylindrical PET system for breast imaging

Energy Technology Data Exchange (ETDEWEB)

Karimian, A. [Amirkabir University of Technology, Tehran (Iran, Islamic Republic of) and Nuclear Research Center for Agriculture and Medicine (NRCAM-AEOI), P.O. BOX. (31485-498), Karaj, Iran, Islamic Republic of and Department of Experimental Medicine and Pathology, University of Rome, La Sapienza, Rome (Italy)]. E-mail: akarimian@nrcam.org; Thompson, C.J. [Montreal Neurological Institute, McGill University, Montreal QC (Canada); Sarkar, S. [Medical physics Department of Tehran University of Medical Sciences and (RCSTIM), Tehran (Iran, Islamic Republic of); Raisali, G. [Nuclear Research Center for Agriculture and Medicine (NRCAM-AEOI), P.O. BOX. (31485-498), Karaj (Iran, Islamic Republic of); Pani, R. [Department of Experimental Medicine and Pathology, University of Rome La Sapienza, Rome (Italy); Davilu, H. [Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Sardari, D. [Amirkabir University of Technology, Tehran (Iran, Islamic Republic of)

2005-06-11

We propose a Cylindrical Breast PET (CYBPET) system for breast imaging with patients in the prone position. An individual pendulous breast is covered by thin plastic to provide reduced pressure fixation and surrounded by the crystals inside the CYBPET ring. Each breast is imaged separately. The rest of the body is shielded properly to minimize the contribution of scattered photons from the other breast and the rest of the body. To compare the CYBPET with whole-body PET (WB-PET) the simulations of CYBPET and a WB-PET (GE-Advance) for a 10 mm tumor inside the breast with a lesion to background (breast) activity concentration of 6 to 1 were made. The noise effective count rate (NECR) of CYBPET is about twice that of WB-PET at activity concentrations less than 3.1 {mu}Ci/cc. The spatial resolution of CYBPET is better by 25% than the WB-PET.

CYBPET: a cylindrical PET system for breast imaging

International Nuclear Information System (INIS)

Karimian, A.; Thompson, C.J.; Sarkar, S.; Raisali, G.; Pani, R.; Davilu, H.; Sardari, D.

2005-01-01

We propose a Cylindrical Breast PET (CYBPET) system for breast imaging with patients in the prone position. An individual pendulous breast is covered by thin plastic to provide reduced pressure fixation and surrounded by the crystals inside the CYBPET ring. Each breast is imaged separately. The rest of the body is shielded properly to minimize the contribution of scattered photons from the other breast and the rest of the body. To compare the CYBPET with whole-body PET (WB-PET) the simulations of CYBPET and a WB-PET (GE-Advance) for a 10 mm tumor inside the breast with a lesion to background (breast) activity concentration of 6 to 1 were made. The noise effective count rate (NECR) of CYBPET is about twice that of WB-PET at activity concentrations less than 3.1 μCi/cc. The spatial resolution of CYBPET is better by 25% than the WB-PET

From Halsted to prevention and beyond: advances in the management of breast cancer during the twentieth century.

Science.gov (United States)

Fisher, B

1999-12-01

This commentary evaluates progress made in the treatment of breast cancer during the twentieth century. Most of the period from 1900 to 1970 was governed by the 'non-science' of anecdotalism and classical inductivism and was marked by the absence of a scientific gestalt. In keeping with the Halstedian concept that breast cancer was a local disease that spread throughout the body by contiguous extension and could be cured by more expansive surgery, the disease was treated with radical surgery. In 1950, however, a new era of enlightenment began to emerge. The awareness that there was a scientific process in which hypotheses generated from laboratory and clinical investigation could be tested by means of randomised clinical trials was a seminal advance, as were findings from studies that laid the groundwork for the modern era of steroid hormone action, including identification of oestrogen receptors. Expanding knowledge regarding tumour cell kinetics, tumour heterogeneity, and technological advances related to mammography and radiation therapy were also to play a role in making possible the advances in therapy that were subsequently to occur. In the past 30 years, as a result of laboratory and clinical investigation, the Halstedian thesis of cancer surgery was displaced by an alternative hypothesis that was supported by findings from subsequent clinical trials. A new paradigm governed surgery for breast cancer, and lumpectomy followed by radiation therapy became accepted practice. A second paradigm that governed the use of adjuvant systemic therapy arose as a result of laboratory and clinical investigation. Treating patients who were free of identifiable metastatic disease with systemic adjuvant therapy because some of them might develop distant disease in the future was a revolutionary departure from prior treatment strategy and became a new exemplar. Not only did the chemotherapy favourably alter the outcome of breast cancer patients, but the anti

Selective anti-proliferation of HER2-positive breast cancer cells by anthocyanins identified by high-throughput screening.

Directory of Open Access Journals (Sweden)

Weihua Liu

Full Text Available Overexpressed Human epidermal growth factor receptor 2 (HER2 drives the biology of 20% breast cancer and is a prediction of a poor prognosis for patients. HER2-targeted therapies significantly improve outcomes for HER2-positive patients. Traditional Chinese herbs/medicines have been used to treat breast cancer patients including HER2-positive patients in Asia for decades. Although the traditional medicines demonstrate efficacy in clinics for HER2-positive patients, the mechanism is largely unknown. In this article, we screened a 10,000 natural product library in 6 different cell lines representing breast cancer, and assessed the ability of each drug to cause cytotoxicity through a high-throughput screening approach. We have identified eight natural compounds that selectively inhibit the proliferation of HER2-positive cells. Two of the hit compounds, peonidin-3-glucoside and cyaniding-3-glucoside, are both extracts from black rice. They inhibit the phospho-HER2 and phospho-AKT and were confirmed to induce HER2-psotive breast cancer cells apoptosis both in vitro and in vivo. Peonidin-3-glucoside and cyaniding-3-glucoside treatments significantly reduced the tumor size and volume in vivo compared to the control group. There is no significant difference of antitumorgenic effects between peonidin-3-glucoside and cyaniding-3-glucoside treatments.

The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial.

Science.gov (United States)

Mohammadianpanah, Mohammad; Ashouri, Yaghoub; Hoseini, Sare; Amadloo, Niloofar; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Nasrolahi, Hamid; Mosalaei, Ahmad; Omidvari, Shapour; Ansari, Mansour; Mosleh-Shirazi, Mohammad Amin

2012-04-01

This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.

WDR26 in Advanced Breast Cancer: A Novel Regulator of the P13K/AKT Pathway

Science.gov (United States)

2017-10-01

5 2 1. Introduction: Breast cancer is the second most common cause of cancer death in women in the US. Despite recent advances in the...breakthrough both in our understanding of the molecular mechanisms that drive TNBC progression and in our effort to eliminate suffering and death caused by...that contribute to breast cancer growth and metastasis. Yet, it is not yet clear how to specifically target the PI3Kβ/AKT2 without causing wide

Role of Estrogen Receptor Signaling in Breast Cancer Metastasis

International Nuclear Information System (INIS)

Roy, S.S.; Vadlamudi, R.K.

2012-01-01

Metastatic breast cancer is a life-threatening stage of cancer and is the leading cause of death in advanced breast cancer patients. Estrogen signaling and the estrogen receptor (ER) are implicated in breast cancer progression, and the majority of the human breast cancers start out as estrogen dependent. Accumulating evidence suggests that ER signaling is complex, involving coregulatory proteins and extranuclear actions. ER-coregualtory proteins are tightly regulated under normal conditions with miss expression primarily reported in cancer. Deregulation of ER coregualtors or ER extranuclear signaling has potential to promote metastasis in ER-positive breast cancer cells. This review summarizes the emerging role of ER signaling in promoting metastasis of breast cancer cells, discusses the molecular mechanisms by which ER signaling contributes to metastasis, and explores possible therapeutic targets to block ER-driven metastasis

Fulvestrant radiosensitizes human estrogen receptor-positive breast cancer cells

International Nuclear Information System (INIS)

Wang, Jing; Yang, Qifeng; Haffty, Bruce G.; Li, Xiaoyan; Moran, Meena S.

2013-01-01

Highlights: ► Fulvestrant radiosensitizes MCF-7 cells. ► Fulvestrant increases G1 arrest and decreases S phase in MCF-7 cells. ► Fulvestrant down-regulates DNA-PKcs and RAD51 in MCF-7 cells. -- Abstract: The optimal sequencing for hormonal therapy and radiation are yet to be determined. We utilized fulvestrant, which is showing promise as an alternative to other agents in the clinical setting of hormonal therapy, to assess the cellular effects of concomitant anti-estrogen therapy (fulvestrant) with radiation (F + RT). This study was conducted to assess the effects of fulvestrant alone vs. F + RT on hormone-receptor positive breast cancer to determine if any positive or negative combined effects exist. The effects of F + RT on human breast cancer cells were assessed using MCF-7 clonogenic and tetrazolium salt colorimetric (MTT) assays. The assays were irradiated with a dose of 0, 2, 4, 6 Gy ± fulvestrant. The effects of F + RT vs. single adjuvant treatment alone on cell-cycle distribution were assessed using flow cytometry; relative expression of repair proteins (Ku70, Ku80, DNA-PKcs, Rad51) was assessed using Western Blot analysis. Cell growth for radiation alone vs. F + RT was 0.885 ± 0.013 vs. 0.622 ± 0.029 @2 Gy, 0.599 ± 0.045 vs. 0.475 ± 0.054 @4 Gy, and 0.472 ± 0.021 vs. 0.380 ± 0.018 @6 Gy RT (p = 0.003). While irradiation alone induced G2/M cell cycle arrest, the combination of F + RT induced cell redistribution in the G1 phase and produced a significant decrease in the proportion of cells in G2 phase arrest and in the S phase in breast cancer cells (p < 0.01). Furthermore, levels of repair proteins DNA-PKcs and Rad51 were significantly decreased in the cells treated with F + RT compared with irradiation alone. F + RT leads to a decrease in the surviving fraction, increased cell cycle arrest, down regulating of nonhomologous repair protein DNA-PKcs and homologous recombination repair protein RAD51. Thus, our findings suggest that F + RT

HER-2 positive and p53 negative breast cancers are associated with poor prognosis.

LENUS (Irish Health Repository)

2011-06-01

p53 and HER-2 coexpression in breast cancer has been controversial. These markers were tested using immunohistochemistry and HercepTest. HER-2 expression is related to reduced breast cancer survival (p = .02) . p53 expression relates to HER-2 expression (p = .029). Coexpression between p53 and HER-2 has no relation to prognosis. On univariate and multivariate analysis, combination of HER-2 positive and p53 negative expression was associated with a poor prognosis (p = .018 and p = .027, respectively), while the combination of HER-2 negative and p53 positive expression was associated with a favorable prognosis (p = .022 and p = .010, respectively). Therefore the expression of these markers should be considered collectively.

HER-2 positive and p53 negative breast cancers are associated with poor prognosis.

LENUS (Irish Health Repository)

2012-02-01

p53 and HER-2 coexpression in breast cancer has been controversial. These markers were tested using immunohistochemistry and HercepTest. HER-2 expression is related to reduced breast cancer survival (p = .02) . p53 expression relates to HER-2 expression (p = .029). Coexpression between p53 and HER-2 has no relation to prognosis. On univariate and multivariate analysis, combination of HER-2 positive and p53 negative expression was associated with a poor prognosis (p = .018 and p = .027, respectively), while the combination of HER-2 negative and p53 positive expression was associated with a favorable prognosis (p = .022 and p = .010, respectively). Therefore the expression of these markers should be considered collectively.

Analysis of false positive and false negative cytological diagnosis of breast lesions

International Nuclear Information System (INIS)

Jamal, Awtif A.; Mansoor, I.

2001-01-01

To study the reasons for interpretive errors in false negative and false positive diagnosis of breast carcinoma on fine needle aspiration cytology material. We reviewed only those cases in which cytohistological discrepancies were found, where the cytologic material was abnormal and to some extent misinterpreted or both. There was only one false negative case (false negative fraction 0.32%) proved histologically as ductal carcinoma and four false positive cases (false positive fraction 1.2%); 2 fibroadenoma; 1 fibrocystic disease; and 1 stromal fibrosis. Smears of the two false positive fibroadenoma cases showed very high cellularity, overcrowded clusters and frequent stripped nuclei. The fibrocystic case showed tight clusters of apocrine cells and sheets of loosely aggregated macrophages that were over interpreted. Smears of the false negative ductal carcinoma was hypocellular overall, and the cells showed minimal nuclear pleomorphism. Overcrowded clusters and hypercellular smears should be carefully assessed for uniformity of cells and detailed nuclear and cytomorphological features. If the full-blown malignant cytomorphological changes are not visible, a diagnosis of suspicious or inconclusive should be made and frozen section recommended before surgery. Hypocellularity and relatively nuclear monomorphism are the reasons for failure to diagnose malignant breast lesions. Careful attention should be paid to extreme nuclear monomorphism and absence of naked bipolar cells. A cytologically atypical or suspicious diagnosis together with positive radiological and clinical findings should suggest a diagnosis of malignancy. (author)

Everolimus plus exemestane as first-line therapy in HR⁺, HER2⁻ advanced breast cancer in BOLERO-2.

Science.gov (United States)

Beck, J Thaddeus; Hortobagyi, Gabriel N; Campone, Mario; Lebrun, Fabienne; Deleu, Ines; Rugo, Hope S; Pistilli, Barbara; Masuda, Norikazu; Hart, Lowell; Melichar, Bohuslav; Dakhil, Shaker; Geberth, Matthias; Nunzi, Martina; Heng, Daniel Y C; Brechenmacher, Thomas; El-Hashimy, Mona; Douma, Shyanne; Ringeisen, Francois; Piccart, Martine

2014-02-01

The present exploratory analysis examined the efficacy, safety, and quality-of-life effects of everolimus (EVE) + exemestane (EXE) in the subgroup of patients in BOLERO-2 whose last treatment before study entry was in the (neo)adjuvant setting. In BOLERO-2, patients with hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2-negative (HER2(-)) advanced breast cancer recurring/progressing after a nonsteroidal aromatase inhibitor (NSAI) were randomly assigned (2:1) to receive EVE (10 mg/day) + EXE (25 mg/day) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local assessment. Overall, 137 patients received first-line EVE + EXE (n = 100) or PBO + EXE (n = 37). Median PFS by local investigator assessment nearly tripled to 11.5 months with EVE + EXE from 4.1 months with PBO + EXE (hazard ratio = 0.39; 95 % CI 0.25-0.62), while maintaining quality of life. This was confirmed by central assessment (15.2 vs 4.2 months; hazard ratio = 0.32; 95 % CI 0.18-0.57). The marked PFS improvement in patients receiving EVE + EXE as first-line therapy for disease recurrence during or after (neo)adjuvant NSAI therapy supports the efficacy of this combination in the first-line setting. Furthermore, the results highlight the potential benefit of early introduction of EVE + EXE in the management of HR(+), HER2(-) advanced breast cancer in postmenopausal patients.

Familial risks and estrogen receptor-positive breast cancer in Hong Kong Chinese women.

Directory of Open Access Journals (Sweden)

Lap Ah Tse

Full Text Available The role of family history to the risk of breast cancer was analyzed by incorporating menopausal status in Hong Kong Chinese women, with a particular respect to the estrogen receptor-positive (ER+ type.Seven hundred and forty seven breast cancer incident cases and 781 hospital controls who had completed information on family cancer history in first-degree relatives (nature father, mother, and siblings were recruited. Odds ratio for breast cancer were calculated by unconditional multiple logistic regression, stratified by menopausal status (a surrogate of endogenous female sex hormone level and age and type of relative affected with the disease. Further subgroup analysis by tumor type according to ER status was investigated.Altogether 52 (6.96% breast cancer cases and 23 (2.95% controls was found that the patients' one or more first-degree relatives had a history of breast cancer, showing an adjusted odds ratio (OR of 2.41 (95%CI: 1.45-4.02. An excess risk of breast cancer was restricted to the ER+ tumor (OR = 2.43, 95% CI: 1.38-4.28, with a relatively higher risk associated with an affected mother (OR = 3.97, 95%CI: 1.46-10.79 than an affected sister (OR = 2.06, 95%CI: 1.07-3.97, while the relative risk was more prominent in the subgroup of pre-menopausal women. Compared with the breast cancer overall, the familial risks to the ER+ tumor increased progressively with the number of affected first-degree relatives.This study provides new insights on a relationship between family breast cancer history, menopausal status, and the ER+ breast cancer. A separate risk prediction model for ER+ tumor in Asian population is desired.

Confirmation of 5p12 as a susceptibility locus for progesterone-receptor- positive, lower grade breast cancer

NARCIS (Netherlands)

R.L. Milne (Roger); E.L. Goode (Ellen); M. García-Closas (Montserrat); F.J. Couch (Fergus); G. Severi (Gianluca); R. Hein (Rebecca); Z. Fredericksen (Zachary); N. Malats (Núria); M.P. Zamora (Pilar); J.I.A. Perez (Jose Ignacio Arias); J. Benítez (Javier); T. Dörk (Thilo); P. Schürmann (Peter); J.H. Karstens (Johann); P. Hillemanns (Peter); A. Cox (Angela); I.W. Brock (Ian); K.S. Elliot (Katherine); S.S. Cross (Simon); S. Seal (Sheila); C. Turnbull (Clare); A. Renwick (Anthony); N. Rahman (Nazneen); C-Y. Shen (Chen-Yang); J-C. Yu (Jyh-Cherng); C.-S. Huang (Chiun-Sheng); M.-F. Hou (Ming-Feng); B.G. Nordestgaard (Børge); S.E. Bojesen (Stig); C. Lanng (Charlotte); G.G. Alnæs (Grethe); V. Kristensen (Vessela); A.-L. Børrensen-Dale (Anne-Lise); J.L. Hopper (John); G.S. Dite (Gillian); C. Apicella (Carmel); M.C. Southey (Melissa); D. Lambrechts (Diether); B.T. Yesilyurt (Betül); O.A.M. Floris; K. Leunen; S. Sangrajrang (Suleeporn); V. Gaborieau (Valerie); P. Brennan (Paul); J.D. McKay (James); J. Chang-Claude (Jenny); S. Wang-Gohrke (Shan); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); M. Barile (Monica); G.G. Giles (Graham); L. Baglietto (Laura); E.M. John (Esther); A. Miron (Alexander); S.J. Chanock (Stephen); J. Lissowska (Jolanta); M.E. Sherman (Mark); J.D. Figueroa (Jonine); N.V. Bogdanova (Natalia); N.N. Antonenkova (Natalia); I.V. Zalutsky (Iosif); Y.I. Rogov (Yuri); P.A. Fasching (Peter); T. Bayer (T.); A.B. Ekici (Arif); M.W. Beckmann (Matthias); H. Brenner (Hermann); H. Müller (Heike); V. Arndt (Volker); C. Stegmaier (Christa); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A.M. Mulligan (Anna Marie); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J. Hartikainen (Jaana); A. Meindl (Alfons); J. Heil (Joerg); C.R. Bartram (Claus); R.K. Schmutzler (Rita); G. Thomas (Gilles); R.N. Hoover (Robert); O. Fletcher (Olivia); L.J. Gibson (Lorna); I. dos Santos Silva (Isabel); J. Peto (Julian); S. Nickels (Stefan); D. Flesch-Janys (Dieter); H. Anton-Culver (Hoda); A. Ziogas (Argyrios); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); M.K. Schmidt (Marjanka); A. Broeks (Annegien); L.J. van 't Veer (Laura); R.A.E.M. Tollenaar (Rob); P.D.P. Pharoah (Paul); A.M. Dunning (Alison); K.A. Pooley (Karen); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); B. Burwinkel (Barbara); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska (Katarzyna); K. Durda (Katarzyna); D. Kang (Daehee); K-Y. Yoo (Keun-Young); D-Y. Noh (Dong-Young); S.-H. Ahn (Sei-Hyun); D. Hunter (David); S.E. Hankinson (Susan); P. Kraft (Peter); S. Lindstrom (Stephen); X. Chen (Xiaoqing); J. Beesley (Jonathan); U. Hamann (Ute); V. Harth (Volker); C. Justenhoven (Christina); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); R.A. Oldenburg (Rogier); M.M.A. Tilanus-Linthorst (Madeleine); E.K. Khusnutdinova (Elza); M. Bermisheva (Marina); D. Prokofieva (Darya); A. Farahtdinova (Albina); J.E. Olson (Janet); X. Wang (Xing); M.K. Humphreys (Manjeet); Q. Wang (Qing); G. Chenevix-Trench (Georgia); D.F. Easton (Douglas)

2011-01-01

textabstractBackground: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer

{sup 18}F-FDG-PET/CT for systemic staging of patients with newly diagnosed ER-positive and HER2-positive breast cancer

Energy Technology Data Exchange (ETDEWEB)

Ulaner, Gary A.; Castillo, Raychel [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Weill Cornell Medical College, Department of Radiology, New York, NY (United States); Wills, Jonathan [Memorial Sloan Kettering Cancer Center, Department of Information Systems, New York, NY (United States); Goenen, Mithat; Goldman, Debra A. [Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States)

2017-08-15

This study assesses {sup 18}F-FDG-PET/CT for patients with newly diagnosed estrogen receptor-positive/human epidermal growth factor receptor-negative (ER+/HER2-) and human epidermal growth factor receptor-positive (HER2+) breast cancer. In this Institutional Review Board-approved retrospective study, our Healthcare Information System was screened for patients with ER+/HER2- and HER2+ breast cancer who underwent {sup 18}F-FDG-PET/CT prior to systemic or radiation therapy. The initial stage was determined from mammography, ultrasound, magnetic resonance imaging, and/or surgery.{sup 18}F-FDG-PET/CT was evaluated to identify unsuspected extra-axillary regional nodal and distant metastases. The proportion of patients upstaged overall and stratified by stage and receptor phenotypes was calculated along with confidence intervals (CI). A total of 238 patients with ER+/HER2- and 245 patients with HER2+ who met inclusion criteria were evaluated. For patients with ER+/HER2-breast cancer, {sup 18}F-FDG-PET/CT revealed unsuspected distant metastases in 3/71 (4%) initial stage IIA, 13/95 (14%) stage IIB, and 15/57 (26%) stage III. For patients with HER2+ breast cancer, {sup 18}F-FDG-PET/CT revealed unsuspected distant metastases in 3/72 (4%) initial stage IIA, 13/93 (14%) stage IIB, and 13/59 (22%) stage III. The overall upstaging rate for IIB was 14% (95% confidence interval (CI): 9-20%). {sup 18}F-FDG-PET/CT revealed distant metastases in 14% (95% CI: 9-20%) of patients with stage IIB ER+/HER2- and HER2+ breast cancer, which is similar to upstaging rates previously seen in patients with stage IIB triple-negative breast cancer (15%, 95% CI: 9-24%). The detection of unsuspected distant metastases in these patients alters treatment and prognosis. NCCN guidelines should consider adding patients with stage IIB breast cancer for consideration of systemic staging with {sup 18}F-FDG-PET/CT at the time of initial diagnosis. (orig.)

Breast MR imaging for the assessment of residual disease following initial surgery for breast cancer with positive margins

Energy Technology Data Exchange (ETDEWEB)

Krammer, Julia [University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Institute of Clinical Radiology and Nuclear Medicine, Mannheim (Germany); Memorial Sloan-Kettering Cancer Center, Breast Imaging Section, Department of Radiology, New York, NY (United States); Price, Elissa R. [University of California, San Francisco, Department of Radiology and Biomedical Imaging, Division of Women' s Imaging, San Francisco, CA (United States); Jochelson, Maxine S.; Watson, Elizabeth; Morris, Elizabeth A. [Memorial Sloan-Kettering Cancer Center, Breast Imaging Section, Department of Radiology, New York, NY (United States); Murray, Melissa P. [Memorial Sloan-Kettering Cancer Center, Department of Pathology, New York, NY (United States); Schoenberg, Stefan O. [University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Institute of Clinical Radiology and Nuclear Medicine, Mannheim (Germany)

2017-11-15

To determine the accuracy of post-operative MR in predicting residual disease in women with positive margins, emphasizing the size thresholds at which residual disease can be confidently identified. This IRB-approved HIPAA-compliant retrospective study included 175 patients with MR after positive margins following initial surgery for breast cancer. Two expert readers independently re-evaluated MR images for evidence of residual disease at the surgical cavity and multifocal/multicentric disease. All patients underwent definitive surgery and MR findings were correlated to histopathology. 139/175 (79.4%) patients had residual disease at surgery. Average overall sensitivity, specificity, PPV and NPV for residual disease at the surgical cavity were 73%, 72%, 91% and 45%, respectively. The readers identified 42/45 (93%, reader 1) and 43/45 (95%, reader 2) patients with residual invasive disease at the cavity of ≥5 mm and 22/22 (100%, both readers) patients with disease ≥10 mm. Average sensitivity, specificity, PPV and NPV for unknown multifocal/multicentric disease were 90%, 96%, 93% and 86%, respectively. Post-operative breast MR can accurately depict ≥5-mm residual disease at the surgical cavity and unsuspected multifocal/multicentric disease. These findings have the potential to lead to more appropriate selection of second surgical procedures in women with positive margins. (orig.)

Breast MR imaging for the assessment of residual disease following initial surgery for breast cancer with positive margins

International Nuclear Information System (INIS)

Krammer, Julia; Price, Elissa R.; Jochelson, Maxine S.; Watson, Elizabeth; Morris, Elizabeth A.; Murray, Melissa P.; Schoenberg, Stefan O.

2017-01-01

To determine the accuracy of post-operative MR in predicting residual disease in women with positive margins, emphasizing the size thresholds at which residual disease can be confidently identified. This IRB-approved HIPAA-compliant retrospective study included 175 patients with MR after positive margins following initial surgery for breast cancer. Two expert readers independently re-evaluated MR images for evidence of residual disease at the surgical cavity and multifocal/multicentric disease. All patients underwent definitive surgery and MR findings were correlated to histopathology. 139/175 (79.4%) patients had residual disease at surgery. Average overall sensitivity, specificity, PPV and NPV for residual disease at the surgical cavity were 73%, 72%, 91% and 45%, respectively. The readers identified 42/45 (93%, reader 1) and 43/45 (95%, reader 2) patients with residual invasive disease at the cavity of ≥5 mm and 22/22 (100%, both readers) patients with disease ≥10 mm. Average sensitivity, specificity, PPV and NPV for unknown multifocal/multicentric disease were 90%, 96%, 93% and 86%, respectively. Post-operative breast MR can accurately depict ≥5-mm residual disease at the surgical cavity and unsuspected multifocal/multicentric disease. These findings have the potential to lead to more appropriate selection of second surgical procedures in women with positive margins. (orig.)

Prognostic factors in advanced breast cancer: Race and receptor status are significant after development of metastasis.

Science.gov (United States)

Ren, Zhiyong; Li, Yufeng; Shen, Tiansheng; Hameed, Omar; Siegal, Gene P; Wei, Shi

2016-01-01

Prognostic factors are well established in early-stage breast cancer (BC), but less well-defined in advanced disease. We analyzed 323 BC patients who had distant relapse during follow-up from 1997 to 2010 to determine the significant clinicopathologic factors predicting survival outcomes. By univariate analysis, race, tumor grade, estrogen and progesterone receptors (ER/PR) and HER2 status were significantly associated with overall survival (OS) and post-metastasis survival (PMS). Applying a Cox regression model revealed that all these factors remained significant for PMS, while race, tumor grade and HER2 were independent factors for OS. Tumor grade was the only significant factor for metastasis-free survival by univariate and multivariate analyses. Our findings demonstrated that being Caucasian, hormonal receptor positive (HR+) and HER2 positive (HER2+) were all associated with a decreased hazard of death and that patients with HR+/HER2+ tumors had superior outcomes to those with HR+/HER2- disease. Further, PR status held a prognostic value over ER, thus reflecting the biologic mechanism of the importance of the functional ER pathway and the heterogeneity in the response to endocrine therapy. These observations indicate that the patients' genetic makeup and the intrinsic nature of the tumor principally govern BC progression and prognosticate the long-term outcomes in advanced disease. Copyright © 2015 Elsevier GmbH. All rights reserved.

The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.

Science.gov (United States)

Finn, Richard S; Crown, John P; Lang, Istvan; Boer, Katalin; Bondarenko, Igor M; Kulyk, Sergey O; Ettl, Johannes; Patel, Ravindranath; Pinter, Tamas; Schmidt, Marcus; Shparyk, Yaroslav; Thummala, Anu R; Voytko, Nataliya L; Fowst, Camilla; Huang, Xin; Kim, Sindy T; Randolph, Sophia; Slamon, Dennis J

2015-01-01

Palbociclib (PD-0332991) is an oral, small-molecule inhibitor of cyclin-dependent kinases (CDKs) 4 and 6 with preclinical evidence of growth-inhibitory activity in oestrogen receptor-positive breast cancer cells and synergy with anti-oestrogens. We aimed to assess the safety and efficacy of palbociclib in combination with letrozole as first-line treatment of patients with advanced, oestrogen receptor-positive, HER2-negative breast cancer. In this open-label, randomised phase 2 study, postmenopausal women with advanced oestrogen receptor-positive and HER2-negative breast cancer who had not received any systemic treatment for their advanced disease were eligible to participate. Patients were enrolled in two separate cohorts that accrued sequentially: in cohort 1, patients were enrolled on the basis of their oestrogen receptor-positive and HER2-negative biomarker status alone, whereas in cohort 2 they were also required to have cancers with amplification of cyclin D1 (CCND1), loss of p16 (INK4A or CDKN2A), or both. In both cohorts, patients were randomly assigned 1:1 via an interactive web-based randomisation system, stratified by disease site and disease-free interval, to receive continuous oral letrozole 2.5 mg daily or continuous oral letrozole 2.5 mg daily plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over 28-day cycles. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Accrual to cohort 2 was stopped after an unplanned interim analysis of cohort 1 and the statistical analysis plan for the primary endpoint was amended to a combined analysis of cohorts 1 and 2 (instead of cohort 2 alone). The study is ongoing but closed to accrual; these are the results of the final analysis of progression-free survival. The study is registered with the ClinicalTrials.gov, number NCT00721409. Between Dec 22, 2009, and May 12, 2012, we randomly assigned 165 patients, 84 to palbociclib

Cardiac dose sparing and avoidance techniques in breast cancer radiotherapy

International Nuclear Information System (INIS)

Shah, Chirag; Badiyan, Shahed; Berry, Sameer; Khan, Atif J.; Goyal, Sharad; Schulte, Kevin; Nanavati, Anish; Lynch, Melanie; Vicini, Frank A.

2014-01-01

Breast cancer radiotherapy represents an essential component in the overall management of both early stage and locally advanced breast cancer. As the number of breast cancer survivors has increased, chronic sequelae of breast cancer radiotherapy become more important. While recently published data suggest a potential for an increase in cardiac events with radiotherapy, these studies do not consider the impact of newer radiotherapy techniques commonly utilized. Therefore, the purpose of this review is to evaluate cardiac dose sparing techniques in breast cancer radiotherapy. Current options for cardiac protection/avoidance include (1) maneuvers that displace the heart from the field such as coordinating the breathing cycle or through prone patient positioning, (2) technological advances such as intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT), and (3) techniques that treat a smaller volume around the lumpectomy cavity such as accelerated partial breast irradiation (APBI), or intraoperative radiotherapy (IORT). While these techniques have shown promise dosimetrically, limited data on late cardiac events exist due to the difficulties of long-term follow up. Future studies are required to validate the efficacy of cardiac dose sparing techniques and may use surrogates for cardiac events such as biomarkers or perfusion imaging

CLINICOPATHOLOGICAL FACTORS ASSOCIATED WITH POSITIVE PREOPERATIVE AXILLARY ULTRASOUND SCANNING IN BREAST CANCER PATIENTS

Directory of Open Access Journals (Sweden)

Lona Jalini

2016-01-01

Full Text Available Background: Axillary lymph node status is the most important breast cancer prognostic factor. Preoperative axillary ultrasound examination (PAUS is used to triage patients for sentinel lymph node biopsy (SLNB or axillary lymph node dissection (ALND. We assessed the detection rate of lymph node metastases by PAUS in a screening unit and evaluated associations between clinicopathological factors and PAUS positivity. Patients and Methods: This was a single-centre retrospective analysis of data extracted from a hospital breast cancer database and clinical records. Clinical, radiological, and pathological and prognostic indices were compared between PAUS-positive and PAUS-negative patients subsequently found to have lymph node metastases on histopathological analysis. Results: Two hundred and two patients were eligible for analysis. 50.5% of lymph node-positive patients were correctly identified as PAUS positive. Patients with PAUS-positive lymph nodes had less favorable disease characteristics, namely clinically palpable lymph nodes, higher Nottingham prognostic (NPI index, high lymph node burden according to the European Society of Medical Oncology (ESMO group classification, and larger, grade 3 tumors with lymphovascular invasion and extranodal spread. Moreover, PAUS-positive patients had more macrometastases and lymph node involvement than PAUS-negative patients. Conclusion: PAUS-positive patients and PAUS-negative (SLNB-positive patients have different clinicopathological characteristics. The presence of LVI, extranodal spread, grade 3 histology, or large tumors with poor prognostic indices in PAUS-negative patients should be regarded with caution and perhaps prompt second-look ultrasound examination.

Proteomic classification of breast cancer.

LENUS (Irish Health Repository)

Kamel, Dalia

2012-11-01

Being a significant health problem that affects patients in various age groups, breast cancer has been extensively studied to date. Recently, molecular breast cancer classification has advanced significantly with the availability of genomic profiling technologies. Proteomic technologies have also advanced from traditional protein assays including enzyme-linked immunosorbent assay, immunoblotting and immunohistochemistry to more comprehensive approaches including mass spectrometry and reverse phase protein lysate arrays (RPPA). The purpose of this manuscript is to review the current protein markers that influence breast cancer prediction and prognosis and to focus on novel advances in proteomic classification of breast cancer.

Metastatic breast cancer to the liver with hepatoid features and Hep Par 1 antibody positive mimicking hepatocellular carcinoma.

Science.gov (United States)

Affleck, Authur; Lyman, William B; Jacobs, W Carl; Livasy, Chad A; Martinie, John B; Iannitti, David A; Vrochides, Dionisios

2018-05-09

The hepatocyte paraffin 1 antibody (Hep Par 1) has a high positive predictive value for differentiating hepatocellular carcinoma from cholangiocarcinoma and metastatic carcinoma. 1 We report a case of metastatic breast cancer to the liver with hepatoid histology and strong positive staining for Hep Par 1 mimicking hepatocellular carcinoma. To our knowledge, primary breast carcinoma staining Hep Par 1 positive has not been reported in the setting of hepatic metastasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Mucoadhesive Oral Wound Rinse in Preventing and Treating Stomatitis in Patients With ER- or PR-Positive Metastatic or Locally Recurrent Breast Cancer That Cannot be Removed by Surgery Receiving Everolimus

Science.gov (United States)

2018-04-26

Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; Oral Complications; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer

International Nuclear Information System (INIS)

Glynn, Sharon A; Ambs, Stefan; Prueitt, Robyn L; Ridnour, Lisa A; Boersma, Brenda J; Dorsey, Tiffany M; Wink, David A; Goodman, Julie E; Yfantis, Harris G; Lee, Dong H

2010-01-01

Inducible cyclooxgenase-2 (COX-2) is commonly overexpressed in breast tumors and is a target for cancer therapy. Here, we studied the association of COX-2 with breast cancer survival and how this association is influenced by tumor estrogen and HER2 receptor status and Akt pathway activation. Tumor COX-2, HER2 and estrogen receptor α (ER) expression and phosphorylation of Akt, BAD, and caspase-9 were analyzed immunohistochemically in 248 cases of breast cancer. Spearman's correlation and multivariable logistic regression analyses were used to examine the relationship between COX-2 and tumor characteristics. Kaplan-Meier survival and multivariable Cox proportional hazards regression analyses were used to examine the relationship between COX-2 and disease-specific survival. COX-2 was significantly associated with breast cancer outcome in ER-negative [Hazard ratio (HR) = 2.72; 95% confidence interval (CI), 1.36-5.41; comparing high versus low COX-2] and HER2 overexpressing breast cancer (HR = 2.84; 95% CI, 1.07-7.52). However, the hazard of poor survival associated with increased COX-2 was highest among patients who were both ER-negative and HER2-positive (HR = 5.95; 95% CI, 1.01-34.9). Notably, COX-2 expression in the ER-negative and HER2-positive tumors correlated significantly with increased phosphorylation of Akt and of the two Akt targets, BAD at Ser136 and caspase-9 at Ser196. Up-regulation of COX-2 in ER-negative and HER2-positive breast tumors is associated with Akt pathway activation and is a marker of poor outcome. The findings suggest that COX-2-specific inhibitors and inhibitors of the Akt pathway may act synergistically as anticancer drugs in the ER-negative and HER2-positive breast cancer subtype

Influence of metabolic indicators, smoking, alcohol and socioeconomic position on mortality after breast cancer

DEFF Research Database (Denmark)

Larsen, Signe Benzon; Kroman, Niels; Ibfelt, Else Helene

2015-01-01

BACKGROUND: Factors differently distributed among social groups like obesity, metabolic syndrome, diabetes, smoking, and alcohol intake predict survival after breast cancer diagnosis and therefore might mediate part of the observed social inequality in survival. MATERIAL AND METHODS: We conducted...... a cohort study among 1250 postmenopausal breast cancer patients identified among 29 875 women in the Danish Diet, Cancer and Health Study. Participants completed questionnaires and anthropometric measurements were made at enrollment. Information on survival, socioeconomic position, and comorbidity...... circumference and diabetes, and smoking and alcohol affected but did not explain the social gradient. CONCLUSION: The findings indicate that these factors explain some but not all the social inequality in survival after breast cancer and that improvement of lifestyle to some extent would improve survival among...

Vinorelbine-based salvage therapy in HER2-positive metastatic breast cancer patients progressing during trastuzumab-containing regimens: a retrospective study

Directory of Open Access Journals (Sweden)

Viale Giuseppe

2008-07-01

Full Text Available Abstract Background The vinka-alkaloyd vinorelbine is a potentially valuable treatment in patients with HER2-positive, trastuzumab-resistant advanced breast cancer. We sought to document the clinical activity of vinorelbine-based salvage treatments in this clinical setting. Methods We analyzed a cohort of 424 consecutive women receiving trastuzumab-based therapy for HER2-positive advanced breast cancer. Of these, 299 were identified as progressing during the initial trastuzumab-based treatment, and 77 received vinorelbine-based therapy as first salvage treatment. Central review of pathological specimens revealed that 70 patients had HER2-amplification detected by FISH. For these patients we determined overall response rate (ORR = complete-CR + partial-PR and clinical benefit (CB = CR+PR+ Stable disease lasting at least 6 months, time to progression (TTP and overall survival (OS from the initiation of vinorelbine-based salvage therapy. Results In 60 patients who were evaluable for tumor response, ORR and CB rates were 28% (95% C.I. 18%-41% and 50% (95% C.I. 38%-62%, respectively. Median follow-up from the initiation of salvage therapy was 15 months (range 1–63 months. Median TTP and OS were 7.1 months (95% C.I. 6.6–7.7 months and 21 months (95% C.I. 14.3–27.7 months, respectively. No differences in clinical outcomes were observed according to whether vinorelbine was administered as a single agent or in combination with other cytostatics, or whether trastuzumab was stopped or continued beyond disease progression. Conclusion our findings suggests that vinorelbine-based combinations are active and should be further evaluated in studies conducted in trastuzumab-resistant patients, including those evaluating newer HER2-targeting agents.

Use of the prone position in radiation treatment for women with early stage breast cancer

International Nuclear Information System (INIS)

Algan, Oezer; Fowble, Barbara; McNeeley, Shawn; Fein, Douglas

1998-01-01

Purpose: The prone position has been advocated for women with large pendulous breasts undergoing breast-conserving treatment with radiation therapy. However, there is no information in the literature regarding the coverage of the target volume with this technique. The purpose of this study was to evaluate the effectiveness of the prone treatment position in including at least the biopsy cavity with a 2-cm margin. Methods and Materials: Eleven consecutive patients who underwent CT simulation in the prone position were included in this study. Patients underwent CT simulation in the prone position using a flat platform containing an aperture for the breast to hang through in a dependent fashion. CT slices were 5-mm thick taken at 3-mm intervals. The biopsy cavity was localized and outlined on sequential CT images using the surgical clips (when present) as well as the residual seroma. A 2-cm margin was included around the biopsy cavity to define the minimal target volume (mTV). Lateral fields were used for treatment planning. The beam arrangements were considered adequate if the mTV was totally included in the lateral fields. Results: Median age of the patient population was 55 years. Bra sizes ranged from 36A-44DD. The majority of patients had mammographically detected T1 lesions. Median volume of the biopsy cavity was 48 cm 3 . Five of 11 (45%) patients underwent reexcision of the biopsy cavity, and 6 of 11 (55%) had surgical clips placed in the biopsy cavity. Overall, 8 of 11 (73%) patients did not have the entire mTV included in the lateral opposed tangential fields in the prone position. This was especially true in patients whose biopsy cavity extended down to the chest wall. There were no other clinical factors that could predict for the adequacy of coverage in the prone position. Conclusion: Special attention must be paid to the location of the surgical clips to determine the proximity of the biopsy cavity to the chest wall, or CT simulation should be performed

Polymer–lipid hybrid anti-HER2 nanoparticles for targeted salinomycin delivery to HER2-positive breast cancer stem cells and cancer cells

Directory of Open Access Journals (Sweden)

Li J

2017-09-01

Full Text Available Jun Li,1,* Wenqing Xu,2,* Xiaoli Yuan,3,* Huaiwen Chen,3 Hao Song,1,4 Bingquan Wang,5 Jun Han5 1College of Pharmacy, Liaocheng University, Liaocheng, Shandong, 2Railway Police College, Zhengzhou, 3Department of Cadre Health Care, Nanjing General Hospital of Nanjing Military Command, Nanjing, Jiangsu, 4Centre for Stem Cell & Regenerative Medicine, Liaocheng People’s Hospital, 5Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng, Shandong, China *These authors contributed equally to this work Purpose: Breast cancer stem cells (CSCs are responsible for the initiation, recurrence, and metastasis of breast cancer. Sufficient evidence has established that breast cancer cells can spontaneously turn into breast CSCs. Thus, it is essential to simultaneously target breast CSCs and cancer cells to maximize the efficacy of breast cancer therapy. HER2 has been found to be overexpressed in both breast CSCs and cancer cells. We developed salinomycin-loaded polymer–lipid hybrid anti-HER2 nanoparticles (Sali-NP-HER2 to target both HER2-positive breast CSCs and cancer cells.Methods: The antitumor activity of Sali-NP-HER2 constructed by conjugating anti-HER2 antibodies to polymer–lipid salinomycin nanoparticles was evaluated in vitro and in vivo.Results: Sali-NP-HER2 efficiently bound to HER2-positive breast CSCs and cancer cells, resulting in enhanced cytotoxic effects compared with non-targeted nanoparticles or salinomycin. In mice bearing breast cancer xenografts, administration of Sali-NP-HER2 exhibited superior efficacy in inhibiting tumor growth. Sali-NP-HER2 reduced the breast tumorsphere formation rate and the proportion of breast CSCs more effectively than non-targeted nanoparticles or salinomycin alone.Conclusion: Sali-NP-HER2 represents a promising approach in treating HER2-positive breast cancer by targeting both breast CSCs and cancer cells. Keywords: nanoparticles, breast cancer, cancer stem cells, salinomycin, HER2

Quality of Breast Cancer Care: The Role of Hispanic Ethnicity, Language, and Socioeconomic Position

National Research Council Canada - National Science Library

Tisnado, Diana M; Kahn, Katherine L

2007-01-01

.... Their physicians, and neighborhood data, our goal is to examine the relative importance of ethnicity, language, and socio-economic position, and how they relate to structure, process, and outcomes of breast cancer care...

Breast cancer-specific survival in patients with lymph node-positive hormone receptor-positive invasive breast cancer and Oncotype DX Recurrence Score results in the SEER database.

Science.gov (United States)

Roberts, Megan C; Miller, Dave P; Shak, Steven; Petkov, Valentina I

2017-06-01

The Oncotype DX ® Breast Recurrence Score™ (RS) assay is validated to predict breast cancer (BC) recurrence and adjuvant chemotherapy benefit in select patients with lymph node-positive (LN+), hormone receptor-positive (HR+), HER2-negative BC. We assessed 5-year BC-specific survival (BCSS) in LN+ patients with RS results in SEER databases. In this population-based study, BC cases in SEER registries (diagnosed 2004-2013) were linked to RS results from assays performed by Genomic Health (2004-2014). The primary analysis included only patients (diagnosed 2004-2012) with LN+ (including micrometastases), HR+ (per SEER), and HER2-negative (per RT-PCR) primary invasive BC (N = 6768). BCSS, assessed by RS category and number of positive lymph nodes, was calculated using the actuarial method. The proportion of patients with RS results and LN+ disease (N = 8782) increased over time between 2004 and 2013, and decreased with increasing lymph node involvement from micrometastases to ≥4 lymph nodes. Five-year BCSS outcomes for those with RS < 18 ranged from 98.9% (95% CI 97.4-99.6) for those with micrometastases to 92.8% (95% CI 73.4-98.2) for those with ≥4 lymph nodes. Similar patterns were found for patients with RS 18-30 and RS ≥ 31. RS group was strongly predictive of BCSS among patients with micrometastases or up to three positive lymph nodes (p < 0.001). Overall, 5-year BCSS is excellent for patients with RS < 18 and micrometastases, one or two positive lymph nodes, and worsens with additionally involved lymph nodes. Further analyses should account for treatment variables, and longitudinal updates will be important to better characterize utilization of Oncotype DX testing and long-term survival outcomes.

Vinorelbine as first-line or second-line therapy for advanced breast cancer: a Phase I-II trial by the Danish Breast Cancer Co-operative Group

DEFF Research Database (Denmark)

Langkjer, S.T.; Ejlertsen, B.; Mouridsen, H.

2008-01-01

INTRODUCTION: This study was conducted to establish the maximum tolerated dose (MTD) of intravenous vinorelbine and on the determined dose to assess efficacy and safety in patients with metastatic breast cancer previously treated with epirubicin. PATIENTS AND METHODS: Patients had histologically...... proven breast cancer and had received a prior epirubicin based regimen either adjuvant or as first line therapy for advanced disease. Vinorelbine was administered intravenously day 1 and 8 in a 3 weeks' schedule. Subsequently 48 additional patients were treated at one dose-level below MTD. RESULTS: Fifty...

False-positive findings in mammography screening induces short-term distress - breast cancer-specific concern prevails longer

DEFF Research Database (Denmark)

Aro, A R; Pilvikki Absetz, S; van Elderen, T M

2000-01-01

-ups at 2 and 12 months postscreening. At 2 months, there was a moderate multivariate effect of group on distress; and intrusive thinking and worry about breast cancer, in particular, were most frequent amongst the false positives. Intrusive thinking still prevailed at 12 months, in addition to a higher...... findings (n=1407), false-positive findings (n=492) and referents from outside the screening programme (n=1718, age 48-49 years). Distress was measured as illness worry, anxiety, depression, cancer beliefs and early detection behaviour. Measurements were one month before screening invitation with follow...... perceived breast cancer risk and susceptibility. Distress related to screening and false-positive findings seems to be moderate, but prevailing cancer-specific concerns call for improvements in screening programmes....

Construction of a device for optimal positioning of the patient in studies of breast gammagraphy

International Nuclear Information System (INIS)

González López, Dagoberto Eloy; Infante Ginarte, José R.; Paumier Valdés, Yonimiler; Corella San Nicolás, Migdalia; Suárez Rosales, Lisandra

2016-01-01

Breast tumors are the most common cause of cancer in women. The ideal way to detect breast cancer is by a mammography examination. But this test may either be questionable or provide inconclusive data on a significant number of cases, leading to invasive biopsy procedures. The aim of this study is to optimize the detection of breast cancer by gammagraphy to improve the complementary diagnosis provided by a mammography. Consequently and for that reason, a device allowing an optimal patient positioning was designed and built. The materials used for its construction had few gamma radiation absorption properties. The effectiveness of breast gammagraphy was evaluated using by the designed device in two study cases. In both, the definite diagnosis obtained through mammography from doubtful cases was conclusively confirmed. A diagnostic protocol mammogram/gammagraphy was recommended to optimize the selection of patients requiring biopsy. (author)

Elevated C1orf63 expression is correlated with CDK10 and predicts better outcome for advanced breast cancers: a retrospective study

International Nuclear Information System (INIS)

Hong, Chao-Qun; Zhang, Fan; You, Yan-Jie; Qiu, Wei-Li; Giuliano, Armando E.; Cui, Xiao-Jiang; Zhang, Guo-Jun; Cui, Yu-Kun

2015-01-01

independent prognostic factor predicting better clinical outcome (HR: 0.41; 95 % CI: 0.17 ~ 0.97; P = 0.042). Additionally, we found that CDK10 mRNA expression was positively correlated with C1orf63, which was consistent with the relationship of protein expression between C1orf63 and CDK10 (r s = 0.391; P < 0.001). Compared to adjacent non-cancerous tissues, C1orf63 expression was elevated in tumor tissues. However, C1orf63 predicts better prognosis for breast cancers with advanced TNM stage, and the underlying mechanism is unknown. In addition, C1orf63 is correlated with the cell cycle related gene, CDK10

Breast-Conserving Surgery Followed by Radiation Therapy With MRI-Detected Stage I or Stage II Breast Cancer

Science.gov (United States)

2011-12-07

Ductal Breast Carcinoma in Situ; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Male Breast Cancer; Medullary Ductal Breast Carcinoma With Lymphocytic Infiltrate; Mucinous Ductal Breast Carcinoma; Papillary Ductal Breast Carcinoma; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Tubular Ductal Breast Carcinoma

Survival advantage by neoadjuvant radiochemotherapy in locally advanced non-inflammatory breast cancer; Ueberlebensvorteil durch praeoperative Radiochemotherapie beim lokal fortgeschrittenen, nicht-inflammatorischen Brustkrebs

Energy Technology Data Exchange (ETDEWEB)

Lang, Innokenti

2011-07-01

This study compares retrospectively, in terms of pathological complete response (pCR) and ten year survival rate, preoperative radiochemotherapy (RCT) with postoperative RCT for locally advanced or surgically in terms of breast conserving surgery or simple mastectomy unfavourable, non inflammatory breast cancers (LABC).

Efficacy and safety of everolimus in combination with trastuzumab and paclitaxel in Asian patients with HER2+ advanced breast cancer in BOLERO-1.

Science.gov (United States)

Toi, Masakazu; Shao, Zhimin; Hurvitz, Sara; Tseng, Ling-Ming; Zhang, Qingyuan; Shen, Kunwei; Liu, Donggeng; Feng, Jifeng; Xu, Binghe; Wang, Xiaojia; Lee, Keun Seok; Ng, Ting Ying; Ridolfi, Antonia; Noel-Baron, Florence; Ringeisen, Francois; Jiang, Zefei

2017-04-11

The current exploratory analysis was performed to evaluate the efficacy and safety of everolimus for treatment of human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer in the Asian subset of patients in the BOLERO-1 trial. Postmenopausal women with HER2+ advanced breast cancer, who had not received systemic therapy for advanced disease, were randomized 2:1 to receive everolimus or placebo, plus trastuzumab and paclitaxel. The two primary end points were investigator-assessed progression-free survival (PFS) in the full population and in the hormone receptor-negative (HR-) subpopulation. Secondary end points included assessment of the objective response rate, the clinical benefit rate, and safety. In the Asian subset, median PFS was similar in the everolimus (n = 198) and placebo (n = 105) arms in the full analysis set (hazard ratio = 0.82 (95% CI 0.61-1.11)). In the HR- subpopulation, everolimus prolonged median PFS by 10.97 months vs placebo (25.46 vs 14.49 months; hazard ratio = 0.48 (95% CI 0.29-0.79)). In the everolimus arm of the Asian subset, the most common adverse events of any grade were stomatitis (62.2%), diarrhea (48.0%), rash (43.4%) and neutropenia (42.3%). Neutropenia (grade 3: 27.6%; grade 4: 4.6%) and decreased neutrophil count (grade 3: 11.2%; grade 4: 3.6%) were the most frequent grade 3/4 adverse events. Serious adverse events included pneumonia (5.1%), pneumonitis (3.1%), and interstitial lung disease (3.1%). There were three deaths (1.5%) during treatment in the everolimus arm vs none in the placebo arm. The efficacy and safety of everolimus plus trastuzumab and paclitaxel as first-line treatment for HER2+ advanced breast cancer in the Asian subset was consistent with that reported previously in the overall population. ClinicalTrials.gov, NCT00876395 . Registered on 2 April 2009.

Chronic thyroiditis in patients with advanced breast carcinoma: metabolic and morphologic changes on PET-CT

Energy Technology Data Exchange (ETDEWEB)

Tateishi, Ukihide [University of Texas, MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Yokohama City University Graduate School of Medicine, Department of Radiology, Yokohama (Japan); University of Texas MD Anderson Cancer Center, Division of Diagnostic Imaging, Houston, TX (United States); Gamez, Cristina; Yeung, Henry W.D.; Macapinlac, Homer A. [University of Texas, MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Dawood, Shaheenah; Cristofanilli, Massimo [University of Texas, MD Anderson Cancer Center, Division of Breast Medical Oncology, Houston, TX (United States); Inoue, Tomio [Yokohama City University Graduate School of Medicine, Department of Radiology, Yokohama (Japan)

2009-06-15

To investigate clinical implications of FDG uptake in the thyroid glands in patients with advanced breast carcinoma by comparing metabolic and morphologic patterns on positron emission tomography (PET)/computed tomography (CT). The institutional review board waived the requirement for informed consent. A retrospective analysis was performed in 146 women (mean age 54 years) with advanced breast carcinoma who received systemic treatment. All patients underwent PET-CT before and after treatment. All PET-CT studies were reviewed in consensus by two reviewers. Morphologic changes including volume and mean parenchymal density of the thyroid glands were evaluated. Maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG) were determined to evaluate metabolic changes. These parameters were compared between patients with chronic thyroiditis who received thyroid hormone replacement therapy and those who did not. Of the 146 patients, 29 (20%) showed bilaterally diffuse uptake in the thyroid glands on the baseline PET-CT scan. The SUVmax showed a linear relationship with volume (r = 0.428, p = 0.021) and the mean parenchymal density (r = -0.385, p = 0.039) of the thyroid glands. In 21 of the 29 patients (72%) with hypothyroidism who received thyroid hormone replacement therapy, the volume, mean parenchymal density, SUVmax, and TLG of the thyroid glands showed no significant changes. In contrast, 8 of the 29 patients (28%) who did not receive thyroid hormone replacement therapy showed marked decreases in SUVmax and TLG. Diffuse thyroid uptake on PET-CT represents active inflammation caused by chronic thyroiditis in patients with advanced breast carcinoma. Diffuse thyroid uptake may also address the concern about subclinical hypothyroidism which develops into overt disease during follow-up. (orig.)

Risk of estrogen receptor-positive and -negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042

DEFF Research Database (Denmark)

Milne, Roger L; Benítez, Javier; Nevanlinna, Heli

2009-01-01

BACKGROUND: A recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium. METHODS: 2q35...

HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab.

Science.gov (United States)

Modi, Shanu; Stopeck, Alison; Linden, Hannah; Solit, David; Chandarlapaty, Sarat; Rosen, Neal; D'Andrea, Gabriella; Dickler, Maura; Moynahan, Mary E; Sugarman, Steven; Ma, Weining; Patil, Sujata; Norton, Larry; Hannah, Alison L; Hudis, Clifford

2011-08-01

HSP90 is a chaperone protein required for the stability of a variety of client proteins. 17-Demethoxygeldanamycin (17-AAG) is a natural product that binds to HSP90 and inhibits its activity, thereby inducing the degradation of these clients. In preclinical studies, HER2 is one of the most sensitive known client proteins of 17-AAG. On the basis of these data and activity in a phase I study, we conducted a phase II study of 17-AAG (tanespimycin) with trastuzumab in advanced trastuzumab-refractory HER2-positive breast cancer. We enrolled patients with metastatic HER2(+) breast cancer whose disease had previously progressed on trastuzumab. All patients received weekly treatment with tanespimycin at 450 mg/m(2) intravenously and trastuzumab at a conventional dose. Therapy was continued until disease progression. The primary endpoint was response rate by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Thirty-one patients were enrolled with a median age of 53 years and a median Karnofsky performance status (KPS) of 90%. The most common toxicities, largely grade 1, were diarrhea, fatigue, nausea, and headache. The overall response rate was 22%, the clinical benefit rate [complete response + partial response + stable disease] was 59%, the median progression-free survival was 6 months (95% CI: 4-9), and the median overall survival was 17 months (95% CI: 16-28). This is the first phase II study to definitively show RECIST-defined responses for 17-AAG in solid tumors. Tanespimycin plus trastuzumab has significant anticancer activity in patients with HER2-positive, metastatic breast cancer previously progressing on trastuzumab. Further research exploring this therapeutic interaction and the activity of HSP90 inhibitors is clearly warranted. ©2011 AACR.

Effect of radiologist experience on the risk of false-positive results in breast cancer screening programs

International Nuclear Information System (INIS)

Zubizarreta Alberdi, Raquel; Llanes, Ana B.F.; Ortega, Raquel Almazan; Exposito, Ruben Roman; Collado, Jose M.V.; Oliveres, Xavier Castells; Queiro Verdes, Teresa; Natal Ramos, Carmen; Sanz, Maria Ederra; Salas Trejo, Dolores

2011-01-01

To evaluate the effect of radiologist experience on the risk of false-positive results in population-based breast cancer screening programmes. We evaluated 1,440,384 single-read screening mammograms, corresponding to 471,112 women aged 45-69 years participating in four Spanish programmes between 1990 and 2006. The mammograms were interpreted by 72 radiologists. The overall percentage of false-positive results was 5.85% and that for false-positives resulting in an invasive procedure was 0.38%. Both the risk of false-positives overall and of false-positives leading to an invasive procedure significantly decreased (p 14,999 mammograms with respect to the reference category (<500). The risk of both categories of false-positives was also significantly reduced (p < 0.001) as radiologists' years of experience increased: OR 0.96 and OR 0.84, respectively, for 1 year's experience and OR 0.72 and OR 0.73, respectively, for more than 4 years' experience with regard to the category of <1 year's experience. Radiologist experience is a determining factor in the risk of a false-positive result in breast cancer screening. (orig.)

Constitutional variants are not associated with HER2-positive breast cancer: results from the SIGNAL/PHARE clinical cohort

OpenAIRE

Pivot, Xavier; Romieu, Gilles; Fumoleau, Pierre; Rios, Maria; Bonnefoi, Herv?; Bachelot, Thomas; Souli?, Patrick; Jouannaud, Christelle; Bourgeois, Hugues; Petit, Thierry; Tennevet, Isabelle; Assouline, David; Mathieu, Marie-Christine; Jacquin, Jean-Philippe; Lavau-Denes, Sandrine

2017-01-01

Human epidermal growth factor receptor 2-positive breast cancer is a subtype of interest regarding its outcome and the impressive impact of human epidermal growth factor receptor 2 targeted therapy. Constitutional variants may be involved in the aetiology of human epidermal growth factor receptor 2-positive breast cancer, and we propose a case?case study to test the hypothesis that single nucleotide polymorphisms may be associated with human epidermal growth factor receptor 2 status. A Genome...

Automated detection of masses on whole breast volume ultrasound scanner: false positive reduction using deep convolutional neural network

Science.gov (United States)

Hiramatsu, Yuya; Muramatsu, Chisako; Kobayashi, Hironobu; Hara, Takeshi; Fujita, Hiroshi

2017-03-01

Breast cancer screening with mammography and ultrasonography is expected to improve sensitivity compared with mammography alone, especially for women with dense breast. An automated breast volume scanner (ABVS) provides the operator-independent whole breast data which facilitate double reading and comparison with past exams, contralateral breast, and multimodality images. However, large volumetric data in screening practice increase radiologists' workload. Therefore, our goal is to develop a computer-aided detection scheme of breast masses in ABVS data for assisting radiologists' diagnosis and comparison with mammographic findings. In this study, false positive (FP) reduction scheme using deep convolutional neural network (DCNN) was investigated. For training DCNN, true positive and FP samples were obtained from the result of our initial mass detection scheme using the vector convergence filter. Regions of interest including the detected regions were extracted from the multiplanar reconstraction slices. We investigated methods to select effective FP samples for training the DCNN. Based on the free response receiver operating characteristic analysis, simple random sampling from the entire candidates was most effective in this study. Using DCNN, the number of FPs could be reduced by 60%, while retaining 90% of true masses. The result indicates the potential usefulness of DCNN for FP reduction in automated mass detection on ABVS images.

[Pregnancy-Associated Breast Cancer: An analytical observational study].

Science.gov (United States)

Baulies, Sonia; Cusidó, Maite; Tresserra, Francisco; Rodríguez, Ignacio; Ubeda, Belén; Ara, Carmen; Fábregas, Rafael

2014-03-04

Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy and up to one year postpartum. A retrospective, analytical, observational study comparing 56 cases of breast cancer and pregnancy (PABC) diagnosed 1976-2008 with 73 patients with breast cancer not associated with pregnancy (non-PABC) was performed. Demographic data, prognostic factors, treatment and survival were reviewed and compared. The prevalence of PABC in our center is 8.3/10,000. The highest frequency (62%) appeared during the postpartum period. The stages are higher in PABC, being 31.3% advanced (EIII and EIV) in PABC versus 13.3% in non-PABC (P < .05). Regarding prognostic factors, 27.3% in PABC had a tumoral grade 3 versus 15.8% of non-PABC. Among women with PABC, 33.3% had negative estrogen receptors, 48.7% negative progesterone receptors and 34.5% positive Her2Neu compared with 22.2, 24.1 and 31%, respectively of non-PABC patients. Finally, positive lymph nodes were found in 52.8% of PABC, versus 33.8% non-PABC (P < .05). Overall and disease-free survival rate at 5 years for PABC was 63.7 and 74.2%, respectively. The poorer survival observed is possibly due to the presence of adverse prognostic features such as lymph node metastases, negative hormone receptors, tumoral grade iii, as well as a delay in diagnosis with a higher rate of advanced stages. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma

International Nuclear Information System (INIS)

Bièche, Ivan; Girault, Igor; Urbain, Estelle; Tozlu, Sengül; Lidereau, Rosette

2004-01-01

Little is known of the function and clinical significance of intratumoral dysregulation of xenobiotic-metabolizing enzyme expression in breast cancer. One molecular mechanism proposed to explain tamoxifen resistance is altered tamoxifen metabolism and bioavailability. To test this hypothesis, we used real-time quantitative RT-PCR to quantify the mRNA expression of a large panel of genes coding for the major xenobiotic-metabolizing enzymes (12 phase I enzymes, 12 phase II enzymes and three members of the ABC transporter family) in a small series of normal breast (and liver) tissues, and in estrogen receptor alpha (ERα)-negative and ERα-positive breast tumors. Relevant genes were further investigated in a well-defined cohort of 97 ERα-positive postmenopausal breast cancer patients treated with primary surgery followed by adjuvant tamoxifen alone. Seven of the 27 genes showed very weak or undetectable expression in both normal and tumoral breast tissues. Among the 20 remaining genes, seven genes (CYP2A6, CYP2B6, FMO5, NAT1, SULT2B1, GSTM3 and ABCC11) showed significantly higher mRNA levels in ERα-positive breast tumors than in normal breast tissue, or showed higher mRNA levels in ERα-positive breast tumors than in ERα-negative breast tumors. In the 97 ERα-positive breast tumor series, most alterations of these seven genes corresponded to upregulations as compared with normal breast tissue, with an incidence ranging from 25% (CYP2A6) to 79% (NAT1). Downregulation was rare. CYP2A6, CYP2B6, FMO5 and NAT1 emerged as new putative ERα-responsive genes in human breast cancer. Relapse-free survival was longer among patients with FMO5-overexpressing tumors or NAT1-overexpressing tumors (P = 0.0066 and P = 0.000052, respectively), but only NAT1 status retained prognostic significance in Cox multivariate regression analysis (P = 0.0013). Taken together, these data point to a role of genes coding for xenobiotic-metabolizing enzymes in breast tumorigenesis, NAT1 being an

New developments in chemotherapy of advanced breast cancer.

Science.gov (United States)

Lebwohl, D E; Canetta, R

1999-01-01

Anthracyclines and taxanes are the two most active classes of chemotherapy for the treatment of advanced breast cancer. Recent studies have investigated combination therapy including doxorubicin (Dox) and paclitaxel. The efficacy of this combination has been established in a phase III study conducted by ECOG, comparing Dox/paclitaxel versus Dox versus paclitaxel. The combination is superior to Dox or paclitaxel with respect to response rate and time to disease progression, indicating that the combination provides a new standard for the first line treatment of metastatic breast cancer [1]. Phase II studies using higher doses of Dox and using shorter infusions of paclitaxel have suggested the combination can be further optimized; Gianni reported a 94% objective response rate using Dox 60 mg/m2 followed by paclitaxel 175 mg/m2 given over three hours [2]. The more active regimens are associated with enhanced cardiotoxicity; this toxicity can be avoided, however, by limiting the exposure to doxorubicin. The newer regimens have now been moved into phase III studies. Future progress for this disease will depend on the introduction of new agents. Two novel drugs are currently being investigated in randomised phase III trials as potentiators of Dox and/or paclitaxel. One is a monoclonal antibody from Genentech (Herceptin, trastuzumab) directed at the HER-2/neu oncogene, which is overexpressed in > 25% of breast cancers [3]. Recent results indicate that Herceptin in combination with paclitaxel (or with a Dox plus cyclophosphamide regimen) induces a higher response rate (RR) and prolongs the time to disease progression when compared to chemotherapy alone. The second agent N,N-diethyl-2[4-(phenylmethyl)-phenoxy] ethanamine.HCl (DPPE, BMS-217380-01), when combined with Dox, was associated with a higher RR than previously observed with Dox alone [4]. A randomized trial of Dox versus Dox plus DPPE is ongoing. The possible mechanisms underlying chemo-potentiation by these agents

Increased risk of breast cancer in women with false-positive test

DEFF Research Database (Denmark)

von Euler-Chelpin, My; Kuchiki, Megumi; Vejborg, Ilse

2014-01-01

of misclassification, i.e. women who were actually false-negatives instead of false-positives. METHOD: We used data from the Copenhagen Mammography Screening Programme, Denmark. The study population was the 295 women, out of 4743 recalled women from a total of 58,003 participants, with a false-positive test during...... the women with misclassified tests had been excluded, there was an excess risk of breast cancer of 27% (RR=1.27, 95% confidence interval (CI), 1.11-1.46) among the women with a false-positive test compared to women with only negative tests. Women with a false-positive test determined at assessment had...... an excess risk of 27%, while false-positives determined at surgery had an excess risk of 30%. CONCLUSIONS: The results indicate that the increased risk is not explained only by misclassification. The excess risk remains for false-positives determined at assessment as well as at surgery, which favours some...

Potential biomarker panels in overall breast cancer management: advancements by multilevel diagnostics.

Science.gov (United States)

Girotra, Shantanu; Yeghiazaryan, Kristina; Golubnitschaja, Olga

2016-09-01

Breast cancer (BC) prevalence has reached an epidemic scale with half a million deaths annually. Current deficits in BC management include predictive and preventive approaches, optimized screening programs, individualized patient profiling, highly sensitive detection technologies for more precise diagnostics and therapy monitoring, individualized prediction and effective treatment of BC metastatic disease. To advance BC management, paradigm shift from delayed to predictive, preventive and personalized medical services is essential. Corresponding step forwards requires innovative multilevel diagnostics procuring specific panels of validated biomarkers. Here, we discuss current instrumental advancements including genomics, proteomics, epigenetics, miRNA, metabolomics, circulating tumor cells and cancer stem cells with a focus on biomarker discovery and multilevel diagnostic panels. A list of the recommended biomarker candidates is provided.

Comparison of Radiation Treatment Plans for Breast Cancer between 3D Conformal in Prone and Supine Positions in Contrast to VMAT and IMRT Supine Positions

Science.gov (United States)

Bejarano Buele, Ana Isabel

The treatment regimen for breast cancer patients typically involves Whole Breast Irradiation (WBI). The coverage and extent of the radiation treatment is dictated by location of tumor mass, breast tissue distribution, involvement of lymph nodes, and other factors. The current standard treatment approach used at our institution is a 3D tangential beam geometry, which involves two fields irradiating the breast, or a four field beam arrangement covering the whole breast and involved nodes, while decreasing the dose to organs as risk (OARs) such as the lung and heart. The coverage of these targets can be difficult to achieve in patients with unfavorable thoracic geometries, especially in those cases in which the planning target volume (PTV) is extended to the chest wall. It is a well-known fact that exposure of the heart to ionizing radiation has been proved to increase the subsequent rate of ischemic heart disease. In these cases, inverse planned treatments have become a proven alternative to the 3D approach. The goal of this research project is to evaluate the factors that affect our current techniques as well as to adapt the development of inverse modulated techniques for our clinic, in which breast cancer patients are one of the largest populations treated. For this purpose, a dosimetric comparison along with the evaluation of immobilization devices was necessary. Radiation treatment plans were designed and dosimetrically compared for 5 patients in both, supine and prone positions. For 8 patients, VMAT and IMRT plans were created and evaluated in the supine position. Skin flash incorporation for inverse modulated plans required measurement of the surface dose as well as an evaluation of breast volume changes during a treatment course. It was found that prone 3D conformal plans as well as the VMAT and IMRT plans are generally superior in sparing OARs to supine plans with comparable PTV coverage. Prone setup leads to larger shifts in breast volume as well as in

Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer.

Science.gov (United States)

Murase, Ryuichi; Kawamura, Rumi; Singer, Eric; Pakdel, Arash; Sarma, Pranamee; Judkins, Jonathon; Elwakeel, Eiman; Dayal, Sonali; Martinez-Martinez, Esther; Amere, Mukkanti; Gujjar, Ramesh; Mahadevan, Anu; Desprez, Pierre-Yves; McAllister, Sean D

2014-10-01

The psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD) can both reduce cancer progression, each through distinct anti-tumour pathways. Our goal was to discover a compound that could efficiently target both cannabinoid anti-tumour pathways. To measure breast cancer cell proliferation/viability and invasion, MTT and Boyden chamber assays were used. Modulation of reactive oxygen species (ROS) and apoptosis was measured using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in combination with cell flow cytometry. Changes in protein levels were evaluated using Western analysis. Orthotopic and i.v. mouse models of breast cancer metastasis were used to test the activity of cannabinoids in vivo. CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC-associated) and discovered the compound O-1663. This analogue inhibited Id1, produced a marked stimulation of ROS, up-regulated autophagy and induced apoptosis. Of all the compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo. O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid anti-tumour pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer. © 2014 The British Pharmacological Society.

Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment

Energy Technology Data Exchange (ETDEWEB)

Koo, Tae Ryool [Dept. of Radiation Oncology, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon (Korea, Republic of); Kim, In Ah [Dept. of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

2016-03-15

Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

DCE-MRI texture analysis with tumor subregion partitioning for predicting Ki-67 status of estrogen receptor-positive breast cancers

KAUST Repository

Fan, Ming; Cheng, Hu; Zhang, Peng; Gao, Xin; Zhang, Juan; Shao, Guoliang; Li, Lihua

2017-01-01

Breast tumor heterogeneity is related to risk factors that lead to worse prognosis, yet such heterogeneity has not been well studied.To predict the Ki-67 status of estrogen receptor (ER)-positive breast cancer patients via analysis of tumor

Plasmacytoma of the Breast

African Journals Online (AJOL)

GB

2015-10-04

Oct 4, 2015 ... The clinical diagnosis of a breast plasmacytoma is ... lead to a diagnosis of breast plasmacytoma (1-3). Bone marrow ... breast cancer cases present at an advanced stage, ... pelvic ultrasonography, were normal, Bence Jones.

Gene expression profiling of histologically normal breast tissue in females with human epidermal growth factor receptor 2‑positive breast cancer.

Science.gov (United States)

Zubor, Pavol; Hatok, Jozef; Moricova, Petra; Kapustova, Ivana; Kajo, Karol; Mendelova, Andrea; Sivonova, Monika Kmetova; Danko, Jan

2015-02-01

Gene expression profile‑based taxonomy of breast cancer (BC) has been described as a significant breakthrough in comprehending the differences in the origin and behavior of cancer to allow individually tailored therapeutic approaches. In line with this, we hypothesized that the gene expression profile of histologically normal epithelium (HNEpi) could harbor certain genetic abnormalities predisposing breast tissue cells to develop human epidermal growth factor receptor 2 (HER2)‑positive BC. Thus, the aim of the present study was to assess gene expression in normal and BC tissue (BCTis) from patients with BC in order to establish its value as a potential diagnostic marker for cancer development. An array study evaluating a panel of 84 pathway‑ and disease‑specific genes in HER2‑positive BC and tumor‑adjacent HNEpi was performed using quantitative polymerase chain reaction in 12 patients using microdissected samples from frozen tissue. Common prognostic and predictive parameters of BC were assessed by immunohistochemistry and in situ hybridization. In the BCTis and HNEpi samples of 12 HER2‑positive subjects with BC, the expression of 2,016 genes was assessed. A total of 39.3% of genes were deregulated at a minimal two‑fold deregulation rate and 10.7% at a five‑fold deregulation rate in samples of HNEpi or BCTis. Significant differences in gene expression between BCTis and HNEpi samples were revealed for BCL2L2, CD44, CTSD, EGFR, ERBB2, ITGA6, NGFB, RPL27, SCBG2A1 and SCGB1D2 genes (Pbreast tissue revealed gene expression abnormalities that may represent potential markers of increased risk for HER2‑positive malignant transformation of breast tissue, and may be able to be employed as predictors of prognosis.

Factors associated with prolonged time to treatment failure with fulvestrant 500 mg in patients with post-menopausal estrogen receptor-positive advanced breast cancer: a sub-group 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

2018-01-01

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 sub-group 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, multi-center cohort study, conducted in 1,072 patients in Japan taking F500 for ER + ABC. The sub-analysis included only patients administered F500 as second-line or later therapy (n = 960). Of these, 828 patients were HER2-. Results Multivariate analysis showed that advanced age (≥65 years; p = .035), longer time (≥3 years) from ABC diagnosis to F500 use (p < .001), no prior chemotherapy (p < .001), and F500 treatment line (p < .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.

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.

Lipid-rich carcinoma of the breast that is strongly positive for estrogen receptor: a case report and literature review

Directory of Open Access Journals (Sweden)

Oba T

2016-03-01

Full Text Available Takaaki Oba,1 Mayu Ono,1 Asumi Iesato,1 Toru Hanamura,1 Takayuki Watanabe,1 Tokiko Ito,1 Toshiharu Kanai,1 Kazuma Maeno,1 Ken-ichi Ito,1 Ayako Tateishi,2 Akihiko Yoshizawa,2 Fumiyoshi Takayama31Division of Breast, Endocrine and Respiratory Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, 2Department of Laboratory Medicine, Shinshu University Hospital, 3Imaging Center, Ichinose Neurosurgical Hospital, Matsumoto, JapanAbstract: Lipid-rich carcinoma (LRC of the breast is a rare breast cancer variant that accounts for <1% of all breast malignancies. It has been reported that LRCs are negative for estrogen receptor. Here, we report a case of LRC of the breast that was strongly positive for estrogen receptor and treated with endocrine adjuvant therapy. A 52-year-old postmenopausal female noticed a lump in her right breast by self-examination and presented to our hospital. Physical examination revealed an elastic 30 mm ×20 mm hard mass in the upper medial part of her right breast. The findings obtained using ultrasonography, mammography, and contrast-enhanced magnetic resonance imaging suggested breast cancer. Core needle biopsy resulted in the diagnosis of invasive carcinoma. The patient underwent mastectomy and sentinel lymph node biopsy. Histopathologically, the tumor cells were abundant in foamy cytoplasm. Because the presence of marked cytoplasmic lipid droplets was confirmed by Sudan IV staining and electron microscopic examination of the tumor and the lipid droplets were negative for periodic acid–Schiff staining, the tumor was diagnosed as an LRC. Immunohistochemically, estrogen and progesterone receptors of the tumor were strongly positive, human epidermal growth factor receptor type 2 was negative, and the ratio of Ki-67-positive cells was ~30%. After surgery, the patient underwent combination chemotherapy with anthracycline, cyclophosphamide, and 5-fluorouracil, followed by docetaxel. Thereafter

Endocrine sensitivity of the receptor-positive T61 human breast carcinoma serially grown in nude mice

DEFF Research Database (Denmark)

Brünner, N; Spang-Thomsen, M; Skovgaard Poulsen, H

1985-01-01

A study was made on the effect of ovariectomy, 17 beta-oestradiol, and tamoxifen on the oestrogen and progesterone receptor-positive T61 human breast carcinoma grown in nude mice. The effect of the treatment was evaluated by the specific growth delay calculated on the basis of Gompertz growth cur...... but is not a sufficiently clear marker to allow prediction of the endocrine sensitivity of individual breast tumours....

In situ aromatase expression in primary tumor is associated with estrogen receptor expression but is not predictive of response to endocrine therapy in advanced breast cancer

DEFF Research Database (Denmark)

Lykkesfeldt, Anne E; Henriksen, Katrine L; Rasmussen, Birgitte B

2009-01-01

BACKGROUND: New, third-generation aromatase inhibitors (AIs) have proven comparable or superior to the anti-estrogen tamoxifen for treatment of estrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancer. AIs suppress total body and intratumoral estrogen levels. It is unclear...... whether in situ carcinoma cell aromatization is the primary source of estrogen production for tumor growth and whether the aromatase expression is predictive of response to endocrine therapy. Due to methodological difficulties in the determination of the aromatase protein, COX-2, an enzyme involved...... of advanced breast cancer. Semi-quantitative immunohistochemical (IHC) analysis was performed for ER, PR, COX-2 and aromatase using Tissue Microarrays (TMAs). Aromatase was also analyzed using whole sections (WS). Kappa analysis was applied to compare association of protein expression levels. Univariate...

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

Science.gov (United States)

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.

The Economics of Prepectoral Breast Reconstruction.

Science.gov (United States)

Glasberg, Scot Bradley

2017-12-01

The world of breast reconstruction over the last several years has seen a dramatic shift in focus to discussion and the application of placing tissue expanders and implants back into the prepectoral space. Although this technique failed during the early advent of breast reconstruction, newer technologies such as advances in fat grafting, improved acellular dermal matrices, better methods of assessing breast flap viability, and enhanced implants appear to have set the stage for the resurgence and positive early results seen with this technique. The main benefits of a switch to prepectoral breast reconstruction clinically appears to be less associated pain, lower incidence of animation deformities, and its associated symptoms as well as presumably better aesthetics. Early data suggest that the results are extremely promising and early adopters have attempted to define the ideal patients for prepectoral breast reconstruction. As with any new operative procedure, an assessment of finances and costs are crucial to its successful implementation. Although current data are minimal, this article attempts to build the fundamentals of an economic model that exhibits and displays potential savings through the use of prepectoral breast reconstruction.

Breast cancer patients' narratives about positive and negative communication experiences

DEFF Research Database (Denmark)

Thomsen, Dorthe K; Pedersen, Anette F; Johansen, Mikael B

2007-01-01

. Thus, qualitative studies of communication are also needed. Fifteen breast cancer patients were interviewed 3 months after finishing adjuvant treatment. They were asked to tell a 10 minute narrative and recall five experiences from treatment. Themes were extracted using categories derived from previous...... research while at the same time being sensitive to new elaborations and categories. The participants reported both positive and negative communication-related experiences from a wide range of treatment situations. Two major themes emerged: Information giving as professional care-giving and meeting......Health staff-patient communication is increasingly considered an important issue in cancer research. However, questionnaires addressing satisfaction with communication limit the issues patients can raise, do not address the context of communication and often show a strong positive skew in responses...

Preferential expression of NY-BR-1 and GATA-3 in male breast cancer.

Science.gov (United States)

Biserni, Giovanni Battista; Di Oto, Enrico; Moskovszky, Linda Eszter; Foschini, Maria Pia; Varga, Zsuzsanna

2018-02-01

Male breast cancer is an uncommon disease often discovered in advanced stage; thus, in the setting of metastatic adenocarcinoma, breast origin must be taken to account. Breast markers as NY-BR-1, GATA-3, mammaglobin, and BRST-2 are established tools for labelling primary and metastatic female breast cancer; however, none of them has been sufficiently studied in male breast cancer. The aim of this study was to analyze the expression of these markers in male breast cancer. Thirty consecutive cases of male breast cancer and eight loco-regional metastases were re-revaluated, assembled in tissue micro array (TMA), and stained with immunohistochemistry (IHC) for NY-BR-1, GATA-3, mammaglobin, and BRST-2. The IHC stains were scored either positive or negative. In addition, concordant expression patterns of primary tumors and matched metastasis were noted. 30 of 30 (100%) primary tumors and 8 of 8 (100%) metastases were positive for NY-BR-1. 30 of 30 (100%) primary tumors and 6 of 8 (75%) metastases were positive for GATA-3. 22 of 30 (73.3%) primary tumors and 6 of 8 (75%) metastases were positive for Mammaglobin. 18 of 30 (60%) primary tumors and 5 of 8 (62.5%) metastases were positive for BRST-2. Differences in staining percentage were not significant with Fisher's exact test. We found a high sensitivity for all the markers analyzed. Moreover, the expression of NY-BR-1 and GATA-3 seemed the most effective for labelling male breast cancer in primary and metastatic setting.

Outcomes of Node-positive Breast Cancer Patients Treated With Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience.

Science.gov (United States)

Kamrava, Mitchell; Kuske, Robert R; Anderson, Bethany; Chen, Peter; Hayes, John; Quiet, Coral; Wang, Pin-Chieh; Veruttipong, Darlene; Snyder, Margaret; Demanes, David J

2018-06-01

To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy in node-positive compared with node-negative patients. From 1992 to 2013, 1351 patients (1369 breast cancers) were treated with breast-conserving surgery and adjuvant APBI using interstitial multicatheter brachytherapy. A total of 907 patients (835 node negative, 59 N1a, and 13 N1mic) had >1 year of data available and nodal status information and are the subject of this analysis. Median age (range) was 59 years old (22 to 90 y). T stage was 90% T1 and ER/PR/Her2 was positive in 87%, 71%, and 7%. Mean number of axillary nodes removed was 12 (SD, 6). Cox multivariate analysis for local/regional control was performed using age, nodal stage, ER/PR/Her2 receptor status, tumor size, grade, margin, and adjuvant chemotherapy/antiestrogen therapy. The mean (SD) follow-up was 7.5 years (4.6). The 5-year actuarial local control (95% confidence interval) in node-negative versus node-positive patients was 96.3% (94.5-97.5) versus 95.8% (87.6-98.6) (P=0.62). The 5-year actuarial regional control in node-negative versus node-positive patients was 98.5% (97.3-99.2) versus 96.7% (87.4-99.2) (P=0.33). The 5-year actuarial freedom from distant metastasis and cause-specific survival were significantly lower in node-positive versus node-negative patients at 92.3% (82.4-96.7) versus 97.8% (96.3-98.7) (P=0.006) and 91.3% (80.2-96.3) versus 98.7% (97.3-99.3) (P=0.0001). Overall survival was not significantly different. On multivariate analysis age 50 years and below, Her2 positive, positive margin status, and not receiving chemotherapy or antiestrogen therapy were associated with a higher risk of local/regional recurrence. Patients who have had an axillary lymph node dissection and limited node-positive disease may be candidates for treatment with APBI. Further research is ultimately needed to better define specific criteria for APBI

Risk determination and prevention of breast cancer.

Science.gov (United States)

Howell, Anthony; Anderson, Annie S; Clarke, Robert B; Duffy, Stephen W; Evans, D Gareth; Garcia-Closas, Montserat; Gescher, Andy J; Key, Timothy J; Saxton, John M; Harvie, Michelle N

2014-09-28

Breast cancer is an increasing public health problem. Substantial advances have been made in the treatment of breast cancer, but the introduction of methods to predict women at elevated risk and prevent the disease has been less successful. Here, we summarize recent data on newer approaches to risk prediction, available approaches to prevention, how new approaches may be made, and the difficult problem of using what we already know to prevent breast cancer in populations. During 2012, the Breast Cancer Campaign facilitated a series of workshops, each covering a specialty area of breast cancer to identify gaps in our knowledge. The risk-and-prevention panel involved in this exercise was asked to expand and update its report and review recent relevant peer-reviewed literature. The enlarged position paper presented here highlights the key gaps in risk-and-prevention research that were identified, together with recommendations for action. The panel estimated from the relevant literature that potentially 50% of breast cancer could be prevented in the subgroup of women at high and moderate risk of breast cancer by using current chemoprevention (tamoxifen, raloxifene, exemestane, and anastrozole) and that, in all women, lifestyle measures, including weight control, exercise, and moderating alcohol intake, could reduce breast cancer risk by about 30%. Risk may be estimated by standard models potentially with the addition of, for example, mammographic density and appropriate single-nucleotide polymorphisms. This review expands on four areas: (a) the prediction of breast cancer risk, (b) the evidence for the effectiveness of preventive therapy and lifestyle approaches to prevention, (c) how understanding the biology of the breast may lead to new targets for prevention, and (d) a summary of published guidelines for preventive approaches and measures required for their implementation. We hope that efforts to fill these and other gaps will lead to considerable advances in our

Patient-reported outcomes from EMILIA, a randomized phase 3 study of trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer.

Science.gov (United States)

Welslau, Manfred; Diéras, Veronique; Sohn, Joo-Hyuk; Hurvitz, Sara A; Lalla, Deepa; Fang, Liang; Althaus, Betsy; Guardino, Ellie; Miles, David

2014-03-01

This report describes the results of an analysis of patient-reported outcomes from EMILIA (TDM4370g/BO21977), a randomized phase 3 study of the antibody-drug conjugate trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer. A secondary endpoint of the EMILIA study was time to symptom worsening (time from randomization to the first documentation of a ≥ 5-point decrease from baseline) as measured by the Trial Outcome Index Physical/Functional/Breast (TOI-PFB) subset of the Functional Assessment of Cancer Therapy-Breast questionnaire. Predefined exploratory patient-reported outcome endpoints included proportion of patients with a clinically significant improvement in symptoms (per TOI-PFB) and proportion of patients with diarrhea symptoms (per Diarrhea Assessment Scale). In the T-DM1 arm, 450 of 495 patients had a baseline and ≥ 1 postbaseline TOI-PFB score versus 445 of 496 patients in the capecitabine-plus-lapatinib arm. Time to symptom worsening was delayed in the T-DM1 arm versus the capecitabine-plus-lapatinib arm (7.1 months versus 4.6 months, respectively; hazard ratio = 0.796; P = .0121). In the T-DM1 arm, 55.3% of patients developed clinically significant improvement in symptoms from baseline versus 49.4% in the capecitabine-plus-lapatinib arm (P = .0842). Although similar at baseline, the number of patients reporting diarrhea symptoms increased 1.5- to 2-fold during treatment with capecitabine and lapatinib but remained near baseline levels in the T-DM1 arm. Together with the EMILIA primary data, these results support the concept that T-DM1 has greater efficacy and tolerability than capecitabine plus lapatinib, which may translate into improvements in health-related quality of life. © 2013 American Cancer Society.

Studies on correlation of positive surgical margin with clinicopathological factors and prognoses in breast conserving surgery

International Nuclear Information System (INIS)

Nishimura, Reiki; Nagao, Kazuharu; Miyayama, Haruhiko

1999-01-01

Out of 484 cases with breast conserving surgery between April 1989 and March 1999, surgical procedures of 34 cases were changed to total mastectomy due to positive surgical margins. In this study we evaluated a clinical significance of surgical margin in relation to clinicopathological factors and prognoses. Ninety-nine cases (20.5%) had positive margins that were judged when cancer cells existed within 5 mm from margin. In multivariate analysis of factors for surgical margin, EIC-comedo status, ly, located site, proliferative activity, and age were significant and independent factors. Regarding local recurrence, positive margin, age, ER and proliferative activity were significant factors in multivariate analysis, especially in cases not receiving postoperative radiation therapy. Radiation therapy may be beneficial for patients with positive surgical margin. And patients with breast recurrence alone had significantly higher survival rates. Therefore, it is suggested that surgical margin may not reflect survival, although it is a significant factor for local recurrence. (author)

Studies on correlation of positive surgical margin with clinicopathological factors and prognoses in breast conserving surgery

Energy Technology Data Exchange (ETDEWEB)

Nishimura, Reiki; Nagao, Kazuharu; Miyayama, Haruhiko [Kumamoto City Hospital (Japan)

1999-09-01

Out of 484 cases with breast conserving surgery between April 1989 and March 1999, surgical procedures of 34 cases were changed to total mastectomy due to positive surgical margins. In this study we evaluated a clinical significance of surgical margin in relation to clinicopathological factors and prognoses. Ninety-nine cases (20.5%) had positive margins that were judged when cancer cells existed within 5 mm from margin. In multivariate analysis of factors for surgical margin, EIC-comedo status, ly, located site, proliferative activity, and age were significant and independent factors. Regarding local recurrence, positive margin, age, ER and proliferative activity were significant factors in multivariate analysis, especially in cases not receiving postoperative radiation therapy. Radiation therapy may be beneficial for patients with positive surgical margin. And patients with breast recurrence alone had significantly higher survival rates. Therefore, it is suggested that surgical margin may not reflect survival, although it is a significant factor for local recurrence. (author)

Drivers of advanced stage at breast cancer diagnosis in the multicountry African breast cancer – disparities in outcomes (ABC‐DO) study

Science.gov (United States)

Zietsman, Annelle; Galukande, Moses; Anele, Angelica; Adisa, Charles; Parham, Groesbeck; Pinder, Leeya; Cubasch, Herbert; Joffe, Maureen; Kidaaga, Frederick; Lukande, Robert; Offiah, Awa U.; Egejuru, Ralph O.; Shibemba, Aaron; Schuz, Joachim; Anderson, Benjamin O.; dos Santos Silva, Isabel; McCormack, Valerie

2017-01-01

Breast cancer (BC) survival rates in sub‐Saharan Africa (SSA) are low in part due to advanced stage at diagnosis. As one component of a study of the entire journey of SSA women with BC, we aimed to identify shared and setting‐specific drivers of advanced stage BC. Women newly diagnosed in the multicountry African Breast Cancer–Disparities in Outcomes (ABC‐DO) study completed a baseline interview and their stage information was extracted from medical records. Ordinal logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for advanced stage (I, II, III, IV) in relation to individual woman‐level, referral and biological factors. A total of 1795 women were included from Nigeria, Uganda, Zambia, and the multiracial populations of Namibia and South Africa, 1091 of whom (61%) were stage III/IV. Stage was lower in women with greater BC knowledge (OR 0.77 (95% CI: 0.70, 0.85) per point on a 6 point scale). More advanced stage was associated with being black (4.00 (2.79, 5.74)), having attended

Religion and spirituality in coping with advanced breast cancer: perspectives from Malaysian Muslim women.

Science.gov (United States)

Ahmad, Farizah; Muhammad, Mazanah binti; Abdullah, Amini Amir

2011-03-01

This article is part of a larger study on the role of spirituality in coping with breast cancer among Malaysian Muslim women. The study seeks to reveal the meaning of the experience through the stories of three Muslim women surviving advanced breast cancer, to better understand the deep meanings that inform their experiences with spirituality and transformation as they cope with the challenges of breast cancer. Data were gathered using in-depth interview. Qualitative methods were used in identifying two themes--illness as an awakening and hope and freedom comes from surrendering to God. The themes were discussed in the context of two broad areas: (1) what are the new meanings these women discovered in their experiences with cancer; and (2) how did the new meanings change their lives? The study suggests that cancer survivors' experiences with cancer and their learning processes must be understood within the appropriate cultural context. This is especially so for spirituality. The common emphasis of spirituality on relationship with God, self and others, may significantly influence how people learn to live with cancer.

Survival is associated with complete response on MRI after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer

NARCIS (Netherlands)

Loo, Claudette E; Rigter, Lisanne S; Pengel, Kenneth E; Wesseling, Jelle; Rodenhuis, Sjoerd; Peeters, Marie-Jeanne T F D Vrancken; Sikorska, Karolina; Gilhuijs, Kenneth G A

2016-01-01

BACKGROUND: Pathological complete remission (pCR) of estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer is rarely achieved after neoadjuvant chemotherapy (NAC). In addition, the prognostic value of pCR for this breast cancer subtype is limited. We

Restricted Boltzmann machines based oversampling and semi-supervised learning for false positive reduction in breast CAD.

Science.gov (United States)

Cao, Peng; Liu, Xiaoli; Bao, Hang; Yang, Jinzhu; Zhao, Dazhe

2015-01-01

The false-positive reduction (FPR) is a crucial step in the computer aided detection system for the breast. The issues of imbalanced data distribution and the limitation of labeled samples complicate the classification procedure. To overcome these challenges, we propose oversampling and semi-supervised learning methods based on the restricted Boltzmann machines (RBMs) to solve the classification of imbalanced data with a few labeled samples. To evaluate the proposed method, we conducted a comprehensive performance study and compared its results with the commonly used techniques. Experiments on benchmark dataset of DDSM demonstrate the effectiveness of the RBMs based oversampling and semi-supervised learning method in terms of geometric mean (G-mean) for false positive reduction in Breast CAD.

SU-E-J-134: An Augmented-Reality Optical Imaging System for Accurate Breast Positioning During Radiotherapy

International Nuclear Information System (INIS)

Nazareth, D; Malhotra, H; French, S; Hoffmann, K; Merrow, C

2014-01-01

Purpose: Breast radiotherapy, particularly electronic compensation, may involve large dose gradients and difficult patient positioning problems. We have developed a simple self-calibrating augmented-reality system, which assists in accurately and reproducibly positioning the patient, by displaying her live image from a single camera superimposed on the correct perspective projection of her 3D CT data. Our method requires only a standard digital camera capable of live-view mode, installed in the treatment suite at an approximately-known orientation and position (rotation R; translation T). Methods: A 10-sphere calibration jig was constructed and CT imaged to provide a 3D model. The (R,T) relating the camera to the CT coordinate system were determined by acquiring a photograph of the jig and optimizing an objective function, which compares the true image points to points calculated with a given candidate R and T geometry. Using this geometric information, 3D CT patient data, viewed from the camera's perspective, is plotted using a Matlab routine. This image data is superimposed onto the real-time patient image, acquired by the camera, and displayed using standard live-view software. This enables the therapists to view both the patient's current and desired positions, and guide the patient into assuming the correct position. The method was evaluated using an in-house developed bolus-like breast phantom, mounted on a supporting platform, which could be tilted at various angles to simulate treatment-like geometries. Results: Our system allowed breast phantom alignment, with an accuracy of about 0.5 cm and 1 ± 0.5 degree. Better resolution could be possible using a camera with higher-zoom capabilities. Conclusion: We have developed an augmented-reality system, which combines a perspective projection of a CT image with a patient's real-time optical image. This system has the potential to improve patient setup accuracy during breast radiotherapy, and could possibly be

SU-E-J-134: An Augmented-Reality Optical Imaging System for Accurate Breast Positioning During Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Nazareth, D; Malhotra, H; French, S [Roswell Park Cancer Institute, Buffalo, NY (United States); Hoffmann, K [Neurosurgery at SUNY at Buffalo, Buffalo, NY (United States); Merrow, C [Bassett Healthcare, Oneonta, NY (United States)

2014-06-01

Purpose: Breast radiotherapy, particularly electronic compensation, may involve large dose gradients and difficult patient positioning problems. We have developed a simple self-calibrating augmented-reality system, which assists in accurately and reproducibly positioning the patient, by displaying her live image from a single camera superimposed on the correct perspective projection of her 3D CT data. Our method requires only a standard digital camera capable of live-view mode, installed in the treatment suite at an approximately-known orientation and position (rotation R; translation T). Methods: A 10-sphere calibration jig was constructed and CT imaged to provide a 3D model. The (R,T) relating the camera to the CT coordinate system were determined by acquiring a photograph of the jig and optimizing an objective function, which compares the true image points to points calculated with a given candidate R and T geometry. Using this geometric information, 3D CT patient data, viewed from the camera's perspective, is plotted using a Matlab routine. This image data is superimposed onto the real-time patient image, acquired by the camera, and displayed using standard live-view software. This enables the therapists to view both the patient's current and desired positions, and guide the patient into assuming the correct position. The method was evaluated using an in-house developed bolus-like breast phantom, mounted on a supporting platform, which could be tilted at various angles to simulate treatment-like geometries. Results: Our system allowed breast phantom alignment, with an accuracy of about 0.5 cm and 1 ± 0.5 degree. Better resolution could be possible using a camera with higher-zoom capabilities. Conclusion: We have developed an augmented-reality system, which combines a perspective projection of a CT image with a patient's real-time optical image. This system has the potential to improve patient setup accuracy during breast radiotherapy, and could

Observed and Predicted Risk of Breast Cancer Death in Randomized Trials on Breast Cancer Screening.

Science.gov (United States)

Autier, Philippe; Boniol, Mathieu; Smans, Michel; Sullivan, Richard; Boyle, Peter

2016-01-01

The role of breast screening in breast cancer mortality declines is debated. Screening impacts cancer mortality through decreasing the number of advanced cancers with poor diagnosis, while cancer treatment works through decreasing the case-fatality rate. Hence, reductions in cancer death rates thanks to screening should directly reflect reductions in advanced cancer rates. We verified whether in breast screening trials, the observed reductions in the risk of breast cancer death could be predicted from reductions of advanced breast cancer rates. The Greater New York Health Insurance Plan trial (HIP) is the only breast screening trial that reported stage-specific cancer fatality for the screening and for the control group separately. The Swedish Two-County trial (TCT)) reported size-specific fatalities for cancer patients in both screening and control groups. We computed predicted numbers of breast cancer deaths, from which we calculated predicted relative risks (RR) and (95% confidence intervals). The Age trial in England performed its own calculations of predicted relative risk. The observed and predicted RR of breast cancer death were 0.72 (0.56-0.94) and 0.98 (0.77-1.24) in the HIP trial, and 0.79 (0.78-1.01) and 0.90 (0.80-1.01) in the Age trial. In the TCT, the observed RR was 0.73 (0.62-0.87), while the predicted RR was 0.89 (0.75-1.05) if overdiagnosis was assumed to be negligible and 0.83 (0.70-0.97) if extra cancers were excluded. In breast screening trials, factors other than screening have contributed to reductions in the risk of breast cancer death most probably by reducing the fatality of advanced cancers in screening groups. These factors were the better management of breast cancer patients and the underreporting of breast cancer as the underlying cause of death. Breast screening trials should publish stage-specific fatalities observed in each group.

Tumour 18 F-FDG Uptake on preoperative PET/CT may predict axillary lymph node metastasis in ER-positive/HER2-negative and HER2-positive breast cancer subtypes

Energy Technology Data Exchange (ETDEWEB)

Kim, Jin You; Lee, Suck Hong; Kim, Suk [Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Department of Radiology, Seo-gu, Busan (Korea, Republic of); Kang, Taewoo [Pusan National University Hospital, Busan Cancer Center, Busan (Korea, Republic of); Bae, Young Tae [Pusan National University Hospital, Department of Surgery, Busan (Korea, Republic of)

2015-04-01

To evaluate the association between tumour FDG uptake on preoperative PET/CT and axillary lymph node metastasis (ALNM) according to breast cancer subtype. The records of 671 patients with invasive breast cancer who underwent {sup 18} F-FDG PET/CT and surgery were reviewed. Using immunohistochemistry, tumours were divided into three subtypes: oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, HER2-positive, and triple-negative. Tumour FDG uptake, expressed as maximum standardized uptake value (SUV{sub max}), and clinicopathological variables were analysed. ALNM was present in 187 of 461 ER-positive/HER2-negative, 54 of 97 HER2-positive, and 38 of 113 triple-negative tumours. On multivariate analysis, high tumour SUV{sub max} (≥4.25) (P < 0.001), large tumour size (>2 cm) (P = 0.003) and presence of lymphovascular invasion (P < 0.001) were independent variables associated with ALNM. On subset analyses, tumour SUV{sub max} maintained independent significance for predicting ALNM in ER-positive/HER2-negative (adjusted odds ratio: 3.277, P < 0.001) and HER2-positive tumours (adjusted odds ratio: 14.637, P = 0.004). No association was found for triple-negative tumours (P = 0.161). Tumour SUV{sub max} may be an independent prognostic factor for ALNM in patients with invasive breast cancer, especially in ER-positive/HER2-negative and HER2-positive subtypes, but not in those with triple-negative subtype. (orig.)

Progranulin as a prognostic biomarker for breast cancer recurrence in patients who had hormone receptor-positive tumors: a cohort study.

Directory of Open Access Journals (Sweden)

Dong Hoe Koo

Full Text Available Progranulin (PGRN is considered to play an important role in breast cancer tumorigenesis and in inhibiting tamoxifen-induced apoptosis. We aimed to determine whether PGRN levels are associated with breast cancer recurrence after curative surgery.We evaluated the associations between preoperative serum PGRN levels and breast cancer recurrence in a cohort of 697 newly diagnosed breast cancer patients who underwent curative surgery between April 2001 and December 2004. The mean age ± standard deviation (SD was 46 ± 9.8 years, and all patients with hormone receptor (HR-positive tumors received adjuvant tamoxifen therapy. At a median follow-up of 62.2 months (range, 2.9-98.2, 89 patients (12.8% had experienced a recurrence and 51 patients (7.3% had died. In the HR-positive group, serum PGRN levels were associated with recurrence according to the log-rank test for trend (p for trend = 0.049. There was no association between PGRN levels and recurrence in the HR-negative group (p for trend = 0.658. Adjusted hazard ratios, including possible confounders, revealed a linear relationship between serum PGRN levels and recurrence in the HR-positive group (p for trend = 0.049, and this association was further strengthened after excluding patients who had no lymph node metastasis (p for trend = 0.038.Serum PGRN levels were clinically significant for predicting recurrence in patients with HR-positive breast cancer during adjuvant tamoxifen therapy.

A gene expression signature of Retinoblastoma loss-of-function predicts resistance to neoadjuvant chemotherapy in ER-positive/HER2-positive breast cancer patients.

Science.gov (United States)

Risi, Emanuela; Grilli, Andrea; Migliaccio, Ilenia; Biagioni, Chiara; McCartney, Amelia; Guarducci, Cristina; Bonechi, Martina; Benelli, Matteo; Vitale, Stefania; Biganzoli, Laura; Bicciato, Silvio; Di Leo, Angelo; Malorni, Luca

2018-07-01

HER2-positive (HER2+) breast cancers show heterogeneous response to chemotherapy, with the ER-positive (ER+) subgroup deriving less benefit. Loss of retinoblastoma tumor suppressor gene (RB1) function has been suggested as a cardinal feature of breast cancers that are more sensitive to chemotherapy and conversely resistant to CDK4/6 inhibitors. We performed a retrospective analysis exploring RBsig, a gene signature of RB loss, as a potential predictive marker of response to neoadjuvant chemotherapy in ER+/HER2+ breast cancer patients. We selected clinical trials of neoadjuvant chemotherapy ± anti-HER2 therapy in HER2+ breast cancer patients with available information on gene expression data, hormone receptor status, and pathological complete response (pCR) rates. RBsig expression was computed in silico and correlated with pCR. Ten studies fulfilled the inclusion criteria and were included in the analysis (514 patients). Overall, of 211 ER+/HER2+ breast cancer patients, 49 achieved pCR (23%). The pCR rate following chemotherapy ± anti-HER2 drugs in patients with RBsig low expression was significantly lower compared to patients with RBsig high expression (16% vs. 30%, respectively; Fisher's exact test p = 0.015). The area under the ROC curve (AUC) was 0.62 (p = 0.005). In the 303 ER-negative (ER-)/HER2+ patients treated with chemotherapy ± anti-HER2 drugs, the pCR rate was 43%. No correlation was found between RBsig expression and pCR rate in this group. Low expression of RBsig identifies a subset of ER+/HER2+ patients with low pCR rates following neoadjuvant chemotherapy ± anti-HER2 therapy. These patients may potentially be spared chemotherapy in favor of anti-HER2, endocrine therapy, and CDK 4/6 inhibitor combinations.

A randomized trial of a cognitive-behavioral therapy and hypnosis intervention on positive and negative affect during breast cancer radiotherapy.

Science.gov (United States)

Schnur, Julie B; David, Daniel; Kangas, Maria; Green, Sheryl; Bovbjerg, Dana H; Montgomery, Guy H

2009-04-01

Breast cancer radiotherapy can be an emotionally difficult experience. Despite this, few studies have examined the effectiveness of psychological interventions to reduce negative affect, and none to date have explicitly examined interventions to improve positive affect among breast cancer radiotherapy patients. The present study examined the effectiveness of a multimodal psychotherapeutic approach, combining cognitive-behavioral therapy and hypnosis (CBTH), to reduce negative affect and increase positive affect in 40 women undergoing breast cancer radiotherapy. Participants were randomly assigned to receive either CBTH or standard care. Participants completed weekly self-report measures of positive and negative affect. Repeated and univariate analyses of variance revealed that the CBTH approach reduced levels of negative affect [F(1, 38)=13.49; p=.0007, omega(2)=.56], and increased levels of positive affect [F(1, 38)=9.67; p=.0035, omega(2)=.48], during the course of radiotherapy. Additionally, relative to the control group, the CBTH group demonstrated significantly more intense positive affect [F(1, 38)=7.09; p=.0113, d=.71] and significantly less intense negative affect [F(1, 38)=10.30; p=.0027, d=.90] during radiotherapy. The CBTH group also had a significantly higher frequency of days where positive affect was greater than negative affect (85% of days assessed for the CBTH group versus 43% of the Control group) [F(1, 38)=18.16; p=.0001, d=1.16]. Therefore, the CBTH intervention has the potential to improve the affective experience of women undergoing breast cancer radiotherapy.

“A rising tide lifts all boats”: establishing a multidisciplinary genomic tumor board for breast cancer patients with advanced disease

Directory of Open Access Journals (Sweden)

Michelle L. McGowan

2016-11-01

Full Text Available Abstract Background Research suggests that multidisciplinary genomic tumor boards (MGTB can inform cancer patient care, though little is known about factors influencing how MGTBs interpret genomic test results, make recommendations, and perceive the utility of this approach. This study’s objective was to observe, describe, and assess the establishment of the Breast Multidisciplinary Genomic Tumor Board, the first MGTB focused on interpreting genomic test results for breast cancer patients with advanced disease. Methods We conducted a qualitative case study involving participant observation at monthly MGTB meetings from October 2013 through November 2014 and interviews with 12 MGTB members. We analyzed social dynamics and interactions within the MGTB regarding interpretation of genomic findings and participants’ views on effectiveness of the MGTB in using genomics to inform patient care. Results Twenty-two physicians, physician-scientists, basic scientists, bioethicists, and allied care professionals comprised the MGTB. The MGTB reviewed FoundationOne™ results for 40 metastatic breast cancer patients. Based on findings, the board mostly recommended referring patients to clinical trials (34 and medical genetics (15, and Food and Drug Administration-approved (FDA breast cancer therapies (13. Though multidisciplinary, recommendations were driven by medical oncologists. Interviewees described providing more precise care recommendations and professional development as advantages and the limited actionability of genomic test results as a challenge for the MGTB. Conclusions Findings suggest both feasibility and desirability of pooling professional expertise in genomically-guided breast cancer care and challenges to institutionalizing a Breast MGTB, specifically in promoting interdisciplinary contributions and managing limited actionability of genomic test results for patients with advanced disease.

Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia

International Nuclear Information System (INIS)

Fujiwara, Ryoichi; Maruo, Yoshihiro; Chen, Shujuan; Tukey, Robert H.

2015-01-01

Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ. It is currently believed that unconjugated bilirubin is metabolized mainly in the liver. However, recent findings support the concept that extrahepatic tissues, such as small intestine and skin, contribute to bilirubin glucuronidation during the neonatal period. We will review the recent advances made towards understanding biological and molecular events impacting BMJ, especially regarding the role of extrahepatic UGT1A1 expression. - Highlights: • Breast-feeding can be a factor for the development of neonatal hyperbilirubinemia. • UDP-glucuronosyltransferase (UGT) 1A1 is the sole bilirubin-metabolizing enzyme. • Extrahepatic UGT1A1 plays an important role in bilirubin metabolism. • We discuss the potential mechanism of breast milk-induced neonatal jaundice.

Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia

Energy Technology Data Exchange (ETDEWEB)

Fujiwara, Ryoichi, E-mail: fujiwarar@pharm.kitasato-u.ac.jp [Department of Pharmaceutics, School of Pharmacy, Kitasato University, Tokyo (Japan); Maruo, Yoshihiro [Department of Pediatrics, Shiga University of Medical Science, Shiga (Japan); Chen, Shujuan [Department of Pharmacology, Laboratory of Environmental Toxicology, University of California at San Diego, La Jolla, CA 92093 (United States); Tukey, Robert H., E-mail: rtukey@ucsd.edu [Department of Pharmacology, Laboratory of Environmental Toxicology, University of California at San Diego, La Jolla, CA 92093 (United States); Department of Chemistry & Biochemistry, Laboratory of Environmental Toxicology, University of California at San Diego, La Jolla, CA 92093 (United States)

2015-11-15

Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ. It is currently believed that unconjugated bilirubin is metabolized mainly in the liver. However, recent findings support the concept that extrahepatic tissues, such as small intestine and skin, contribute to bilirubin glucuronidation during the neonatal period. We will review the recent advances made towards understanding biological and molecular events impacting BMJ, especially regarding the role of extrahepatic UGT1A1 expression. - Highlights: • Breast-feeding can be a factor for the development of neonatal hyperbilirubinemia. • UDP-glucuronosyltransferase (UGT) 1A1 is the sole bilirubin-metabolizing enzyme. • Extrahepatic UGT1A1 plays an important role in bilirubin metabolism. • We discuss the potential mechanism of breast milk-induced neonatal jaundice.

How I report breast magnetic resonance imaging studies for breast cancer staging and screening.

Science.gov (United States)

Vinnicombe, Sarah

2016-07-25

Magnetic resonance imaging (MRI) of the breast is the most sensitive imaging technique for the diagnosis and local staging of primary breast cancer and yet, despite the fact that it has been in use for 20 years, there is little evidence that its widespread uncritical adoption has had a positive impact on patient-related outcomes.This has been attributed previously to the low specificity that might be expected with such a sensitive modality, but with modern techniques and protocols, the specificity and positive predictive value for malignancy can exceed that of breast ultrasound and mammography. A more likely explanation is that historically, clinicians have acted on MRI findings and altered surgical plans without prior histological confirmation. Furthermore, modern adjuvant therapy for breast cancer has improved so much that it has become a very tall order to show a an improvement in outcomes such as local recurrence rates.In order to obtain clinically useful information, it is necessary to understand the strengths and weaknesses of the technique and the physiological processes reflected in breast MRI. An appropriate indication for the scan, proper patient preparation and good scan technique, with rigorous quality assurance, are all essential prerequisites for a diagnostically relevant study.The use of recognised descriptors from a standardised lexicon is helpful, since assessment can then dictate subsequent recommendations for management, as in the American College of Radiology BI-RADS (Breast Imaging Reporting and Data System) lexicon (Morris et al., ACR BI-RADS® Atlas, Breast Imaging Reporting and Data System, 2013). It also enables audit of the service. However, perhaps the most critical factor in the generation of a meaningful report is for the reporting radiologist to have a thorough understanding of the clinical question and of the findings that will influence management. This has never been more important than at present, when we are in the throes of a

Predicting Likelihood of Having Four or More Positive Nodes in Patient With Sentinel Lymph Node-Positive Breast Cancer: A Nomogram Validation Study

International Nuclear Information System (INIS)

Unal, Bulent; Gur, Akif Serhat; Beriwal, Sushil; Tang Gong; Johnson, Ronald; Ahrendt, Gretchen; Bonaventura, Marguerite; Soran, Atilla

2009-01-01

Purpose: Katz suggested a nomogram for predicting having four or more positive nodes in sentinel lymph node (SLN)-positive breast cancer patients. The findings from this formula might influence adjuvant radiotherapy decisions. Our goal was to validate the accuracy of the Katz nomogram. Methods and Materials: We reviewed the records of 309 patients with breast cancer who had undergone completion axillary lymph node dissection. The factors associated with the likelihood of having four or more positive axillary nodes were evaluated in patients with one to three positive SLNs. The nomogram developed by Katz was applied to our data set. The area under the curve of the corresponding receiver operating characteristics curve was calculated for the nomogram. Results: Of the 309 patients, 80 (25.9%) had four or more positive axillary lymph nodes. On multivariate analysis, the number of positive SLNs (p < .0001), overall metastasis size (p = .019), primary tumor size (p = .0001), and extracapsular extension (p = .01) were significant factors predicting for four or more positive nodes. For patients with <5% probability, 90.3% had fewer than four positive nodes and 9.7% had four or more positive nodes. The negative predictive value was 91.7%, and sensitivity was 80%. The nomogram was accurate and discriminating (area under the curve, .801). Conclusion: The probability of four or more involved nodes is significantly greater in patients who have an increased number of positive SLNs, increased overall metastasis size, increased tumor size, and extracapsular extension. The Katz nomogram was validated in our patients. This nomogram will be helpful to clinicians making adjuvant treatment recommendations to their patients.

The prognostic value of Her4 receptor isoform expression in triple-negative and Her2 positive breast cancer patients

International Nuclear Information System (INIS)

Machleidt, Anna; Buchholz, Stefan; Diermeier-Daucher, Simone; Zeman, Florian; Ortmann, Olaf; Brockhoff, Gero

2013-01-01

Not only four but rather seven different human epidermal growth factor receptor related (Her) receptor tyrosine kinases (RTKs) have been described to be expressed in a variety of normal and neoplastic tissues: Her1, Her2, Her3, and additionally four Her4 isoforms have been identified. A differential expression of Her4 isoforms does not, however, play any role in either the molecular diagnostics or treatment decision for breast cancer patients. The prognostic and predictive impact of Her4 expression in breast cancer is basically unclear. We quantified the Her4 variants JM-a/CYT1, JM-a/CYT2, JM-b/CYT1, and JM-b/CYT2 by isoform-specific polymerase chain reaction (qPCR) in (i) triple-negative, (ii) Her2 positive breast cancer tissues and (iii) in benign breast tissues. In all three tissue collectives we never found the JM-b/CYT1 or the JM-b/CYT2 isoform expressed. In contrast, the two JM-a/CYT1 and JM-a/CYT2 isoforms were always simultaneously expressed but at different ratios. We identified a positive prognostic impact on overall survival (OS) in triple-negative and event-free survival (EFS) in Her2 positive patients. This finding is independent of the absolute JM-a/CYT1 to JM-a/CYT2 expression ratio. In Her2 positive patients, Her4 expression only has a favorable effect in estrogen-receptor (ER)-positive but not in ER-negative individuals. In summary, JM-a/CYT1 and JM-a/CYT2 but not JM-b isoforms of the Her4 receptor are simultaneously expressed in both triple-negative and Her2 positive breast cancer tissues. Although different expression ratios of the two JM-a isoforms did not reveal any additional information, Her4 expression basically indicates a prolonged EFS and OFS. An extended expression analysis that takes all Her receptor homologs, including the Her4 isoforms, into account might render more precisely the molecular diagnostics required for the development of optimized targeted therapies

Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability

Directory of Open Access Journals (Sweden)

Lu Kun

2008-12-01

Full Text Available Abstract Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself. Methods Immunohistochemistry for Her2 and Pin1 were performed on two hundred twenty-three human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence. Results Sixty-four samples (28.7% stained positive for Her2 (IHC 3+, and 54% (122/223 of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5% were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2

Mammography with and without radiolucent positioning sheets : Comparison of projected breast area, pain experience, radiation dose and technical image quality

NARCIS (Netherlands)

Timmers, Janine; ten Voorde, Marloes; van Engen, Ruben E.; van Landsveld-Verhoeven, Cary; Pijnappel, Ruud; Droogh-de Greve, Kitty; den Heeten, Gerard J.; Broeders, Mireille J. M.

2015-01-01

Purpose: To compare projected breast area, image quality, pain experience and radiation dose between mammography performed with and without radiolucent positioning sheets. Methods: 184 women screened in the Dutch breast screening programme (May-June 2012) provided written informed consent to have

Treating ER+ Breast Cancer with CDK4/6 Inhibitors.

Science.gov (United States)

2017-08-01

Data from the MONARCH2, PALOMA-1, and TREnd trials strongly support using CDK4/6 inhibitors alongside standard endocrine therapy for advanced ER-positive breast cancer. Including these targeted agents not only improves progression-free survival but may reverse acquired resistance to hormone treatment. ©2017 American Association for Cancer Research.

Should breast density influence patient selection for breast-conserving surgery?

Science.gov (United States)

Kapoor, Nimmi S; Eaton, Anne; King, Tari A; Patil, Sujata; Stempel, Michelle; Morris, Elizabeth; Brogi, Edi; Morrow, Monica

2013-02-01

In a previous study of the relationship between breast density and primary tumor features, we observed a higher mastectomy rate in patients with extremely dense breasts. Here we examine possible reasons for this finding. Data were obtained from a prospectively maintained database of 1,056 invasive breast cancer patients from January 2005 to June 2007. Mammographic density was assigned by Breast Imaging-Reporting and Data System (BI-RADS) classification. Initial and final surgical procedures, and patient and tumor variables were recorded. Breast-conserving surgery (BCS) was attempted in 758 patients (72 %), 385 (51 %) of whom had preoperative magnetic resonance imaging (MRI). Initial BCS was less common among patients with the highest (BI-RADS 4) breast density compared to patients with less-dense breasts (52 vs. 74 %; p mastectomy compared to patients with less-dense breasts. After initial BCS, 387 patients (51 %) had positive shaved margins, 96 (25 %) of whom converted to mastectomy. MRI did not correlate with the rate of positive margins overall or among those with dense breasts. Adjusting for clinical and pathologic variables, density did not predict margin status or conversion to mastectomy. In a multivariate model, age, histologic grade, extensive intraductal component, and multicentricity/multifocality were independently associated with conversion to mastectomy. Density alone seems to influence the decision to proceed with initial mastectomy. When BCS was attempted, breast density was not associated with positive margins or conversion to mastectomy. A benefit of MRI in decreasing positive margins was not observed. These data do not support the use of breast density as a selection criterion for BCS.

Digital Breast Tomosynthesis: State of the Art

Science.gov (United States)

Vedantham, Srinivasan; Vijayaraghavan, Gopal R.; Kopans, Daniel B.

2015-01-01

This topical review on digital breast tomosynthesis (DBT) is provided with the intent of describing the state of the art in terms of technology, results from recent clinical studies, advanced applications, and ongoing efforts to develop multimodality imaging systems that include DBT. Particular emphasis is placed on clinical studies. The observations of increase in cancer detection rates, particularly for invasive cancers, and the reduction in false-positive rates with DBT in prospective trials indicate its benefit for breast cancer screening. Retrospective multireader multicase studies show either noninferiority or superiority of DBT compared with mammography. Methods to curtail radiation dose are of importance. © RSNA, 2015 PMID:26599926

Abemaciclib: a CDK4/6 inhibitor for the treatment of HR+/HER2– advanced breast cancer

Directory of Open Access Journals (Sweden)

Corona SP

2018-02-01

Full Text Available Silvia Paola Corona,1 Daniele Generali2 1Radiation Oncology Department, Peter MacCallum Cancer Centre, Bentleigh East, VIC, Australia; 2Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy Abstract: Although early breast cancer (BC is highly curable, advanced or metastatic disease poses numerous challenges in terms of medical management and treatment decisions and is associated with significantly worse prognosis. Among the new targeted agents, anticancer drugs exploiting the cell-cycle machinery have shown great potential in preclinical studies. CDK4/6 inhibitors target the cyclin D/CDK/retinoblastoma signaling pathway, inducing cell-cycle arrest, reduced cell viability and tumor shrinking. As the cyclin D/CDK complex is activated downstream of estrogen signaling, the combination of CDK4/6 inhibitors with standard endocrine therapies represents a rational approach to elicit synergic antitumor activity in hormone receptor-positive BC. The results of clinical trials have indeed confirmed the superiority of the combination of CDK4/6 inhibitors plus endocrine therapies over endocrine therapy alone. Currently approved are three compounds that exhibit similar structural characteristics as well as biological and clinical activities. Abemaciclib is the latest CDK4/6 inhibitor approved by the US Food and Drug Administration (FDA in view of the results of the MONARCH 1 and 2 trials. Further trials are ongoing as other important questions await response. In this review, we focus on abemaciclib to examine preclinical and clinical results, describing current therapeutic indications, open questions and ongoing clinical trials. Keywords: CDK4/6 inhibitor, abemaciclib, breast cancer, hormone receptor-positive BC, metastatic BC, mBC

Mammography with and without radiolucent positioning sheets: Comparison of projected breast area, pain experience, radiation dose and technical image quality

NARCIS (Netherlands)

Timmers, Janine; ten Voorde, Marloes; van Engen, Ruben E.; van Landsveld-Verhoeven, Cary; Pijnappel, Ruud; Droogh-de Greve, Kitty; den Heeten, Gerard J.; Broeders, Mireille J. M.

2015-01-01

To compare projected breast area, image quality, pain experience and radiation dose between mammography performed with and without radiolucent positioning sheets. 184 women screened in the Dutch breast screening programme (May-June 2012) provided written informed consent to have one additional image

Comparison of Clinicopathological Characteristics and Outcome of Inflammatory and Non-inflammatory Locally Advanced Breast Cancer: A Study in Iran

Directory of Open Access Journals (Sweden)

Saeed Arefanian

2014-05-01

Full Text Available Background: Inflammatory breast cancer (IBC, a subgroup of locally advanced breast cancer (LABC, is diagnosed based on clinical findings, and seems to be different from other types of LABC. The purpose of this study was to compare clinicopathological characteristics and outcomes between inflammatory and non-inflammatory LABC patients at Breast Cancer Research Center (BCRC, Tehran, Iran.Methods: The medical records of all patients who were diagnosed as LABC in BCRC  since  1997  to  2011  were  extracted  from  the database. Then,  clinical  and pathological characteristics and overall survival of IBC patients were compared with non-inflammatory LABC (NI-LABC.Results: A total number of 340 patients were identified as LABC from which 17 patients (5% were diagnosed as IBC. Menopausal status, body mass index (BMI, family history of breast cancer, nodal status, and Her2/neu and PR positivity were not statistically different between IBC and NI-LABC groups. The difference in estrogen receptor (ER between the two groups was significant (P = 0.028. Median duration of follow-up was 26.50 months. Patients with IBC had overall survival of 27.9 months (95% CI: 22.7–33.1 which was lower than patients in the NI-LABC group with a survival of 118.9 months (95% CI: 107.3–130.6 (P = 0.015. The difference between the disease-free survivals of the two groups were also statistically significant (P < 0.001.Conclusions: Compared to NI-LABC, IBC is more frequently ER negative and more commonly associated with lower survival rate. These findings reinforce the idea that IBC has a more aggressive biology and more unfavorable outcome than NI-LABC and needs close follow-up. Normal 0 false false false EN-US X-NONE X-NONE

Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer--8-year results of the Breast International Group 02-98 phase III trial

DEFF Research Database (Denmark)

Oakman, C; Francis, P A; Crown, J

2013-01-01

Background In women with node-positive breast cancer, the Breast International Group (BIG) 02-98 tested the incorporation of docetaxel (Taxotere) into doxorubicin (Adriamycin)-based chemotherapy, and compared sequential and concurrent docetaxel. At 5 years, there was a trend for improved disease...

Impact of intermediate mammography assessment on the likelihood of false-positive results in breast cancer screening programmes

International Nuclear Information System (INIS)

Ascunce, Nieves; Ederra, Maria; Delfrade, Josu; Erdozain, Nieves; Baroja, Araceli; Zubizarreta, Raquel; Salas, Dolores; Castells, Xavier

2012-01-01

Breast cancer screening is offered to 100% of the target population in Spain and intermediate mammograms (IMs) are sometimes indicated. This study was aimed at analysing the frequency of IMs, the factors determining their recommendation, and their impact on the risk of false-positive results and the detection rate. Data from 3,471,307 mammograms from Spanish breast cancer screening programmes were included. 3.36% of the mammograms were IMs. The factors associated with the use of IMs were age, initial screening, previous invasive tests, a familial history of breast cancer and use of hormone replacement therapy. In screening episodes with an IM, the probability of a false-positive result was 13.74% (95% CI: 13.43-14.05), almost double that in episodes without IMs (6.02%, 95% CI 5.99-6.05). In young women with previous invasive procedures, a familial history of breast cancer or hormone replacement therapy use who were undergoing their initial screen, this probability was lower when IMs were performed. IMs always increased the detection rate. The factors prompting IMs should be characterised so that radiologists can systematise their recommendations according to the presence of the factors maximising the benefits and minimising the adverse effects of this procedure. (orig.)

Impact of intermediate mammography assessment on the likelihood of false-positive results in breast cancer screening programmes

Energy Technology Data Exchange (ETDEWEB)

Ascunce, Nieves [Public Health Institute, CIBERESP, Navarra Breast Cancer Screening Programme, Pamplona (Spain); Instituto de Salud Publica, Navarra Breast Cancer Screening Programme, Pamplona (Spain); Ederra, Maria; Delfrade, Josu; Erdozain, Nieves [Public Health Institute, CIBERESP, Navarra Breast Cancer Screening Programme, Pamplona (Spain); Baroja, Araceli [Fundacion Rioja Salud, Logrono (Spain); Zubizarreta, Raquel [Public Health and Planning Directorate, Health Office, Galician Breast Cancer Screening Programme, Galicia (Spain); Salas, Dolores [General Directorate Public Health and Centre for Public Health Research (CSISP), Valencia (Spain); Castells, Xavier [Mar Teaching Hospital, CIBERESP, Department of Clinical Epidemiology, Barcelona (Spain)

2012-02-15

Breast cancer screening is offered to 100% of the target population in Spain and intermediate mammograms (IMs) are sometimes indicated. This study was aimed at analysing the frequency of IMs, the factors determining their recommendation, and their impact on the risk of false-positive results and the detection rate. Data from 3,471,307 mammograms from Spanish breast cancer screening programmes were included. 3.36% of the mammograms were IMs. The factors associated with the use of IMs were age, initial screening, previous invasive tests, a familial history of breast cancer and use of hormone replacement therapy. In screening episodes with an IM, the probability of a false-positive result was 13.74% (95% CI: 13.43-14.05), almost double that in episodes without IMs (6.02%, 95% CI 5.99-6.05). In young women with previous invasive procedures, a familial history of breast cancer or hormone replacement therapy use who were undergoing their initial screen, this probability was lower when IMs were performed. IMs always increased the detection rate. The factors prompting IMs should be characterised so that radiologists can systematise their recommendations according to the presence of the factors maximising the benefits and minimising the adverse effects of this procedure. (orig.)

64Cu-DOTA-trastuzumab PET imaging in patients with HER2-positive breast cancer.

Science.gov (United States)

Tamura, Kenji; Kurihara, Hiroaki; Yonemori, Kan; Tsuda, Hitoshi; Suzuki, Junko; Kono, Yuzuru; Honda, Natsuki; Kodaira, Makoto; Yamamoto, Harukaze; Yunokawa, Mayu; Shimizu, Chikako; Hasegawa, Koki; Kanayama, Yousuke; Nozaki, Satoshi; Kinoshita, Takayuki; Wada, Yasuhiro; Tazawa, Shusaku; Takahashi, Kazuhiro; Watanabe, Yasuyoshi; Fujiwara, Yasuhiro

2013-11-01

The purpose of this study was to determine the safety, distribution, internal dosimetry, and initial human epidermal growth factor receptor 2 (HER2)-positive tumor images of (64)Cu-DOTA-trastuzumab in humans. PET was performed on 6 patients with primary or metastatic HER2-positive breast cancer at 1, 24, and 48 h after injection of approximately 130 MBq of the probe (64)Cu-DOTA-trastuzumab. Radioactivity data were collected from the blood, urine, and normal-tissue samples of these 6 patients, and the multiorgan biodistribution and internal dosimetry of the probe were evaluated. Safety data were collected for all the patients after the administration of (64)Cu-DOTA-trastuzumab and during the 1-wk follow-up period. According to our results, the best timing for the assessment of (64)Cu-DOTA-trastuzumab uptake by the tumor was 48 h after injection. Radiation exposure during (64)Cu-DOTA-trastuzumab PET was equivalent to that during conventional (18)F-FDG PET. The radioactivity in the blood was high, but uptake of (64)Cu-DOTA-trastuzumab in normal tissues was low. In 2 patients, (64)Cu-DOTA-trastuzumab PET showed brain metastases, indicative of blood-brain barrier disruptions. In 3 patients, (64)Cu-DOTA-trastuzumab PET imaging also revealed primary breast tumors at the lesion sites initially identified by CT. The findings of this study indicated that (64)Cu-DOTA-trastuzumab PET is feasible for the identification of HER2-positive lesions in patients with primary and metastatic breast cancer. The dosimetry and pharmacologic safety results were acceptable at the dose required for adequate PET imaging.

Efficacy of Anti-HER2 Agents in Combination With Adjuvant or Neoadjuvant Chemotherapy for Early and Locally Advanced HER2-Positive Breast Cancer Patients: A Network Meta-Analysis

Directory of Open Access Journals (Sweden)

Márcio Debiasi

2018-05-01

Full Text Available BackgroundSeveral (neoadjuvant treatments for patients with HER2-positive breast cancer have been compared in different randomized clinical trials. Since it is not feasible to conduct adequate pairwise comparative trials of all these therapeutic options, network meta-analysis offers an opportunity for more detailed inference for evidence-based therapy.MethodsPhase II/III randomized clinical trials comparing two or more different (neoadjuvant treatments for HER2-positive breast cancer patients were included. Relative treatment effects were pooled in two separate network meta-analyses for overall survival (OS and disease-free survival (DFS.Results17 clinical trials met our eligibility criteria. Two different networks of trials were created based on the availability of the outcomes: OS network (15 trials: 37,837 patients; and DFS network (17 trials: 40,992 patients. Two studies—the ExteNET and the NeoSphere trials—were included only in this DFS network because OS data have not yet been reported. The concept of the dual anti-HER2 blockade proved to be the best option in terms of OS and DFS. Chemotherapy (CT plus trastuzumab (T and lapatinib (L and CT + T + Pertuzumab (P are probably the best treatment options in terms of OS, with 62.47% and 22.06%, respectively. In the DFS network, CT + T + Neratinib (N was the best treatment option with 50.55%, followed by CT + T + P (26.59% and CT + T + L (20.62%.ConclusionThis network meta-analysis suggests that dual anti-HER2 blockade with trastuzumab plus either lapatinib or pertuzumab are probably the best treatment options in the (neoadjuvant setting for HER2-positive breast cancer patients in terms of OS gain. Mature OS results are still expected for the Aphinity trial and for the sequential use of trastuzumab followed by neratinib, the treatment that showed the best performance in terms of DFS in our analysis.

Response to neoadjuvant chemotherapy in locally advanced breast cancer according to tumor subtypes

International Nuclear Information System (INIS)

Tabassum, S.; Zahid, N.

2017-01-01

To compare the pathological response to neoadjuvant chemotherapy in different molecular subtypes of breast cancer Study Design: Prospective cohort study. Place and Duration of Study: Department of Oncology Liaquat National Hospital Karachi from Jan 2013 to Dec 2014. Material and Methods: A total of 119 patients received neo-adjuvant chemotherapy for locally advanced breast cancer followed by definitive surgery. Demographic, clinical and pathological data of 101 patients were available for analysis. Tumors were divided into different molecular subtypes, luminal A, luminal B human epidermal growth factor receptor 2 (HER 2) was negative, luminal B (HER 2 positive), HER 2 over expressed and triple negative. Neoadjuvant chemotherapy was given for total of eight cycles. Primary end point was pathological response [pathological complete response (PCR) versus no PCR] after surgery. Results: A total of 101 patients data were analyzed. Seventeen (16.8%) were luminal A, thirty eight (37.6%) were luminal B, out of 38 luminal B patients, twenty one (55.2%) were HER 2 + and seventeen (44.7%) were HER 2 -ve. Sixteen (15.8%) patients were HER 2 over expressed and thirty (29.7%) were triple negative. Out of 101 patients, twenty eight (27.72%) achieved PCR. A total of 5.9% achieved PCR in luminal A, 4.8% had PCR in luminal B (HER 2 -ve type), 23.5% had in luminal B (HER 2 +ve type), 50% achieved PCR in HER-2 over expressed type and 46.7% had PCR in triple negative subtype, (p=0.001). There was no significant association of PCR with age, tumor size, lymph node status, histology or grade. Conclusion: Molecular subtypes of breat cancer were found to be statistically significant predictor of PCR after neoadjuvant chemotherapy. (author)

Prognostic Impact of Adjuvant Radiotherapy in Breast Cancer Patients with One to Three Positive Axillary Lymph Nodes

OpenAIRE

Mansour Ansari; Behnam Kadkhodaei; Mehdi Shariat; Abdolrasoul Talei; Majid Akrami; Vahid Zangouri; Niloofar Ahmadloo; Mohammad Mohammadianpanah; Sayed Hasan Hamedi; Hamid Nasrolahi; Shapour Omidvari; Ahmad Mosalaei

2018-01-01

Background: Radiotherapy, as an adjuvant treatment, plays a well-known role in prevention of locoregional recurrence in breast cancer patients. This study aims to investigate the impact of radiotherapy in patients with N1 disease. Methods: In this retrospective study, we reviewed the characteristics and treatment outcomes of 316 patients with a biopsy proven diagnosis of breast carcinoma and 1-3 positive axillary lymph nodes. The patients received treatment between 1995 and 201...

Neoadjuvant radiotherapy followed by mastectomy and immediate breast reconstruction. An alternative treatment option for locally advanced breast cancer

Energy Technology Data Exchange (ETDEWEB)

Pazos, Montserrat; Corradini, Stefanie; Schoenecker, Stephan; Scheithauer, Heike; Belka, Claus [LMU Munich, Department of Radiation Oncology, Munich (Germany); Dian, Darius [Mednord Munich Clinic, Munich (Germany); Bodungen, Vera von; Ditsch, Nina; Wuerstlein, Rachel; Harbeck, Nadia [LMU Munich, Breast Center, Department of Obstetrics and Gynecology, Munich (Germany)

2017-04-15

The optimal sequence of mastectomy with immediate breast reconstruction (IBR) and radiotherapy (RT) for the treatment of locally advanced breast cancer (LABC) is still under debate. Increased rates of postoperative complications are described following postmastectomy RT. Neoadjuvant RT aims to improve the aesthetic results and simplify the reconstructive pathway. A total of 22 patients diagnosed with LABC and treated with neoadjuvant RT followed by mastectomy and IBR between 04/2012 and 03/2015 were retrospectively analyzed. RT consisted of external beam RT to the breast and the regional lymphatics, if indicated. Both implant-based and autologous tissue-transfer reconstruction techniques were used. At the time of RT, 10 patients had no prior surgery and 12 patients had previously undergone breast-conserving surgery (BCS) with positive resection margins without the possibility to perform a second BCS. Additional neoadjuvant chemotherapy was administered in 18 patients prior to RT. A complete pathological response was achieved in 55.0% of patients. The 2-year overall survival rate was 89.3%, the 2-year disease-free-survival 79.8% and the local-recurrence-free survival was 95.2%. The cosmetic result was excellent or good in 66% of the patients treated with upfront mastectomy and 37% of the patients who had previously undergone BCS. Among patients who received implant-based IBR, 4 patients developed serious wound-healing problems with implant loss. The most satisfactory results were achieved with autologous tissue reconstruction. A sequential neoadjuvant chemo-/radiotherapy to allow IBR following mastectomy in selected cases of LABC seems feasible and can be safely attempted. Careful patient selection, close monitoring, and continuous patient support is mandatory to ensure compliance in this treatment strategy. (orig.) [German] Die optimale Therapiesequenz von Mastektomie mit sofortiger Brustrekonstruktion (IBR) und Radiotherapie (RT) beim lokal fortgeschrittenen

Breast cancer in young women.

Science.gov (United States)

Radecka, Barbara; Litwiniuk, Maria

2016-01-01

Breast cancer (BC) in young women is rare, affecting only 4-6% of women under the age of 40. Regardless, BC remains the most common malignancy among younger patients. Recently, a significant increase in BC rates has been observed among pre-menopausal subjects. Breast cancer in young women requires special attention due to its specific morphologic and prognostic characteristics and unique aspects, including fertility preservation and psychosocial issues (e.g. its impact on family life and career). Young women are more likely to have tumors with higher incidence of negative clinicopathologic features (higher histological grade, more lymph node positivity, lower estrogen receptor (ER) positivity, higher rates of Her2/neu overexpression). Also, they tend to be diagnosed at more advanced stages of the disease. That, in turn, contributes to less favorable prognosis as compared to older women. Young women are generally treated similarly to older patients. Surgical management includes mastectomy or breast-conserving surgery, followed by radiation therapy (younger women have higher local recurrence rates than older women, especially after breast-conserving therapy). Although the basics of chemotherapy are the same for patients of all ages, younger women have some special considerations. It is important to consider options for fertility preservation before starting systemic treatment. Patients should have access to genetic testing as their results may affect the choice of therapy. Younger women and their families should receive adequate psychological support and counselling.

Potential clinical applications of {sup 18}F-fluorodeoxyglucose position emission tomography/magnetic resonance mammography in breast cancer

Energy Technology Data Exchange (ETDEWEB)

Cho, Ihn Ho; Kong, Eun Jung [Dept. of Nuclear Medicine, Yeugnam University Hospital, Daegu (Korea, Republic of)

2017-09-15

The whole-body positron emission tomography (PET)/magnetic resonance (MR) scan is a cutting edge technology providing comprehensive structural information from MR imaging and functional features from PET in a single session. Recent research findings and clinical experience have shown that 18F-fluorodeoxyglucose (FDG) whole-body PET/MR imaging has a diagnostic performance comparable with or superior to that of PET/CT in the field of oncology, including for breast cancer. In particular, FDG PET/MR mammography in the prone position with the breast hanging in a pendant manner can provide more comprehensive information about the metabolism, anatomy, and functional features of a breast lesion than a whole-body PET/MR scan. This article reports on current state-of-the-art PET/MR mammography in patients with breast cancer and the prospects for potential application in the future.

Role of extrahepatic UDP-glucuronosyltransferase 1A1: Advances in understanding breast milk-induced neonatal hyperbilirubinemia.

Science.gov (United States)

Fujiwara, Ryoichi; Maruo, Yoshihiro; Chen, Shujuan; Tukey, Robert H

2015-11-15

Newborns commonly develop physiological hyperbilirubinemia (also known as jaundice). With increased bilirubin levels being observed in breast-fed infants, breast-feeding has been recognized as a contributing factor for the development of neonatal hyperbilirubinemia. Bilirubin undergoes selective metabolism by UDP-glucuronosyltransferase (UGT) 1A1 and becomes a water soluble glucuronide. Although several factors such as gestational age, dehydration and weight loss, and increased enterohepatic circulation have been associated with breast milk-induced jaundice (BMJ), deficiency in UGT1A1 expression is a known cause of BMJ. It is currently believed that unconjugated bilirubin is metabolized mainly in the liver. However, recent findings support the concept that extrahepatic tissues, such as small intestine and skin, contribute to bilirubin glucuronidation during the neonatal period. We will review the recent advances made towards understanding biological and molecular events impacting BMJ, especially regarding the role of extrahepatic UGT1A1 expression. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel Antiangiogenic/Cytotoxic Therapies for Advanced Breast Cancer

National Research Council Canada - National Science Library

Fett, James

2000-01-01

.... In order to evaluate whether these inhibitors may be useful for treating breast cancer, we have during the grant period developed mouse models for both primary and metastatic growth of human breast cancer cells...

Clinicopathologic features of sentinel node metastases predictive of positive axillary clearance in grade 1 invasive breast carcinoma.

LENUS (Irish Health Repository)

Hayes, B

2012-02-01

BACKGROUND: Sentinel node (SN) biopsy is widely used to stage breast carcinoma and, when positive, typically leads to axillary clearance (AC). AIMS: This study assesses clinicopathologic features of grade 1 breast carcinoma SNs with the aim of identifying a group of patients, who are likely to have a negative AC and can, therefore, safely be spared further surgery. RESULTS: Two hundred and forty-seven patients with grade 1 invasive carcinoma were identified, of whom 29 had a positive SN. Four patients (13.8%) had a positive AC. Positive AC occurred in 3 of 6 (50%) patients whose SN showed extranodal extension (EE), but in only 1 of 23 (4.3%) patients without EE. All patients were staged as pN1(sn) following SN biopsy: only one, who had a 5.27 mm metastasis with EE, was pN2 following AC. CONCLUSIONS: Extranodal extension is a significant predictor of a positive AC in this group. In its absence, AC did not alter the post-SN biopsy pN stage.

HER2-positive breast cancer, how far away from the cure?-on the current situation of anti-HER2 therapy in breast cancer treatment and survival of patients.

Science.gov (United States)

Liao, Ning

2016-06-01

With the diagnosis and treatment of tumor enter into the area of precision medical, based on selected targeted molecular typing of patients with individualized diagnosis and treatment play an important role. HER gene encoded epidermal growth factor receptor 2 (HER2) leading to increased early distant metastasis of breast cancer in patients and poor prognosis. However, a number of clinical studies provided evidence-based anti-HER2 targeted therapy and confirmed the benefit of anti-HER2 targeted therapy in patient survival. In recent years, through the tireless efforts of scholars in the field of breast cancer in our country, the whole diagnosis and treatment of breast cancer has accomplished an international standard. But based on a variety of factors, the anti-HER2 targeted therapy between China and the developed countries, and between different areas in China still exists certain gaps, is now a problem need to be solved. This article will analyzing the diagnostic and treatment on HER2-positive breast cancer in the United States and China, exploring reasons and looking for answers to narrow down the gap in the treatment of HER2-positive breast cancer between China and the United States. Improve the anti-HER2 targeted therapy in our country, let the patients get maximum benefit from anti-HER2 targeted therapy.

Advancements of antisense oligonucleotides in treatment of breast cancer

Institute of Scientific and Technical Information of China (English)

YANGShuan-Ping; SONGSan-Tai; 等

2003-01-01

Breast cancer is one kind of multi-gene related malignancy.Overexpression of some oncogenes such as HER-2(c-erbB-2,Neu),bcl-2/bcl-xL,protein kinase A(PKA),and transferrin receptor gene(TfR gene),etc significantly affect the prognosis of breast cancer.It was shown that specific suppression of the overexpressed genes above resulted in the improvement of the therapy of breast cancer.Antisense interference.one of useful tools for inhibiting the overexpression of specific oncogenes,was involved in the therapy of breast cancer in recent years. Data indicated that antisense oligonucleotides(ON)could inhibit specially the expression of the target genes on mRNA or protein levels in most of cases;some ON candidates showed encouraging therapeutic effects in vitro and in vivo on breast cancer cell lines or xenografts.Furthermore,the combination use of the antisense ON and normal chemotherapeutic agents indicated synergistic antitumor effects,which was probably the best utilization of antisense ON in the treatment of breast cancer.

Sanctuary site leptomeningeal metastases in HER-2 positive breast cancer: A review in the era of trastuzumab.

Science.gov (United States)

Kordbacheh, T; Law, W Y; Smith, I E

2016-04-01

The development of trastuzumab and other targeted systemic therapies has transformed the management of HER-2 positive breast cancers. However, as patients live longer and systemic therapies may not cross the blood brain barrier a rising number of patients are developing leptomeningeal metastases and brain metastases as a sanctuary site of disease. Intrathecal trastuzumab has been reported to treat these. We describe a breast cancer patient with HER-2 positive leptomeningeal disease in the spinal cord successfully treated with intrathecal trastuzumab and methotrexate, alongside systemic anti-HER-2 therapy and radiotherapy. We also review the literature to date on the efficacy and safety of intrathecal trastuzumab, and recent evidence suggesting that intrathecal trastuzumab passes via the blood brain barrier into the serum to achieve intravenous concentrations similar to that seen with systemic therapy alone. Overall, intrathecal trastuzumab appears to be a safe and often effective treatment for leptomeningeal metastases in HER-2 positive breast cancer. Ongoing phase I and II studies are required to determine optimum dosing schedules, validate CSF and CSF-to-serum pharmacokinetics, determine efficacy, and to assess the added benefits or disadvantages of prior radiotherapy and concomitant systemic therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular Characterization of ERα-positive and Triple Negative Breast Cancer

NARCIS (Netherlands)

Severson, T.M.

2016-01-01

Breast cancer, one of the most common of all cancers, is diagnosed in over 1.5 million people world-wide each year. Overall, treatments for breast cancer are considered relatively successful, however recurrence is a clinical problem of paramount importance. Molecular subtypes of breast cancer,

Decreased background parenchymal enhancement of the contralateral breast after two cycles of neoadjuvant chemotherapy is associated with tumor response in HER2-positive breast cancer.

Science.gov (United States)

You, Chao; Gu, Yajia; Peng, Wen; Li, Jianwei; Shen, Xuxia; Liu, Guangyu; Peng, Weijun

2018-07-01

Background Several recent studies have focused on the association between background parenchymal enhancement (BPE) and tumor response to neoadjuvant chemotherapy (NAC), but early prediction of tumor response based on BPE has yet not been investigated. Purpose To retrospectively investigate whether changes in the BPE of the contralateral breast following NAC could help predict tumor response in early stage HER2-positive breast cancer. Material and Methods Data from 71 patients who were diagnosed with unilateral HER2 positive breast cancer and then underwent NAC with trastuzumab before surgery were analyzed retrospectively. Two experienced radiologists independently categorized the patients' levels of BPE of the contralateral breast into four categories (1 = minimal, 2 = mild, 3 = moderate, 4 = marked) at baseline and after the second cycle of NAC. After undergoing surgery, 34 patients achieved pathologic complete response (pCR) and 37 patients had residual disease (non-pCR). The association between BPE and histopathologic tumor response was analyzed. Result The level of BPE was higher in premenopausal than post-menopausal women both at baseline and after the second cycle of NAC ( P < 0.005). A significant reduction in BPE ( P < 0.001) was observed after the second NAC cycle; however, a more obvious decrease in BPE was identified in premenopausal relative to post-menopausal women ( P = 0.041). No significant association was identified between pCR and baseline BPE ( P = 0.287). However, after the second NAC cycle, decreased BPE was significantly associated with pCR ( P = 0.003). Conclusion For HER2-positive patients, changes in BPE may serve as an additional imaging biomarker of treatment response at an early stage.

SU-E-T-307: Dosimetric Comparison of Prone Versus Supine Positioning for Adjuvant Breast Radiation Therapy

International Nuclear Information System (INIS)

Pope, C; O’Connor, B; Hayes, L; Rella, J; Ruiz, B; Yang, J

2015-01-01

Purpose: The prone treatment position has been used to reduce ipsilateral lung and heart dose in left breast radiation. We conducted a retrospective study to evaluate the difference in the dosimetry between prone and supine treatment positions. Methods: Eight left breast cancer patients were simulated in both the supine and prone positions as a pretreatment evaluation for the optimal treatment position. Treatment plans were created for all patients in both the supine and prone positions using a field in field three dimensional planning technique. Prescribed dose was 45 Gy delivered by two tangential photon fields. Irradiated volume (IV) was evaluated by V50, V100, and dose to lung and heart by V5, V10, V20, and the mean dose were evaluated. Results: All dosimetry metrics for both the supine and prone plans met our internal normal structure guidelines which are based on Quantec data. The average IVs (50% and 100%) were 2223cc and 1361cc prone, 2315cc and 1315cc supine. The average ipsilateral lung Mean dose (0.83Gy prone vs 5.8Gy supine), V5 (1.6% prone vs 20.9% supine), V10 (0.78% prone vs 15% supine) and V20 (0.36% prone vs 11% supine) were significantly lower in prone position. Heart Mean dose (1.4Gy prone vs 2.9Gy supine), V10 (1.4% prone vs 5.0% supine) and V20 (0.4% prone vs 3.5% supine) were found improved for all patients except one where the mean dose was the same and all other values were improved. Conclusion: The prone position offer preferable dosimetry for all patients planned in our study. These patients were chosen based on the physician’s belief that they would benefit from prone treatment either because they had large pendulous breasts or due to the amount of heart seen in the field on CT simulation

Breast cancer imaging

International Nuclear Information System (INIS)

Funke, M.; Villena, C.

2008-01-01

Advances in female breast imaging have substantially influenced the diagnosis, therapy, and prognosis of breast cancer in the past few years. Mammography using conventional or digital technique is considered the gold standard for the early detection of breast cancer. Other modalities such as breast ultrasound and contrast-enhanced magnetic resonance imaging of the breast play an important role in diagnostic imaging, staging, and follow-up of breast cancer. Percutaneous needle biopsy is a faster, less invasive, and more cost-effective method than surgical biopsy for verifying the histological diagnosis. New methods such as breast tomosynthesis, contrast-enhanced mammography, and positron emission tomography promise to further improve breast imaging. Further studies are mandatory to adapt these new methods to clinical needs and to evaluate their performance in clinical practice. (orig.) [de

Effect of radiologist experience on the risk of false-positive results in breast cancer screening programs

Energy Technology Data Exchange (ETDEWEB)

Zubizarreta Alberdi, Raquel [Galician Breast Cancer Screening Programme, Public Health and Planning Directorate, Health Office, Galicia (Spain); Edificio Administrativo da Conselleria de Sanidade, Servicio de Programas Poboacionais de Cribado, Direccion Xeral de Saude Publica e Planificacion, Santiago de Compostela, Galicia (Spain); Llanes, Ana B.F.; Ortega, Raquel Almazan [Galician Breast Cancer Screening Programme, Public Health and Planning Directorate, Health Office, Galicia (Spain); Exposito, Ruben Roman; Collado, Jose M.V.; Oliveres, Xavier Castells [Department of Epidemiology and Evaluation, Institut Municipal d' Investigacio Medica-Parc de Salut Mar. CIBERESP, Barcelona (Spain); Queiro Verdes, Teresa [Galician Agency for Health Technology Assessment, Public Health and Planning Directorate, Health Office, Galicia (Spain); Natal Ramos, Carmen [Principality of Asturias Breast Cancer Screening Programme, Principality of Asturias (Spain); Sanz, Maria Ederra [Public Health Institute, Navarra Breast Cancer Screening Programme, Pamplona (Spain); Salas Trejo, Dolores [General Directorate Public Health and Centre for Public Health Research (CSISP), Valencia Breast Cancer Screening Programme, Valencia (Spain)

2011-10-15

To evaluate the effect of radiologist experience on the risk of false-positive results in population-based breast cancer screening programmes. We evaluated 1,440,384 single-read screening mammograms, corresponding to 471,112 women aged 45-69 years participating in four Spanish programmes between 1990 and 2006. The mammograms were interpreted by 72 radiologists. The overall percentage of false-positive results was 5.85% and that for false-positives resulting in an invasive procedure was 0.38%. Both the risk of false-positives overall and of false-positives leading to an invasive procedure significantly decreased (p < 0.001) with greater reading volume in the previous year: OR 0.77 and OR 0.78, respectively, for a reading volume 500-1,999 mammograms and OR 0.59 and OR 0.60 for a reading volume of >14,999 mammograms with respect to the reference category (<500). The risk of both categories of false-positives was also significantly reduced (p < 0.001) as radiologists' years of experience increased: OR 0.96 and OR 0.84, respectively, for 1 year's experience and OR 0.72 and OR 0.73, respectively, for more than 4 years' experience with regard to the category of <1 year's experience. Radiologist experience is a determining factor in the risk of a false-positive result in breast cancer screening. (orig.)

Timing of Radiation Therapy and Chemotherapy After Breast-Conserving Surgery for Node-Positive Breast Cancer: Long-Term Results From International Breast Cancer Study Group Trials VI and VII

International Nuclear Information System (INIS)

Karlsson, Per; Cole, Bernard F.; Price, Karen N.; Gelber, Richard D.; Coates, Alan S.; Goldhirsch, Aron; Castiglione, Monica; Colleoni, Marco; Gruber, Günther

2016-01-01

Purpose: To update the previous report from 2 randomized clinical trials, now with a median follow-up of 16 years, to analyze the effect of radiation therapy timing on local failure and disease-free survival. Patients and Methods: From July 1986 to April 1993, International Breast Cancer Study Group trial VI randomly assigned 1475 pre-/perimenopausal women with node-positive breast cancer to receive 3 or 6 cycles of initial chemotherapy (CT). International Breast Cancer Study Group trial VII randomly assigned 1212 postmenopausal women with node-positive breast cancer to receive tamoxifen for 5 years, or tamoxifen for 5 years with 3 early cycles of initial CT. For patients who received breast-conserving surgery (BCS), radiation therapy (RT) was delayed until initial CT was completed; 4 or 7 months after BCS for trial VI and 2 or 4 months for trial VII. We compared RT timing groups among 433 patients on trial VI and 285 patients on trial VII who received BCS plus RT. Endpoints were local failure, regional/distant failure, and disease-free survival (DFS). Results: Among pre-/perimenopausal patients there were no significant differences in disease-related outcomes. The 15-year DFS was 48.2% in the group allocated 3 months initial CT and 44.9% in the group allocated 6 months initial CT (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.87-1.45). Among postmenopausal patients, the 15-year DFS was 46.1% in the no-initial-CT group and 43.3% in the group allocated 3 months initial CT (HR 1.11; 95% CI 0.82-1.51). Corresponding HRs for local failures were 0.94 (95% CI 0.61-1.46) in trial VI and 1.51 (95% CI 0.77-2.97) in trial VII. For regional/distant failures, the respective HRs were 1.15 (95% CI 0.80-1.63) and 1.08 (95% CI 0.69-1.68). Conclusions: This study confirms that, after more than 15 years of follow-up, it is reasonable to delay radiation therapy until after the completion of standard CT.

Timing of Radiation Therapy and Chemotherapy After Breast-Conserving Surgery for Node-Positive Breast Cancer: Long-Term Results From International Breast Cancer Study Group Trials VI and VII

Energy Technology Data Exchange (ETDEWEB)

Karlsson, Per, E-mail: per.karlsson@oncology.gu.se [Department of Oncology, Institute of Clinical Sciences, Sahgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg (Sweden); Cole, Bernard F. [Department of Mathematics and Statistics, University of Vermont, Burlington, Vermont (United States); Price, Karen N. [International Breast Cancer Study Group Statistical Center, Frontier Science and Technology Research Foundation, Boston, Massachusetts (United States); Gelber, Richard D. [International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Frontier Science and Technology Research Foundation, Harvard T. F. Chan School of Public Health, Boston, Massachusetts (United States); Coates, Alan S. [International Breast Cancer Study Group and University of Sydney, Sydney (Australia); Goldhirsch, Aron [Senior Consultant Breast Cancer, European Institute of Oncology and International Breast Cancer Study Group, Milan (Italy); Castiglione, Monica [International Breast Cancer Study Group, Bern (Switzerland); Colleoni, Marco [Division of Medical Senology, European Institute of Oncology and International Breast Cancer Study Group, Milan (Italy); Gruber, Günther [Institute of Radiotherapy, Klinik Hirslanden, Zürich (Switzerland)

2016-10-01

Purpose: To update the previous report from 2 randomized clinical trials, now with a median follow-up of 16 years, to analyze the effect of radiation therapy timing on local failure and disease-free survival. Patients and Methods: From July 1986 to April 1993, International Breast Cancer Study Group trial VI randomly assigned 1475 pre-/perimenopausal women with node-positive breast cancer to receive 3 or 6 cycles of initial chemotherapy (CT). International Breast Cancer Study Group trial VII randomly assigned 1212 postmenopausal women with node-positive breast cancer to receive tamoxifen for 5 years, or tamoxifen for 5 years with 3 early cycles of initial CT. For patients who received breast-conserving surgery (BCS), radiation therapy (RT) was delayed until initial CT was completed; 4 or 7 months after BCS for trial VI and 2 or 4 months for trial VII. We compared RT timing groups among 433 patients on trial VI and 285 patients on trial VII who received BCS plus RT. Endpoints were local failure, regional/distant failure, and disease-free survival (DFS). Results: Among pre-/perimenopausal patients there were no significant differences in disease-related outcomes. The 15-year DFS was 48.2% in the group allocated 3 months initial CT and 44.9% in the group allocated 6 months initial CT (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.87-1.45). Among postmenopausal patients, the 15-year DFS was 46.1% in the no-initial-CT group and 43.3% in the group allocated 3 months initial CT (HR 1.11; 95% CI 0.82-1.51). Corresponding HRs for local failures were 0.94 (95% CI 0.61-1.46) in trial VI and 1.51 (95% CI 0.77-2.97) in trial VII. For regional/distant failures, the respective HRs were 1.15 (95% CI 0.80-1.63) and 1.08 (95% CI 0.69-1.68). Conclusions: This study confirms that, after more than 15 years of follow-up, it is reasonable to delay radiation therapy until after the completion of standard CT.

New Advances in Nanotechnology-Based Diagnosis and Therapeutics for Breast Cancer: An Assessment of Active-Targeting Inorganic Nanoplatforms.

Science.gov (United States)

Falagan-Lotsch, Priscila; Grzincic, Elissa M; Murphy, Catherine J

2017-01-18

Breast cancer is a major cause of suffering and mortality among women. Limitations in the current diagnostic methods and treatment approaches have led to new strategies to positively impact the survival rates and quality of life of breast cancer patients. Nanotechnology offers a real possibility of mitigating breast cancer mortality by early-stage cancer detection and more precise diagnosis as well as more effective treatments with minimal side effects. The current nanoplatforms approved for breast cancer therapeutics are based on passive tumor targeting using organic nanoparticles and have not provided the expected significant improvements in the clinic. In this review, we present the emerging approaches in breast cancer nanomedicine based on active targeting using versatile inorganic nanoplatforms with biomedical relevance, such as gold, silica, and iron oxide nanoparticles, as well as their efficacy in breast cancer imaging, drug and gene delivery, thermal therapy, combinational therapy, and theranostics in preclinical studies. The main challenges for clinical translation and perspectives are discussed.

Clinical efficacy and safety of T-DM1 for patients with HER2-positive breast cancer

Directory of Open Access Journals (Sweden)

Ma B

2016-02-01

Full Text Available Bo Ma,1 Qianqian Ma,2 Hongqiang Wang,3 Guolei Zhang,1 Huiying Zhang,1 Xiaohong Wang1 1Affiliated Central Hospital of Huzhou Teachers College, Huzhou, Zhejiang, People’s Republic of China; 2University Hospital of Tuebingen, Tuebingen, Germany; 3Department of Oncology, Hospital of Zhoushan, Zhoushan, Zhejiang, People’s Republic of China Purpose: The aim of this study was to evaluate the therapeutic efficacy and safety of trastuzumab emtansine (T-DM1 for the treatment of patients with human epidermal growth factor receptor 2-positive breast cancer.  Methods: We performed a systemic review and meta-analysis of the relevant published clinical studies. A computerized search was performed for controlled clinical trials of T-DM1 in targeted treatment. Overall survival, progression-free survival, objective response rate, symptom progression free, and adverse events (AEs were evaluated.  Results: Eight eligible trials with a total of 2,016 patients with breast cancer were included in the present meta-analysis. The treatment of patients with breast cancer with T-DM1 was associated with significantly increased overall and progression-free survival when compared with controls (P<0.0001. An analysis of the objective response rate and symptom progression free also demonstrated favorable results for T-DM1 treatment (P≤0.0001. There was no significant difference between the T-DM1 and control groups with respect to nonhematologic or hematologic AEs (P=0.99 and P=0.30, respectively.  Conclusion: Overall, T-DM1 is efficacious in the treatment of patients with human epidermal growth factor receptor 2-positive breast cancer and low rates of AEs compared with controls. Keywords: breast cancer, meta-analysis, HER2, T-DM1, efficacy

Identification of breast cancer cell subtypes sensitive to ATG4B inhibition.

Science.gov (United States)

Bortnik, Svetlana; Choutka, Courtney; Horlings, Hugo M; Leung, Samuel; Baker, Jennifer H; Lebovitz, Chandra; Dragowska, Wieslawa H; Go, Nancy E; Bally, Marcel B; Minchinton, Andrew I; Gelmon, Karen A; Gorski, Sharon M

2016-10-11

Autophagy, a lysosome-mediated degradation and recycling process, functions in advanced malignancies to promote cancer cell survival and contribute to cancer progression and drug resistance. While various autophagy inhibition strategies are under investigation for cancer treatment, corresponding patient selection criteria for these autophagy inhibitors need to be developed. Due to its central roles in the autophagy process, the cysteine protease ATG4B is one of the autophagy proteins being pursued as a potential therapeutic target. In this study, we investigated the expression of ATG4B in breast cancer, a heterogeneous disease comprised of several molecular subtypes. We examined a panel of breast cancer cell lines, xenograft tumors, and breast cancer patient specimens for the protein expression of ATG4B, and found a positive association between HER2 and ATG4B protein expression. We showed that HER2-positive cells, but not HER2-negative breast cancer cells, require ATG4B to survive under stress. In HER2-positive cells, cytoprotective autophagy was dependent on ATG4B under both starvation and HER2 inhibition conditions. Combined knockdown of ATG4B and HER2 by siRNA resulted in a significant decrease in cell viability, and the combination of ATG4B knockdown with trastuzumab resulted in a greater reduction in cell viability compared to trastuzumab treatment alone, in both trastuzumab-sensitive and -resistant HER2 overexpressing breast cancer cells. Together these results demonstrate a novel association of ATG4B positive expression with HER2 positive breast cancers and indicate that this subtype is suitable for emerging ATG4B inhibition strategies.

Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death

DEFF Research Database (Denmark)

Yde, Christina Westmose; Gyrd-Hansen, Mads; Lykkesfeldt, Anne E

2007-01-01

Antiestrogens are currently used for treating breast cancer patients who have estrogen receptor-positive tumors. However, patients with advanced disease will eventually develop resistance to the drugs. Therefore, compounds effective on antiestrogen-resistant tumors will be of great importance for...

THE CLINICAL SIGNIFICANCE OF 99mTc-MIBI BREAST IMAGING IN THE DIAGNOSIS OF EARLY BREAST CANCER

Institute of Scientific and Technical Information of China (English)

任长才; 金少津; 邹强; 朱汇庆; 王红鹰; 梁春立

2001-01-01

Objective: To find an effective, sensitive, specific and noninvasive diagnostic method of breast cancer. Methods: 109 masses of 102 patients with breast lesions smaller than 2 cm in diameter were divided into three groups to undergo 99mTc-MIBI imaging and compared with the results of pathology examination. 20 cases without breast lesions were selected as control. Abnormal condensation of 99mTc-MIBI in the breast reaching 10% higher than that in the counterpart of the healthy breast was regarded as positive. Results: Of 32 breast cancers, positive imaging appeared in 25. Negative imaging were found in 31 of 38 benign breast lesions. Of 39 occult breast lesions, positive imaging appeared in 6 and 3 of them were breast cancer, 2 of 3 patients with slightly increased 99mTc-MIBI imaging threshold were breast cancer also. No positive imaging was found in the control group. The diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value of 99mTc-MIBI was 88.4%, 89.2%, 88.0%, 75.0% and 95.3%, respectively. Conclusion: 99mTc-MIBI imaging had higher sensitivity and accuracy in the diagnosis of breast cancer and differentiation between benign and malignant breast lesions. It could provide useful information for the diagnosis of clinically suspected breast cancer.

Optical Imaging of the Breast

International Nuclear Information System (INIS)

Kim, Min Jung; Kim, Eun Kyung

2011-01-01

As the increased prevalence of breast cancer and the advances in breast evaluation awareness have resulted in an increased number of breast examinations and benign breast biopsies, several investigations have been performed to improve the diagnostic accuracy for breast lesions. Optical imaging of the breast that uses nearinfrared light to assess the optical properties of breast tissue is a novel non-invasive imaging technique to characterize breast lesions in clinical practice. This review provides a summary of the current state of optical breast imaging and it describes the basic concepts of optical imaging, the potential clinical applications for breast cancer imaging and its potential incorporation with other imaging modalities

Locoregional Recurrence Risk for Patients With T1,2 Breast Cancer With 1-3 Positive Lymph Nodes Treated With Mastectomy and Systemic Treatment

International Nuclear Information System (INIS)

McBride, Andrew; Allen, Pamela; Woodward, Wendy; Kim, Michelle; Kuerer, Henry M.; Drinka, Eva Katherine; Sahin, Aysegul; Strom, Eric A.; Buzdar, Aman; Valero, Vicente; Hortobagyi, Gabriel N.; Hunt, Kelly K.; Buchholz, Thomas A.

2014-01-01

Purpose: Postmastectomy radiation therapy (PMRT) has been shown to benefit breast cancer patients with 1 to 3 positive lymph nodes, but it is unclear how modern changes in management have affected the benefits of PMRT. Methods and Materials: We retrospectively analyzed the locoregional recurrence (LRR) rates in 1027 patients with T1,2 breast cancer with 1 to 3 positive lymph nodes treated with mastectomy and adjuvant chemotherapy with or without PMRT during an early era (1978-1997) and a later era (2000-2007). These eras were selected because they represented periods before and after the routine use of sentinel lymph node surgery, taxane chemotherapy, and aromatase inhibitors. Results: 19% of 505 patients treated in the early era and 25% of the 522 patients in the later era received PMRT. Patients who received PMRT had significantly higher-risk disease features. PMRT reduced the rate of LRR in the early era cohort, with 5-year rates of 9.5% without PMRT and 3.4% with PMRT (log-rank P=.028) and 15-year rates 14.5% versus 6.1%, respectively; (Cox regression analysis: adjusted hazard ratio [AHR] 0.37, P=.035). However, PMRT did not appear to benefit patients treated in the later cohort, with 5-year LRR rates of 2.8% without PMRT and 4.2% with PMRT (P=.48; Cox analysis: AHR 1.41, P=.48). The most significant factor predictive of LRR for the patients who did not receive PMRT was the era in which the patient was treated (AHR 0.35 for later era, P<.001). Conclusion: The risk of LRR for patients with T1,2 breast cancer with 1 to 3 positive lymph nodes treated with mastectomy and systemic treatment is highly dependent on the era of treatment. Modern treatment advances and the selected use of PMRT for those with high-risk features have allowed for identification of a cohort at very low risk for LRR without PMRT

Locoregional Recurrence Risk for Patients With T1,2 Breast Cancer With 1-3 Positive Lymph Nodes Treated With Mastectomy and Systemic Treatment

Energy Technology Data Exchange (ETDEWEB)

McBride, Andrew [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Arizona School of Medicine, Phoenix, Arizona (United States); Allen, Pamela; Woodward, Wendy; Kim, Michelle [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kuerer, Henry M. [Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Drinka, Eva Katherine; Sahin, Aysegul [Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Strom, Eric A. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Buzdar, Aman; Valero, Vicente; Hortobagyi, Gabriel N. [Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hunt, Kelly K. [Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Buchholz, Thomas A., E-mail: tbuchhol@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2014-06-01

Purpose: Postmastectomy radiation therapy (PMRT) has been shown to benefit breast cancer patients with 1 to 3 positive lymph nodes, but it is unclear how modern changes in management have affected the benefits of PMRT. Methods and Materials: We retrospectively analyzed the locoregional recurrence (LRR) rates in 1027 patients with T1,2 breast cancer with 1 to 3 positive lymph nodes treated with mastectomy and adjuvant chemotherapy with or without PMRT during an early era (1978-1997) and a later era (2000-2007). These eras were selected because they represented periods before and after the routine use of sentinel lymph node surgery, taxane chemotherapy, and aromatase inhibitors. Results: 19% of 505 patients treated in the early era and 25% of the 522 patients in the later era received PMRT. Patients who received PMRT had significantly higher-risk disease features. PMRT reduced the rate of LRR in the early era cohort, with 5-year rates of 9.5% without PMRT and 3.4% with PMRT (log-rank P=.028) and 15-year rates 14.5% versus 6.1%, respectively; (Cox regression analysis: adjusted hazard ratio [AHR] 0.37, P=.035). However, PMRT did not appear to benefit patients treated in the later cohort, with 5-year LRR rates of 2.8% without PMRT and 4.2% with PMRT (P=.48; Cox analysis: AHR 1.41, P=.48). The most significant factor predictive of LRR for the patients who did not receive PMRT was the era in which the patient was treated (AHR 0.35 for later era, P<.001). Conclusion: The risk of LRR for patients with T1,2 breast cancer with 1 to 3 positive lymph nodes treated with mastectomy and systemic treatment is highly dependent on the era of treatment. Modern treatment advances and the selected use of PMRT for those with high-risk features have allowed for identification of a cohort at very low risk for LRR without PMRT.

Prospectively measured triiodothyronine levels are positively associated with breast cancer risk in postmenopausal women

Science.gov (United States)

2010-01-01

Introduction The potential association between hypo- and hyperthyroid disorders and breast cancer has been investigated in a large number of studies during the last decades without conclusive results. This prospective cohort study investigated prediagnostic levels of thyrotropin (TSH) and triiodothyronine (T3) in relation to breast cancer incidence in pre- and postmenopausal women. Methods In the Malmö Preventive Project, 2,696 women had T3 and/or TSH levels measured at baseline. During a mean follow-up of 19.3 years, 173 incident breast cancer cases were retrieved using record linkage with The Swedish Cancer Registry. Quartile cut-points for T3 and TSH were based on the distribution among all women in the study cohort. A Cox's proportional hazards analysis was used to estimate relative risks (RR), with a confidence interval (CI) of 95%. Trends over quartiles of T3 and TSH were calculated considering a P-value < 0.05 as statistically significant. All analyses were repeated for pre- and peri/postmenopausal women separately. Results Overall there was a statistically significant association between T3 and breast cancer risk, the adjusted RR in the fourth quartile, as compared to the first, was 1.87 (1.12 to 3.14). In postmenopausal women the RRs for the second, third and fourth quartiles, as compared to the first, were 3.26 (0.96 to 11.1), 5.53 (1.65 to 18.6) and 6.87 (2.09 to 22.6), (P-trend: < 0.001). There were no such associations in pre-menopausal women, and no statistically significant interaction between T3 and menopausal status. Also, no statistically significant association was seen between serum TSH and breast cancer. Conclusions This is the first prospective study on T3 levels in relation to breast cancer risk. T3 levels in postmenopausal women were positively associated with the risk of breast cancer in a dose-response manner. PMID:20540734

Trastuzumab use during pregnancy: long-term survival after locally advanced breast cancer and long-term infant follow-up.

Science.gov (United States)

Andrade, Jurandyr M de; Brito, Luiz G O; Moises, Elaine C D; Amorim, Andréa C; Rapatoni, Liane; Carrara, Hélio H A; Tiezzi, Daniel G

2016-04-01

Here, we describe the case of a patient diagnosed with locally advanced breast cancer 8 years ago. Her treatment course was neoadjuvant chemotherapy, followed by mastectomy and then adjuvant radiotherapy and trastuzumab (TTZ). During the use of adjuvant targeted therapy, an incidental pregnancy was diagnosed. Four years later, she developed bone and cerebral metastases, and since then, she has received courses of TTZ, capecitabine, lapatinib, and radiotherapy with intermittent control of the disease. Her 7-year-old son presents a normal physical and long-term neurological developmental curve according to specialized evaluation. This case is unique for several reasons: the patient received the highest dose of TTZ yet described during pregnancy (4400 mg); there has been a long period of disease-free survival after treatment for locally advanced breast cancer and long overall survival despite successive disease progressions during the metastatic phase of the disease (97 months), and there was a monitored pediatric follow-up period (7 years).

Background parenchymal enhancement on breast MRI and mammographic breast density: correlation with tumour characteristics

International Nuclear Information System (INIS)

Kim, M.Y.; Choi, N.; Yang, J.-H.; Yoo, Y.B.; Park, K.S.

2015-01-01

Aim: To investigate the relationship between mammographic breast density (MGD) and background parenchymal enhancement (BPE) at breast MRI and histopathological features of invasive breast cancers. Materials and methods: A total of 178 women with unilateral invasive breast cancer who preoperatively underwent mammography and breast MRI were included in the study. Two radiologists rated MGD and BPE according to BI-RADS criteria in consensus. The relationship between MGD and BPE was investigated, and compared with histopathological features of invasive breast cancers according to the level of MGD and BPE. Results: At MRI, there is no significant difference in the distribution of MGD and BPE of the contralateral breast in women with invasive breast cancer according to menopausal status (p=0.226, 0.384). Women with high MGD (>50% glandular) were more likely to have oestrogen-receptor (ER)-positive breast cancer (p=0.045) and progesterone receptor (PR)-positive breast cancer (p=0.020). With regard to BPE, PR positivity correlated with moderate or marked BPE with borderline significance (p=0.054). Multivariate logistic regression analyses revealed that women with high MGD were less likely to have triple-negative (i.e., a cancer that is ER negative, PR negative, and human epidermal growth factor receptor type 2 [HER2] negative) breast cancer compared with ER (+)/HER2 (−) cancer (OR=0.231, 95% CI: 0.070, 0.760; p=0.016). No association between the histological tumour characteristics and BPE was observed. Conclusion: In women with invasive breast cancer, high MGD is associated with ER positivity of the invasive breast cancer. However, at MRI, BPE of the contralateral breast seems to be independent of tumour characteristics. -- Highlights: •There is no difference in distribution of MGD and BPE of contralateral breast on MRI. •High MGD is associated with ER positivity of the invasive breast cancer. •BPE of the contralateral breast on MRI is independent of tumor

Laser immunotherapy for treatment of patients with advanced breast cancer and melanoma

International Nuclear Information System (INIS)

Li Xiaosong; Hode, Tomas; Guerra, Maria C; Ferrel, Gabriela L; Nordquist, Robert E; Chen, Wei R

2011-01-01

Laser immunotherapy (LIT) was developed for the treatment of metastatic tumors. It combines local selective photothermal interaction and active immunological stimulation to induce a long-term, systemic anti-tumor immunity. During the past sixteen years, LIT has been advanced from bench-top to bedside, with promising outcomes. In our pre-clinical and preliminary clinical studies, LIT has demonstrated the capability in inducing immunological responses, which not only can eradicate the treated primary tumors, but also can eliminate untreated metastases at distant sites. Specifically, LIT has been used to treat advanced melanoma and breast cancer patients during the past five years. LIT was shown to be effective in controlling both primary tumors and distant metastases in late-stage patients, who have failed conventional therapies such as surgery, chemotherapy, radiation, and other more advanced approaches. The methodology and the development of LIT are presented in this paper. The patients' responses to LIT are also reported in this paper. The preliminary results obtained in these studies indicated that LIT could be an effective modality for the treatment of patients with late-stage, metastatic cancers, who are facing severely limited options.

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.

Study on predictive role of AR and EGFR family genes with response to neoadjuvant chemotherapy in locally advanced breast cancer in Indian women.

Science.gov (United States)

Singh, L C; Chakraborty, Anurupa; Mishra, Ashwani K; Devi, Thoudam Regina; Sugandhi, Nidhi; Chintamani, Chintamani; Bhatnagar, Dinesh; Kapur, Sujala; Saxena, Sunita

2012-06-01

Locally advanced breast cancer (LABC) remains a clinical challenge as the majority of patients with this diagnosis develop distant metastases despite appropriate therapy. We analyzed expression of steroid and growth hormone receptor genes as well as gene associated with metabolism of chemotherapeutic drugs in locally advanced breast cancer before and after neoadjuvant chemotherapy (NACT) to study whether there is a change in gene expression induced by chemotherapy and whether such changes are associated with tumor response or non-response. Fifty patients were included with locally advanced breast cancer treated with cyclophosphamide, adriamycin, 5-fluorouracil (CAF)-based neoadjuvant chemotherapy before surgery. Total RNA was extracted from 50 match samples of pre- and post-NACT tumor tissues. RNA expression levels of epidermal growth factor receptor family genes including EGFR, ERBB2, ERBB3, androgen receptor (AR), and multidrug-resistance gene 1 (MDR1) were determined by quantitative real-time reverse transcriptase-polymerase chain reaction. Responders show significantly high levels of pre-NACT AR gene expression (P = 0.016), which reduces following NACT (P = 0.008), and hence can serve as a useful tool for the prediction of the success of neoadjuvant chemotherapy in individual cancer patients with locally advanced breast carcinoma. Moreover, a significant post-therapeutic increase in the expression levels of EGFR and MDR1 gene in responders (P = 0.026 and P < 0.001) as well as in non-responders (P = 0.055, P = 0.001) suggests that expression of these genes changes during therapy but they do not have any impact on tumor response, whereas a post-therapeutic reduction was observed in AR in responders. This indicates an independent predictive role of AR with response to NACT.

A multidisciplinary protocol for planned skin-preserving delayed breast reconstruction for patients with locally advanced breast cancer requiring postmastectomy radiation therapy: 3-year follow-up.

Science.gov (United States)

Kronowitz, Steven J; Lam, Candace; Terefe, Welela; Hunt, Kelly K; Kuerer, Henry M; Valero, Vicente; Lance, Samuel; Robb, Geoffrey L; Feng, Lei; Buchholz, Thomas A

2011-06-01

The authors examined the safety of a protocol for planned skin-preserving delayed breast reconstruction after postmastectomy radiotherapy with placement of a tissue expander for patients with locally advanced breast cancer (stages IIB and III). The authors compared 47 patients treated according to the protocol between December 2003 and May 2008 with 47 disease-stage-matched control patients who underwent standard delayed reconstruction after postmastectomy radiotherapy (no skin preservation or tissue expander) during the same period. Protocol-group complication rates were 21 percent for skin-preserving mastectomy and placement of the expander (stage 1), 5 percent for postmastectomy radiotherapy, 25 percent for expander reinflation after radiotherapy, and 24 percent for skin-preserving delayed reconstruction. The complication rate for standard delayed reconstruction was 38 percent. Tissue-expander loss rates were 32 percent overall, 9 percent for stage 1, 5 percent for postmastectomy radiotherapy, and 22 percent for reinflation. Wound-healing complications after reconstruction occurred in 3 percent of protocol-group and 10 percent of control-group patients. The median follow-up time for patients still alive at last follow-up was 40 months (range, 8.5 to 85.3 months). Three-year recurrence-free survival rates were 92 percent (95 percent CI, 83 to 100 percent) and 86 percent (95 percent CI, 76 to 98 percent) for the protocol and control groups, respectively (p = 0.87). In patients with locally advanced breast cancer, skin-preserving mastectomy with a deflated tissue expander on the chest wall during postmastectomy radiotherapy does not increase locoregional recurrence risk and is associated with lower complication rates of definitive reconstruction.

Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells.

Science.gov (United States)

Cheng, Ran; Liu, Ya-Jing; Cui, Jun-Wei; Yang, Man; Liu, Xiao-Ling; Li, Peng; Wang, Zhan; Zhu, Li-Zhang; Lu, Si-Yi; Zou, Li; Wu, Xiao-Qin; Li, Yu-Xia; Zhou, You; Fang, Zheng-Yu; Wei, Wei

2017-05-02

Tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.

β-Catenin Is a Positive Regulator of Estrogen Receptor-α Function in Breast Cancer Cells

Energy Technology Data Exchange (ETDEWEB)

Gupta, Nibedita; Schmitt, Fee; Grebhardt, Sina; Mayer, Doris, E-mail: d.mayer@dkfz.de [Hormones and Signal Transduction Group, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, 69120 Heidelberg (Germany)

2011-07-22

Estrogen receptor-alpha (ERα) is a key factor in the development of breast cancer in humans. The expression and activity of ERα is regulated by a multitude of intracellular and extracellular signals. Here we show a cross-talk between β-catenin and ERα in human breast cancer cells. Knockdown of β-catenin by RNAi resulted in significant reduction of ERα mRNA and/or protein levels in MCF-7, T-47D, and BT-474 breast cancer cells and in significant reduction of estradiol-induced expression of the ERα target genes pS2 and GREB1. In addition β-catenin silencing resulted in significant decrease of growth of MCF-7 cells both in the absence and presence of estradiol. β-catenin and ERα could not be co-immunoprecipitated by ERα antibodies from lysates of E2-treated or untreated cells suggesting lack of direct physical interaction. It is concluded that β-catenin is a positive regulator of ERα mRNA and protein expression.

Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.

Science.gov (United States)

Paik, Soonmyung; Tang, Gong; Shak, Steven; Kim, Chungyeul; Baker, Joffre; Kim, Wanseop; Cronin, Maureen; Baehner, Frederick L; Watson, Drew; Bryant, John; Costantino, Joseph P; Geyer, Charles E; Wickerham, D Lawrence; Wolmark, Norman

2006-08-10

The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.

Fertility Preservation and Pregnancy in Women With and Without BRCA Mutation–Positive Breast Cancer

Science.gov (United States)

Rodriguez-Wallberg, Kenny A.

2012-01-01

Women with breast cancer face many challenges when considering fertility preservation. Delayed referral results in the limitation of fertility preservation options because most established methods, such as embryo and oocyte cryopreservation, require several weeks to complete. Women with BRCA mutations, on the other hand, may be more aware of fertility issues and motivated to see fertility preservation specialists earlier. Fear of exposure to estrogen limits access to fertility preservation via embryo or oocyte cryopreservation; however, the use of aromatase inhibitors as ovarian stimulants reduces such concern. Ovarian cryopreservation can be used when there is insufficient time to perform ovarian stimulation because this technique does not require hormonal stimulation, but there are safety concerns both in women with BRCA mutations and in patients with hormone receptor–positive disease as well. There does not seem to be a proven ovarian suppression strategy to preserve fertility in women with breast cancer. Pregnancy appears to be safe for breast cancer survivors but studies specific for women with BRCA mutations are lacking. Women with BRCA mutations may elect to use preimplantation genetic diagnosis during in vitro fertilization to avoid transmitting the mutation, but there may be psychosocial difficulties in entertaining this option. Overall, the last decade has brought many options for women with breast cancer considering fertility preservation, but numerous challenges remain. The presence of BRCA mutations further contributes to these challenges. PMID:23006497

Association between breast cancer, breast density, and body adiposity evaluated by MRI