Circulating sex hormones and breast cancer risk factors in postmenopausal women : reanalysis of 13 studies

NARCIS (Netherlands)

Key, T. J.; Appleby, P. N.; Reeves, G. K.; Roddam, A. W.; Helzlsouer, K. J.; Alberg, A. J.; Rollison, D. E.; Dorgan, J. F.; Brinton, L. A.; Overvad, K.; Kaaks, R.; Trichopoulou, A.; Clavel-Chapelon, F.; Panico, S.; Duell, E. J.; Peeters, P. H. M.; Rinaldi, S.; Riboli, E.; Fentiman, I. S.; Dowsett, M.; Manjer, J.; Lenner, P.; Hallmans, G.; Baglietto, L.; English, D. R.; Giles, G. G.; Hopper, J. L.; Severi, G.; Morris, H. A.; Koenig, K.; Zeleniuch-Jacquotte, A.; Arslan, A. A.; Toniolo, P.; Shore, R. E.; Krogh, V.; Micheli, A.; Berrino, F.; Muti, P.; Barrett-Connor, E.; Laughlin, G. A.; Kabuto, M.; Akiba, S.; Stevens, R. G.; Neriishi, K.; Land, C. E.; Cauley, J. A.; Lui, Li Yung; Cummings, Steven R.; Gunter, M. J.; Rohan, T. E.

2011-01-01

BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone

Hormone-metabolic status in moderately smoking breast cancer patients.

Science.gov (United States)

Berstein, L M; Tsyrlina, E V; Semiglazov, V F; Kovalenko, I G; Gamayunova, V B; Evtushenko, T P; Ivanova, O A

1997-01-01

One hundred and eighteen primary breast cancer (BC) patients, 35 of whom were smokers, in clinical stages I-II of the disease were examined. In order to investigate whether smoking changes endocrine function in BC patients, some indices of the hormone-metabolic status of smoking and non-smoking patients of reproductive and menopausal age were compared. It was found that in smokers with BC there was a decline in body weight and body fat content, a lack of lean body mass accumulation along with body mass increase, a tendency to hypotriglyceridemia and hypoinsulinemia, accelerated development of the upper type of body fat distribution with ageing, intensified gonadotropin secretion, shifts in steroidogenesis and SHBG level and elevated catecholamine execretion. It is suggested that a possible relation between hormone-mediated effects inherent to smoking and the mechanisms promoting genotoxic type of hormonal carcinogenesis and the factors of breast cancer prognosis cannot be excluded.

Review of hormonal treatment of breast cancer

African Journals Online (AJOL)

2011-07-28

Jul 28, 2011 ... Although tamoxifen is the established drug for hormonal treatment of breast cancer, cases of .... This is a growth factor protein which is over‑expressed in different types of .... These groups of drugs act as receptor binding competitors of estrogens and ... Mechanism of Action of Selective Estrogen. Receptor ...

Autocine and Paracrine Control of Breast Cancer Growth by Sex Hormone-Binding Globulin

National Research Council Canada - National Science Library

Rosner, William

2004-01-01

We propose that the expression of Sex Hormone-Binding Globulin (SHBG) by breast cancer cells is biologically regulated and this SHBG functions to alter the effects of estrogens within the breast cancer cell...

Autocrine and Paracrine Control of Breast Cancer Growth by Sex Hormone-Binding Globulin

National Research Council Canada - National Science Library

Rosner, Wiliam

2003-01-01

We propose that the expression of Sex Hormone-Binding Globulin (SHBG) by breast cancer cells is biologically regulated and that this SHBG functions to alter the effects of estrogens within the breast cancer cell...

Hormones and tumour therapy: current clinical status and future developments in endocrine therapy of breast cancer

International Nuclear Information System (INIS)

Szepesi, T.; Schratter-Sehn, A.U.

1982-01-01

Postoperative adjuvant hormone therapy and hormone therapy in disseminated breast cancer will be discussed systematically. The classical ablative and additive endocrine therapeutic measures - with the exception of ovarectomy and gestagen therapy - are increasinlgy being replaced by antagonists. Individual chapters discuss recent experience with combined hormone-radiotherapy or hormone-chemotherapy. In addition, a successful therapy scheme for the treatment of disseminated breast cancer will be presented. (Author)

Hormonal enzymatic systems in normal and cancerous human breast: control, prognostic factors, and clinical applications.

Science.gov (United States)

Pasqualini, Jorge R; Chetrite, Gérard S

2012-04-01

The bioformation and transformation of estrogens and other hormones in the breast tissue as a result of the activity of the various enzymes involved attract particular attention for the role they play in the development and pathogenesis of hormone-dependent breast cancer. The enzymatic process concerns the aromatase, which transforms androgens into estrogens; the sulfatase, which hydrolyzes the biologically inactive sulfates to the active hormone; the 17β-hydroxysteroid dehydrogenases, which are involved in the interconversion estradiol/estrone or testosterone/androstenedione; hydroxylases, which transform estrogens into mitotic and antimitotic derivatives; and sulfotransferases and glucuronidases, which, respectively convert into the biologically inactive sulfates and glucuronides. These enzymatic activities are more intense in the carcinoma than in the normal tissue. Concerning aromatase, the application of antiaromatase agents has been largely developed in the treatment of breast cancer patients, with very positive results. Various studies have shown that the activity levels of these enzymes and their mRNA can be involved as interesting prognostic factors for breast cancer. In conclusion, the application of new antienzymatic molecules can open attractive perspectives in the treatment of hormone-dependent breast cancer.

Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy

DEFF Research Database (Denmark)

Stahlberg, Claudia; Pedersen, A T; Andersen, Zorana Jovanovic

2004-01-01

of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2......The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were...... retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk...

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

Estrogen signalling and the DNA damage response in hormone dependent breast cancers

Directory of Open Access Journals (Sweden)

C Elizabeth Caldon

2014-05-01

Full Text Available Estrogen is necessary for the normal growth and development of breast tissue, but high levels of estrogen are a major risk factor for breast cancer. One mechanism by which estrogen could contribute to breast cancer is via the induction of DNA damage. This perspective discusses the mechanisms by which estrogen alters the DNA damage response (DDR and DNA repair through the regulation of key effector proteins including ATM, ATR, CHK1, BRCA1 and p53 and the feedback on estrogen receptor signalling from these proteins. We put forward the hypothesis that estrogen receptor signalling converges to suppress effective DNA repair and apoptosis in favour of proliferation. This is important in hormone-dependent breast cancer as it will affect processing of estrogen-induced DNA damage, as well as other genotoxic insults. DDR and DNA repair proteins are frequently mutated or altered in estrogen responsive breast cancer which will further change the processing of DNA damage. Finally the action of estrogen signalling on DNA damage is also relevant to the therapeutic setting as the suppression of a DNA damage response by estrogen has the potential to alter the response of cancers to anti-hormone treatment or chemotherapy that induces DNA damage.

Vegetable and fruit consumption and the risk of hormone receptor-defined breast cancer in the EPIC cohort.

Science.gov (United States)

Emaus, Marleen J; Peeters, Petra H M; Bakker, Marije F; Overvad, Kim; Tjønneland, Anne; Olsen, Anja; Romieu, Isabelle; Ferrari, Pietro; Dossus, Laure; Boutron-Ruault, Marie Christine; Baglietto, Laura; Fortner, Renée T; Kaaks, Rudolf; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Masala, Giovanna; Pala, Valeria; Panico, Salvatore; Tumino, Rosario; Polidoro, Silvia; Skeie, Guri; Lund, Eiliv; Weiderpass, Elisabete; Quirós, J Ramón; Travier, Noémie; Sánchez, María-José; Chirlaque, Maria-Dolores; Ardanaz, Eva; Dorronsoro, Miren; Winkvist, Anna; Wennberg, Maria; Bueno-de-Mesquita, H Bas; Khaw, Kay-Tee; Travis, Ruth C; Key, Timothy J; Aune, Dagfinn; Gunter, Marc; Riboli, Elio; van Gils, Carla H

2016-01-01

The recent literature indicates that a high vegetable intake and not a high fruit intake could be associated with decreased steroid hormone receptor-negative breast cancer risk. This study aimed to investigate the association between vegetable and fruit intake and steroid hormone receptor-defined breast cancer risk. A total of 335,054 female participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were included in this study (mean ± SD age: 50.8 ± 9.8 y). Vegetable and fruit intake was measured by country-specific questionnaires filled out at recruitment between 1992 and 2000 with the use of standardized procedures. Cox proportional hazards models were stratified by age at recruitment and study center and were adjusted for breast cancer risk factors. After a median follow-up of 11.5 y (IQR: 10.1-12.3 y), 10,197 incident invasive breast cancers were diagnosed [3479 estrogen and progesterone receptor positive (ER+PR+); 1021 ER and PR negative (ER-PR-)]. Compared with the lowest quintile, the highest quintile of vegetable intake was associated with a lower risk of overall breast cancer (HRquintile 5-quintile 1: 0.87; 95% CI: 0.80, 0.94). Although the inverse association was most apparent for ER-PR- breast cancer (ER-PR-: HRquintile 5-quintile 1: 0.74; 95% CI: 0.57, 0.96; P-trend = 0.03; ER+PR+: HRquintile 5-quintile 1: 0.91; 95% CI: 0.79, 1.05; P-trend = 0.14), the test for heterogeneity by hormone receptor status was not significant (P-heterogeneity = 0.09). Fruit intake was not significantly associated with total and hormone receptor-defined breast cancer risk. This study supports evidence that a high vegetable intake is associated with lower (mainly hormone receptor-negative) breast cancer risk. © 2016 American Society for Nutrition.

Radiation-associated breast cancer and gonadal hormone exposure: a report from the Childhood Cancer Survivor Study

NARCIS (Netherlands)

Moskowitz, Chaya S.; Chou, Joanne F.; Sklar, Charles A.; Barnea, Dana; Ronckers, Cécile M.; Friedman, Danielle Novetsky; Neglia, Joseph P.; Turcotte, Lucie; Howell, Rebecca M.; Henderson, Tara O.; Armstrong, Gregory T.; Leisenring, Wendy M.; Robison, Leslie L.; van Leeuwen, Flora E.; Pike, Malcolm C.; Oeffinger, Kevin C.

2017-01-01

The relationship between hormone exposure and breast cancer risk in women treated with chest radiotherapy for childhood cancer is uncertain. Participants included 1108 females from the Childhood Cancer Survivor Study who were diagnosed with childhood cancer 1970-1986, treated with chest

Breast Cancer Suspicion in a Transgender Male-to-Female Patient on Hormone Replacement Therapy Presenting with Right Breast Mass: Breast Cancer Risk Assessment and Presentation of a Rare Lesion

Directory of Open Access Journals (Sweden)

Krystina Tongson

2017-01-01

Full Text Available There has been an increasing use of hormonal therapy among male-to-female (MtF transgender individuals. This long-term hormone replacement therapy (HRT renders MtF individuals a unique patient subgroup in terms of breast cancer risk. This case describes a MtF transgender who presented with a breast lesion concerning for malignancy following hormonal replacement therapy. The patient additionally had a strong family history of breast cancer. Final pathology revealed lobular hyperplasia in the setting of gynecomastia and pseudoangiomatous stromal hyperplasia (PASH. Both pathology findings are rare in biological females, let alone in the setting of hormone replacement therapy in a MtF individual. While the number of reported cases of suspicious breast lesions in this population remains scarce, it presents both a diagnostic and therapeutic challenge due to the nature of the treatment course and the lack of research in this recently growing subgroup of patients.

Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones

Energy Technology Data Exchange (ETDEWEB)

Hansen, R K; Bissell, M J

2000-06-01

The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellular matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function.

Prospective study of exogenous hormone use and breast cancer in Seventh-day Adventists.

Science.gov (United States)

Mills, P K; Beeson, W L; Phillips, R L; Fraser, G E

1989-08-01

Exogenous hormone use as either oral contraceptives (OC) or hormone replacement therapy (HRT) was evaluated in reference to subsequent breast cancer risk in a cohort study of 20,341 Seventh-day Adventist women, residing in California, who completed a detailed lifestyle questionnaire in 1976 and who were followed for 6 years. During the follow-up period, 215 histologically confirmed primary breast cancers were detected in the cohort. The mean age at diagnosis was 66 years, indicating a primarily postmenopausal case series. In this cohort, after taking into account potentially confounding variables, current use of HRT (in 1976) was associated with a 69% increase in breast cancer risk, which was statistically significant (RR = 1.69; CI = 1.12-2.55). However, there was no strong increase in risk with increasing duration of use of HRT. Subgroups of women who did experience HRT associated increases in breast cancer risk included those women who had ever used HRT (RR = 1.39; CI = 1.00-1.94) and those with no history of maternal breast cancer (RR = 1.45), those women with prior benign breast disease (RR = 2.80), and those women who experienced menopause at 44 years of age or later (RR = 1.56). There was no substantial increase in breast cancer risk associated with use of OC in this population, although among women with exposure to both OC and HRT there was a suggested increase in risk (RR = 1.42; CI = 0.71-2.85).

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.

Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones

Science.gov (United States)

Hansen, R K; Bissell, M J

2010-01-01

The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellular matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function. PMID:10903527

Non-hormonal interventions for hot flushes in women with a history of breast cancer

Directory of Open Access Journals (Sweden)

Gabriel Rada

2013-04-01

Full Text Available BACKGROUND Hot flushes are common in women with a history of breast cancer. Hormonal therapies are known to reduce these symptoms but are not recommended in women with a history of breast cancer due to their potential adverse effects. The efficacy of non-hormonal therapies is still uncertain. OBJECTIVE To assess the efficacy of non-hormonal therapies in reducing hot flushes in women with a history of breast cancer. METHODS Search methods: We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL (The Cochrane Library, Medline, Embase, Lilacs, CINAHL, PsycINFO (August 2008 and WHO ICTRP Search Portal. We handsearched reference lists of reviews and included articles, reviewed conference proceedings and contacted experts. Selection criteria: Randomized controlled trials (RCTs comparing non-hormonal therapies with placebo or no therapy for reducing hot flushes in women with a history of breast cancer. Data collection and analysis: Two authors independently selected potentially relevant studies, decided upon their inclusion and extracted data on participant characteristics, interventions, outcomes and the risk of bias of included studies. MAIN RESULTS Sixteen RCTs met our inclusion criteria. We included six studies on selective serotonin (SSRI and serotonin-norepinephrine (SNRI reuptake inhibitors, two on clonidine, one on gabapentin, two each on relaxation therapy and homeopathy, and one each on vitamin E, magnetic devices and acupuncture. The risk of bias of most studies was rated as low or moderate. Data on continuous outcomes were presented inconsistently among studies, which precluded the possibility of pooling the results. Three pharmacological treatments (SSRIs and SNRIs, clonidine and gabapentin reduced the number and severity of hot flushes. One study assessing vitamin E did not show any beneficial effect. One of two studies on relaxation therapy showed a significant benefit. None of the other non-pharmacological therapies

Non-hormonal interventions for hot flushes in women with a history of breast cancer

Directory of Open Access Journals (Sweden)

Gabriel Rada

Full Text Available BACKGROUND Hot flushes are common in women with a history of breast cancer. Hormonal therapies are known to reduce these symptoms but are not recommended in women with a history of breast cancer due to their potential adverse effects. The efficacy of non-hormonal therapies is still uncertain. OBJECTIVE To assess the efficacy of non-hormonal therapies in reducing hot flushes in women with a history of breast cancer. METHODS Search methods: We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL (The Cochrane Library, Medline, Embase, Lilacs, CINAHL, PsycINFO (August 2008 and WHO ICTRP Search Portal. We handsearched reference lists of reviews and included articles, reviewed conference proceedings and contacted experts. Selection criteria: Randomized controlled trials (RCTs comparing non-hormonal therapies with placebo or no therapy for reducing hot flushes in women with a history of breast cancer. Data collection and analysis: Two authors independently selected potentially relevant studies, decided upon their inclusion and extracted data on participant characteristics, interventions, outcomes and the risk of bias of included studies. MAIN RESULTS Sixteen RCTs met our inclusion criteria. We included six studies on selective serotonin (SSRI and serotonin-norepinephrine (SNRI reuptake inhibitors, two on clonidine, one on gabapentin, two each on relaxation therapy and homeopathy, and one each on vitamin E, magnetic devices and acupuncture. The risk of bias of most studies was rated as low or moderate. Data on continuous outcomes were presented inconsistently among studies, which precluded the possibility of pooling the results. Three pharmacological treatments (SSRIs and SNRIs, clonidine and gabapentin reduced the number and severity of hot flushes. One study assessing vitamin E did not show any beneficial effect. One of two studies on relaxation therapy showed a significant benefit. None of the other non-pharmacological therapies

Preeclampsia-Associated Hormonal Profiles and Reduced Breast Cancer Risk Among Older Mothers

National Research Council Canada - National Science Library

Laudenslager, Mark

2003-01-01

... to cases on race/ethnicity, current age, age at delivery, and breast-feeding status. A fasting blood and saliva sample was collected from each subject during the luteal phase (day 19-22) of the menstrual cycle and assayed for specific steroid and peptide hormones thought to be linked to breast cancer.

Inflammatory Breast Cancer

Science.gov (United States)

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... white women. Inflammatory breast tumors are frequently hormone receptor negative, which means they cannot be treated with ...

Postmenopausal Serum Sex Steroids and Risk of Hormone Receptor-Positive and -Negative Breast Cancer : a Nested Case-Control Study

NARCIS (Netherlands)

James, Rebecca E.; Lukanova, Annekatrin; Dossus, Laure; Becker, Susen; Rinaldi, Sabina; Tjonneland, Anne; Olsen, Anja; Overvad, Kim; Mesrine, Sylvie; Engel, Pierre; Clavel-Chapelon, Francoise; Chang-Claude, Jenny; Vrieling, Alina; Boeing, Heiner; Schuetze, Madlen; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Krogh, Vittorio; Panico, Salvatore; Tumino, Rosario; Sacerdote, Carlotta; Rodriguez, Laudina; Buckland, Genevieve; Sanchez, Maria-Jose; Amiano, Pilar; Ardanaz, Eva; Bueno-de-Mesquita, Bas; Ros, Martine M.; van Gils, Carla H.; Peeters, Petra H.; Khaw, Kay-Tee; Wareham, Nick; Key, Timothy J.; Allen, Naomi E.; Romieu, Isabelle; Siddiq, Afshan; Cox, David; Riboli, Elio; Kaaks, Rudolf

2011-01-01

Prediagnostic endogenous sex steroid hormone levels have well established associations with overall risk of breast cancer. While evidence toward the existence of distinct subtypes of breast cancer accumulates, few studies have investigated the associations of sex steroid hormone levels with risk of

Postmenopausal serum sex steroids and risk of hormone receptor-positive and -negative breast cancer: a nested case-control study

NARCIS (Netherlands)

James, R.E.; Lukanova, A.; Dossus, L.; Becker, S.; Rinaldi, S.; Tjonneland, A.; Olsen, A.; Overvad, K.; Mesrine, S.; Engel, P.; Clavel-Chapelon, F.; Chang-Claude, J.; Vrieling, A.; Boeing, H.; Schutze, M.; Trichopoulou, A.; Lagiou, P.; Trichopoulos, D.; Palli, D.; Krogh, V.; Panico, S.; Tumino, R.; Sacerdote, C.; Rodriguez, L.; Buckland, G.; Sanchez, M.J.; Amiano, P.; Ardanaz, E.; Bueno-de-Mesquita, B.; Ros, M.M.; Gils, C.H. van; Peeters, P.H.M.; Khaw, K.T.; Wareham, N.; Key, T.J.; Allen, N.E.; Romieu, I.; Siddiq, A.; Cox, D.; Riboli, E.; Kaaks, R.

2011-01-01

Prediagnostic endogenous sex steroid hormone levels have well established associations with overall risk of breast cancer. While evidence toward the existence of distinct subtypes of breast cancer accumulates, few studies have investigated the associations of sex steroid hormone levels with risk of

Breast cancer with Her-22 hormone receptor-positive neu: primary systemic treatment, sentinel node biopsy and hormone

International Nuclear Information System (INIS)

Lopez C, Nayara; Sanchez M, Jose Ignacio; De Santiago G, Javier

2013-01-01

Neoadjuvant chemotherapy is an interesting option in the therapy of some breast cancer cases. Cases in which the timing for sentinel lymph node biopsy is controversial. Co-expression of estrogen receptors and Her2/neu (cc-erbB-2) in breast cancer may imply hormone resistance, especially to tamoxifen. We present a clinic case with co-expression of estrogen receptors and Her2/neu that was treated with neoadjuvant chemotherapy and previous sentinel lymph node biopsy followed by breast tumorectomy with axillar lympha- denectomy, radiotherapy and hormonotherapy with letrozol, geserelina and trastuzumab. A good treatment response as found

Reproductive hormones in breast cancer bone metastasis: The role of inhibins

Directory of Open Access Journals (Sweden)

Caroline Wilson

2016-09-01

Full Text Available The spread of breast cancer cells to bone and survival in this new metastatic environment is influenced not only by the genetic signature of the cells, but also multiple host cells and soluble factors produced locally (paracrine or from distant sites (endocrine. Disrupting this metastatic process has been evaluated in clinical trials of the bone targeted agents bisphosphonates and denosumab and have shown that these agents reduce the recurrence of breast cancer in postmenopausal women only, suggesting the efficacy of the drugs are influenced by levels of reproductive endocrine hormones. The molecular mechanism driving this differential effect has not been definitively identified, however, there is evidence that both reproductive hormones and bisphosphonates can affect similar paracrine factors and cellular components of the bone metastatic niche. This review focuses on how the ovarian endocrine hormone, inhibin, interacts with the paracrine factors activin and follistatin, abundant in the primary tumour and bone microenvironment, with subsequent effects on tumour cell survival. Inhibin also affects the cellular components of the bone microenvironment primarily the osteoblastic niche. Recent evidence has shown that bisphosphonates also alter this niche, which may represent a common mechanism by which inhibin and bisphosphonates interact to influence disease outcomes in early breast cancer. Further research is needed to fully elucidate these molecular mechanisms to enable understanding and future development of alternative bone targeted treatments with anti-tumour efficacy in premenopausal women.

Multiple bony metastases of breast cancer. Role of CA 15.3 and response to hormone therapy

International Nuclear Information System (INIS)

Lopez C, Nayara; Ramon G, Natividad; Sanchez M, Jose Ignacio; De Santiago G, Javier

2012-01-01

Bone metastases are involved in a 65-75% of advanced metastatic breast cancer cases. Tumoral markers (CEA, CA 15.3) are useful in the follow-up and evaluation of response to treatment. Hormonal therapy is the optimal treatment option in low grade metastatic breast cancer due to low toxicity and general long term good response. We present a breast cancer case treated with surgery, chemotherapy and radiotherapy. The patient was asymptomatic during the follow-up and multiple bone metastases were diagnosed as a result of an increased CA 15.3 marker found. Hormone therapy was the recommended initial treatment with good response and tolerance. Bone lesions remained stabilized for 7 years but after treatment suspension new bone lesions appeared. CA 15.3 marker had increased again. Reintroduction of hormonal therapy achieved again the stabilization of the lesions

Interrelationships of Prenatal and Postnatal Growth, Hormones, Diet, and Breast Cancer

Science.gov (United States)

2006-03-01

infants to investigate the association between maternal age, diet, preeclampsia , and infant birth weight, and hormone levels using the infants’ cord... etiology of breast cancer. Br J Cancer 1983;47:757–62. 31. Wang CC, Vittinghoff E, Hua LS, Yun WH, Rong KM. Reducing pregnancy and induced abortion...the etiology of oral and pharyngeal cancer among women from the Southern United States. Cancer Res. 1984; 44: 1216–22. 8 Franco EL, Kowalski LP

Obesity and Breast Cancer.

Science.gov (United States)

Fortner, Renée T; Katzke, Verena; Kühn, Tilman; Kaaks, Rudolf

The relationship between adiposity and breast cancer risk and prognosis is complex, with associations that differ depending on when body size is assessed (e.g., pre- vs. postmenopausal obesity) and when breast cancer is diagnosed (i.e., pre- vs. postmenopausal disease). Further, the impact of obesity on risk differs by tumor hormone receptor status (e.g., estrogen (ER) and progesterone (PR) receptor) and, among postmenopausal women, use of exogenous hormones (i.e., hormone replacement therapy (HRT)). In the context of these complexities, this review focuses on associations between childhood and adolescent adiposity, general adiposity, weight changes (i.e., loss and gain), abdominal adiposity, and breast cancer risk and survival. Finally, we discuss potential mechanisms linking adiposity to breast cancer.

Hormonal and reproductive risk factors associated with breast cancer in Isfahan patients

Science.gov (United States)

Tazhibi, Mehdi; Dehghani, Mohsen; Babazadeh, Shadi; Makkarian, Fariborz; Tabatabaeian, Maryam; Sadeghi, Masoumeh; Rezaei, Parisa; Faghihi, Mehri

2014-01-01

Background: Breast cancer is the most prevalent type of cancer among Iranian females; it is noteworthy that the condition of this type of cancer among Iranian women does not significantly differ from what has been reported from other countries. Considering the importance of this issue, identification of the backgrounds factors and risk factors of the breast cancer risk are highly needed. Therefore, the present study is aimed to compare the risk factors of resident patients of Isfahan province, Iran, with accredited risk factors by other countries and also identify the importance of each factor in the incidence of cancer. Materials and Methods: The present work is a case-control study, which was conducted in 2011. In order to conduct the study, 216 women who had been clinically identified with breast cancer were selected from Seiedo-Shohada Hospital, Isfahan, Iran, as the case group. Moreover, 41 healthy women who were the relatives of the selected patients (i.e., sisters and aunts) were selected as the control group. The data and information of the patients from 1999 to 2010 were collected from either assessing the database system of the center for breast cancer research or interviewing the patients through phone. To analyze the data, multiple logistic regression method was applied. Results: The range of age among selected individuals in this study was from 20-75 years old. The determinant factors for odds of breast cancer included in the applied multiple logistic regression model were the use of oral contraceptive pills (OCPs) (odds ratio [OR] =0.18, 95% confidence interval [CI] = 0.04-0.75) as the protective factor, hormone replacement therapy (OR = 10.2, 95% CI = 1.18-88.89) and menopause at old age (OR = 1.26, 95% CI = 1.11-2.12) as the risk factors. Furthermore, there was not seen any significant relationship between age, vocation, and marital status with odds of breast cancer in multiple model. Conclusion: Based on the results, use of OCPs as protective

Progesterone in Breast Cancer Angiogenesis

OpenAIRE

Botelho, Monica C.; Soares, Raquel; Alves, Helena

2015-01-01

The involvement of steroid hormones in breast carcinogenesis is well established. Recent evidence suggests that angiogenesis can be regulated by hormones. Both oestrogen and progesterone have been implicated in the angiogenic process of hormone-dependent cancers, such as breast cancer. Vascular Endothelial Growth Factor (VEGF) is a growth factor involved in angiogenesis in breast cancer that is up-regulated by estrogens. In our study we evaluated the role of progesterone in the expression of ...

Hormonal modulation of breast cancer gene expression: implications for intrinsic subtyping in pre-menopausal women

Directory of Open Access Journals (Sweden)

Sarah M Bernhardt

2016-11-01

Full Text Available Clinics are increasingly adopting gene expression profiling to diagnose breast cancer subtype, providing an intrinsic, molecular portrait of the tumour. For example, the PAM50-based Prosigna test quantifies expression of 50 key genes to classify breast cancer subtype, and this method of classification has been demonstrated to be superior over traditional immunohistochemical methods that detect proteins, to predict risk of disease recurrence. However, these tests were largely developed and validated using breast cancer samples from post-menopausal women. Thus, the accuracy of such tests has not been explored in the context of the hormonal fluctuations in estrogen and progesterone that occur during the menstrual cycle in pre-menopausal women. Concordance between traditional methods of subtyping and the new tests in pre-menopausal women is likely to depend on the stage of the menstrual cycle at which the tissue sample is taken, and the relative effect of hormones on expression of genes versus proteins. The lack of knowledge around the effect of fluctuating estrogen and progesterone on gene expression in breast cancer patients raises serious concerns for intrinsic subtyping in pre-menopausal women, which comprise about 25% of breast cancer diagnoses. Further research on the impact of the menstrual cycle on intrinsic breast cancer profiling is required if pre-menopausal women are to benefit from the new technology of intrinsic subtyping.

[Hormonotherapy for breast cancer prevention: What about women with genetic predisposition to breast cancer?].

Science.gov (United States)

Sénéchal, Claire; Reyal, Fabien; Callet, Nasrine; This, Pascale; Noguès, Catherine; Stoppa-Lyonnet, Dominique; Fourme, Emmanuelle

2016-03-01

In France, women carrying BRCA1/2 mutation, at an identified high risk of breast cancer are recommended to undergo breast MRI screening. That screening does not however prevent the risk of developing a breast cancer. The only alternative to breast cancer screening available in France is surgical prevention by prophylactic mastectomy. An interesting option for women who wish to reduce their breast cancer risk, but are unready for prophylactic mastectomy is a preventive hormonal treatment by aromatase inhibitors, or selective estrogens receptor modulators (SERMs). Reliable clinical trials show the efficiency of tamoxifen, raloxifen, exemestane, and anastrozole especially, in reducing breast cancer incidence by 33%, 34%, 65% and 53% respectively. This article tries to sum up the main published trials of breast cancer prevention with hormonal treatment, and presents the latest American and English clinical guidelines concerning hormonal prevention for women at high risk of breast cancer, and starts thinking about the possibilities of hormonoprevention, especially among women carrying a BRCA1/2 mutation in France. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Interleukin 8 in progression of hormone-dependent early breast cancer

Indian Academy of Sciences (India)

2017-04-18

Apr 18, 2017 ... significance of IL8 in hormone-dependent breast cancer. The aim of this study was to evaluate the prognostic ... types characterized by a particularly poor prognosis (Aceto et al. ... Progesterone receptor status. PRlow. 70. 76.9. PRhigh. 21. 23.1. NA .... (M<88.82 pg/mg) had lower percentage of relapses and.

Hormonal balance of breast cancer patients treated by various radiotherapy schemes

International Nuclear Information System (INIS)

Lozinskaya, I.N.; Yakimova, T.P.

1993-01-01

Examination of patients with breast cancer has shown a relationship between disease stage, on the one hand, and thyroid function depression, carcinoembryonic antigen and somatotropin levels, on the other. High levels of carcinoembrionic antigen are conducive to depression of immune stromal reactions in the tumor and unfavorably tell on five-year survival. Radiotherapy leads to nonuniversal changes in the hormonal system, related to cancer stage

Cognitive Deficits in Breast Cancer Survivors After Chemotherapy and Hormonal Therapy.

Science.gov (United States)

Frank, Jennifer Sandson; Vance, David E; Triebel, Kristen L; Meneses, Karen M

2015-12-01

Adjuvant treatments, specifically chemotherapy and hormonal therapy, have dramatically increased breast cancer survival, resulting in increased attention to the residual effects of treatment. Breast cancer survivors (BCS) frequently report that cognitive deficits are a particular source of distress, interfering with many aspects of quality of life. The literature on neuropsychological performance measures in BCS supports the reality of subtle cognitive deficits after both chemotherapy and hormonal therapy. This premise is supported by recent imaging studies, which reveal anatomical changes after chemotherapy as well as changes in patterns of neural activation while performing cognitive tasks. This review suggests that, even when performance on neuropsychological performance measures is within normal limits, BCS may be using increased cognitive resources in the face of reduced cognitive reserve. Potential interventions for cognitive deficits after adjuvant therapy include prescriptions for healthy living, pharmacotherapy, complementary therapy, and cognitive remediation therapy directed toward specific cognitive deficits or a combination of several strategies.

Machine learning approaches to decipher hormone and HER2 receptor status phenotypes in breast cancer.

Science.gov (United States)

Adabor, Emmanuel S; Acquaah-Mensah, George K

2017-10-16

Breast cancer prognosis and administration of therapies are aided by knowledge of hormonal and HER2 receptor status. Breast cancer lacking estrogen receptors, progesterone receptors and HER2 receptors are difficult to treat. Regarding large data repositories such as The Cancer Genome Atlas, available wet-lab methods for establishing the presence of these receptors do not always conclusively cover all available samples. To this end, we introduce median-supplement methods to identify hormonal and HER2 receptor status phenotypes of breast cancer patients using gene expression profiles. In these approaches, supplementary instances based on median patient gene expression are introduced to balance a training set from which we build simple models to identify the receptor expression status of patients. In addition, for the purpose of benchmarking, we examine major machine learning approaches that are also applicable to the problem of finding receptor status in breast cancer. We show that our methods are robust and have high sensitivity with extremely low false-positive rates compared with the well-established methods. A successful application of these methods will permit the simultaneous study of large collections of samples of breast cancer patients as well as save time and cost while standardizing interpretation of outcomes of such studies. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk

DEFF Research Database (Denmark)

Rudolph, Anja; Hein, Rebecca; Lindström, Sara

2013-01-01

Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case...

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.

Alimentary triggers of hormone dependent breast cancers

Directory of Open Access Journals (Sweden)

T. Y. Lykholat

2014-04-01

Full Text Available Breast cancer (BC consistently holds the leading positions in the structure of morbidity and mortality of the female population. Food containing veterinary hormones is extremely dangerous to human health: estrogens are female sex hormones. Excessive level of estrogen in the body gives rise to diseases of varying severity: in women (especially of older age it may cause breast cancer. The paper investigates the processes of lipid peroxidation and the status of antioxidant protection system in rats of different ages exposed to exogenous estrogens. The purpose of the work is to study lipid peroxidation and antioxidative protection status in rats of different ages exposed to exogenous estrogens for determining the trigger mechanisms for tumor development. Experiments were conducted on female Wistar rats exposed to exogenous estrogen for 45 days. At the beginning of the experiment, age of experimental animals was 3 months in pubertal period and 6 months as mature ones. The control groups consisted of intact animals of appropriate age. To simulate the influence of exogenous estrogen, rats’ food was treated with the Sinestron drug at the rate of 2 mg per kg. The research materials were serum and liver of rats. Objects of the research were indicators of lipid peroxidation activity (content of TBA-active products and antioxidant protection system (reduced glutathione (RG level, glutathione transferase (GT, glutathione reductase (GR, glutathione peroxidase (GP, superoxide dismutase (SOD activity, and total antioxidative activity (AOA. Data obtained was treated with standard methods of estimation of variation series. Various degrees of peroxidation intensification depending on the age and organs were determined. Maximum excess of control indexes in the serum was observed and it indicated synthetic estrogen effect of on all major body systems. In prepubertal period females’ liver the reaction of prooxidant system and tension in the antioxidant

An Automatic Framework for Assessing Breast Cancer Risk Due to Various Hormone Replacement Therapies (HRT)

DEFF Research Database (Denmark)

Karemore, Gopal Raghunath; Brandt, Sami; Nielsen, Mads

Background: It is well known that Menopausal Hormone therapy increases mammographic density. Increase in breast density may relate to breast cancer risk. Several computer assisted automatic methods for assessing mammographic density have been suggested by J.W. Byng (1996), N. Karssemeijer (1998),...

Prolactin response to thyrotropin-releasing hormone in early and advanced human breast cancer

International Nuclear Information System (INIS)

Barni, S.; Lissoni, P.; Tancini, G.

1986-01-01

While prolactin (PRL) has been shown to stimulate the development of mammary carcinoma in several animal species, its role in human breast cancer remains to be established. To further investigate PRL secretion in human breast cancer, its basal levels and response to thyrotropin-releasing hormone (TRH) were evaluated in 16 patients (6 with no metastases and 10 with metastatic locations). The control group consisted of 19 healthy women. High PRL basal concentrations were seen in 2 patients only; no significant differences were found between the other patients and the normal subjects. The PRL increase induced by TRH administration was significantly higher in patients than in controls. Finally a change in the hormonal secretion was found after chemotherapy in 3 of the 5 patients in whom PRL response to TRH was evaluated either before or 10-12 days after a cycle of intravenous CMF adjuvant chemotherapy. These results demostrate the existence of an exaggerated response of PRL to TRH in patients with breast cancer, even in the presence of normal basal levels. Moreover, they would seem to suggest a possible influence of CMF on PRL response to TRH stimulation

An automatic framework for assessing breast cancer risk due to various hormone replacement therapies (HRT)

DEFF Research Database (Denmark)

Karemore, Gopal; Brandt, Sami; Nielsen, Mads

It is well known that menopausal hormone therapy increases mammographic density. Increase in breast density may relate to breast cancer risk. Several computer assisted automatic methods for assessing mammographic density have been suggested by J.W. Byng (1996), N. Karssemeijer (1998), J.M. Boone(...

Use of menopausal hormone therapy and risk of ductal and lobular breast cancer among women 55–74 years of age

Science.gov (United States)

Li, Christopher I.; Daling, Janet R.; Haugen, Kara L.; Tang, Mei Tzu Chen; Porter, Peggy L.; Malone, Kathleen E.

2014-01-01

Background The Women’s Health Initiative (WHI) randomized trials found that use of combined estrogen and progestin menopausal hormone therapy (CHT) increases breast cancer risk, but use of unopposed estrogen hormone therapy (EHT) does not. However, several questions regarding the impact of hormone use on risk of different types of breast cancer and what thresholds of use confer elevations in risk remain. Methods We conducted a population-based case-control study among women 55–74 years of age to assess the association between menopausal hormone use and risk of invasive ductal and invasive lobular breast carcinomas. Associations were evaluated using polytomous logistic regression and analyses included 880 ductal cases, 1,027 lobular cases, and 856 controls. Results Current EHT and CHT use were associated with 1.6-fold [95% confidence interval (CI): 1.1–2.2] and 2.3-fold (95% CI: 1.7–3.2) increased risks of lobular breast cancer, respectively, but neither was associated with risk of ductal cancer. Lobular cancer risk was increased after nine years of EHT use, but after only three years of CHT use. Discussion Evidence across more than a dozen studies indicates that lobular carcinoma is the type of breast cancer most strongly influenced by menopausal hormones. Here we characterize what thresholds of duration of use of both EHT and CHT that confer elevations in risk. Impact Despite the rapid decline in hormone therapy use the WHI results were published, study of the hazards associated with these medications remains relevant given the estimated 38 million hormone therapy prescriptions that are still filled in the United States annually. PMID:24748570

Treatment Option Overview (Breast Cancer)

Science.gov (United States)

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... only hormone therapy after a hysterectomy . Selective estrogen receptor modulators (SERMs). Aromatase inhibitors . Less exposure of breast ...

Polymorphisms in steroid hormone biosynthesis genes and risk of breast cancer and fibrocystic breast conditions in Chinese women.

Science.gov (United States)

Sakoda, Lori C; Blackston, Christie; Doherty, Jennifer A; Ray, Roberta M; Lin, Ming Gang; Stalsberg, Helge; Gao, Dao Li; Feng, Ziding; Thomas, David B; Chen, Chu

2008-05-01

Common variants in genes encoding for key enzymes involved in steroidogenesis may alter sex steroid hormone levels, thereby influencing susceptibility to breast carcinoma and related conditions. In a case-control study of Chinese women, we examined genotypes of the CYP11A1 pentanucleotide [(TAAAA)n] repeat (D15S520), CYP17A1 rs743572, and HSD17B1 rs605059 polymorphisms in relation to the risk of breast cancer and fibrocystic breast conditions, comparing 615 women with breast cancer and 467 women with fibrocystic breast conditions separately with 879 women without clinical breast disease. We also evaluated whether these relationships differed by the presence of proliferation in the extratumoral epithelium or fibrocystic lesions, menopausal status, or body mass index. Only CYP11A1 genotype was related to breast cancer risk, with women homozygous for the 4-repeat allele, relative to those homozygous for the 6-repeat allele, at reduced risk (age-adjusted odds ratio, 0.58; 95% confidence interval, 0.37-0.91). There was some suggestion of a stronger inverse association for breast cancer with evidence of proliferation in the extratumoral epithelium than for breast cancer without extratumoral proliferation. Breast cancer risk associated with CYP11A1 genotype did not differ by menopausal status or body mass index level. No associations between CYP11A1, CYP17A1, and HSD17B1 genotypes and risk of fibrocystic breast conditions were observed. Our findings support the possibility that common allelic variation at the CYP11A1 D15S520 locus alters breast cancer risk in Chinese women.

Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe

DEFF Research Database (Denmark)

Stahlberg, Claudia; Pedersen, Anette Tønnes; Lynge, Elsebeth

2004-01-01

was established in 1993, where all female nurses aged 45 years and above received a mailed questionnaire (n = 23,178). A total of 19,898 women returned the questionnaire (86%). The questionnaire included information on HRT types and regimens, reproductive history and lifestyle-related factors. Breast cancer cases......Epidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort...

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

Directory of Open Access Journals (Sweden)

Sri Lakshmi Hyndavi Yeruva

2015-01-01

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

First pregnancy characteristics, postmenopausal breast density, and salivary sex hormone levels in a population at high risk for breast cancer

Directory of Open Access Journals (Sweden)

Mary Mockus

2015-06-01

Conclusions and general significance: While reproductive characteristics, in particular parity, generally demonstrated independent associations with postmenopausal breast density and E, P and DHEA levels, T levels showed concordant inverse associations with age-at-first birth and breast density. These findings suggest that reproductive effects and later life salivary sex steroid hormone levels may have independent effects on later life breast density and cancer risk.

Body Fat Phenotypes, Sex Hormones and Breast Cancer Risk in Postmenopausal African-American Women

National Research Council Canada - National Science Library

Barnett, Junaidah

2000-01-01

... in this country, with very little known about their sex hormone profile. Recent findings have suggested that body fat distribution may be a better marker for breast cancer risk than degree of obesity...

Body Fat Phenotypes, Sex Hormones and Breast Cancer Risk in Postmenopausal African-American Women

National Research Council Canada - National Science Library

Barnett, Junaidah

2002-01-01

... in this country, with very little known about their sex hormone profile. Recent findings have suggested that body fat distribution may be a better marker for breast cancer risk than degree of obesity...

Serum estrogen and SHBG levels and breast cancer incidence among users and never users of hormone replacement therapy

DEFF Research Database (Denmark)

Würtz, Anne Mette Lund; Tjønneland, Anne; Christensen, Jane

2012-01-01

OBJECTIVE: Levels of endogenous estrogen and SHBG are associated with risk of breast cancer among women who have never used hormone replacement therapy (HRT). We investigated these associations in both never and baseline users of HRT. METHODS: A nested case-control study was conducted within the ...... and baseline HRT users. More studies are needed to support the findings for HRT users and to further investigate estrogen levels in relation to estrogen receptor-specific breast cancer and other histological and molecular subtypes.......OBJECTIVE: Levels of endogenous estrogen and SHBG are associated with risk of breast cancer among women who have never used hormone replacement therapy (HRT). We investigated these associations in both never and baseline users of HRT. METHODS: A nested case-control study was conducted within...... logistic regression yielded incidence rate ratios and 95 % confidence intervals for exposures analyzed continuously and categorically in models adjusted for potential confounders. RESULTS: Modest direct associations were identified between estrogen levels and breast cancer incidence among both never...

Clinical relevance of hormone receptors in breast cancer diagnosis

International Nuclear Information System (INIS)

Knapstein, P.

1981-01-01

After an outline of the epidemiology of breast cancer, risk factors such as age, family history, ethnic factors, environmental effects, pregnancy, and hormonal factors are presented. The most efficient methods of early detection are palpation, mammography, and xeroradiography, although repeated mammography involves a risk of tumour induction. Further methods not suited for screeening are puncture cytology and thermography, of which the latter often yields wrong findings. New ways of mass screening may be found in sonography and microwave thermography. (MG) [de

Hormones and breast cancer: can we use them in ways that could reduce the risk?

OpenAIRE

Khalid Mahmud

2011-01-01

Many hormones promote or inhibit breast cancer in different ways. These effects and the mechanisms involved are reviewed in order to suggest a potentially safer use of hormones. Natural estrogens, administered transdermally, and natural progesterone may be the safest combination of female hormones. Increased intake of cruciferous vegetables could provide additional safety by improving 2-hydoxyestrone and diminishing 16 alphahydroxyestrone. Testosterone and dehydroepiandrosterone (DHEA) may di...

[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.

Reproductive History and Breast Cancer Risk

Science.gov (United States)

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... 4 ). This risk reduction is limited to hormone receptor –positive breast cancer; age at first full-term ...

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

Directory of Open Access Journals (Sweden)

Simon Turcotte

2007-10-01

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

Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3

Directory of Open Access Journals (Sweden)

Lund Eiliv

2009-07-01

Full Text Available Abstract Background Gonadotropin releasing hormone (GNRH1 triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3. Methods We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs were genotyped and used to identify haplotype-tagging SNPs (htSNPS in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II, European Prospective Investigation on Cancer and Nutrition (EPIC, Multiethnic Cohort (MEC, Nurses' Health Study (NHS, and Women's Health Study (WHS. Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone were also measured in 4713 study subjects. Results Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Conclusion Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.

Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)

International Nuclear Information System (INIS)

Canzian, Federico; Calle, Eugenia E; Chanock, Stephen; Clavel-Chapelon, Francoise; Dossus, Laure; Feigelson, Heather Spencer; Haiman, Christopher A; Hankinson, Susan E; Hoover, Robert; Hunter, David J; Isaacs, Claudine; Kaaks, Rudolf; Lenner, Per; Lund, Eiliv; Overvad, Kim; Palli, Domenico; Pearce, Celeste Leigh; Quiros, Jose R; Riboli, Elio; Stram, Daniel O; Thomas, Gilles; Thun, Michael J; Cox, David G; Trichopoulos, Dimitrios; Gils, Carla H van; Ziegler, Regina G; Henderson, Katherine D; Henderson, Brian E; Berg, Christine; Bingham, Sheila; Boeing, Heiner; Buring, Julie

2009-01-01

Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3). We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition (EPIC), Multiethnic Cohort (MEC), Nurses' Health Study (NHS), and Women's Health Study (WHS). Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects. Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians

The theory of modulated hormone therapy for the treatment of breast cancer in pre- and post-menopausal women

Science.gov (United States)

Wiley, Teresa S.; Haraldsen, Jason T.

2012-03-01

We present a theory that questions the standard of care for pre- and post-menopausal women with breast cancer. Through the use of modulated hormones to mimic the natural multiphasic fluctuations of estrogen and progesterone cycles of healthy young women, it can be expected that patients will not only exhibit increased quality of life such as better sleep, well-being, and libido, but also memory improvement and less joint pain. Additionally, this regimen may engage genetic pathways that protect women in youth from breast cancers. We present a mathematical basis for the coupling of the hormone cycles through the use of Gaussian curves that provides the foundation of a new format of hormone replacement in women.

The theory of modulated hormone therapy for the treatment of breast cancer in pre- and post-menopausal women

Directory of Open Access Journals (Sweden)

Teresa S. Wiley

2012-03-01

Full Text Available We present a theory that questions the standard of care for pre- and post-menopausal women with breast cancer. Through the use of modulated hormones to mimic the natural multiphasic fluctuations of estrogen and progesterone cycles of healthy young women, it can be expected that patients will not only exhibit increased quality of life such as better sleep, well-being, and libido, but also memory improvement and less joint pain. Additionally, this regimen may engage genetic pathways that protect women in youth from breast cancers. We present a mathematical basis for the coupling of the hormone cycles through the use of Gaussian curves that provides the foundation of a new format of hormone replacement in women.

Interaction of mammographic breast density with menopausal status and postmenopausal hormone use in relation to the risk of aggressive breast cancer subtypes.

Science.gov (United States)

Yaghjyan, Lusine; Tamimi, Rulla M; Bertrand, Kimberly A; Scott, Christopher G; Jensen, Matthew R; Pankratz, V Shane; Brandt, Kathy; Visscher, Daniel; Norman, Aaron; Couch, Fergus; Shepherd, John; Fan, Bo; Chen, Yunn-Yi; Ma, Lin; Beck, Andrew H; Cummings, Steven R; Kerlikowske, Karla; Vachon, Celine M

2017-09-01

We examined the associations of mammographic breast density with breast cancer risk by tumor aggressiveness and by menopausal status and current postmenopausal hormone therapy. This study included 2596 invasive breast cancer cases and 4059 controls selected from participants of four nested case-control studies within four established cohorts: the Mayo Mammography Health Study, the Nurses' Health Study, Nurses' Health Study II, and San Francisco Mammography Registry. Percent breast density (PD), absolute dense (DA), and non-dense areas (NDA) were assessed from digitized film-screen mammograms using a computer-assisted threshold technique and standardized across studies. We used polytomous logistic regression to quantify the associations of breast density with breast cancer risk by tumor aggressiveness (defined as presence of at least two of the following tumor characteristics: size ≥2 cm, grade 2/3, ER-negative status, or positive nodes), stratified by menopausal status and current hormone therapy. Overall, the positive association of PD and borderline inverse association of NDA with breast cancer risk was stronger in aggressive vs. non-aggressive tumors (≥51 vs. 11-25% OR 2.50, 95% CI 1.94-3.22 vs. OR 2.03, 95% CI 1.70-2.43, p-heterogeneity = 0.03; NDA 4th vs. 2nd quartile OR 0.54, 95% CI 0.41-0.70 vs. OR 0.71, 95% CI 0.59-0.85, p-heterogeneity = 0.07). However, there were no differences in the association of DA with breast cancer by aggressive status. In the stratified analysis, there was also evidence of a stronger association of PD and NDA with aggressive tumors among postmenopausal women and, in particular, current estrogen+progesterone users (≥51 vs. 11-25% OR 3.24, 95% CI 1.75-6.00 vs. OR 1.93, 95% CI 1.25-2.98, p-heterogeneity = 0.01; NDA 4th vs. 2nd quartile OR 0.43, 95% CI 0.21-0.85 vs. OR 0.56, 95% CI 0.35-0.89, p-heterogeneity = 0.01), even though the interaction was not significant. Our findings suggest that associations of mammographic

Body Fat Phenotypes, Sex Hormones and Breast Cancer Risk in Post Manopausal African-American Women

National Research Council Canada - National Science Library

Barnett, Junaidah

2001-01-01

... in this country, with very little known about their sex hormone profile. Recent findings have suggested that body fat distribution may be a better marker for breast cancer risk than degree of obesity...

Remarkable change in age-specific breast cancer incidence in the Swiss canton of Geneva and its possible relation with the use of hormone replacement therapy

International Nuclear Information System (INIS)

Bouchardy, Christine; Morabia, Alfredo; Verkooijen, Helena M; Fioretta, Gérald; Wespi, Yves; Schäfer, Peter

2006-01-01

This article aims to explain the reasons for the remarkable change in age of breast cancer occurrence in the Swiss canton of Geneva. We used population-based data from the Geneva cancer registry, which collects information on method of detection, stage and tumour characteristics since 1975. For patients diagnosed between 1997–2003, we obtained additional information on use of hormone replacement therapy from a large prospective study on breast cancer. Using generalized log linear regression analysis, we compared age-specific incidence rates with respect to period, stage, oestrogen receptor status, method of detection and use of hormone replacement therapy. In the periods 1975–1979 and 1985–1989, breast cancer risk increased with age, showing the highest incidence rates among women aged ≥ 85 years. From 1997, the age-specific incidence curve changed completely (p < 0.0001), showing an incidence peak at 60–64 years and a reduced incidence among elderly women. This incidence peak concerned mainly early stage and oestrogen positive cancers and was exclusively observed among women who ever used hormone replacement therapy, regardless whether the tumour was screen-detected or not. The increasing prevalence of hormone replacement therapy use during the 1990s could explain the important change in age-specific breast cancer incidence, not only by increasing breast cancer risk, but also by revealing breast cancer at an earlier age

Digital versus screen-film mammography: impact of mammographic density and hormone therapy on breast cancer detection.

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Chiarelli, Anna M; Prummel, Maegan V; Muradali, Derek; Shumak, Rene S; Majpruz, Vicky; Brown, Patrick; Jiang, Hedy; Done, Susan J; Yaffe, Martin J

2015-11-01

Most studies that have examined the effects of mammographic density and hormone therapy use on breast cancer detection have included screen-film mammography. This study further examines this association in post-menopausal women screened by digital mammography. Approved by the University of Toronto Research Ethics Board, this study identified 688,418 women of age 50-74 years screened with digital or screen-film mammography from 2008 to 2009 within the Ontario Breast Screening Program. Of 2993 eligible women with invasive breast cancer, 2450 were contacted and 1421 participated (847 screen-film mammography, 574 digital direct radiography). Mammographic density was measured by study radiologists using the standard BI-RADS classification system and by a computer-assisted method. Information on hormone therapy use was collected by a telephone-administered questionnaire. Logistic regression and two-tailed tests for significance evaluated associations between factors and detection method by mammography type. Women with >75 % radiologist-measured mammographic density compared to those with diagnosed with an interval than screen-detected cancer, with the difference being greater for those screened with screen-film (OR = 6.40, 95 % CI 2.30-17.85) than digital mammography (OR = 2.41, 95 % CI 0.67-8.58) and aged 50-64 years screened with screen-film mammography (OR = 10.86, 95 % CI 2.96-39.57). Recent former hormone therapy users were also at an increased risk of having an interval cancer with the association being significant for women screened with digital mammography (OR = 2.08, 95 % CI 1.17-3.71). Breast screening using digital mammography lowers the risk of having an interval cancer for post-menopausal women aged 50-64 with greater mammographic density.

Breast Cancer Risk After Radiation Therapy for Hodgkin Lymphoma : Influence of Gonadal Hormone Exposure

NARCIS (Netherlands)

Krul, Inge M; Opstal-van Winden, Annemieke W J; Aleman, Berthe M P; Janus, Cécile P M; van Eggermond, Anna M; De Bruin, Marie L; Hauptmann, Michael; Krol, Augustinus D G; Schaapveld, Michael; Broeks, Annegien; Kooijman, Karen R; Fase, Sandra; Lybeert, Marnix L; Zijlstra, Josée M; van der Maazen, Richard W M; Kesminiene, Ausrele; Diallo, Ibrahima; de Vathaire, Florent; Russell, Nicola S; van Leeuwen, Flora E

2017-01-01

BACKGROUND: Young women treated with chest radiation therapy (RT) for Hodgkin lymphoma (HL) experience a strongly increased risk of breast cancer (BC). It is unknown whether endogenous and exogenous gonadal hormones affect RT-associated BC risk. METHODS: We conducted a nested case-control study

The hormone response element mimic sequence of GAS5 lncRNA is sufficient to induce apoptosis in breast cancer cells

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Pickard, Mark R.; Williams, Gwyn T.

2016-01-01

Growth arrest-specific 5 (GAS5) lncRNA promotes apoptosis, and its expression is down-regulated in breast cancer. GAS5 lncRNA is a decoy of glucocorticoid/related receptors; a stem-loop sequence constitutes the GAS5 hormone response element mimic (HREM), which is essential for the regulation of breast cancer cell apoptosis. This preclinical study aimed to determine if the GAS5 HREM sequence alone promotes the apoptosis of breast cancer cells. Nucleofection of hormone-sensitive and –insensitive breast cancer cell lines with a GAS5 HREM DNA oligonucleotide increased both basal and ultraviolet-C-induced apoptosis, and decreased culture viability and clonogenic growth, similar to GAS5 lncRNA. The HREM oligonucleotide demonstrated similar sequence specificity to the native HREM for its functional activity and had no effect on endogenous GAS5 lncRNA levels. Certain chemically modified HREM oligonucleotides, notably DNA and RNA phosphorothioates, retained pro-apoptotic. activity. Crucially the HREM oligonucleotide could overcome apoptosis resistance secondary to deficient endogenous GAS5 lncRNA levels. Thus, the GAS5 lncRNA HREM sequence alone is sufficient to induce apoptosis in breast cancer cells, including triple-negative breast cancer cells. These findings further suggest that emerging knowledge of structure/function relationships in the field of lncRNA biology can be exploited for the development of entirely novel, oligonucleotide mimic-based, cancer therapies. PMID:26862727

Lifestyle influences on the association between pre-diagnostic hormone replacement therapy and breast cancer prognosis - results from The Danish 'Diet, Cancer and Health' prospective cohort

DEFF Research Database (Denmark)

Holm, Marianne; Olsen, Anja; Kroman, Niels

2014-01-01

OBJECTIVES: The association between pre-diagnostic hormone replacement therapy (HRT) and breast cancer specific mortality as well as potential influences from other lifestyle factors on the association was investigated. STUDY DESIGN: Female participants from the prospective cohort "Diet, Cancer......, and Health" diagnosed with breast cancer (BC) were identified and their pre-diagnostic HRT use evaluated for association with tumour biology and breast cancer outcome in multivariate analysis. MAIN OUTCOME MEASURE: Breast cancer specific mortality. RESULTS: Of the 1212 patients originally considered 1064...... were included. Of these, 105 women died from breast cancer during a median follow-up of 6.3 years (range 0.2-14.3 years). In multivariate analyses women who used HRT at enrolment into the cohort study had 47% lower risk of dying from breast cancer as compared to women who had previously or never used...

Hormone Replacement Therapy and Risk of Breast Cancer in Korean Women: A Quantitative Systematic Review

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Jong-Myon Bae

2015-09-01

Full Text Available Objectives: The epidemiological characteristics of breast cancer incidence by age group in Korean women are unique. This systematic review aimed to investigate the association between hormone replacement therapy (HRT and breast cancer risk in Korean women. Methods: We searched electronic databases such as KoreaMed, KMbase, KISS, and RISS4U as well as PubMed for publications on Korean breast cancer patients. We also conducted manual searching based on references and citations in potential papers. All of the analytically epidemiologic studies that obtained individual data on HRT exposure and breast cancer occurrence in Korean women were selected. We restricted the inclusion of case-control studies to those that included age-matched controls. Estimates of summary odds ratio (SOR with 95% confidence intervals (CIs were calculated using random effect models. Results: One cohort and five case-control studies were finally selected. Based on the heterogeneity that existed among the six studies (I-squared=70.2%, a random effect model was applied. The summary effect size of HRT history from the six articles indicated no statistical significance in breast cancer risk (SOR, 0.983; 95% CI, 0.620 to 1.556. Conclusions: These facts support no significant effect of HRT history in the risk of breast cancer in Korean women. It is necessary to conduct a pooled analysis.

Intake of whole grain products and risk of breast cancer by hormone receptor status and histology among postmenopausal women

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Egeberg, Rikke; Olsen, Anja; Loft, Steffen

2009-01-01

No clear relationship between whole grain products and risk of breast cancer has been established. In a large prospective cohort study, we investigated the association between intake of whole grain products and risk of breast cancer by tumour receptor status [oestrogen receptor (ER......) and progesterone receptor (PR)] and tumour histology (ductal/lobular). It was further investigated whether the association differed by use of hormone replacement therapy (HRT). The study included 25,278 postmenopausal women participating in the Danish Diet, Cancer and Health cohort study (1993-1997). During a mean...... follow-up time of 9.6 years, 978 breast cancer cases were diagnosed. Associations between intake of whole grain products and the breast cancer rate were analysed using Cox's regression model. A higher intake of whole grain products was not associated with a lower risk of breast cancer. Per an increment...

Bilateral male breast cancer with male potential hypogonadism

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Kurokawa Yasushi

2007-06-01

Full Text Available Abstract Background Male breast cancer is a comparatively rare disease, and simultaneous bilateral male breast cancer is considered to be an extremely rare event. Risk factors are said to be genetic factors and hormonal abnormalities due to obesity or testicular diseases. Case presentation The patient was a 47-year-old Japanese male. His family had no history of female breast cancer. This patient also had hypospadias and hormonal examination indicated the presence of primary testicular potential hypogonadism, and these hormonal abnormalities seemed to be present since childhood or the fetal period. The bilateral breast cancer developed in this man at a comparatively young age, and histopathological studies of multiple sections showed that there was almost no normal epithelial cell in the ducts, while the ducts were almost completely filled with breast cancer cells. Conclusion It is thought that male breast cancer is caused by an imbalance between estrogen and testosterone. We cannot rule out the possibility that the breast cancer developed due to the effect of the slight elevation of estrogen over a long period of time, but the actual causative factors in this patient were unable to be definitively identified. In the future, we hope to further elucidate the causes of male breast cancer.

Obesity-associated Breast Cancer: Analysis of risk factors.

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Engin, Atilla

2017-01-01

Several studies show that a significantly stronger association is obvious between increased body mass index (BMI) and higher breast cancer incidence. Furthermore, obese women are at higher risk of all-cause and breast cancer specific mortality when compared to non-obese women with breast cancer. In this context, increased levels of estrogens due to excessive aromatization activity of the adipose tissue, overexpression of pro-inflammatory cytokines, insulin resistance, hyperactivation of insulin-like growth factors (IGFs) pathways, adipocyte-derived adipokines, hypercholesterolemia and excessive oxidative stress contribute to the development of breast cancer in obese women. While higher breast cancer risk with hormone replacement therapy is particularly evident among lean women, in postmenopausal women who are not taking exogenous hormones, general obesity is a significant predictor for breast cancer. Moreover, increased plasma cholesterol leads to accelerated tumor formation and exacerbates their aggressiveness. In contrast to postmenopausal women, premenopausal women with high BMI are inversely associated with breast cancer risk. Nevertheless, life-style of women for breast cancer risk is regulated by avoiding the overweight and a high-fat diet. Estrogen-plus-progestin hormone therapy users for more than 5 years have elevated risks of both invasive ductal and lobular breast cancer. Additionally, these cases are more commonly node-positive and have a higher cancer-related mortality. Collectively, in this chapter, the impacts of obesity-related estrogen, cholesterol, saturated fatty acid, leptin and adiponectin concentrations, aromatase activity, leptin and insulin resistance on breast cancer patients are evaluated. Obesity-related prognostic factors of breast cancer also are discussed at molecular basis.

Phyto-oestrogens and breast cancer chemoprevention

International Nuclear Information System (INIS)

Limer, Jane L; Speirs, Valerie

2004-01-01

Phytoestrogens are polyphenol compounds of plant origin that exhibit a structural similarity to the mammalian steroid hormone 17β-oestradiol. In Asian nations the staple consumption of phyto-oestrogen-rich foodstuffs correlates with a reduced incidence of breast cancer. Human dietary intervention trials have noted a direct relationship between phyto-oestrogen ingestion and a favourable hormonal profile associated with decreased breast cancer risk. However, these studies failed to ascertain the precise effect of dietary phyto-oestrogens on the proliferation of mammary tissue. Epidemiological and rodent studies crucially suggest that breast cancer chemoprevention by dietary phyto-oestrogen compounds is dependent on ingestion before puberty, when the mammary gland is relatively immature. Phyto-oestrogen supplements are commercially marketed for use by postmenopausal women as natural and safe alternatives to hormone replacement therapy. Of current concern is the effect of phyto-oestrogen compounds on the growth of pre-existing breast tumours. Data are contradictory, with cell culture studies reporting both the oestrogenic stimulation of oestrogen receptor-positive breast cancer cell lines and the antagonism of tamoxifen activity at physiological phyto-oestrogen concentrations. Conversely, phyto-oestrogen ingestion by rodents is associated with the development of less aggressive breast tumours with reduced metastatic potential. Despite the present ambiguity, current data do suggest a potential benefit from use of phyto-oestrogens in breast cancer chemoprevention and therapy. These aspects are discussed

Role of Aspirin in Breast Cancer Survival.

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Chen, Wendy Y; Holmes, Michelle D

2017-07-01

Chemotherapy and hormonal therapy have significantly decreased breast cancer mortality, although with considerable side effects and financial costs. In the USA, over three million women are living after a breast cancer diagnosis and are eager for new treatments that are low in toxicity and cost. Multiple observational studies have reported improved breast cancer survival with regular aspirin use. Furthermore, pooled data from five large randomized trials of aspirin for cardiovascular disease showed that subjects on aspirin had decreased risk of cancer mortality and decreased risk of metastatic cancer. Although the potential mechanism for aspirin preventing breast cancer is not known, possible pathways may involve platelets, inflammation, cyclooxygenase (COX) 2, hormones, or PI3 kinase. This review article summarizes the current epidemiologic and clinical trial evidence as well as possible underlying mechanisms that justify current phase III randomized trials of aspirin to improve breast cancer survival.

MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer: the hOrmone and Diet in the ETiology of breast cancer prospective study.

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Muti, Paola; Donzelli, Sara; Sacconi, Andrea; Hossain, Ahmed; Ganci, Federica; Frixa, Tania; Sieri, Sabina; Krogh, Vittorio; Berrino, Franco; Biagioni, Francesca; Strano, Sabrina; Beyene, Joseph; Yarden, Yosef; Blandino, Giovanni

2018-02-09

MicroRNAs (miRNAs) might be considered both predictors and players of cancer development. The aim of the present report was to investigate whether many years before the diagnosis of breast cancer miRNA expression is already disregulated. In order to test this hypothesis, we compared miRNAs extracted from leukocytes in healthy women who later developed breast cancer and in women who remain healthy during the whole 15-year follow-up time. Accordantly, we used a case-control study design nested in the hOrmone and Diet in the ETiology of breast cancer (ORDET) prospective cohort study addressing the possibility that miRNAs can serve as both early biomarkers and components of the hormonal etiological pathways leading to breast cancer development in premenopausal women. We compared leukocyte miRNA profiles of 191 incident premenopausal breast cancer cases and profiles of 191 women who remained healthy over a follow-up period of 20 years. The analysis identified 20 differentially expressed miRNAs in women candidate to develop breast cancer versus control women. The upregulated miRNAs, miR-513-a-5p, miR-513b-5p and miR-513c-5p were among the most significantly deregulated miRNAs. In multivariate analysis, miR-513a-5p upregulation was directly and statistically significant associated with breast cancer risk (OR = 1.69; 95% CI 1.08-2.64; P = 0.0293). In addition, the upregulation of miR-513-a-5p displayed the strongest direct association with serum progesterone and testosterone levels. The experimental data corroborated the inhibitory function of miR-513a-5p on progesterone receptor expression confirming that progesterone receptor is a target of miR-513a-5p. The identification of upregulated miR-513a-5p with its oncogenic potential further validates the use of miRNAs as long-term biomarker of breast cancer risk. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Association between lifetime exposure to passive smoking and risk of breast cancer subtypes defined by hormone receptor status among non-smoking Caucasian women.

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Loreta Strumylaite

Full Text Available Tobacco smoking is inconsistently associated with breast cancer. Although some studies suggest that breast cancer risk is related to passive smoking, little is known about the association with breast cancer by tumor hormone receptor status. We aimed to explore the association between lifetime passive smoking and risk of breast cancer subtypes defined by estrogen receptor and progesterone receptor status among non-smoking Caucasian women. A hospital-based case-control study was performed in 585 cases and 1170 controls aged 28-90 years. Information on lifetime passive smoking and other factors was collected via a self-administered questionnaire. Logistic regression was used for analyses restricted to the 449 cases and 930 controls who had never smoked actively. All statistical tests were two-sided. Adjusted odds ratio of breast cancer was 1.01 (95% confidence interval (CI: 0.72-1.41 in women who experienced exposure to passive smoking at work, 1.88 (95% CI: 1.38-2.55 in women who had exposure at home, and 2.80 (95% CI: 1.84-4.25 in women who were exposed at home and at work, all compared with never exposed regularly. Increased risk was associated with longer exposure: women exposed ≤ 20 years and > 20 years had 1.27 (95% CI: 0.97-1.66 and 2.64 (95% CI: 1.87-3.74 times higher risk of breast cancer compared with never exposed (Ptrend 0.05. There was evidence of interaction between passive smoking intensity and menopausal status in both overall group (P = 0.02 and hormone receptor-positive breast cancer group (P < 0.05. In Caucasian women, lifetime exposure to passive smoking is associated with the risk of breast cancer independent of tumor hormone receptor status with the strongest association in postmenopausal women.

Breast Cancer and Estrogen-Alone Update

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... Current Issue Past Issues Research News From NIH Breast Cancer and Estrogen-Alone Update Past Issues / Summer 2006 ... hormone therapy does not increase the risk of breast cancer in postmenopausal women, according to an updated analysis ...

Menopausal hormone therapy and breast cancer risk : impact of different treatments. The European Prospective Investigation into Cancer and Nutrition

NARCIS (Netherlands)

Bakken, Kjersti; Fournier, Agnes; Lund, Eiliv; Waaseth, Marit; Dumeaux, Vanessa; Clavel-Chapelon, Francoise; Fabre, Alban; Hemon, Bertrand; Rinaldi, Sabina; Chajes, Veronique; Slimani, Nadia; Allen, Naomi E.; Reeves, Gillian K.; Bingham, Sheila; Khaw, Kay-Tee; Olsen, Anja; Tjonneland, Anne; Rodriguez, Laudina; Sanchez, Maria-Jose; Amiano Etxezarreta, Pilar; Ardanaz, Eva; Tormo, Maria-Jose; Peeters, Petra H.; van Gils, Carla H.; Steffen, Annika; Schulz, Mandy; Chang-Claude, Jenny; Kaaks, Rudolf; Tumino, Rosario; Gallo, Valentina; Norat, Teresa; Riboli, Elio; Panico, Salvatore; Masala, Giovanna; Gonzalez, Carlos A.; Berrino, Franco

2011-01-01

Menopausal hormone therapy (MHT) is characterized by use of different constituents, regimens and routes of administration. We investigated the association between the use of different types of MHT and breast cancer risk in the EPIC cohort study. The analysis is based on data from 133,744

Rapid response of breast cancer to neoadjuvant intramammary testosterone-anastrozole therapy: neoadjuvant hormone therapy in breast cancer.

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Glaser, Rebecca L; Dimitrakakis, Constantine

2014-06-01

Experimental and clinical data support the inhibitory effect of testosterone on breast tissue and breast cancer. However, testosterone is aromatized to estradiol, which exerts the opposite effect. The aim of this study was to determine the effect of testosterone, combined with the aromatase inhibitor anastrozole, on a hormone receptor positive, infiltrating ductal carcinoma in the neoadjuvant setting. To determine clinical response, we obtained serial ultrasonic measurements and mammograms before and after therapy. Three combination implants-each containing 60 mg of testosterone and 4 mg of anastrozole-were placed anterior, superior, and inferior to a 2.4-cm tumor in the left breast. Three additional testosterone-anastrozole implants were again placed peritumorally 48 days later. By day 46, there was a sevenfold reduction in tumor volume, as measured on ultrasound. By week 13, we documented a 12-fold reduction in tumor volume, demonstrating a rapid logarithmic response to intramammary testosterone-anastrozole implant therapy, equating to a daily response rate of 2.78% and a tumor half-life of 23 days. Therapeutic systemic levels of testosterone were achieved without elevation of estradiol, further demonstrating the efficacy of anastrozole combined with testosterone. This novel therapy, delivered in the neoadjuvant setting, has the potential to identify early responders and to evaluate the effectiveness of therapy in vivo. This may prove to be a new approach to both local and systemic therapies for breast cancer in subgroups of patients. In addition, it can be used to reduce tumor volume, allowing for less surgical intervention and better cosmetic oncoplastic results.

Impact of chemotherapy-induced amenorrhea in breast cancer patients: the evaluation of ovarian function by menstrual history and hormonal levels

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2013-01-01

Background Chemotherapy-induced amenorrhea (CIA) is one of the most frequent therapy-related adverse events observed in breast cancer patients who have undergone chemotherapy. Although the characteristics of CIA have been studied in Western countries, little is known about CIA in Asian. We conducted a retrospective analysis to assess the characteristics and influencing factors of CIA and its association with menopause in Chinese women who underwent adjuvant chemotherapy for early-stage breast cancer. Methods Seventy-three premenopausal women who underwent adjuvant chemotherapy for early stage (stages I to III) breast cancer were analyzed. Patient clinical characteristics, treatment regimes, menstrual information, and serum hormone values were collected retrospectively. Characteristic factors relevant to the onset of CIA and menopause were also estimated. Results Approximately 83.6% of patients developed CIA. Older patients (>40 years old) had higher CIA incidence compared with younger patients (P amenorrhea as determined by menstrual history and hormone levels (P = 0.0028). In women aged 46 to 49 years, the beginning of permanent amenorrhea was detected earlier via the clinical method than via the hormonal method (2 months versus 23 months, P amenorrhea was 19 months in the hormonal test and 2 months in the clinical test (P = 0.0112). Conclusions Age at diagnosis is a predictor of the onset of amenorrhea and transformation into menopause among premenopausal breast cancer patients. Adjuvant tamoxifen therapy substantially affects the onset of menopause. A delay of the onset of serum hormone postmenopausal status was observed compared with clinical symptoms. This interval was approximately 21 months in patients aged 46 to 49 years and 17 months in patients aged over 50 years. This interval is significant in the clinical estimate of the menstrual status. PMID:23688389

Preeclampsia-Associated Hormonal Profiles and Reduced Breast Cancer Risk Among Older Mothers

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2003-04-01

Preeclampsia has been linked to reduced breast cancer risk, and this reduction may be especially marked among women who bear their first child later...in life. In this ongoing case-control study, we examine the hormonal profiles of older Colorado mothers with and without a history of preeclampsia in...premenopausal, and are free of serious chronic disease. Cases are 14 Denver area women who experienced preeclampsia in their first pregnancy; controls are 13

Thyroid Hormone, Cancer, and Apoptosis.

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Lin, Hung-Yun; Chin, Yu-Tan; Yang, Yu-Chen S H; Lai, Husan-Yu; Wang-Peng, Jacqueline; Liu, Leory F; Tang, Heng-Yuan; Davis, Paul J

2016-06-13

Thyroid hormones play important roles in regulating normal metabolism, development, and growth. They also stimulate cancer cell proliferation. Their metabolic and developmental effects and growth effects in normal tissues are mediated primarily by nuclear hormone receptors. A cell surface receptor for the hormone on integrin [alpha]vβ3 is the initiation site for effects on tumor cells. Clinical hypothyroidism may retard cancer growth, and hyperthyroidism was recently linked to the prevalence of certain cancers. Local levels of thyroid hormones are controlled through activation and deactivation of iodothyronine deiodinases in different organs. The relative activities of different deiodinases that exist in tissues or organs also affect the progression and development of specific types of cancers. In this review, the effects of thyroid hormone on signaling pathways in breast, brain, liver, thyroid, and colon cancers are discussed. The importance of nuclear thyroid hormone receptor isoforms and of the hormone receptor on the extracellular domain of integrin [alpha]vβ3 as potential cancer risk factors and therapeutic targets are addressed. We analyze the intracellular signaling pathways activated by thyroid hormones in cancer progression in hyperthyroidism or at physiological concentrations in the euthyroid state. Determining how to utilize the deaminated thyroid hormone analog (tetrac), and its nanoparticulate derivative to reduce risks of cancer progression, enhance therapeutic outcomes, and prevent cancer recurrence is also deliberated. © 2016 American Physiological Society. Compr Physiol 6:1221-1237, 2016. Copyright © 2016 John Wiley & Sons, Inc.

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.

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

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

2015-06-01

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

Maintenance of prolactin receptors in human breast cancer

International Nuclear Information System (INIS)

Ben-David, M.; Dror, Y.; Biran, S.

1981-01-01

Breast tissue specimens of 110 women with various stages of breast cancer were tested in vitro to determine their specific binding sites for human prolactin. In contrast to the case of steroid receptors, binding sites for prolactin were found in the vast majority of breast cancer tissue. Distribution profiles giving amount of prolactin receptor and their affinity coefficients were found to be similar in the tissues of women whose ages, hormonal status, or stage of breast cancer varied. These findings show that in contrast to steroid receptors, human breast cancer tissue maintains binding sites for prolactin. The findings also indicate that there may be a higher dependency of breast cancer on prolactin than on steroids. Clinical trials must be carried out to determine the role of ''positive'' prolactin receptors in prognosis and prediction of response to future hormone therapy. (author)

Long chain fatty Acyl-CoA synthetase 4 is a biomarker for and mediator of hormone resistance in human breast cancer.

Directory of Open Access Journals (Sweden)

Xinyu Wu

Full Text Available The purpose of this study was to determine the role of long-chain fatty acyl-CoA synthetase 4 (ACSL4 in breast cancer. Public databases were utilized to analyze the relationship between ACSL4 mRNA expression and the presence of steroid hormone and human epidermal growth factor receptor 2 (HER2 in both breast cancer cell lines and tissue samples. In addition, cell lines were utilized to assess the consequences of either increased or decreased levels of ACSL4 expression. Proliferation, migration, anchorage-independent growth and apoptosis were used as biological end points. Effects on mRNA expression and signal transduction pathways were also monitored. A meta-analysis of public gene expression databases indicated that ACSL4 expression is positively correlated with a unique subtype of triple negative breast cancer (TNBC, characterized by the absence of androgen receptor (AR and therefore referred to as quadruple negative breast cancer (QNBC. Results of experiments in breast cancer cell lines suggest that simultaneous expression of ACSL4 and a receptor is associated with hormone resistance. Forced expression of ACSL4 in ACSL4-negative, estrogen receptor α (ER-positive MCF-7 cells resulted in increased growth, invasion and anchorage independent growth, as well as a loss of dependence on estrogen that was accompanied by a reduction in the levels of steroid hormone receptors. Sensitivity to tamoxifen, triacsin C and etoposide was also attenuated. Similarly, when HER2-positive, ACSL4-negative, SKBr3 breast cancer cells were induced to express ACSL4, the proliferation rate increased and the apoptotic effect of lapatinib was reduced. The growth stimulatory effect of ACSL4 expression was also observed in vivo in nude mice when MCF-7 control and ACSL4-expressing cells were utilized to induce tumors. Our data strongly suggest that ACSL4 can serve as both a biomarker for, and mediator of, an aggressive breast cancer phenotype.

New Treatment Option for Young Women with Hormone-Sensitive Breast Cancer

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... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... breast cancer, defined as estrogen and/or progesterone receptor-positive breast cancer, represents 79 percent of breast ...

The role of hormones in the differences in the incidence of breast cancer between Mongolia and the United Kingdom.

Directory of Open Access Journals (Sweden)

Rebecca Troisi

Full Text Available There are striking differences in breast cancer incidence between Asian and western women. Rates vary substantially within Asia also, with Mongolia's even lower than China's. These profound differences have been speculated to be due in part to diet, mediated by circulating hormone concentrations.Sex steroid hormone concentrations were measured in women living in Ulaanbaatar, Mongolia and the United Kingdom (U.K.. Diet was obtained by interview and national survey data. Mean hormone differences were compared by country, and systematic variation by number of days since last menstrual period was modeled and adjusted for age and parity; difference in overall area under the curves was assessed.The diet in Mongolia was higher in meat and dairy than in the U.K. Mean testosterone concentrations were 18.5% lower (p<0.0001 while estradiol concentrations were 19.1% higher (p = 0.02 in Mongolian than British women, adjusted for age and parity. Progesterone was almost 50% higher in Mongolian women (p = 0.04, particularly during the follicular phase and early luteal surge. Hormone concentrations generally were similar in Mongolian women born in Ulaanbaatar compared with those born in rural areas, although there was a decreasing progesterone trend by degree of westernization (rural Mongolia; urban Mongolia; U.K.. Mean hormone differences were similar when restricted to parous women, and with further adjustment for body mass index, height, and smoking status.These data augment accumulating evidence that circulating estrogens are unlikely to explain reduced breast cancer rates in Asia compared with the west, and suggest casting a wider net with respect to biomarkers. Lower testosterone and higher progesterone in Mongolian women raise the possibility that these hormones may be important to consider. In addition, the almost exclusive dietary reliance of Mongolians on meat and dairy argues against beneficial effects of a low-fat diet on circulating hormones

UDP-glucuronosyltransferase and sulfotransferase polymorphisms, sex hormone concentrations, and tumor receptor status in breast cancer patients

International Nuclear Information System (INIS)

Sparks, Rachel; Yuan, Xiaopu; Lin, Ming Gang; McVarish, Lynda; Aiello, Erin J; McTiernan, Anne; Ulrich, Cornelia M; Bigler, Jeannette; Tworoger, Shelley S; Yasui, Yutaka; Rajan, Kumar B; Porter, Peggy; Stanczyk, Frank Z; Ballard-Barbash, Rachel

2004-01-01

UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) enzymes are involved in removing sex hormones from circulation. Polymorphic variation in five UGT and SULT genes – UGT1A1 ((TA) 6 /(TA) 7 ), UGT2B4 (Asp 458 Glu), UGT2B7 (His 268 Tyr), UGT2B15 (Asp 85 Tyr), and SULT1A1 (Arg 213 His) – may be associated with circulating sex hormone concentrations, or the risk of an estrogen receptor-negative (ER - ) or progesterone receptor-negative (PR - ) tumor. Logistic regression analysis was used to estimate the odds ratios of an ER - or PR - tumor associated with polymorphisms in the genes listed above for 163 breast cancer patients from a population-based cohort study of women in western Washington. Adjusted geometric mean estradiol, estrone, and testosterone concentrations were calculated within each UGT and SULT genotype for a subpopulation of postmenopausal breast cancer patients not on hormone therapy 2–3 years after diagnosis (n = 89). The variant allele of UGT1A1 was associated with reduced risk of an ER - tumor (P for trend = 0.03), and variants of UGT2B15 and SULT1A1 were associated with non-statistically significant risk reductions. There was some indication that plasma estradiol and testosterone concentrations varied by UGT2B15 and SULT1A1 genotypes; women with the UGT2B15 Asp/Tyr and Tyr/Tyr genotypes had higher concentrations of estradiol than women with the Asp/Asp genotype (P = 0.004). Compared with women with the SULT1A1 Arg/Arg and Arg/His genotypes, women with the His/His genotype had elevated concentrations of testosterone (P = 0.003). The risk of ER - breast cancer tumors may vary by UGT or SULT genotype. Further, plasma estradiol and testosterone concentrations in breast cancer patients may differ depending on some UGT and SULT genotypes

Avoidable cancers in the Nordic countries. Exogenous hormones

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Winther, J F; Dreyer, L; Tryggvadottir, L

1997-01-01

of the breast and uterine cervix) and beneficial effects (protection against cancers of the ovary and endometrium), indicate that 95 cases of breast cancer and 40 of cervical cancer will be caused by oral contraceptives annually around 2000 in the Nordic countries, which corresponds to 0.6% of all breast......The well-described influence of several aspects of reproductive life on the risk for cancer in the reproductive organs has raised concern regarding the safety of exogenous hormones, particularly since sex hormones have become one of the most widely used drugs among women in the western world...... aged 15-45 years in 1985 ranging between 6% (Norway) and 19% (Sweden) and proportions of current users in 1994 ranging between 20% (Norway) and 28% (Sweden). Such data on the current and long-term use of oral contraceptives by the female populations, linked with relative estimates of adverse (cancers...

Breast Cancer Treatment (PDQ®)—Patient Version

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Breast cancer treatment depends on several factors and can include combinations of surgery, chemotherapy, radiation, hormone, and targeted therapy. Learn more about how breast cancer is diagnosed and treated in this expert-reviewed summary.

Physical activity, hormone replacement therapy and breast cancer risk: A meta-analysis of prospective studies.

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Pizot, Cécile; Boniol, Mathieu; Mullie, Patrick; Koechlin, Alice; Boniol, Magali; Boyle, Peter; Autier, Philippe

2016-01-01

Lower risk of breast cancer has been reported among physically active women, but the risk in women using hormone replacement therapy (HRT) appears to be higher. We quantified the association between physical activity and breast cancer, and we examined the influence that HRT use and other risk factors had on this association. After a systematic literature search, prospective studies were meta-analysed using random-effect models applied on highest versus lowest level of physical activity. Dose-response analyses were conducted with studies reporting physical activity either in hours per week or in hours of metabolic equivalent per week (MET-h/week). The literature search identified 38 independent prospective studies published between 1987 and 2014 that included 116,304 breast cancer cases. Compared to the lowest level of physical activity, the highest level was associated with a summary relative risk (SRR) of 0.88 (95% confidence interval [CI] 0.85, 0.90) for all breast cancer, 0.89 (95% CI 0.83, 0.95) for ER+/PR+ breast cancer and 0.80 (95% CI 0.69, 0.92) for ER-/PR- breast cancer. Risk reductions were not influenced by the type of physical activity (occupational or non-occupational), adiposity, and menopausal status. Risk reductions increased with increasing amounts of physical activity without threshold effect. In six studies, the SRR was 0.78 (95% CI 0.70, 0.87) in women who never used HRT and 0.97 (95% CI 0.88, 1.07) in women who ever used HRT, without heterogeneity in results. Findings indicate that a physically inactive women engaging in at least 150 min per week of vigorous physical activity would reduce their lifetime risk of breast cancer by 9%, a reduction that might be two times greater in women who never used HRT. Increasing physical activity is associated with meaningful reductions in the risk of breast cancer, but in women who ever used HRT, the preventative effect of physical activity seems to be cancelled out. Copyright © 2015 Elsevier Ltd. All

Risk of Recurrence or Contralateral Breast Cancer More than 5 Years After Diagnosis of Hormone Receptor-Positive Early-Stage Breast Cancer.

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Wilson, Sheridan; Speers, Caroline; Tyldesley, Scott; Chia, Stephen; Kennecke, Hagen; Ellard, Susan; Lohrisch, Caroline

2016-08-01

Three large studies have shown a survival benefit from 10 years of adjuvant hormone therapy (AHT). We evaluated the risk of an event 5 years after the initial breast cancer (BC) diagnosis and identified the prognostic factors to assist clinicians considering extended AHT. Patients newly referred to the BC Cancer Agency with stage I to III estrogen receptor-positive BC diagnosed from 1989 to 2004 who had undergone AHT were identified by the BC Cancer Agency's Breast Cancer Outcomes Unit. Cases with recurrence, death, or contralateral BC occurring within the first 5 years were excluded. The 10-year event-free survival (EFS) and 95% confidence intervals (CIs) were calculated using the Kaplan-Meier method. This provided estimates of recurrence risk after the fifth year following the diagnosis. The histopathologic and age variables were examined for prognostic value by univariate analysis. Within our cohort, 6615 women were postmenopausal and 1886 were premenopausal at the BC diagnosis. The median follow-up period was 11 years. The 10-year EFS for women aged cancer (any grade) and for stage II (node-negative and node-positive), grade I cancer. Our data have identified BCs associated with a very low recurrence risk 5 to 10 years after diagnosis, providing women with such cancers confidence about a decision to discontinue AHT after 5 years. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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

2017-10-01

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

Racial differences in receipt of adjuvant hormonal therapy among Medicaid enrollees in South Carolina diagnosed with breast cancer

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Felder, Tisha M.; Do, D. Phuong; Lu, Z. Kevin; Lal, Lincy S.; Heiney, Sue P.; Bennett, Charles L.

2016-01-01

Purpose Several factors contribute to the pervasive Black-White disparity in breast cancer mortality in the U.S., such as tumor biology, access to care and treatments received including adjuvant hormonal therapy (AHT), which significantly improves survival for hormone-receptor positive breast cancers (HR+). We analyzed South Carolina Central Cancer Registry-Medicaid linked data to determine if, in an equal access health care system, racial differences in the receipt of AHT exist. Methods We evaluated 494 study-eligible, Black (n=255) and White women (n=269) who were under 65 years old and diagnosed with stages I–III, HR+ breast cancers between 2004 and 2007. Bivariate and multivariate analyses were conducted to assess receipt of ≥ 1 AHT prescriptions at any point in time following (ever-use) or within 12 months of (early-use) breast cancer diagnosis. Results Seventy-two percent of the participants were ever-users (70% Black, 74% White) and 68% were early-users (65% Black, 71% White) of AHT. Neither ever-use (adjusted OR (AOR)=0.75, 95% CI: 0.48–1.17) nor early-use (AOR=0.70, 95% CI: 0.46–1.06) of AHT differed by race. However, receipt of other breast cancer-specific treatments was independently associated with ever-use and early-use of AHT [ever-use: receipt of surgery (AOR= 2.15, 95% CI: 1.35–3.44); chemotherapy (AOR=1.97, 95% CI: 1.22–3.20); radiation (AOR=2.33, 95% CI: 1.50–3.63); early-use: receipt of surgery (AOR=2.03, 95% CI: 1.30–3.17); chemotherapy (AOR=1.90, 95% CI: 1.20–3.03); radiation (AOR=1.73, 95% CI: 1.14–2.63)]. Conclusions No racial variations in use of AHT among women with HR+ breast cancers insured by Medicaid in South Carolina were identified, but overall rates of AHT use by these women is low. Strategies to improve overall use of AHT should include targeting breast cancer patients who do not receive adjuvant chemotherapy and/or radiation. PMID:27120468

From bench to bedside: What do we know about hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer?

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Wu, Victoria Shang; Kanaya, Noriko; Lo, Chiao; Mortimer, Joanne; Chen, Shiuan

2015-09-01

Breast cancer is a heterogeneous disease. Thanks to extensive efforts from research scientists and clinicians, treatment for breast cancer has advanced into the era of targeted medicine. With the use of several well-established biomarkers, such as hormone receptors (HRs) (i.e., estrogen receptor [ER] and progesterone receptor [PgR]) and human epidermal growth factor receptor-2 (HER2), breast cancer patients can be categorized into multiple subgroups with specific targeted treatment strategies. Although therapeutic strategies for HR-positive (HR+) HER2-negative (HER2-) breast cancer and HR-negative (HR-) HER2-positive (HER2+) breast cancer are well-defined, HR+ HER2+ breast cancer is still an overlooked subgroup without tailored therapeutic options. In this review, we have summarized the molecular characteristics, etiology, preclinical tools and therapeutic options for HR+ HER2+ breast cancer. We hope to raise the attention of both the research and the medical community on HR+ HER2+ breast cancer, and to advance patient care for this subtype of disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Endogenous estrogens and the risk of breast, endometrial, and ovarian cancers.

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Brown, Susan B; Hankinson, Susan E

2015-07-01

Data from laboratory and epidemiologic studies support a relationship between endogenous hormones and the increased risk of several female cancers. In epidemiologic studies, consistent associations have been observed between risk of breast, ovarian and endometrial cancers and reproductive and hormonal risk factors such as high postmenopausal body mass index (BMI) and postmenopausal hormone use, which suggest the importance of endogenous hormones in the etiology of these diseases. The relationship between circulating estrogen levels in postmenopausal women and the risk of breast cancer is well established, with an approximately 2-fold higher risk among women in the top 20-25% (versus bottom 20-25%) of levels. However, data evaluating the relationship between endogenous estrogens and premenopausal breast cancer risk are more limited and less consistent. Two studies to date have evaluated the relationship between circulating estrogens and breast cancer risk by menstrual cycle phase at blood collection and only one study has examined this relationship by menopausal status at diagnosis. Three prospective studies have evaluated circulating estrogen levels and endometrial cancer risk in postmenopausal women, with consistent strong positive associations reported (with relative risks of 2-4 comparing high versus low hormone levels), while this relationship has not been studied in premenopausal women. Compared to breast and endometrial cancers, reproductive and hormonal characteristics such as postmenopausal hormone use are generally weaker and less consistent risk factors for ovarian cancer, and the only small prospective study conducted to date indicated a non-significant positive relationship between circulating estrogen levels and ovarian cancer risk. In this review, we summarize current evidence and identify key areas to be addressed in future epidemiologic studies of endogenous estrogens and the risk of breast, endometrial, and ovarian cancers. Copyright © 2015

Identification of hormonal receptors in human breast cancer

International Nuclear Information System (INIS)

Rosa Pascual, M.; Lage, A.; Diaz, J.W.; Moreno, L.; Marta Diaz, T.

1981-01-01

The experience in the implementation of a technique for determining hormono-dependence of human breast cancer is presented. The results found with the use of the technique in 50 patients with malignant breast cancer treated at IOR are examined and discussed. (author)

Feature of amenorrhea in postoperative tamoxifen users with breast cancer.

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Kim, Hoon; Han, Wonshik; Ku, Seung Yup; Suh, Chang Suk; Kim, Seok Hyun; Choi, Young Min

2017-03-01

Tamoxifen has been used to prevent the recurrence of breast cancer. However, tamoxifen-users frequently experience amenorrhea and it can be confused from that caused by other hormonal abnormalities. In amenorrheic patients without breast cancer, clinicians usually measure the sex hormone levels that are known to be associated with ovarian or menstrual function. This study aimed to investigate the feature of female sex hormones in premenopausal breast cancer patients undergoing tamoxifen treatment. The medical records of fifty-nine premenopausal breast cancer patients who underwent tamoxifen treatment were reviewed retrospectively. The study population consisted of amenorrheic patients (n=36) and patients with menstruation (n=23). Serum hormone levels were measured either specifically between cycle days 2 and 5 in menstruating patients or at any time in amenorrheic participants. Serum levels of lutenizing hormone and estradiol were not statistically different according to the presence of menstruation. Serum follicle stimulating hormone level was significantly higher in amenorrheic patients (8.1±5.7 mIU/mL) than those in menstruating subjects (5.1±2.2 mIU/mL) (p=0.01). Serum concentration of thyroid stimulating hormone was lower in patients with amenorrhea (1.5±0.9 vs. 2.3±2.2 μIU/mL, p=0.04), although the prevalence of hypo- or hyperthyroidism was not different according to the pattern of menstruation. Menstruation status and hormone levels can be influenced by tamoxifen use in reproductive age breast cancer patients. Physicians should be attentive to the alteration of pituitary hormone levels in addition to sex steroid hormones in this population. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

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

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E. V. Artamonova

2017-01-01

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

Ablative dual-phase Erbium:YAG laser treatment of atrophy-related vaginal symptoms in post-menopausal breast cancer survivors omitting hormonal treatment.

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Mothes, A R; Runnebaum, M; Runnebaum, I B

2018-05-01

First evaluation of dual-phase vaginal Er:YAG laser to omit hormonal treatment for atrophy-related symptoms in post-menopausal breast cancer survivors following prolapse surgery. Patients with a history of breast cancer at the time of surgery for pelvic organ prolapse were offered non-hormonal vaginal Er:YAG laser treatment when complaining of atrophy-related genitourinary syndrome of menopause. A single 10-min course of dual-phase protocol of pulsed Er:YAG laser (2940 nm, fractional ablative and thermal mode, fluence according to tissue thickness). Follow-up included subjective satisfaction, vaginal pH, vaginal health index (VHI), and complications after 6 weeks. A total of 16 breast cancer survivors (age 71 years, SD 7) had been seeking treatment for pelvic floor symptoms related to vaginal atrophy at follow-up visits after prolapse surgery. All ablative vaginal Er:YAG laser outpatient procedures were successfully completed, all patients returned to daily activities without a need for analgetic medication. Evaluation was performed after 8.3 (SD 2.5) weeks. Pre-laser VHI scored 16 (SD 4.6) and post-laser VHI 20 (SD 3) with p = 0.01. Patients were satisfied in 94% (n = 15) regarding symptom relief. Breast cancer survivors with atrophy-related complaints after pelvic floor surgery may benefit from vaginal application of this innovative dual protocol of Er:YAG laser technology as a non-hormonal treatment approach.

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

International Nuclear Information System (INIS)

Gradishar, William J

2016-01-01

Community-based oncologists are faced with challenges and opportunities when delivering quality patient care, including high patient volumes and diminished resources; however, there may be the potential to deliver increased patient education and subsequently improve outcomes. This review discusses the treatment of postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2- negative advanced breast cancer in order to illustrate considerations in the provision of pertinent quality education in the treatment of these patients and the management of therapy-related adverse events. An overview of endocrine-resistant breast cancer and subsequent treatment challenges is also provided. Approved treatment options for endocrine-resistant breast cancer include hormonal therapies and mammalian target of rapamycin inhibitors. Compounds under clinical investigation are also discussed

Risk of Breast Cancer in Relation to Combined Effects of Hormone Therapy, Body Mass Index, and Alcohol Use, by Hormone-receptor Status

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Hvidtfeldt, Ulla Arthur; Tjonneland, Anne; Keiding, Niels

2015-01-01

BACKGROUND: Alcohol consumption, increased body mass index (BMI), and hormone therapy are risk factors for postmenopausal breast cancer, but their combined effects are not well understood. Because hormone therapy is effective for the relief of menopausal symptoms, the identification of "high......,789 women ages 50+ years (study period 1981 to 2009). Information on risk factors was obtained in baseline questionnaires. We performed analyses using the Aalen additive hazards model. Serum estradiol and testosterone measurements were obtained in a subsample of approximately 1000 women. RESULTS: During 392...

Estrogen sulfotransferases in breast and endometrial cancers.

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Pasqualini, Jorge Raul

2009-02-01

Estrogen sulfotransferase is significantly more active in the normal breast cell (e.g., Human 7) than in the cancer cell (e.g., MCF-7). The data suggest that in breast cancer sulfoconjugated activity is carried out by another enzyme, the SULT1A, which acts at high concentration of the substrates. In breast cancer cells sulfotransferase (SULT) activity can be stimulated by various progestins: medrogestone, promegestone, and nomegestrol acetate, as well as by tibolone and its metabolites. SULT activities can also be controlled by other substances including phytoestrogens, celecoxib, flavonoids (e.g., quercetin, resveratrol), and isoflavones. SULT expression was localized in breast cancer cells, which can be stimulated by promegestone and correlated with the increase of the enzyme activity. The estrogen sulfotransferase (SULT1E1), which acts at nanomolar concentration of estradiol, can inactivate most of this hormone present in the normal breast; however, in the breast cancer cells, the sulfotransferase denoted as SULT1A1 is mainly present, and this acts at micromolar concentrations of E(2). A correlation was postulated among breast cancer cell proliferation, the effect of various progestins, and sulfotransferase stimulation. In conclusion, it is suggested that factors involved in the stimulation of the estrogen sulfotransferases could provide new possibilities for the treatment of patients with hormone-dependent breast and endometrial cancers.

Prevention of breast cancer.

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Olver, Ian N

2016-11-21

Modifiable lifestyle factors may reduce the risk of developing breast cancer. Obesity is associated particularly with post-menopausal breast cancer. Diet is important, and exercise equivalent to running for up to 8 hours each week reduces the risk of breast cancer, both in its own right and through reducing obesity. Alcohol consumption may be responsible for 5.8% of breast cancers in Australia and it is recommended to reduce this to two standard drinks per day. Drinking alcohol and smoking increases the risk for breast cancer and, therefore, it is important to quit tobacco smoking. Prolonged use of combined oestrogen and progesterone hormone replacement therapy and oral contraceptives may increase breast cancer risk and this must be factored into individual decisions about their use. Ionising radiation, either from diagnostic or therapeutic radiation or through occupational exposure, is associated with a high incidence of breast cancer and exposure may be reduced in some cases. Tamoxifen chemoprevention may reduce the incidence of oestrogen receptor positive cancer in 51% of women with high risk of breast cancer. Uncommon but serious side effects include thromboembolism and uterine cancer. Raloxifene, which can also reduce osteoporosis, can be used in post-menopausal women and is not associated with the development of uterine cancer. Surgical prophylaxis with bilateral mastectomy and salpingo-oophorectomy can reduce the risk of breast cancer in patients carrying BRCA1 or BRCA2 mutations. For preventive treatments, mammographic screening can identify other women at high risk.

Increased risk for invasive breast cancer associated with hormonal therapy: a nation-wide random sample of 65,723 women followed from 1997 to 2008.

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Jung-Nien Lai

Full Text Available BACKGROUND: Hormonal therapy (HT either estrogen alone (E-alone or estrogen plus progesterone (E+P appears to increase the risk for breast cancer in Western countries. However, limited information is available on the association between HT and breast cancer in Asian women characterized mainly by dietary phytoestrogens intake and low prevalence of contraceptive pills prescription. METHODOLOGY: A total of 65,723 women (20-79 years of age without cancer or the use of Chinese herbal products were recruited from a nation-wide one-million representative sample of the National Health Insurance of Taiwan and followed from 1997 to 2008. Seven hundred and eighty incidents of invasive breast cancer were diagnosed. Using a reference group that comprised 40,052 women who had never received a hormone prescription, Cox proportional hazard models were constructed to determine the hazard ratios for receiving different types of HT and the occurrence of breast cancer. CONCLUSIONS: 5,156 (20% women ever used E+P, 2,798 (10.8% ever used E-alone, and 17,717 (69% ever used other preparation types. The Cox model revealed adjusted hazard ratios (HRs of 2.05 (95% CI 1.37-3.07 for current users of E-alone and 8.65 (95% CI 5.45-13.70 for current users of E+P. Using women who had ceased to take hormonal medication for 6 years or more as the reference group, the adjusted HRs were significantly elevated and greater than current users and women who had discontinued hormonal medication for less than 6 years. Current users of either E-alone or E+P have an increased risk for invasive breast cancer in Taiwan, and precautions should be taken when such agents are prescribed.

HDAC2 and HDAC5 Up-Regulations Modulate Survivin and miR-125a-5p Expressions and Promote Hormone Therapy Resistance in Estrogen Receptor Positive Breast Cancer Cells

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Wen-Tsung Huang

2017-12-01

Full Text Available Intrinsic or acquired resistance to hormone therapy is frequently reported in estrogen receptor positive (ER+ breast cancer patients. Even though dysregulations of histone deacetylases (HDACs are known to promote cancer cells survival, the role of different HDACs in the induction of hormone therapy resistance in ER+ breast cancer remains unclear. Survivin is a well-known pro-tumor survival molecule and miR-125a-5p is a recently discovered tumor suppressor. In this study, we found that ER+, hormone-independent, tamoxifen-resistant MCF7-TamC3 cells exhibit increased expression of HDAC2, HDAC5, and survivin, but show decreased expression of miR-125a-5p, as compared to the parental tamoxifen-sensitive MCF7 breast cancer cells. Molecular down-regulations of HDAC2, HDAC5, and survivin, and ectopic over-expression of miR-125a-5p, increased the sensitivity of MCF7-TamC3 cells to estrogen deprivation and restored the sensitivity to tamoxifen. The same treatments also further increased the sensitivity to estrogen-deprivation in the ER+ hormone-dependent ZR-75-1 breast cancer cells in vitro. Kaplan–Meier analysis and receiver operating characteristic curve analysis of expression cohorts of breast tumor showed that high HDAC2 and survivin, and low miR-125a-5p, expression levels correlate with poor relapse-free survival in endocrine therapy and tamoxifen-treated ER+ breast cancer patients. Further molecular analysis revealed that HDAC2 and HDAC5 positively modulates the expression of survivin, and negatively regulates the expression miR-125a-5p, in ER+ MCF7, MCF7-TamC3, and ZR-75-1 breast cancer cells. These findings indicate that dysregulations of HDAC2 and HDAC5 promote the development of hormone independency and tamoxifen resistance in ERC breast cancer cells in part through expression regulation of survivin and miR-125a-5p.

New treatment option for women with hormone-sensitive breast cancer

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A drug used for treating breast cancer, known as exemestane, is more effective than a common breast cancer prevention drug, tamoxifen, in preventing breast cancer recurrence in young women who also receive post-surgical treatment to suppress ovarian funct

Pregnancy and its role in breast cancer

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Filipe Correia Martins

2011-12-01

Full Text Available Early full-term pregnancy is the only recognized factor able to prevent breast cancer. There are several hypotheses to explain the mechanisms of this protection, namely an altered hormonal milieu, a differentiation process or a switch in stem cell properties. To explore them, authors have been using animal models, mainly in rodents. Hormonal administration with estrogen and progesterone was the most widely used process to mimic the mammary changes during pregnancy. We have recently proposed that this enigmatic protective role of a full-term birth in breast cancer is carried out by tumor inhibition mediated by differentiated mammary epithelial cells. This explanation may give a new perspective of breast cancer prevention and treatment.

Breast Cancer Types: What Your Type Means

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... B breast cancers are likely to benefit from chemotherapy and may benefit from hormone therapy and treatment targeted to HER2. ... HER2 positive. HER2 breast cancers are likely to benefit from chemotherapy and treatment targeted to HER2. Group 4 (basal- ...

Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer

International Nuclear Information System (INIS)

Leissner, Philippe; Verjat, Thibault; Bachelot, Thomas; Paye, Malick; Krause, Alexander; Puisieux, Alain; Mougin, Bruno

2006-01-01

One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA) and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1). In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer. The study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR. uPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS) and Breast Cancer specific Survival (BCS) were significantly shorter in patients expressing high levels of PAI-1 mRNA (p < 0.0001; p < 0.0001; respectively). In Cox multivariate analysis, the level of PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR) = 10.12; p = 0.0002) and for BCS (HR = 13.17; p = 0.0003). Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41) nor with BCS (p = 0.19). In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value. These findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer

Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer

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Krause Alexander

2006-08-01

Full Text Available Abstract Background One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1. In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer. Methods The study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR. Results uPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS and Breast Cancer specific Survival (BCS were significantly shorter in patients expressing high levels of PAI-1 mRNA (p PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR = 10.12; p = 0.0002 and for BCS (HR = 13.17; p = 0.0003. Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41 nor with BCS (p = 0.19. In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value. Conclusion These findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer patients.

Risk of second breast cancers after lobular carcinoma in situ according to hormone receptor status.

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Kai Mao

Full Text Available Although subsequent breast cancer risk after primary lobular carcinoma in situ (LCIS has been studied intensively, whether the risk of second breast cancer after first LCIS varies with hormone receptor (HR status of primary tumor remains unclear.We identified 10,304 women with primary pure unilateral LCIS between 1998 and 2007 from the Surveillance, Epidemiology and End Results (SEER 18 Registries. Kaplan-Meier estimates of 5 or 10-year probabilities of second ipsilateral breast cancers (IBCs and contralateral breast cancers (CBCs were calculated. Multivariable Cox proportional model was performed to identify impact of HR status of primary LCIS, and other demographic, clinicopathologic or treatment characteristics on risk of second IBCs or CBCs.Of the 10,304 women with primary LCIS included in this study, 9949 (96.5% patients had HR+ tumors, and 355 (3.5% had HR- tumors. Multivariable-adjusted analyses showed that although there was no difference in risk of total second IBCs between women with HR+ and HR- LCIS (P = 0.152, patients with HR+ LCIS had a statistically lower risk of second invasive IBCs compared to those with HR- LCIS (hazard ratio 0.356, 95% CI 0.141-0.899, P = 0.029. Women with primary HR+ LCIS had lower risks of both second total and invasive CBCs compared to those with HR- LCIS (total CBCs: hazard ratio 0.340, 95% CI 0.228-0.509, P<0.001; invasive CBCs: hazard ratio 0.172, 95% CI 0.108-0.274, P<0.001. Additionally, black women had a 2-fold risk of developing subsequent total IBCs than white women (P = 0.028.This population-based study demonstrated that the risk of second breast cancers was significantly increased in women with HR- first LCIS compared to those with HR+ LCIS. These findings warrant intensive surveillance for second breast cancers in HR- LCIS survivors.

Low-risk factor profile, estrogen levels, and breast cancer risk among postmenopausal women

DEFF Research Database (Denmark)

Rod, Naja Hulvej; Hansen, Ase Marie; Nielsen, Jens

2008-01-01

Obesity, alcohol consumption, physical inactivity and postmenopausal hormone use are known modifiable risk factors for breast cancer. We aim to measure incidence rates of breast cancer for women with favorable levels on all 4 risk factors (BMI......Obesity, alcohol consumption, physical inactivity and postmenopausal hormone use are known modifiable risk factors for breast cancer. We aim to measure incidence rates of breast cancer for women with favorable levels on all 4 risk factors (BMI...

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...

Evaluation of Therapy Management and Patient Compliance in Postmenopausal Patients with Hormone Receptor-positive Breast Cancer Receiving Letrozole Treatment: The EvaluateTM Study

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Fasching, P. A.; Fehm, T.; Kellner, S.; de Waal, J.; Rezai, M.; Baier, B.; Baake, G.; Kolberg, H.-C.; Guggenberger, M.; Warm, M.; Harbeck, N.; Würstlein, R.; Deuker, J.-U.; Dall, P.; Richter, B.; Wachsmann, G.; Brucker, C.; Siebers, J. W.; Fersis, N.; Kuhn, T.; Wolf, C.; Vollert, H.-W.; Breitbach, G.-P.; Janni, W.; Landthaler, R.; Kohls, A.; Rezek, D.; Noesslet, T.; Fischer, G.; Henschen, S.; Praetz, T.; Heyl, V.; Kühn, T.; Krauß, T.; Thomssen, C.; Kümmel, S.; Hohn, A.; Tesch, H.; Mundhenke, C.; Hein, A.; Rauh, C.; Bayer, C. M.; Jacob, A.; Schmidt, K.; Belleville, E.; Hadji, P.; Wallwiener, D.; Grischke, E.-M.; Beckmann, M. W.; Brucker, S. Y.

2014-01-01

Introduction: The EvaluateTM study (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor-positive breast cancer patients receiving letrozole treatment) is a prospective, non-interventional study for the assessment of therapy management and compliance in the routine care of postmenopausal women with invasive hormone receptor-positive breast cancer receiving letrozole. The parameters for inclusion in the study are presented and discussed here. Material and Methods: Between January 2008 and December 2009 a total of 5045 patients in 310 study centers were recruited to the EvaluateTM study. Inclusion criteria were hormone receptor-positive breast cancer and adjuvant treatment or metastasis. 373 patients were excluded from the analysis for various reasons. Results: A total of 4420 patients receiving adjuvant treatment and 252 patients with metastasis receiving palliative treatment were included in the study. For 4181 patients receiving adjuvant treatment, treatment with the aromatase inhibitor letrozole commenced immediately after surgery (upfront). Two hundred patients had initially received tamoxifen and started aromatase inhibitor treatment with letrozole at 1–5 years after diagnosis (switch), und 39 patients only commenced letrozole treatment 5–10 years after diagnosis (extended endocrine therapy). Patient and tumor characteristics were within expected ranges, as were comorbidities and concurrent medication. Conclusion: The data from the EvaluateTM study will offer a good overview of therapy management in the routine care of postmenopausal women with hormone receptor-positive breast cancer. Planned analyses will look at therapy compliance and patient satisfaction with how information is conveyed and the contents of the conveyed information. PMID:25568468

Awareness and current knowledge of breast cancer.

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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.

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

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

2014-11-01

Whether moderate to severe obesity (body mass index (BMI)≥30 to women, recruited within 12 months of their diagnosis of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) invasive breast cancer completed an enrolment questionnaire and an annual follow-up questionnaire every 12 months for another 5 years. The impact of obesity on time to either local or distant recurrence or new breast cancer, or death due to breast cancer was determined by Cox regression. Women in the most extreme categories of BMI (women, mean age, 58.4±11.6 years, 53.8% had Stage 1 disease and 88.9% received oral adjuvant endocrine therapy (OAET) within 2 years of diagnosis. The likelihood of an event was significantly associated with moderate to severe obesity (HR=1.71, 95%CI, 1.12-2.62, p=0.014), disease beyond Stage 1 (HR=2.87, 95% CI 1.73-4.75, pobesity (HR 3.23, 95%CI 1.48-7.03, p=0.003) and OAET use (HR 0.41, 95%CI 0.17-0.98, p=0.046) were significantly associated with an event. Moderate to severe obesity is associated with a poorer invasive breast cancer prognosis; this is also true for women with Stage 1 disease, and is independent of age and treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Screening and association testing of common coding variation in steroid hormone receptor co-activator and co-repressor genes in relation to breast cancer risk: the Multiethnic Cohort

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Stallcup Michael R

2009-01-01

Full Text Available Abstract Background Only a limited number of studies have performed comprehensive investigations of coding variation in relation to breast cancer risk. Given the established role of estrogens in breast cancer, we hypothesized that coding variation in steroid receptor coactivator and corepressor genes may alter inter-individual response to estrogen and serve as markers of breast cancer risk. Methods We sequenced the coding exons of 17 genes (EP300, CCND1, NME1, NCOA1, NCOA2, NCOA3, SMARCA4, SMARCA2, CARM1, FOXA1, MPG, NCOR1, NCOR2, CALCOCO1, PRMT1, PPARBP and CREBBP suggested to influence transcriptional activation by steroid hormone receptors in a multiethnic panel of women with advanced breast cancer (n = 95: African Americans, Latinos, Japanese, Native Hawaiians and European Americans. Association testing of validated coding variants was conducted in a breast cancer case-control study (1,612 invasive cases and 1,961 controls nested in the Multiethnic Cohort. We used logistic regression to estimate odds ratios for allelic effects in ethnic-pooled analyses as well as in subgroups defined by disease stage and steroid hormone receptor status. We also investigated effect modification by established breast cancer risk factors that are associated with steroid hormone exposure. Results We identified 45 coding variants with frequencies ≥ 1% in any one ethnic group (43 non-synonymous variants. We observed nominally significant positive associations with two coding variants in ethnic-pooled analyses (NCOR2: His52Arg, OR = 1.79; 95% CI, 1.05–3.05; CALCOCO1: Arg12His, OR = 2.29; 95% CI, 1.00–5.26. A small number of variants were associated with risk in disease subgroup analyses and we observed no strong evidence of effect modification by breast cancer risk factors. Based on the large number of statistical tests conducted in this study, the nominally significant associations that we observed may be due to chance, and will need to be confirmed in other

Screening and association testing of common coding variation in steroid hormone receptor co-activator and co-repressor genes in relation to breast cancer risk: the Multiethnic Cohort

International Nuclear Information System (INIS)

Haiman, Christopher A; Stallcup, Michael R; Greene, Geoffrey L; Press, Michael F; Garcia, Rachel R; Hsu, Chris; Xia, Lucy; Ha, Helen; Sheng, Xin; Le Marchand, Loic; Kolonel, Laurence N; Henderson, Brian E

2009-01-01

Only a limited number of studies have performed comprehensive investigations of coding variation in relation to breast cancer risk. Given the established role of estrogens in breast cancer, we hypothesized that coding variation in steroid receptor coactivator and corepressor genes may alter inter-individual response to estrogen and serve as markers of breast cancer risk. We sequenced the coding exons of 17 genes (EP300, CCND1, NME1, NCOA1, NCOA2, NCOA3, SMARCA4, SMARCA2, CARM1, FOXA1, MPG, NCOR1, NCOR2, CALCOCO1, PRMT1, PPARBP and CREBBP) suggested to influence transcriptional activation by steroid hormone receptors in a multiethnic panel of women with advanced breast cancer (n = 95): African Americans, Latinos, Japanese, Native Hawaiians and European Americans. Association testing of validated coding variants was conducted in a breast cancer case-control study (1,612 invasive cases and 1,961 controls) nested in the Multiethnic Cohort. We used logistic regression to estimate odds ratios for allelic effects in ethnic-pooled analyses as well as in subgroups defined by disease stage and steroid hormone receptor status. We also investigated effect modification by established breast cancer risk factors that are associated with steroid hormone exposure. We identified 45 coding variants with frequencies ≥ 1% in any one ethnic group (43 non-synonymous variants). We observed nominally significant positive associations with two coding variants in ethnic-pooled analyses (NCOR2: His52Arg, OR = 1.79; 95% CI, 1.05–3.05; CALCOCO1: Arg12His, OR = 2.29; 95% CI, 1.00–5.26). A small number of variants were associated with risk in disease subgroup analyses and we observed no strong evidence of effect modification by breast cancer risk factors. Based on the large number of statistical tests conducted in this study, the nominally significant associations that we observed may be due to chance, and will need to be confirmed in other studies. Our findings suggest that common coding

Worry and risk perception of breast cancer in a prevention trial of low dose tamoxifen in midlife postmenopausal hormone users.

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Rondanina, Gabriella; Puntoni, Matteo; Guerrieri-Gonzaga, Aliana; Marra, Domenico; Bonanni, Bernardo; DeCensi, Andrea

2017-08-01

There is increasing interest in combining postmenopausal hormone therapy (HT) and SERMs in midlife women. We previously showed that refusal to participate in a prevention trial of low dose tamoxifen in HT users was associated with higher worry about breast cancer. Given this counterintuitive finding, we studied which factors influenced worry and risk perception of breast cancer. We assessed the relationships of breast cancer worry and risk perception with age, age at menopause, Gail risk, education, adherence to mammographic screening, BMI, smoking, physical activity, alcohol use, anxiety and depression in 457 midlife HT users who were eligible to participate in the trial. Women with menopause 52 years (OR = 5.0, 95% CI, 1.2-21.1). Worry was also associated with high absolute risk perception and former smoking. Factors associated with higher risk perception were age>60 years, at-risk life style, worry about breast cancer and depression. The inverse association between early menopause and worry about breast cancer is in contrast with the known protective effect of early menopause on breast cancer risk and seems to reflect a feeling of aging and disease vulnerability. Our findings indicate that worry about cancer has an affective construct which is independent of breast cancer biology but is engaged in health decision making. Increasing breast cancer risk awareness in subjects high in worry without a plan of emotional coping may therefore be counterproductive because of avoidant attitudes. Copyright © 2017. Published by Elsevier Ltd.

Breast Cancer Treatment (PDQ®)—Health Professional Version

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Breast cancer treatment commonly includes various combinations of surgery, radiation therapy, chemotherapy, and hormone therapy. Prognosis and selection of therapy is influenced by clinical and pathology features. Get detailed information about breast cancer in this summary for clinicians.

Synthesis and in vitro anti-cancer evaluation of luteinizing hormone-releasing hormone-conjugated peptide.

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Deng, Xin; Qiu, Qianqian; Ma, Ke; Huang, Wenlong; Qian, Hai

2015-11-01

Luteinizing hormone-releasing hormone (LHRH) is a decapeptide hormone released from the hypothalamus and shows high affinity binding to the LHRH receptors. It is reported that several cancer cells also express LHRH receptors such as breast, ovarian, prostatic, bladder and others. In this study, we linked B1, an anti-cancer peptide, to LHRH and its analogs to improve the activity against cancer cells with LHRH receptor. Biological evaluation revealed that TB1, the peptide contains triptorelin sequence, present favorable anti-cancer activity as well as plasma stability. Further investigations disclosed that TB1 trigger apoptosis by activating the mitochondria-cytochrome c-caspase apoptotic pathway, it also exhibited the anti-migratory effect on cancer cells.

Biochemical study on some tumour angiogenesis factors and inhibitors in breast cancer

International Nuclear Information System (INIS)

Mohamed, N.M.E

2007-01-01

This pilot study was undertaken to investigate the significance of some tumour angiogenic factors (e.g. MMP, ADAM-12 and VEGF) and tumour angiogenic inhibitors (endostatin and TIMP-1) in the aetiology of breast cancer and their responsiveness to cancer treatment as well . We also sought to assess the significance of these angiogenic and antiangiogenic factors in the prognosis and diagnosis of breast cancer. The cases were allocated into five groups: Normal control group (Gr.l), fibroadenoma (Gr.l l), breast cancer (invasive duct carcinoma type grade l l) (Gr.lll) , breast cancer + chemo hormonal therapy (Gr.IV), and breast cancer + chemo hormonal and radiotherapy (Gr.V).Results obtained from this study reported absence of matrix metalloproteinase-9 (MMP-9)activity in the urine and serum of normal subjects and fibroadenoma patients and its significant depression in the urine and serum of breast cancer patients treated with chemo hormonal therapy alone or followed by radiotherapy, compared to breast cancer group as reference. A significantly mild elevation in urinary MMP-2 activity and a non significant change in its activity in the serum of fibroadenoma patients, compared to the dramatic rise in the urine and serum of breast cancer patients were observed

The rate and factors associated with non-adherence to surgery, chemotherapy, radiotherapy and hormonal therapy among breast cancer patients attending public hospitals in Malaysia

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Nur Aishah Taib

2017-12-01

Full Text Available Background: The role of breast cancer treatments in reducing recurrence and death has been established. However, the treatments side effects greatly impact on quality of life and little is known about the non-adherence rates. The purpose of this study was to determine the non-adherence rates to surgery, chemotherapy, radiotherapy and hormonal therapy, and factors that affect it in public hospitals in Malaysia. Methods: A multicentre cross-sectional study was conducted in six public hospitals involving all newly diagnosed breast cancer patients in 2012. Data were collected through medical record reviews and interview by using structured questionnaire. Non-adherence was categorized as any breast cancer patients refusing or discontinuing any treatment due to non-medical reasons. Univariable logistic regression and multiple logistic regressions were used for analysis. Results: A total of 340 breast cancer patients were included in the study. The proportion for non-adherence to surgery, chemotherapy, radiotherapy and hormonal therapy were 14%, 30.1%, 33.3% and 36.3% respectively. Factors associated with non-adherence to surgery were localities involving Kuala Lumpur (2 (OR: 3.41, Johor (OR: 8.38 and Kelantan (OR: 6.32, and those required mastectomy (OR: 5.66. No factors were found to be associated with non-adherence to chemotherapy, radiotherapy and hormonal therapy. These three treatment modalities were then combined as oncology therapy and the only independent factor associated with non-adherence to oncology therapy was Perak locality (OR: 1.42. Conclusion: Non-adherence to breast cancer treatments was high among breast cancer patients at public hospitals in Malaysia. Factors influencing non-adherence were locations and mastectomy implicating of socio-culture, body image issues, psychological disturbance and treatment navigation. Community educational programs focusing on correcting misconceptions, treatment outcomes and treatments’ side effects

Circulating sex hormones and terminal duct lobular unit involution of the normal breast.

Science.gov (United States)

Khodr, Zeina G; Sherman, Mark E; Pfeiffer, Ruth M; Gierach, Gretchen L; Brinton, Louise A; Falk, Roni T; Patel, Deesha A; Linville, Laura M; Papathomas, Daphne; Clare, Susan E; Visscher, Daniel W; Mies, Carolyn; Hewitt, Stephen M; Storniolo, Anna Maria V; Rosebrock, Adrian; Caban, Jesus J; Figueroa, Jonine D

2014-12-01

Terminal duct lobular units (TDLU) are the predominant source of breast cancers. Lesser degrees of age-related TDLU involution have been associated with increased breast cancer risk, but factors that influence involution are largely unknown. We assessed whether circulating hormones, implicated in breast cancer risk, are associated with levels of TDLU involution using data from the Susan G. Komen Tissue Bank (KTB) at the Indiana University Simon Cancer Center (2009-2011). We evaluated three highly reproducible measures of TDLU involution, using normal breast tissue samples from the KTB (n = 390): TDLU counts, median TDLU span, and median acini counts per TDLU. RRs (for continuous measures), ORs (for categorical measures), 95% confidence intervals (95% CI), and Ptrends were calculated to assess the association between tertiles of estradiol, testosterone, sex hormone-binding globulin (SHBG), progesterone, and prolactin with TDLU measures. All models were stratified by menopausal status and adjusted for confounders. Among premenopausal women, higher prolactin levels were associated with higher TDLU counts (RRT3vsT1:1.18; 95% CI: 1.07-1.31; Ptrend = 0.0005), but higher progesterone was associated with lower TDLU counts (RRT3vsT1: 0.80; 95% CI: 0.72-0.89; Ptrend < 0.0001). Among postmenopausal women, higher levels of estradiol (RRT3vsT1:1.61; 95% CI: 1.32-1.97; Ptrend < 0.0001) and testosterone (RRT3vsT1: 1.32; 95% CI: 1.09-1.59; Ptrend = 0.0043) were associated with higher TDLU counts. These data suggest that select hormones may influence breast cancer risk potentially through delaying TDLU involution. Increased understanding of the relationship between circulating markers and TDLU involution may offer new insights into breast carcinogenesis. Cancer Epidemiol Biomarkers Prev; 23(12); 2765-73. ©2014 AACR. ©2014 American Association for Cancer Research.

Aging Impacts Transcriptome but not Genome of Hormone-dependentBreast Cancers

Energy Technology Data Exchange (ETDEWEB)

Yau, Christina; Fedele, Vita; Roydasgupta, Ritu; Fridlyand, Jane; Hubbard, Alan; Gray, Joe W.; Chew, Karen; Dairkee, Shanaz H.; Moore, DanH.; Schittulli, Francesco; Tommasi, Stefania; Paradiso, Angelo; Albertson, Donna G.; Benz, Christopher C.

2007-10-09

Age is one of the most important risk factors for human malignancies, including breast cancer; in addition, age-at-diagnosis has been shown to be an independent indicator of breast cancer prognosis. However, except for inherited forms of breast cancer, there is little genetic or epigenetic understanding of the biological basis linking aging with sporadic breast cancer incidence and its clinical behavior.

The history of hormone therapy use and recent controversy related to heart disease and breast cancer arising from prevention trial outcomes.

Science.gov (United States)

Alexander, Ivy M

2012-01-01

The reasons for hormone therapy use have changed dramatically over time from being very popular for the purpose of preserving youth in women to menopause-related symptom management, disease prevention, and now back to menopause-related symptom management. Over time, several important risks associated with the use of hormone therapy have become evident, causing dramatic reductions in the use of hormone therapy for periods of time following identification of these risks. Most recently, randomized controlled prevention trials that evaluated hormone therapy for the purpose of reducing or preventing coronary heart disease among women have found that hormone therapy is associated with increased rather than decreased risks for coronary heart disease. The most recent of these trials again identified increased risks for breast cancer associated with estrogen plus progestogen therapy. The evolving evidence base from these randomized controlled prevention trials is complicated and in some cases contradictory. Specifically, the data suggest that the timing of when hormone therapy is initiated once a woman is postmenopausal may influence her risk for developing heart disease and breast cancer. In this article, contradictory evidence is carefully sifted so risks and benefits can be weighed by clinicians when partnering with women to individualize decisions about using hormone therapy. © 2012 by the American College of Nurse-Midwives.

Estrogens and breast cancer

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HANKINSON SUSAN E

1997-01-01

Full Text Available In this review, we summarize the epidemiologic evidence for the associations of oral contraceptives and postmenopausal hormones with risk of breast cancer. We also describe the biologic plausibility of these relationships. Overall, there appears to be little, if any, increase in risk with oral contraceptive use in general, even among users for 10 or more years. However, compared to never users, current oral contraceptive users appear to have a modest elevation in risk that subsides within about 10 years after cessation of use. For postmenopausal hormones, the weight of the evidence suggests little or no increase in risk among users of short duration, or for use in the past. However, current longer term use is associated with an increased risk of breast cancer that increases with duration. This increase in risk is large enough, and well enough supported, to be considered along with the other risks and benefits of postmenopausal hormone therapy.

Clinical implications of recent studies using mTOR inhibitors to treat advanced hormone receptor-positive breast cancer

International Nuclear Information System (INIS)

Arena, Francis

2014-01-01

Breast cancer is a leading cause of cancer-related death worldwide. Approximately 75% of breast cancer is hormone receptor-positive (HR + ) and is managed with endocrine therapies. However, relapse or disease progression caused by primary or acquired endocrine resistance is frequent. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)-mediated signaling is one of the molecular mechanisms leading to endocrine resistance. mTOR inhibitors that target the PI3K/Akt/mTOR pathway are the first of the targeted therapies to be evaluated in clinical trials to overcome endocrine resistance. Although the clinical trial with temsirolimus, an mTOR inhibitor, did not show any benefit when compared with endocrine therapy alone, a Phase II clinical trial with sirolimus has been promising. Recently, everolimus was approved in combination with exemestane by the US Food and Drug Administration for treating postmenopausal women with advanced HR + breast cancer, based on the results of a Phase III trial. Therefore, everolimus represents the first and only targeted agent approved for combating endocrine resistance

Management of menopause in women with breast cancer.

Science.gov (United States)

Vincent, A J

2015-10-01

Increasing breast cancer incidence and decreasing mortality have highlighted the importance of survivorship issues related to breast cancer. A consideration of the issues related to menopause is therefore of great importance to both women and clinicians. Menopause/menopausal symptoms, with significant negative effects on quality of life and potential long-term health impacts, may in women with breast cancer be associated with: (1) natural menopause occurring concurrently with a breast cancer diagnosis; (2) recurrence of menopausal symptoms following cessation of hormone replacement therapy; (3) treatment-induced menopause (chemotherapy, ovarian ablation/suppression) and adjuvant endocrine therapy. A variety of non-hormonal pharmacological and non-pharmacological therapies have been investigated as therapeutic options for menopausal symptoms with mixed results, and ongoing research is required. This review presents a summary of the causes, common problematic symptoms of menopause (vasomotor, genitourinary and sexual dysfunction), and longer-term consequences (cardiovascular disease and osteoporosis) related to menopause. It proposes an evidenced-based multidisciplinary approach to the management of menopause/menopausal symptoms in women with breast cancer.

Calcitonin and parathyroid hormone in blood serum of cancer patients

Energy Technology Data Exchange (ETDEWEB)

Tkacheva, G A; Kirsanov, A G; Burenin, I S [Akademiya Meditsinskikh Nauk SSSR, Moscow. Onkologicheskij Nauchnyj Tsentr

1982-01-01

A comparative radiommunoassay in the ratio of calcitonin and parathyroid hormone secretion was carried out in healthy controls (young and older than 40 years), patients with benign tumors, inflamatory processes and malignancies of the stomach, kidney, breast, prostate and lung. A significant increase in the ''calcitonin index'' (ratio of molar concentrations of calcitonin and parathyroid hormone) was established in patients with cancer of the breast, prostate and skeletal metastases of lung cancer, irrespective of the presence of primary tumor. This index is irrelevant in cases of gastric and renal carcinoma and cannot be used as indication of skeletal dissemination because of the predominant level of parathyroid hormone secretion.

Triple negative breast cancer: an Indian perspective

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Akhtar M

2015-08-01

Full Text Available Murtaza Akhtar, Subhrajit Dasgupta, Murtuza Rangwala Department of Surgery, NKP Salve Institute of Medical Sciences and Research Centre, Nagpur, Maharashtra, India Introduction: Breast cancer is the most common female cancer in the world. Triple negative breast cancer (TNBC is a recently identified biological variant with aggressive tumor behavior and poor prognosis. Data of hormonal status from the Indian population is scarce due to financial constraints in performing immunohistochemistry evaluation. The present study aims to prospectively analyze receptor status of all breast cancer patients and identify TNBC and compare their clinical profile and short term survival with other non-TNBC group. Materials and methods: All cytologically and histopathologically confirmed cases of carcinoma breast were prospectively enrolled. In a longitudinal study at tertiary care hospital in central India based on the hormonal status, they were further divided into TNBC and other groups. Comparison of risk factors, clinical profile and short-term survival was carried out. Results: A total 85 patients were enrolled and of them 37 (43.7% were TNBC. On comparing risk factors ie, age, age at menarche, total reproductive age, age at first child birth, and menopausal status – no statistical significance was observed between the TNBC and non-TNBC groups. But on comparison of clinical profile TNBC tumors were significantly large with majority of patients presenting as locally advanced breast cancer (83%. No statistical difference was observed in axillary lymph node status between two groups. TNBC tumors were histologically more aggressive (grade 3 compared to other groups. No statistically significant difference was observed in short term overall survival but all three deaths were observed in the TNBC group only and two local recurrences after surgery were observed in the TNBC group. Conclusion: TNBC forms a large proportion of carcinoma breast patients in a central

Risk factors for breast cancer in the breast cancer risk model study of Guam and Saipan.

Science.gov (United States)

Leon Guerrero, Rachael T; Novotny, Rachel; Wilkens, Lynne R; Chong, Marie; White, Kami K; Shvetsov, Yurii B; Buyum, Arielle; Badowski, Grazyna; Blas-Laguaña, Michelle

2017-10-01

Chamorro Pacific Islanders in the Mariana Islands have breast cancer incidence rates similar to, but mortality rates higher than, those of U.S. women. As breast cancer risk factors of women of the Mariana Islands may be unique because of ethnic and cultural differences, we studied established and suspected risk factors for breast cancer in this unstudied population. From 2010-2013, we conducted retrospective case-control study of female breast cancer (104 cases and 185 controls) among women in the Mariana Islands. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each of various lifestyle-related factors from logistic regression of breast cancer, in all women and in pre- and postmenopausal women separately. Tests for interaction of risk factors with ethnicity were based on the Wald statistics for cross-product terms. Of the medical and reproductive factors considered - age at menarche, breastfeeding, number of live births, age at first live birth, hormone use, and menopause - only age at first live birth was confirmed. Age at first live birth, among parous women, was higher among cases (mean 24.9 years) than controls (mean 23.2 years); with increased breast cancer risk (OR=2.53; 95% CI, 1.04-6.19 for age≥30y compared to risk and only in Filipino women. The association with many other established risk factors, such as BMI, hormone use and physical activity, were in the expected direction but were not significant. Associations for family history of breast cancer and alcohol intake were not evident CONCLUSIONS: The results provide a basis for cancer prevention guidance for women in the Mariana Islands. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

A phase II study of preoperative capecitabine in women with operable hormone receptor positive breast cancer

International Nuclear Information System (INIS)

Tolaney, Sara M; Jeong, Joon; Guo, Hao; Brock, Jane; Morganstern, Daniel; Come, Steven E; Golshan, Mehra; Bellon, Jennifer; Winer, Eric P; Krop, Ian E

2014-01-01

Conventional preoperative chemotherapy regimens have only limited efficacy in hormone receptor positive (HR+) breast cancer and new approaches are needed. We hypothesized that capecitabine, which is effective in metastatic breast cancer, may be an active preoperative treatment for HR+ breast cancer. Women with HR+, HER2-negative operable breast cancer received capecitabine, 2000 mg/m 2 daily in divided doses for 14 days, followed by a 7-day rest period. Treatment was repeated every 21 days for a total of four cycles. The primary endpoint of the study was to determine the rate of pathological complete response (pCR). Because of slow accrual, the study was closed after 24 patients were enrolled. Three patients had a complete clinical response, and eight patients had a partial clinical response, for an overall clinical response rate of 45.8%. There were no cases of pCR. Of the 22 patients who had pathological response assessment by the Miller–Payne grading system, there were six grade 3 responses, and no grade 4 or 5 responses. Toxicity was manageable: the only grade 3 toxicities observed were one case each of diarrhea, palmar plantar erythrodysesthesia, hypokalemia, and mucositis. There was no association between baseline levels, or change in level from baseline to cycle 1, or from baseline to time of surgery, of thymidine phosphorylase (TYMP), thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), or Ki67 and pathological, clinical, or radiographic response. Preoperative capecitabine is a well-tolerated regimen, but appears not lead to pCR when used as monotherapy in HR+ breast cancer

Leptin and Pathological Indexes in Women with Breast Cancer

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B Noori Alavicheh

2015-06-01

Full Text Available Background & aim: Breast cancer is the most common cancer among women and one of the factors threatening the health of women worldwide. Leptin is a 16 kD glycoprotein hormone produced predominantly by white adipose tissue. Leptin binds to receptors in the hypothalamus and plays a key role in regulation of metabolism. Both leptin and leptin receptor have recently been implicated in processes and progress leading to breast cancer initiation. The aim of this study was to identify if there is association between leptin and pathological indexes in patients with breast cancer Methods: 45women with breast cancer were enrolled. Serum leptin levels of patients were measured by the ELISA method. Pathological information such as stage of the breast cancer, Hormonal receptor (ER, PR and Her2 status in these patients were determined. Result: Results revealed that the patients who were in stage one and two, the mean serum leptin level was (34.18±21.22 ng/ml And patients who were in stage three and four, the mean serum leptin level was (32.21±21/93 ng/ml. Also the mean serum leptin levels in patients whose receptor status of ER, PR and HER2 positive were (35.90±23.55, 35.74±23.91and 37.02±24.25ng/ml, respectively. The Patients whose receptor status of ER, PR and HER2 negative were 26.64±13.13, 28.17±14.26and31.32±19.9ng/ml respectively. No significant association was found between leptin leveland stage of the breast cancer, hormonal receptor (ER, PR and Her2 status in Patients with Breast cancer(p>0.05. Conclusions: In this study, no association was found between serum leptin level and pathological indices in women with Breast cancer in Yasuj, Iran.

Inhibition of autophagy enhances the cytotoxic effect of PA-MSHA in breast cancer

International Nuclear Information System (INIS)

Xu, Wen-Huan; Liu, Zhe-Bin; Hou, Yi-Feng; Hong, Qi; Hu, Da-Li; Shao, Zhi-Ming

2014-01-01

PA-MSHA, a genetically engineered Pseudomonas aeruginosa (PA) strain, is currently under investigation as a new anti-cancer drug. It can induce cell cycle arrest and apoptosis in different human cancer cells, including hormone receptor negative breast cancer cells. However, the underlying mechanism of tumor lethality mediated by PA-MSHA remains to be fully investigated. The effect of PA-MSHA on human hormone receptor negative breast cancer cells was analyzed by morphological measurement, western blot, cell proliferation assay and mouse xenograft model. PA-MSHA was found to induce endoplasmic reticulum (ER) stress in breast cancer cell lines through the IRE1 signaling pathway. Inhibiting autophagy potentiated the cytotoxic effect of PA-MSHA while treating breast cancer cell lines. In mouse xenograft model, PA-MSHA produced more pronounced tumor suppression in mice inoculated with IRE1 gene knockdown. MDA-MB-231HM cells. These findings demonstrated inhibiting autophagy together with PA-MSHA might be a promising therapeutic strategy in treating hormone receptor negative breast cancer cells

Compliance of patients concerning recommended radiotherapy in breast cancer. Association with recurrence, age, and hormonal therapy

International Nuclear Information System (INIS)

Winzer, K.J.; Gruber, C.; Badakhshi, H.; Charite Universitaetsmedizin Berlin; Hinkelbein, M.; Denkert, C.

2012-01-01

Background and purpose: In this study, we investigated how often guidelines for radiation therapy in patients with breast cancer are not complied with, which patient group is mostly affected, and how this influences local recurrence. Patients and methods: All patients (n = 1,903) diagnosed between November 2003 and December 2008 with primary invasive or intraductal breast cancer in the interdisciplinary breast center of the Charite Hospital Berlin were included and followed for a median 2.18 years. Results: Patients who, in contrast to the recommendation of the interdisciplinary tumor board, did not undergo postoperative radiation experienced a fivefold higher local recurrence rate (p < 0.0005), corresponding to a 5-year locoregional recurrence-free survival of 74.5% in this group. The 5-year locoregional recurrence-free survival of patients following the recommendations was 93.3%. Guideline compliance was dependent on age of patients, acceptance of adjuvant hormonal treatment or chemotherapy, and increased diameter of the primary tumor. Multiple logistic regression analysis showed an association between compliance and age or hormonal therapy. Conclusion: In order to avoid local recurrence patients should be motivated to comply with guideline driven therapy. Since a higher number of local recurrences is observed in health services research compared to clinical research, studies on the value of adjuvant treatment following local recurrence should be performed. (orig.)

Hormone replacement therapy in cancer survivors: Utopia?

Science.gov (United States)

Angioli, Roberto; Luvero, Daniela; Armento, Grazia; Capriglione, Stella; Plotti, Francesco; Scaletta, Giuseppe; Lopez, Salvatore; Montera, Roberto; Gatti, Alessandra; Serra, Giovan Battista; Benedetti Panici, Pierluigi; Terranova, Corrado

2018-04-01

As growing of old women population, menopausal women will also increase: an accurate estimation of postmenopausal population is an essential information for health care providers considering that with aging, the incidence of all cancers is expected to increase. Hormone replacement therapy (HRT) has proven to be highly effective in alleviating menopausal symptoms such as hot flashes, night sweats, dyspareunia, sexual disorders, and insomnia and in preventing osteoporosis. According to preclinical data, estrogen and progesterone are supposed to be involved in the induction and progression of breast and endometrial cancers. Similarly, in epithelial ovarian cancer (EOC), the pathogenesis seems to be at least partly hormonally influenced. Is HRT in gynecological cancer survivors possible? The literature data are controversial. Many clinicians remain reluctant to prescribe HRT for these patients due to the fear of relapse and the risk to develop coronary heart disease or breast cancer. Before the decision to use HRT an accurate counselling should be mandatory in order to individualizing on the basis of potential risks and benefits, including a close follow-up. Nevertheless, we do believe that with strong informed consent doctors may individually consider to prescribe some course of HRT in order to minimize menopausal symptoms and disease related to hormonal reduction. Copyright © 2018 Elsevier B.V. All rights reserved.

Optimal systemic therapy for premenopausal women with hormone receptor-positive breast cancer.

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Jankowitz, Rachel C; McGuire, Kandace P; Davidson, Nancy E

2013-08-01

Although systemic therapy is one of the cornerstones of therapy for premenopausal women with early stage breast cancer, there remain many unknowns regarding its optimal use. By accident of clinical trial design, much clinical investigation in premenopausal women has focused on chemotherapy. More recently the value of endocrine therapy (tamoxifen and ovarian suppression/ablation via surgery, LHRH agonists, or chemotherapy-induced menopause) has become apparent, and some form of endocrine therapy is viewed as standard for virtually all premenopausal women with early stage invasive breast cancer that expresses estrogen and/or progesterone receptor. Critical open questions include type and duration of endocrine therapy and the development of prognostic/predictive markers to help identify patients who are likely to benefit from chemotherapy in addition to endocrine therapy. For some years, five years of tamoxifen has been viewed as the standard endocrine therapy for premenopausal hormone-responsive breast cancer, although the ATLAS trial suggests that an additional five years of tamoxifen can be considered. The MA17 trial also suggests that an additional five years of an aromatase inhibitor can be considered for women who become postmenopausal during tamoxifen therapy. Information about the value of ovarian suppression continues to emerge, most recently with the demonstration of excellent outcome with goserelin plus tamoxifen in the ABCSG12 trial. The SOFT and TEXT trials, whose accrual is now complete, should help to define optimal endocrine therapy. In addition, use of the 21-gene recurrence score assay may help to delineate the additional value of chemotherapy for patients with node-negative breast cancer, and its utility in the setting of women with 1-3 positive lymph nodes is under study in the RxPONDER trial. Nonetheless, the need for other predictive biomarkers to select appropriate therapy remains real. Finally, attention to long term benefits and side effects

Breast cancer radiotherapy: controversies and prospectives

Institute of Scientific and Technical Information of China (English)

YU Jin-ming; WANG Yong-sheng

2008-01-01

@@ Despite consensus on breast cancer radiotherapy, there are still some controversies over post-mastectomy radiotherapy (PMRT) in patients with 1-3 positive lymph nodes, accelerated partial breast irradiation (APBI), appropriate sequence of radiotherapy, chemotherapy and hormonal treatment, and radiotherapy after preoperative systemic therapy.

Breast cancer incidence and menopausal hormone therapy in Norway from 2004 to 2009: a register-based cohort study

International Nuclear Information System (INIS)

Suhrke, Pål; Zahl, Per-Henrik

2015-01-01

In Norway, the breast cancer incidence increased by 50% in the 1990s, during a period with initiation of mammography screening as well as a fourfold increase in use of menopausal hormone therapy (HT). After 2002, the HT use has dropped substantially; however, the breast cancer incidence has declined only marginally. How much mammography screening contributed to the breast cancer incidence increase in the 1990s compared with HT use and specifically different types of HT use, has thus been discussed. Whether HT affects the incidence of subtypes of breast cancer differently has also been questioned. We have linked individual data from several national registries from 2004 to 2009 on 449,717 women aged 50–65 years. 4597 cases of invasive cancer and 681 cases of ductal carcinoma in situ (DCIS) were included in the analysis. We used Cox regression to estimate hazard ratio (HR) as a measure of the relative risk of breast cancer associated with use of HT. The HRs associated with prescriptions of HT for more than 1 year were 2.06 (1.90–2.24) for estrogen and progesterone combinations, 1.03 (0.85–1.25) for systemic estrogens, and 1.23 (1.01–1.51) for tibolone. Invasive lobular carcinoma was more strongly associated with use of estrogen and progesterone combinations, HR = 3.10 (2.51–3.81), than nonlobular carcinoma, HR = 1.94 (1.78–2.12). The corresponding value for DCIS was 1.61 (1.28–2.02). We estimated the population attributable fraction to 8.2%, corresponding to 90 breast cancer cases in 2006 indicating that HT use still caused a major number of breast cancer cases

Environmental chemical exposures and breast cancer

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E. Stanley

2016-02-01

Full Text Available As a hormone-sensitive condition with no single identifiable cause, breast cancer is a major health problem. It is characterized by a wide range of contributing factors and exposures occurring in different combinations and strengths across a lifetime that may be amplified during periods of enhanced developmental susceptibility and impacted by reproductive patterns and behaviours. The vast majority of cases are oestrogen-receptor positive and occur in women with no family history of the disease suggesting that modifiable risk factors are involved. A substantial body of evidence now links oestrogen-positive breast cancer with environmental exposures. Synthetic chemicals capable of oestrogen mimicry are characteristic of industrial development and have been individually and extensively assessed as risk factors for oestrogen-sensitive cancers. Existing breast cancer risk assessment tools do not take such factors into account. In the absence of consensus on causation and in order to better understand the problem of escalating incidence globally, an expanded, integrated approach broadening the inquiry into individual susceptibility breast cancer is proposed. Applying systems thinking to existing data on oestrogen-modulating environmental exposures and other oestrogenic factors characteristic of Westernisation and their interactions in the exposure, encompassing social, behavioural, environmental, hormonal and genetic factors, can assist in understanding cancer risks and the pursuit of prevention strategies. A new conceptual framework based on a broader understanding of the “system” that underlies the development of breast cancer over a period of many years, incorporating the factors known to contribute to breast cancer risk, could provide a new platform from which government and regulators can promulgate enhanced and more effective prevention strategies.

Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer.

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Mathew, Aju; Davidson, Nancy E

2015-11-01

Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed and results have been presented over the last two years. These include tamoxifen for 5-10 years (ATLAS and aTTom), tamoxifen for 5 years followed by aromatase inhibitor (AI) for 5 years for women who have become postmenopausal (MA-17); ovarian ablation (OA) by surgery (EBCTCG overview); ovarian function suppression (OFS) by LHRH agonist (LHRH agonist meta-analysis); or combinations of approaches including OFS plus tamoxifen or AI (SOFT, TEXT, ABCSG 12 and E3193). Many of these trials have taken place in the backdrop of (neo)adjuvant chemotherapy which can confound interpretation because such therapy can suppress ovarian function either transiently or permanently. Nonetheless these trials suggest in aggregate that 10 years of tamoxifen are better than 5 years and that a program of extended adjuvant therapy of tamoxifen for 5 years followed by aromatase inhibitor for 5 years is effective for suitable candidates. The SOFT and E3193 trials do not show a major advantage for use of OFS + tamoxifen compared to tamoxifen alone. The joint SOFT/TEXT analysis and ABCGS12 trials both suggest that outcomes can be excellent with the use of combined endocrine therapy alone in properly selected patients but give conflicting results with regard to potential benefits for OFS + AI compared with OFS + tamoxifen. Further work will be needed to ascertain long-term outcomes, identify factors that predict who will benefit from extended adjuvant endocrine therapy, and assess role of OFS by medical or surgical means. It is clear, however, that endocrine therapy is a critical part of the adjuvant regimen for most premenopausal women with hormone-responsive breast cancer, and a subset of these women with luminal A-type tumors can be safely treated with endocrine therapy alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effect of hormonal replacement therapy on breast

International Nuclear Information System (INIS)

Jeong, Mi Gyoung; Oh, Ki Keun; Kim, Mi Hye

1995-01-01

To evaluate mammographic and sonographic breast parenchymal changes and the risk of breast cancer in women on hormonal replacement therapy (HRT). The study group consisted of 50 patients examined with serial mammograms and/or ultrasonograms during HRT. The control group consisted of 50 patients examined with serial mammogram for a routine health check. Mammographic parenchymal changes in both the study and control groups and sonographic findings of 27/50 patients in study group were evaluated. Follow-up mammogram of the control group showed no interval change or slight evolution of parenchyma with increasing age, but the study group showed increasing parenchymal densities. Most frequently encountered finding on sonogram in 11 women treated by estrogen alone, was ductal dilatation (7 cases; 64%), whereas in 16 women treated by estrogen and progesteron it was ductal epithelial hyperplasia (8 cases; 50%). Overall, four breast cancers developed; one infiltrating ductal carcinoma and three ductal carcinoma in situ. HRT causes the changes of breast parenchyma on mammogram and sonogram of postmenopausal women, and increases the risk of developing breast cancer. Therefore, careful and regular examination should be followed in those on postmenopausal HRT

Psychosocial aspects of breast cancer treatement in Accra, Ghana ...

African Journals Online (AJOL)

Objectives: To evaluate psychosocial influences and effects of breast cancer treatment. Design: Cohort questionnaire survey. Setting: Surgical Outpatient Department, Korle Bu Teaching Hospital (KBTH), Accra, Ghana. Subjects: Women previously treated for breast cancer, including those still on hormonal therapy.

Management of male breast cancer

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Nikolay V. Dimitro v

2011-12-01

Full Text Available The management of male breast cancer is still under discussion due to lack of information from prospective, randomized clinical trials and low incidence of this disease. Current management is based largely on extrapolation from data related to treatment of female breast cancer. Over the last two decades, several review articles have discussed mainly retrospective and anecdotal data related to hormonal and chemotherapy treatment modalities. In this review, we present the most recent information and future considerations related to the management of male breast cancer. In addition to the conventional treatment options we will discuss the possible role of targeted therapy. Establishing a national or global registry for male breast cancer will provide more precise information about the natural history of the disease and will facilitate the design and execution of prospective, randomized multicenter clinical trials.

Breast cancer and steroid metabolizing enzymes: the role of progestogens.

Science.gov (United States)

Pasqualini, Jorge R

2009-12-01

It is well documented that breast tissue, both normal and cancerous, contains all the enzymatic systems necessary for the bioformation and metabolic transformation of estrogens, androgens and progesterone. These include sulfatases, aromatase, hydroxysteroid-dehydrogenases, sulfotransferases, hydroxylases and glucuronidases. The control of these enzymes plays an important role in the development and pathogenesis of hormone-dependent breast cancer. As discussed in this review, various progestogens including dydrogesterone and its 20alpha-dihydro-derivative, medrogestone, promegestone, nomegestrol acetate and norelgestromin can reduce intratissular levels of estradiol in breast cancer by blocking sulfatase and 17beta-hydroxysteroid-dehydrogenase type 1 activities. A possible correlation has been postulated between breast cell proliferation and estrogen sulfotransferase activity. Progesterone is largely transformed in the breast; normal breast produces mainly 4-ene derivatives, whereas 5alpha-derivatives are most common in breast cancer tissue. It has been suggested that this specific conversion of progesterone may be involved in breast carcinogenesis. In conclusion, treatment with anti-aromatases combined with anti-sulfatase or 17beta-hydroxysteroid-dehydrogenase type 1 could provide new therapeutic possibilities in the treatment of patients with hormone-dependent breast cancer. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Breast Cancer and its Radiotherapeutic Methods

International Nuclear Information System (INIS)

Zeinali Rafsanjani, B.; Mosleh-Shirazi, M. A.; Faghihi, R.; Mosalaei, A.; Omidvar, Sh.; Hadad, K.; Karbasi, S.

2012-01-01

Breast cancer is the most common cancer in women after skin cancer. In Iran, the presentation age of this cancer is younger than the global average. There are different therapeutic methods for treatment of breast cancer and the choice of treatment depends on the stage of the disease as well as its type and characteristics. Therapeutic methods include surgery, radiotherapy, and systemic therapies, each consisting of a variety of techniques. The two main surgical techniques are lumpectomy and mastectomy. The main systemic methods are biological therapy (immunotherapy), hormone therapy, and chemotherapy. Radiotherapy is mainly categorized into external-beam radiotherapy and brachytherapy. In this paper, we present a brief review of the different types of breast cancer and their treatments using conventional and modern radiotherapy methods, as well as the treatment efficacy and side effects of breast radiotherapy.

Breast Cancer and its Radiotherapeutic Methods

Directory of Open Access Journals (Sweden)

Banafsheh Zeinali Rafsanjani

2012-03-01

Full Text Available Breast cancer is the most common cancer in women after skin cancer. In Iran, the presentation age of this cancer is younger than the global average. There are different therapeutic methods for treatment of breast cancer and the choice of treatment depends on the stage of the disease as well as its type and characteristics. Therapeutic methods include surgery, radiotherapy, and systemic therapies, each consisting of a variety of techniques. The two main surgical techniques are lumpectomy and mastectomy. The main systemic methods are biological therapy (immunotherapy, hormone therapy, and chemotherapy. Radiotherapy is mainly categorized into external-beam radiotherapy and brachytherapy. In this paper, we present a brief review of the different types of breast cancer and their treatments using conventional and modern radiotherapy methods, as well as the treatment efficacy and side effects of breast radiotherapy.

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

Science.gov (United States)

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

2015-11-01

To review palbociclib, a novel small-molecule inhibitor of cyclin-dependent kinases 4 and 6, and its current place in therapy for the treatment of hormone receptor (HMR)-positive, human epidermal growth factor receptor 2 (Her2)-negative advanced breast cancer. Four phase I trials, 2 phase II trials, and 1 phase III trial were identified from May 2004 to May 2015 using PubMed, American Society of Clinical Oncology (ASCO) abstracts, and European Society of Medical Oncology (ESMO) abstracts. In the first-line setting, the phase II PALbociclib: Ongoing trials in the Management of breast cAncer (PALOMA)-1 trial randomized patients to receive letrozole alone or letrozole plus palbociclib 125 mg daily for 3 weeks, followed by 1 week off, as initial therapy for advanced breast cancer. The investigator-assessed median progression-free survival (PFS) was 20. 2 months for the combination versus 10.2 months for letrozole alone (hazard ratio [HR] = 0.488; 95% CI = 0.319-0.748; 1-sided P = 0.0004). The ensuing Food and Drug Administration approval of palbociclib was given a "breakthrough therapy" designation, where preliminary evidence suggests substantial improvement over existing therapies for a serious or life-threatening disease. A confirmatory phase III trial, PALOMA-2, is under way. In patients who were previously treated with endocrine therapy for advanced breast cancer, the phase III PALOMA-3 trial randomized patients to fulvestrant plus palbociclib versus fulvestrant plus placebo. The investigator-assessed median PFS at the time of a preplanned analysis was 9.2 months with palbociclib-fulvestrant compared with 3.8 months with placebo-fulvestrant (HR = 0.42; 95% CI = 0.32-0.56; P < 0.001). Palbociclib, the first-in-class CDK4/6 inhibitor, significantly extended PFS in combination with endocrine therapy in the first and subsequent lines of treatment for HMR-positive, Her2-negative advanced breast cancer. © The Author(s) 2015.

Testosterone and breast cancer prevention.

Science.gov (United States)

Glaser, R; Dimitrakakis, C

2015-11-01

Testosterone (T) is the most abundant biologically active hormone in women. Androgen receptors (AR) are located throughout the body including the breast where T decreases tissue proliferation. However, T can be aromatized to estradiol (E2), which increases proliferation and hence, breast cancer (BCA) risk. Increased aromatase expression and an imbalance in the ratio of stimulatory estrogens to protective androgens impacts breast homeostasis. Recent clinical data supports a role for T in BCA prevention. Women with symptoms of hormone deficiency treated with pharmacological doses of T alone or in combination with anastrozole (A), delivered by subcutaneous implants, had a reduced incidence of BCA. In addition, T combined with A effectively treated symptoms of hormone deficiency in BCA survivors and was not associated with recurrent disease. Most notably, T+A implants placed in breast tissue surrounding malignant tumors significantly reduced BCA tumor size, further supporting T direct antiproliferative, protective and therapeutic effect. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Update on fertility preservation in young women undergoing breast cancer and ovarian cancer therapy.

Science.gov (United States)

Lambertini, Matteo; Ginsburg, Elizabeth S; Partridge, Ann H

2015-02-01

The purpose of the article is to review the available options for fertility preservation in patients with breast and ovarian cancer, and the special issues faced by BRCA mutation carriers. Future fertility is an important consideration for many young patients with cancer. There are both experimental and standard available strategies for patients with breast and ovarian cancer to preserve fertility, and each has potential advantages and disadvantages. Embryo cryopreservation is widely available with a highly successful track record. Improvements in laboratory techniques have led to oocyte cryopreservation recently being recategorized as nonexperimental. Conservative gynecologic surgery is a standard consideration for patients with stage I ovarian cancer who desire future fertility. Ovarian tissue cryopreservation as well as ovarian suppression with luteinizing hormone-releasing hormone analogs during chemotherapy are considered experimental methods at this time, although recent data suggest both safety and efficacy for the use of luteinizing hormone-releasing hormone analogs in women receiving (neo)adjuvant chemotherapy for breast cancer. Special issues should be considered for women with BRCA mutations because of the need to undergo preventive surgery at young age. Multidisciplinary teams and well functioning relationships between the oncology and reproductive units are crucial to manage the fertility issues of young women with cancer.

Care of the cancer survivor: metabolic syndrome following hormone-modifying therapy

OpenAIRE

Redig, Amanda J.; Munshi, Hidayatullah G.

2010-01-01

Emerging evidence implicates metabolic syndrome as a long-term cancer risk factor but also suggests that certain cancer therapies may increase patients’ risk of developing metabolic syndrome secondary to cancer therapy. In particular, breast cancer and prostate cancer are driven in part by sex hormones, thus treatment for both diseases is often based on hormone-modifying therapy. Androgen suppression therapy in men with prostate cancer is associated with dyslipidemia, increasing risk of cardi...

Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine

Science.gov (United States)

2013-01-01

Background Thyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy. Methods Thyroid hormones and NTIS prevalence at initial diagnosis and during chemotherapy were analyzed in 685 breast diseases patients (369 breast cancer, 316 breast benign lesions). The influence of thyroid hormones on chemotherapeutic efficacy was evaluated by chemosensitization test, to compare chemotherapeutic efficacy between breast cancer cells with chemotherapeutics plus triiodothyronine (T3) and chemotherapeutics only. Results In breast cancer, NTIS prevalence at the initial diagnosis was higher and increased during chemotherapy, but declined before the next chemotherapeutic course. Thyroid hormones decreased signigicantly during chemotherapy. T3 can enhance the chemosensitivity of MCF-7 to 5-Fu and taxol, with progression from G0-G1 phase to S phase. The similar chemosensitization role of T3 were found in MDA-MB-231. We compared chemotherapeutic efficacy among groups with different usage modes of T3, finding pretreatment with lower dose of T3, using

Targeted Therapy for Breast Cancer Prevention

Science.gov (United States)

den Hollander, Petra; Savage, Michelle I.; Brown, Powel H.

2013-01-01

With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer. PMID:24069582

Aromatase inhibitors and breast cancer prevention.

Science.gov (United States)

Litton, Jennifer Keating; Arun, Banu K; Brown, Powel H; Hortobagyi, Gabriel N

2012-02-01

Endocrine therapy with selective estrogen receptor modulators (SERMs) has been the mainstay of breast cancer prevention trials to date. The aromatase inhibitors, which inhibit the final chemical conversion of androgens to estrogens, have shown increased disease-free survival benefit over tamoxifen in patients with primary hormone receptor-positive breast cancer, as well as reducing the risk of developing contralateral breast cancers. The aromatase inhibitors are being actively evaluated as prevention agents for women with a history of ductal carcinoma in situ as well as for women who are considered to be at high risk for developing primary invasive breast cancer. This review evaluates the available prevention data, as evidenced by the decrease in contralateral breast cancers, when aromatase inhibitors are used in the adjuvant setting, as well as the emerging data of the aromatase inhibitors specifically tested in the prevention setting for women at high risk. Exemestane is a viable option for breast cancer prevention. We continue to await further follow-up on exemestane as well as other aromatase inhibitors in the prevention setting for women at high risk of developing breast cancer or with a history of ductal carcinoma in situ.

Combined effects of goserelin and tamoxifen on estradiol level, breast density, and endometrial thickness in premenopausal and perimenopausal women with early-stage hormone receptor-positive breast cancer: a randomised controlled clinical trial.

Science.gov (United States)

Yang, H; Zong, X; Yu, Y; Shao, G; Zhang, L; Qian, C; Bian, Y; Xu, X; Sun, W; Meng, X; Ding, X; Chen, D; Zou, D; Xie, S; Zheng, Y; Zhang, J; He, X; Sun, C; Yu, X; Ni, J

2013-08-06

This study is to investigate the effects of geserelin+tamoxifen (TAM) on estradiol level, breast density (BD), endometrial thickness (ET), and blood lipids in premenopausal and perimenopausal women with hormone receptor-positive early-stage breast cancer. This study recruited 110 premenopausal and perimenopausal patients with hormone receptor-positive early-stage breast cancer between 22 June 2008 and 31 December 2009 and randomly assigned them to receive either goserelin plus TAM or TAM alone for 1.5 years. Blood levels of sex hormones and lipids and ET were determined at 0, 3, 6, 12, and 18 months. Contralateral BD was also measured at 0, 12, and 18 months. Five participants dropped out of the goserelin plus TAM group, and two participants dropped out of the TAM-alone group before initiation of endocrine therapy. The rest of patients received scheduled treatment and 3 years of median follow-up. No serious adverse effects were observed, and only two local recurrences have been observed in these patients. Estradiol level and BD were lower in the goserelin plus TAM group than in the TAM-alone group (Pwomen in the TAM-alone group exhibited endometrial thickening over the course of the study. Furthermore, no significant differences in blood lipid levels were reported between the two groups. The data from the current study demonstrated that the addition of goserelin to TAM results in downregulation of estradiol level, followed by significant reduction in BD and ET in premenopausal and perimenopausal women with hormone receptor-positive breast cancer, which may eventually lead to better outcome in these patients.

Management of fertility preservation in young breast cancer patients in a large breast cancer centre.

Science.gov (United States)

Lawrenz, B; Neunhoeffer, E; Henes, M; Lessmann-Bechle, S; Krämer, B; Fehm, Tanja

2010-11-01

The increase of breast cancer in young women under 40 years and the increasing age of women at the time of the birth of their first child underlines the importance to implement counselling for fertility-preserving strategies in the management of breast cancer care. We present the fertility-preserving procedures performed after routine counselling for primary breast cancer patients in a large certified breast cancer centre. Since November 2006, patients aged below 40 years with histologically confirmed breast cancer are routinely counselled on fertility-preserving possibilities before breast surgery and chemotherapy in the fertility centre of the University Women's Hospital in Tuebingen. The recommendations are based on the treatment recommendations of the network FertiPROTEKT. During the last 40 months, 56 primary breast cancer patients were counselled. Forty-one of these patients were hormone receptor positive. Thirty-four patients (63%) underwent fertility-preserving strategies. The majority of the patients (n = 22) decided on ovarian tissue cryopreservation. GnRH protection was performed in 14 patients. In 12 patients an ovarian stimulation protocol was initiated to cryopreserve fertilized or unfertilized oocytes. A combination of different fertility-preserving methods was performed in 12 patients. The preservation of ovarian function and fertility are of great importance to young breast cancer patients. Counselling on fertility-preserving strategies is therefore critical in these patients and should be routinely performed.

Breast cancer survival and season of surgery

DEFF Research Database (Denmark)

Teilum, Dorthe; Bjerre, Karsten D; Tjønneland, Anne M

2012-01-01

Background Vitamin D has been suggested to influence the incidence and prognosis of breast cancer, and studies have found better overall survival (OS) after diagnosis for breast cancer in summer-autumn, where the vitamin D level are expected to be highest. Objective To compare the prognostic...... outcome for early breast cancer patients operated at different seasons of the year. Design Open population-based cohort study. Setting Danish women operated 1978-2010. Cases 79 658 adjusted for age at surgery, period of surgery, tumour size, axillary lymph node status and hormone receptor status...

[Medical treatment of breast cancer: chemotherapy and tailored therapy].

Science.gov (United States)

Dalenc, Florence

2013-12-01

The utility of adjuvant chemotherapy is clearly demonstrated because she significantly improved relapse and mortality. Globally, we report a one-third breast cancer mortality reduction. Nevertheless, the absolute or individual benefit is uncertain and the final decision depends on benefit-risk balance, integrating tumor biologic characteristics and comorbidities. The most effective regimen must contain an anthracycline and a taxane. This regimen must be proposed if chemotherapy indication is considered: this concerns the majority of triple-negative and HER2-positive cancer For hormone-receptor-positive and HER2-negative breast cancer, the decision of adjuvant or not (in addition to hormonal therapy) is most difficult, particularly for grade 2 tumors. The trastuzumab is an essential treatment for HER2-positive breast cancer, because this tailored therapy has considerably improved the prognosis.

Melatonin, Aging and Breast Cancer

National Research Council Canada - National Science Library

Hill, Steven

2001-01-01

... conditions for tumor induction, promotion and progression. The pineal gland, via its hormone melatonin, has been shown by numerous laboratories to inhibit the proliferation of both human and animal models of breast cancer...

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

Science.gov (United States)

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

2017-09-01

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

Ovarian reserve in breast cancer: assessment with anti-Müllerian hormone.

Science.gov (United States)

Hamy, Anne-Sophie; Porcher, Raphaël; Cuvier, Caroline; Giacchetti, Sylvie; Schlageter, Marie-Hélène; Coussieu, Christiane; Gronier, Héloise; Feugeas, Jean-Paul; Adoui, Nadir; Lacorte, Jean-Marc; Poirot, Catherine; Habdous, Mohamed; Espié, Marc

2014-11-01

Anti-Müllerian hormone (AMH) levels fall during chemotherapy. Treatment-induced amenorrhoea is a reversible phenomenon, but few data are available on long-term AMH changes in breast cancer. The aim of the study was to describe serum AMH levels before, during and in the long term after chemotherapy, and to show a potential AMH recovery. Between May 2010 and June 2011, we selected 134 women aged 18-43 years at the time of breast cancer diagnosis who received chemotherapy between 2005 and 2011, and had not undergone an oophorectomy or had previous cytotoxic treatment. The AMH levels were assessed before, during and 4 months to 5.5 years after the end of chemotherapy. During chemotherapy, AMH was undetectable in 69% of women. After chemotherapy, a significant increase in AMH was found, with an average magnitude of +1.2% per month (95% credibility interval: 0.7 to 1.6). Older age and 12 months of amenorrhoea were found to be associated with a lower AMH recovery rate, whereas baseline AMH and number of chemotherapy cycles were not. The process of AMH changes during and after chemotherapy is dynamic, and shows recovery after ovarian injury. Caution should be exercised in interpreting individual AMH assessment in this context. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

DEFF Research Database (Denmark)

Song, Honglin; Ramus, Susan J; Kjaer, Susanne Krüger

2009-01-01

Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasiv...

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

Patient-provider communication and hormonal therapy side effects in breast cancer survivors.

Science.gov (United States)

Lin, Jenny J; Chao, Jennifer; Bickell, Nina A; Wisnivesky, Juan P

2017-09-01

Side effects from hormonal therapy (HT) for breast cancer treatment occur frequently and are associated with worse quality of life and HT non-adherence. Whether improved patient-physician communication is associated with patients' reporting of side effects is unknown. We undertook this study to assess factors associated with women's reports of HT side effects. Between December 2012 and April 2013, we conducted a cross-sectional survey of breast cancer patients undergoing HT in an urban medical center. Descriptive statistics, univariate analyses, and multivariate analyses were used to evaluate associations. Of the 100 participants, 67% reported having HT side effects. However, when prompted, an additional 9% reported experiencing specific HT-related symptoms. Despite very high communication scores, one-third of participants reported they had not discussed side effects with providers. Multivariate analysis showed that after controlling for age, education, race, and medication beliefs, women who had difficulty asking providers for more information were more likely to report side effects (odds ratio 8.27, 95% confidence interval 1.01-69.88). Although HT side effects often occur and are bothersome, patient-provider discussions about side effects remain suboptimal. Providers should actively ask patients about medication side effects so that they can be addressed to improve quality of life and potentially, medication adherence.

Differential action of glycoprotein hormones: significance in cancer progression.

Science.gov (United States)

Govindaraj, Vijayakumar; Arya, Swathy V; Rao, A J

2014-02-01

Growth of multicellular organisms depends on maintenance of proper balance between proliferation and differentiation. Any disturbance in this balance in animal cells can lead to cancer. Experimental evidence is provided to conclude with special reference to the action of follicle-stimulating hormone (FSH) on Sertoli cells, and luteinizing hormone (LH) on Leydig cells that these hormones exert a differential action on their target cells, i.e., stimulate proliferation when the cells are in an undifferentiated state which is the situation with cancer cells and promote only functional parameters when the cell are fully differentiated. Hormones and growth factors play a key role in cell proliferation, differentiation, and apoptosis. There is a growing body of evidence that various tumors express some hormones at high levels as well as their cognate receptors indicating the possibility of a role in progression of cancer. Hormones such as LH, FSH, and thyroid-stimulating hormone have been reported to stimulate cell proliferation and act as tumor promoter in a variety of hormone-dependent cancers including gonads, lung, thyroid, uterus, breast, prostate, etc. This review summarizes evidence to conclude that these hormones are produced by some cancer tissues to promote their own growth. Also an attempt is made to explain the significance of the differential action of hormones in progression of cancer with special reference to prostate cancer.

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)

Accuracy of Self-Reported Breast Cancer Information among Women from the Ontario Site of the Breast Cancer Family Registry

International Nuclear Information System (INIS)

Barisic, A.; Glendon, G.; Andrulis, I. L.; Knight, J. A.; Barisic, A.; Knight, J. A.; Glendon, G.; Weerasooriya, N.; Andrulis, I. L.

2012-01-01

Obtaining complete medical record information can be challenging and expensive in breast cancer studies. The current literature is limited with respect to the accuracy of self-report and factors that may influence this. We assessed the agreement between self-reported and medical record breast cancer information among women from the Ontario site of the Breast Cancer Family Registry. Women aged 20-69 years diagnosed with incident breast cancer 1996-1998 were identified from the Ontario Cancer Registry, sampled on age and family history. We calculated kappa statistics, proportion correct, sensitivity, specificity, and positive and negative predictive values and conducted unconditional logistic regression to examine whether characteristics of the women influenced agreement. The proportions of women who correctly reported having received a broad category of therapy (hormone therapy, chemotherapy, radiation, or surgery) as well as sensitivity and specificity were above 90%, and the kappa statistics were above 0.80. The specific type of hormonal or chemotherapy was reported with low-to-moderate agreement. Aside from recurrence, no factors were consistently associated with agreement. Thus, most women were able to accurately report broad categories of treatment but not necessarily specific treatment types. The finding of this study can aid researchers in the use and design of self-administered treatment questionnaires

14. Breast cancer prevention.

Science.gov (United States)

Salih, A K; Fentiman, I S

2002-05-01

Increased risk of breast cancer may result from potentially modifiable causes such as endogenous hormone levels, obesity, HRT, and non-lactation, or non-modifiable factors including genetic susceptibility and increasing age. The Gail model, based on known factors, may be useful for estimating lifetime risk in some individuals, but those risk factors that are easier to modify may have a limited impact on the totality of breast cancer. Tamoxifen prevention still remains contentious, with a significant reduction in risk of breast cancer in women given tamoxifen in the NSABP P1 study but no effect in the Italian and Royal Marsden trials. Raloxifene, tested in the MORE trial, reduced the incidence of breast cancer by 65% but this was restricted to oestrogen receptor positive tumours. Lifestyle factors such as diet, obesity, exercise and age at first full term pregnancy and number of pregnancies have a mild to moderate impact on risk, so may have little effect on the incidence of breast cancer. Reduction of alcohol intake could lead to a modest reduction in the risk of breast cancer but possibly adversely affect other diseases. Fat reduction and GnRH analogue reduce mammographic density but have not yet been shown to affect risk. For women with BRCA1/2 mutation, options include unproven surveillance and prophylactic mastectomy with an unquantified risk reduction. Interesting new candidates for chemoprevention include aromatase inhibitors, new generation SERMs, demethylating agents, non-selective COX inhibitors, tyrosine kinase inhibitors and polyamine synthetic inhibitors.

Trastuzumab and survival of patients with metastatic breast cancer.

Science.gov (United States)

Kast, Karin; Schoffer, Olaf; Link, Theresa; Forberger, Almuth; Petzold, Andrea; Niedostatek, Antje; Werner, Carmen; Klug, Stefanie J; Werner, Andreas; Gatzweiler, Axel; Richter, Barbara; Baretton, Gustavo; Wimberger, Pauline

2017-08-01

Prognosis of Her2-positive breast cancer has changed since the introduction of trastuzumab for treatment in metastatic and early breast cancer. It was described to be even better compared to prognosis of Her2-negative metastatic breast cancer. The purpose of this study was to evaluate the effect of trastuzumab in our cohort. Besides the effect of adjuvant pretreatment with trastuzumab on survival of patients with metastatic Her2-positive breast cancer was analyzed. All patients with primary breast cancer of the Regional Breast Cancer Center Dresden diagnosed during the years 2001-2013 were analyzed for treatment with or without trastuzumab in the adjuvant and in the metastatic treatment setting using Kaplan-Meier survival estimation and Cox regression. Age and tumor stage at time of first diagnosis of breast cancer as well as hormone receptor status, grading, time, and site of metastasis at first diagnosis of distant metastatic disease were analyzed. Of 4.481 female patients with primary breast cancer, 643 presented with metastatic disease. Her2-positive status was documented in 465 patients, including 116 patients with primary or secondary metastases. Median survival of patients with Her2-positive primary metastatic disease was 3.0 years (95% CI 2.3-4.0). After adjustment for other factors, survival was better in patients with Her2-positive breast cancer with trastuzumab therapy compared to Her2-negative metastatic disease (HR 2.10; 95% CI 1.58-2.79). Analysis of influence of adjuvant therapy with and without trastuzumab by Kaplan-Meier showed a trend for better survival in not pretreated patients. Median survival was highest in hormone receptor-positive Her2-positive (triple-positive) primary metastatic breast cancer patients with 3.3 years (95% CI 2.3-4.6). Prognosis of patients with Her2-positive metastatic breast cancer after trastuzumab treatment is more favorable than for Her2-negative breast cancer. The role of adjuvant chemotherapy with or without

Effects of a high-fiber, low-fat diet intervention on serum concentrations of reproductive steroid hormones in women with a history of breast cancer.

Science.gov (United States)

Rock, Cheryl L; Flatt, Shirley W; Thomson, Cynthia A; Stefanick, Marcia L; Newman, Vicky A; Jones, Lovell A; Natarajan, Loki; Ritenbaugh, Cheryl; Hollenbach, Kathryn A; Pierce, John P; Chang, R Jeffrey

2004-06-15

Diet intervention trials are testing whether postdiagnosis dietary modification can influence breast cancer recurrence and survival. One possible mechanism is an effect on reproductive steroid hormones. Serum reproductive steroid hormones were measured at enrollment and 1 year in 291 women with a history of breast cancer who were enrolled onto a randomized, controlled diet intervention trial. Dietary goals for the intervention group were increased fiber, vegetable, and fruit intakes and reduced fat intake. Estradiol, bioavailable estradiol, estrone, estrone sulfate, androstenedione, testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone, and sex hormone-binding globulin were measured. The intervention (but not the comparison) group reported a significantly lower intake of energy from fat (21% v 28%), and higher intake of fiber (29 g/d v 22 g/d), at 1-year follow-up (P <.001). Significant weight loss did not occur in either group. A significant difference in the change in bioavailable estradiol concentration from baseline to 1 year in the intervention (-13 pmol/L) versus the comparison (+3 pmol/L) group was observed (P <.05). Change in fiber (but not fat) intake was significantly and independently related to change in serum bioavailable estradiol (P <.01) and total estradiol (P <.05) concentrations. Results from this study indicate that a high-fiber, low-fat diet intervention is associated with reduced serum bioavailable estradiol concentration in women diagnosed with breast cancer, the majority of whom did not exhibit weight loss. Increased fiber intake was independently related to the reduction in serum estradiol concentration.

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.

KRAS rs61764370 is associated with HER2-overexpressed and poorly-differentiated breast cancer in hormone replacement therapy users: a case control study

International Nuclear Information System (INIS)

Cerne, Jasmina-Ziva; Stegel, Vida; Gersak, Ksenija; Novakovic, Srdjan

2012-01-01

A single nucleotide polymorphism located in the 3'-untranslated region of the KRAS oncogene (KRAS variant; rs61764370) disrupts a let-7 miRNA binding and was recently reported to act as a genetic marker for increased risk of developing human cancers. We aimed to investigate an association of the KRAS variant with sporadic and familial breast cancer and breast tumor characteristics. Genotyping was accomplished in 530 sporadic postmenopausal breast cancer cases, 165 familial breast cancer cases (including N = 29, who test positive for BRCA1/2 mutations) and 270 postmenopausal control women using the flurogenic 5' nuclease assay. Information on hormone replacement therapy (HRT) use and tumor characteristics in sporadic breast cancer cases was ascertained from a postal questionnaire and pathology reports, respectively. Associations between the KRAS genotype and breast cancer or breast tumor characteristics were assessed using chi-square test and logistic regression models. No evidence of association was observed between the KRAS variant and risk of sporadic and familial breast cancer - either among BRCA carriers or non-BRCA carriers. The KRAS variant was statistically significantly more often associated with human epidermal growth factor receptor 2 (HER2) - positive tumors and tumors of higher histopathologic grade. However, both associations were detected only in HRT users. Our data do not support the hypothesis that the KRAS variant rs61764370 is implicated in the aetiology of sporadic or of familial breast cancer. In postmenopausal women using HRT, the KRAS variant might lead to HER2 overexpressed and poorly-differentiated breast tumors, both indicators of a worse prognosis

PTH Gene Polymorphism and Breast Cancer Risk in Kazakhstan

Directory of Open Access Journals (Sweden)

Nurgul Sikhayeva

2014-12-01

Full Text Available Introduction. Breast cancer is the most common type of cancer among women. In Kazakhstan, breast cancer holds first place among causes of women death caused by cancer in the 45-55 year age group . Many studies have shown that the risk of acquiring breast cancer may be related to the level of calcium in the blood serum. One of the important regulators of calcium metabolism in the body is the parathyroid hormone. Single nucleotide polymorphisms in the gene encoding the parathyroid hormone (PTH are associated with breast cancer development risk, and may modify the associative interaction between the levels of calcium intake and breast cancer. Experimental studies have shown that PTH gene has a carcinogenic effect. At least three studies showed a weak positive correlation between the risk of acquiring breast cancer and primary hyperparathyroidism, a state with high levels of PTH and often high levels of calcium. The aim of this investigation was to evaluate potential association between PTH gene polymorphism and breast cancer risk among Kazakhstani women.Methods. Female breast cancer patients (n = 429 and matched control women (n = 373 were recruited into a case – control study,. Genomic DNA was extracted from peripheral venous blood of study participants using Wizard® Genomic DNA Purification Kit (Promega, USA. Detection of PTH gene polymorphism (rs1459015 was done by means of the TaqMan® SNP Genotyping Assay of real-time PCR. Statistical analysis was conducted using SPSS 19.0.Results. PTH gene alleles were in Hardy–Weinberg equilibrium (p > 0.05. Distribution was 59% CC, 35% CT, 6% TT in the group with breast cancer and 50% CC, 43% CT, 6% TT in the control group. Total difference (between the group with breast cancer and the control group in allele frequencies for PTH polymorphism was not significant (p > 0.05. No association was found between rs1459015 TT and breast cancer risk (OR = 1.039; 95%, CI 0.740 - 1.297; p = 0.893.Conclusion. We

Metabolomics Analysis of Hormone-Responsive and Triple-Negative Breast Cancer Cell Responses to Paclitaxel Identify Key Metabolic Differences.

Science.gov (United States)

Stewart, Delisha A; Winnike, Jason H; McRitchie, Susan L; Clark, Robert F; Pathmasiri, Wimal W; Sumner, Susan J

2016-09-02

To date, no targeted therapies are available to treat triple negative breast cancer (TNBC), while other breast cancer subtypes are responsive to current therapeutic treatment. Metabolomics was conducted to reveal differences in two hormone receptor-negative TNBC cell lines and two hormone receptor-positive Luminal A cell lines. Studies were conducted in the presence and absence of paclitaxel (Taxol). TNBC cell lines had higher levels of amino acids, branched-chain amino acids, nucleotides, and nucleotide sugars and lower levels of proliferation-related metabolites like choline compared with Luminal A cell lines. In the presence of paclitaxel, each cell line showed unique metabolic responses, with some similarities by type. For example, in the Luminal A cell lines, levels of lactate and creatine decreased while certain choline metabolites and myo-inositol increased with paclitaxel. In the TNBC cell lines levels of glutamine, glutamate, and glutathione increased, whereas lysine, proline, and valine decreased in the presence of drug. Profiling secreted inflammatory cytokines in the conditioned media demonstrated a greater response to paclitaxel in the hormone-positive Luminal cells compared with a secretion profile that suggested greater drug resistance in the TNBC cells. The most significant differences distinguishing the cell types based on pathway enrichment analyses were related to amino acid, lipid and carbohydrate metabolism pathways, whereas several biological pathways were differentiated between the cell lines following treatment.

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

DEFF Research Database (Denmark)

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

2011-01-01

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

Mammary Ductal Environment Is Necessary for Faithful Maintenance of Estrogen Signaling in ER+ Breast Cancer

OpenAIRE

Haricharan, Svasti; Lei, Jonathan; Ellis, Matthew

2016-01-01

In this issue of Cancer Cell, Sflomos et al. (2016) describe a robust preclinical animal model of ER+ breast cancer. The authors identify the critical role of the breast microenvironment in determining hormone response of ER+ breast cancer cells and in driving the luminal phenotype of breast cancer.

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

African Journals Online (AJOL)

The ANNALS of AFRICAN SURGERY | www.sskenya.org. The ANNALS of ... metastatic lesions and survival among breast cancer patients. ... year survival rate (2). Breast ... Three core ... ER negative and 35 (49.3%) had PR positive tumours.

A breast cancer case-control study in Girona, Spain. Endocrine, familial and lifestyle factors.

Science.gov (United States)

Viladiu, P; Izquierdo, A; de Sanjosé, S; Bosch, F X

1996-10-01

This study was designed to explore risk factors for breast cancer with emphasis on the detection of clinical markers of the hormonal imbalance during the perimenarche. Three hundred and thirty women diagnosed with breast cancer and 346 population controls were identified and interviewed in Girona, Spain between 1986 and 89. Cases were more likely than controls to have had long menstrual periods in the first 5 years after menarche [odds ratio (OR) = 3.0], to experience menopause at a late age (OR = 1.5) and to report acne during adolescence (OR = 1.6). Family history of breast cancer was associated with an increased risk (OR = 2.3). Cases reported a lower use of drug treatments for anxiety and sleep disorders than controls. Moderate alcohol drinkers and smokers were at lower risk for breast cancer. No statistically significant association with breast cancer was observed for number of children, age at last pregnancy, oral contraceptive use, hormonal treatment after menopause and weight perception during the teenage years. Hormonal changes in the years following menarche may be relevant to breast cancer risk. The roles of menstrual period length and acne during adolescence should be further explored.

Risk Factors for Breast Cancer, Including Occupational Exposures

Directory of Open Access Journals (Sweden)

Elisabete Weiderpass

2011-03-01

Full Text Available The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs (www.iarc.fr. For breast cancer the following substances have been classified as “carcinogenic to humans” (Group 1: alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure. Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification “probably carcinogenic to humans” (Group 2A includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women.

Body mass index and survival after breast cancer diagnosis in Japanese women

International Nuclear Information System (INIS)

Kawai, Masaaki; Minami, Yuko; Nishino, Yoshikazu; Fukamachi, Kayoko; Ohuchi, Noriaki; Kakugawa, Yoichiro

2012-01-01

Body mass index (BMI) may be an important factor affecting breast cancer outcome. Studies conducted mainly in Western countries have reported a relationship between higher BMI and a higher risk of all-cause death or breast cancer-specific death among women with breast cancer, but only a few studies have been reported in Japan so far. In the present prospective study, we investigated the associations between BMI and the risk of all-cause and breast cancer-specific death among breast cancer patients overall and by menopausal status and hormone receptor status. The study included 653 breast cancer patients admitted to a single hospital in Japan, between 1997 and 2005. BMI was assessed using a self-administered questionnaire. The patients were completely followed up until December, 2008. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated according to quartile points of BMI categories, respectively: <21.2, ≥21.2 to <23.3 (reference), ≥23.3 to <25.8 and ≥25.8 kg/m 2 . During the follow-up period, 136 all-cause and 108 breast cancer-specific deaths were observed. After adjustment for clinical and confounding factors, higher BMI was associated with an increased risk of all-cause death (HR = 2.61; 95% CI: 1.01–6.78 for BMI ≥25.8 vs. ≥21.2 to <23.3 kg/m 2 ) among premenopausal patients. According to hormonal receptor status, BMI ≥25.8 kg/m 2 was associated with breast cancer-specific death (HR = 4.95; 95% CI: 1.05–23.35) and BMI <21.2 kg/m 2 was associated with all-cause (HR = 2.91; 95% CI: 1.09–7.77) and breast cancer-specific death (HR = 7.23; 95% CI: 1.57–33.34) among patients with ER + or PgR + tumors. Analysis by hormonal receptor status also showed a positive association between BMI and mortality risk among patients with ER + or PgR + tumors and with BMI ≥21.2 kg/m 2 (p for trend: 0.020 and 0.031 for all-cause and breast cancer-specific death, respectively). Our results suggest that both higher BMI and lower BMI are associated

Involvement of Human Estrogen Related Receptor Alpha 1 (hERR Alpha 1) in Breast Cancer and Hormonally Insensitive Disease

Science.gov (United States)

2001-08-01

Identification of a new class of steroid hormone receptors. Nature, 331: 91-94, 1988. 4. Vanacker , J. M ., Pettersson, K., Gustafsson, J. A., and...Lippman, M . E., Thompson, E. B., Simon, R., Barlock, A., Green, L., Huff, K. K., Do, H. M ., Aitken, S. C., and Warren, R. Estrogen receptor status: an...important variable in predicting response to endocrine therapy in metastatic breast cancer. Eur J Cancer, 16: 323-331, 1980. 2. Clark, G. M . and

Computerized database management system for breast cancer patients.

Science.gov (United States)

Sim, Kok Swee; Chong, Sze Siang; Tso, Chih Ping; Nia, Mohsen Esmaeili; Chong, Aun Kee; Abbas, Siti Fathimah

2014-01-01

Data analysis based on breast cancer risk factors such as age, race, breastfeeding, hormone replacement therapy, family history, and obesity was conducted on breast cancer patients using a new enhanced computerized database management system. My Structural Query Language (MySQL) is selected as the application for database management system to store the patient data collected from hospitals in Malaysia. An automatic calculation tool is embedded in this system to assist the data analysis. The results are plotted automatically and a user-friendly graphical user interface is developed that can control the MySQL database. Case studies show breast cancer incidence rate is highest among Malay women, followed by Chinese and Indian. The peak age for breast cancer incidence is from 50 to 59 years old. Results suggest that the chance of developing breast cancer is increased in older women, and reduced with breastfeeding practice. The weight status might affect the breast cancer risk differently. Additional studies are needed to confirm these findings.

Mammary Ductal Environment Is Necessary for Faithful Maintenance of Estrogen Signaling in ER+ Breast Cancer

Science.gov (United States)

Haricharan, Svasti; Lei, Jonathan; Ellis, Matthew

2016-01-01

In this issue of Cancer Cell, Sflomos et al. (2016) describe a robust preclinical animal model of ER+ breast cancer. The authors identify the critical role of the breast microenvironment in determining hormone response of ER+ breast cancer cells and in driving the luminal phenotype of breast cancer. PMID:26977876

Mastopathy and breast cancer

International Nuclear Information System (INIS)

Herman, K.

2007-01-01

Mastopathy (mastopathia fibroso-cystica) and breast cancer are two major epidemiologic, economic and medical problems of women. In Poland, annually, 0.2 - 1.6 billion Polish zlotys is spent on diagnosis and treatment of mastopathy; half of that sum is spent improperly. Many papers suggest relationships between these two diseases, however, it is not certain, whether, or how much, mastopathy increases breast cancer incidence. The available papers from the recent years indicate increased risk, but the methodology of these data is not perfect. It is not excluded that fibrocystic diseases of the breast increase breast cancer incidence. If such an influence exists, independent of other well-know factors, it is probably very small. Moreover, due to the diversity of medical information there is a lack of diagnostic and therapeutic standards in mastopathy. Different types of scans, hormonal, biochemical and immunohistochemical examinations are performed improperly, and there has been no genetic analysis of mastopathy. Therefore, there is a strong need of well planned, prospective trials in this field. (author)

Effect of adjuvant chemotherapy in postmenopausal patients with invasive ductal versus lobular breast cancer.

Science.gov (United States)

Truin, W; Voogd, A C; Vreugdenhil, G; van der Heiden-van der Loo, M; Siesling, S; Roumen, R M

2012-11-01

On the basis of the lack of response of invasive lobular breast cancer to neoadjuvant chemotherapy, we questioned the effectiveness of adjuvant chemotherapy in relation to histology. Women with primary nonmetastatic invasive ductal or (mixed type) lobular breast cancer, aged 50-70 years, diagnosed between 1995 and 2008, were selected from the Netherlands Cancer Registry and followed until January 1, 2010. The patients were divided in two groups: one group receiving adjuvant hormonal therapy only and the other receiving adjuvant hormonal therapy in combination with adjuvant chemotherapy. In total, 19,609 patients had ductal cancer and 3685 had lobular cancer. The 10-year overall survival rate in ductal cancer when treated with hormonal therapy alone was 69%, compared with 74% with the combination therapy (P lobular cancer, 10-year survival rates were 68% after hormonal treatment alone and 66% after the combination therapy (P = 0.45). The hazard ratio (HR) for mortality in ductal cancer after combination therapy was 0.70 [95% confidence interval (CI) 0.64-0.76; P lobular cancer was 1.00 (95% CI 0.82-1.21; P = 0.97). Adjuvant chemotherapy seems to confer no additional beneficial effects in postmenopausal patients with pure or mixed type lobular breast cancer receiving hormonal therapy.

Oligoadenylate synthetase 1 (OAS1 expression in human breast and prostate cancer cases, and its regulation by sex steroid hormones

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Cláudio Jorge Maia

2016-06-01

Full Text Available Oligoadenylate synthetase 1 (OAS1 is an interferon-induced protein characterised by its capacity to catalyse the synthesis of 2ʹ-5ʹ-linked oligomers of adenosine from adenosine triphosphate (2-5A. The 2-5A binds to a latent Ribonuclease L (RNase L, which subsequently dimerises into its active form and may play an important role in the control of cell growth, differentiation and apoptosis. Previously, our research group identified OAS1 as a differentially-expressed gene in breast and prostate cancer cell lines when compared to normal cells. This study evaluates: i the expression of OAS1 in human breast and prostate cancer specimens; and ii the effect of sex steroid hormones in regulating the expression of OAS1 in breast (MCF-7 and prostate (LNCaP cancer cell lines. The obtained results showed that OAS1 expression was down-regulated in human infiltrative ductal carcinoma of breast, adenocarcinoma of prostate, and benign prostate hyperplasia, both at mRNA and protein level. In addition, OAS1 expression was negatively correlated with the progression of breast and prostate cancer. With regards to the regulation of OAS1 gene, it was demonstrated that 17β-estradiol (E2 down-regulates OAS1 gene in MCF-7 cell lines, an effect that seems to be dependent on the activation of oestrogen receptor (ER. On the other hand, 5α-dihydrotestosterone (DHT treatment showed no effect on the expression of OAS1 in LNCaP cell lines. The lower levels of OAS1 in breast and prostate cancer cases indicated that the OAS1/RNaseL apoptotic pathway may be compromised in breast and prostate tumours. Moreover, the present findings suggested that this effect may be enhanced by oestrogen in ER-positive breast cancers.

Comprehensive Analysis of Hormone and Genetic Variation in 36 Genes Related to Steroid Hormone Metabolism in Pre- and Postmenopausal Women from the Breast and Prostate Cancer Cohort Consortium (BPC3)

DEFF Research Database (Denmark)

Beckmann, L.; Husing, A.; Setiawan, V. W.

2011-01-01

Context: Sex steroids play a central role in breast cancer development.Objective: This study aimed to relate polymorphic variants in 36 candidate genes in the sex steroid pathway to serum concentrations of sex steroid hormones and SHBG.Design: Data on 700 genetic polymorphisms were combined...

Sex Differences and Bone Metastases of Breast, Lung, and Prostate Cancers: Do Bone Homing Cancers Favor Feminized Bone Marrow?

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Mary C. Farach-Carson

2017-08-01

Full Text Available Sex-associated differences in bone metastasis formation from breast, lung, and prostate cancer exist in clinical studies, but have not been systematically reviewed. Differences in the bone marrow niche can be attributed to sexual dimorphism, to genetic variations that affect sex hormone levels, or to the direct effects of sex hormones, natural or exogenously delivered. This review describes the present understanding of sex-associated and sex hormone level differences in the marrow niche and in formation of bone metastasis during the transition of these three cancers from treatable disease to an often untreatable, lethal metastatic one. Our purpose is to provide insight into some underlying molecular mechanisms for hormonal influence in bone metastasis formation, and to the potential influence of sexual dimorphism, genetic differences affecting sex assignment, and sex hormone level differences on the bone niche and its favorability for metastasis formation. We reviewed publications in PubMed and EMBASE, including full length manuscripts, case reports, and clinical studies of relevance to our topic. We focused on bone metastasis formation in breast, lung, and prostate cancer because all three commonly present with bone metastases. Several clear observations emerged. For breast cancer bone metastasis formation, estrogen receptor (ER signaling pathways indicate a role for ER beta (ERβ. Estrogen influences the bone microenvironment, creating and conditioning a favorable niche for colonization and breast cancer progression. For lung cancer, studies support the hypothesis that females have a more favorable bone microenvironment for metastasis formation. For prostate cancer, a decrease in the relative androgen to estrogen balance or a “feminization” of bone marrow favors bone metastasis formation, with a potentially important role for ERβ that may be similar to that in breast cancer. Long-term estrogen administration or androgen blockade in males

Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study

International Nuclear Information System (INIS)

Ritte, Rebecca; Grote, Verena; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Berrino, Franco; Mattiello, Amalia; Tumino, Rosario; Tikk, Kaja; Sacerdote, Carlotta; Quirós, José Ramón; Buckland, Genevieve; Molina-Montes, Esther; Chirlaque, María-Dolores; Ardanaz, Eva; Amiano, Pilar; Bueno-de-Mesquita, H Bas; Gils, Carla H van; Peeters, Petra HM; Lukanova, Annekatrin; Wareham, Nick; Khaw, Kay-Tee; Key, Timothy J; Travis, Ruth C; Weiderpass, Elisabete; Dumeaux, Vanessa; Lund, Eliv; Sund, Malin; Andersson, Anne; Romieu, Isabelle; Tjønneland, Anne; Rinaldi, Sabina; Vineis, Paulo; Merritt, Melissa A; Riboli, Elio; Kaaks, Rudolf; Olsen, Anja; Overvad, Kim; Dossus, Laure; Fournier, Agnès; Clavel-Chapelon, Françoise

2013-01-01

The association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain. Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR- (n = 998) and ER+PR+ (n = 3,567) breast tumors. A later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR- tumors (≥35 vs. ≤19 years HR: 1.47 [95% CI 1.15-1.88] p trend < 0.001 for ER+PR+ tumors; ≥35 vs. ≤19 years HR: 0.93 [95% CI 0.53-1.65] p trend = 0.96 for ER-PR- tumors; P het = 0.03). The risk associations of menarcheal age, and time period between menarche and first full-term childbirth with ER-PR-tumors were in the similar direction with risk of ER+PR+ tumors (p het = 0.50), although weaker in magnitude and statistically only borderline significant. Other parity related factors such as ever a full-term birth, number of births, age- and time since last birth were associated only with ER+PR+ malignancies, however no statistical heterogeneity between breast cancer subtypes was observed. Breastfeeding and OC use were generally not associated with breast cancer subtype risk. Our study provides possible evidence that age at menarche, and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although the associations with HR-negative breast cancer were only borderline significant

KRAS rs61764370 is associated with HER2-overexpressed and poorly-differentiated breast cancer in hormone replacement therapy users: a case control study

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Cerne Jasmina-Ziva

2012-03-01

Full Text Available Abstract Background A single nucleotide polymorphism located in the 3'-untranslated region of the KRAS oncogene (KRAS variant; rs61764370 disrupts a let-7 miRNA binding and was recently reported to act as a genetic marker for increased risk of developing human cancers. We aimed to investigate an association of the KRAS variant with sporadic and familial breast cancer and breast tumor characteristics. Methods Genotyping was accomplished in 530 sporadic postmenopausal breast cancer cases, 165 familial breast cancer cases (including N = 29, who test positive for BRCA1/2 mutations and 270 postmenopausal control women using the flurogenic 5' nuclease assay. Information on hormone replacement therapy (HRT use and tumor characteristics in sporadic breast cancer cases was ascertained from a postal questionnaire and pathology reports, respectively. Associations between the KRAS genotype and breast cancer or breast tumor characteristics were assessed using chi-square test and logistic regression models. Results No evidence of association was observed between the KRAS variant and risk of sporadic and familial breast cancer - either among BRCA carriers or non-BRCA carriers. The KRAS variant was statistically significantly more often associated with human epidermal growth factor receptor 2 (HER2 - positive tumors and tumors of higher histopathologic grade. However, both associations were detected only in HRT users. Conclusion Our data do not support the hypothesis that the KRAS variant rs61764370 is implicated in the aetiology of sporadic or of familial breast cancer. In postmenopausal women using HRT, the KRAS variant might lead to HER2 overexpressed and poorly-differentiated breast tumors, both indicators of a worse prognosis.

Metastasis of breast cancer rectum

International Nuclear Information System (INIS)

Suárez, L.; Santander, G.

2004-01-01

Introduction: Metastases to the breast are rare, corresponding approximately to 3% of breast cancers. Primary tumors that spread more commonly are own breast, often following them in melanomas, neuroendocrine, ovarian and lymphoma. Medical history: A 59-year consultation rectoragias repeated and thinning. It is studied and finally intervenes (low anterior resection) diagnosed with rectal cancer whose Histopathology revealed a poorly differentiated adenocarcinoma stage III. Concomitantly the patient has a left breast lump that was studied with mammography, which revealed a dense mass of larger diameter 4 cm in topografiada 3 hour left breast with well defined contours and ultrasonographic structure solid. MI lumpectomy is performed whose pathology reports a poorly differentiated adenocarcinoma with cytoarchitectural features matching the lesion of rectum. Hormone receptors were negative. The patient is treated as a rectal cancer with RT spread over QT (5FU i /c). Died 7 months after diagnosis. Discusion: In literature are reported only 3 cases of breast metastases secondary to rectal cancer; how unusual this presentation justify this report.In this event they occurred in patients with a previous diagnosis of rectal cancer and in the context of systemic lesion progression. In our case clinician early diagnosis of rectal and breast metastases was synchronous. The mammographic image consistent with those described for these cases in the literature.The development of metastases in breast tissue is associated with a poor prognosis as which correlates with the survival of the patient

Glycolytic overload and the genesis of breast cancer.

Science.gov (United States)

Robson, J R

1984-03-01

It is suggested that the development of breast cancer is due to overloading of the glycolytic pathways. An excess of substrates or an excessive delivery rate of substrates to the Krebs Cycle is believed to result in the formation of acetyl CoA. Feedback mechanisms controlling the conversion of acetyl CoA to cholesterol may be overcome; the resulting high concentration of cholesterol induces the formation of pregnenolone which may then be converted into androgens, estrogens and progesterone. These steroids are in addition to those produced by gonads and adrenal glands. Glycolytic overload is also associated with an increase in fat stores which have been shown to be the site of interconversion of sex hormones. Excess sex hormones or abnormal sex hormones are believed to be the cause of breast cancer. The hypothesis presented links glycolytic overload with clinical biochemical phenomena and explains some of the anomalies observed in breast cancer experience in different ethnic groups. Changes in dietary habits during the history of man resulting in " gorging " and the consumption of highly refined sugars are possible causes of glycolytic overload. So, also, is impaired thermogenesis due to Brown Fat deficits in certain ethnic groups.

Application of photoshop-based image analysis to quantification of hormone receptor expression in breast cancer.

Science.gov (United States)

Lehr, H A; Mankoff, D A; Corwin, D; Santeusanio, G; Gown, A M

1997-11-01

The benefit of quantifying estrogen receptor (ER) and progesterone receptor (PR) expression in breast cancer is well established. However, in routine breast cancer diagnosis, receptor expression is often quantified in arbitrary scores with high inter- and intraobserver variability. In this study we tested the validity of an image analysis system employing inexpensive, commercially available computer software on a personal computer. In a series of 28 invasive ductal breast cancers, immunohistochemical determinations of ER and PR were performed, along with biochemical analyses on fresh tumor homogenates, by the dextran-coated charcoal technique (DCC) and by enzyme immunoassay (EIA). From each immunohistochemical slide, three representative tumor fields (x20 objective) were captured and digitized with a Macintosh personal computer. Using the tools of Photoshop software, optical density plots of tumor cell nuclei were generated and, after background subtraction, were used as an index of immunostaining intensity. This immunostaining index showed a strong semilogarithmic correlation with biochemical receptor assessments of ER (DCC, r = 0.70, p < 0.001; EIA, r = 0.76, p < 0.001) and even better of PR (DCC, r = 0.86; p < 0.01; EIA, r = 0.80, p < 0.001). A strong linear correlation of ER and PR quantification was also seen between DCC and EIA techniques (ER, r = 0.62, p < 0.001; PR, r = 0.92, p < 0.001). This study demonstrates that a simple, inexpensive, commercially available software program can be accurately applied to the quantification of immunohistochemical hormone receptor studies.

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

Science.gov (United States)

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

2013-06-01

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

Hormone resistance in two MCF-7 breast cancer cell lines is associated with reduced mTOR signaling, decreased glycolysis and increased sensitivity to cytotoxic drugs

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Euphemia Yee Leung

2014-09-01

Full Text Available The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume and resistance to mTOR inhibition. Here we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, docetaxel and hydrogen peroxide. The mechanisms underlying these changes have not yet been characterized but may include a shift from glycolysis to mitochondrial respiration. If this phenotype is found in clinical hormone-resistant breast cancers, conventional cytotoxic therapy may be a preferred option for treatment.

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

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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.

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

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Olivier Nguyen

2012-01-01

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

Breast density and mode of detection in relation to breast cancer specific survival: a cohort study

International Nuclear Information System (INIS)

Olsson, Åsa; Sartor, Hanna; Borgquist, Signe; Zackrisson, Sophia; Manjer, Jonas

2014-01-01

The aim of this study was to examine breast density in relation to breast cancer specific survival and to assess if this potential association was modified by mode of detection. An additional aim was to study whether the established association between mode of detection and survival is modified by breast density. The study included 619 cases from a prospective cohort, The Malmö Diet and Cancer Study. Breast density estimated qualitatively, was analyzed in relation to breast cancer death, in non-symptomatic and symptomatic women, using Cox regression calculating hazard ratios (HR) with 95% confidence intervals. Adjustments were made in several steps for; diagnostic age, tumour size, axillary lymph node involvement, grade, hormone receptor status, body mass index (baseline), diagnostic period, use of hormone replacement therapy at diagnosis and mode of detection. Detection mode in relation to survival was analyzed stratified for breast density. Differences in HR following different adjustments were analyzed by Freedmans%. After adjustment for age and other prognostic factors, women with dense, as compared to fatty breasts, had an increased risk of breast cancer death, HR 2.56:1.07-6.11, with a statistically significant trend over density categories, p = 0.04. In the stratified analysis, the effect was less pronounced in non-symptomatic women, HR 2.04:0.49-8.49 as compared to symptomatic, HR 3.40:1.06-10.90. In the unadjusted model, symptomatic women had a higher risk of breast cancer death, regardless of breast density. Analyzed by Freedmans%, age, tumour size, lymph nodes, grade, diagnostic period, ER and PgR explained 55.5% of the observed differences in mortality between non-symptomatic and symptomatic cases. Additional adjustment for breast density caused only a minor change. High breast density at diagnosis may be associated with decreased breast cancer survival. This association appears to be stronger in women with symptomatic cancers but breast density could

An estrogen-associated dietary pattern and breast cancer risk in the Swedish Mammography Cohort.

Science.gov (United States)

Harris, Holly R; Bergkvist, Leif; Wolk, Alicja

2015-11-01

High endogenous hormone levels have been associated with breast cancer and dietary factors have the potential to influence breast cancer risk through effects on hormone levels. Dietary patterns derived from reduced rank regression provide a way to identify food groups correlated with hormones and subsequently examine food patterns that may be associated with breast cancer risk. We investigated whether a dietary pattern previously correlated with estradiol and estrone sulfate was associated with breast cancer in the prospective Swedish Mammography Cohort. Among 37,004 primarily postmenopausal women diet was assessed with a food frequency questionnaire. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During 15 years of follow-up 1,603 cases of breast cancer were identified. A higher estrogen dietary pattern score was associated with an increased risk of breast cancer. Women in the highest quartile of estrogen pattern score had a 29% (95% CI = 1.08-1.55) increased risk of breast cancer compared to women in the lowest quartile (p(trend) = 0.006). When the association was examined by estrogen-receptor status, it was only significant for those with estrogen-receptor-positive tumors; however, in the competing risk analysis there were no significant differences in the effect estimates by receptor subtype (p(heterogeneity) = 0.65). Our findings suggest that a dietary pattern associated with higher estrogen levels may increase breast cancer risk. However, whether the influence of this dietary pattern is through a direct effect on estrogen levels deserves further study. © 2015 UICC.

Hormonal receptors and response to treatment of breast cancer

International Nuclear Information System (INIS)

Loven, D.; Rakowsky, E.; Stein, J.A.

1981-01-01

Response to several types of endocrine therapy or chemotherapy was evaluated in 60 patients with breast cancer. Estrogen and progesterone receptors were determined by radioimmunoassay. Response to endocrine therapy was significantly higher (P<0.01) among estrogen receptor (ER)-positive cases than among ER-negative cases. The response to chemotherapy did not differ significantly between the two groups. The results of this small series support the conclusion that determination of ER is valuable in planning endocrine treatment of the breast cancer patient, whereas response to chemotherapy does not correlate with ER levels. (author)

Could hormonal influences and lifestyle factors affect the risk of developing breast cancer?

International Nuclear Information System (INIS)

Kilford, J.

2003-01-01

Breast cancer is the most common cancer in women throughout the world and the third most common cause of cancer deaths in adults, according to recent figures. Many authorities, both medical and non-medical, have written about the risks and causes of breast cancer, and research has been conducted into many diverse theories. This paper is a review of some of these ideas and possible risks of breast cancer

Chemotherapy-Related Amenorrhea and Menopause in Young Chinese Breast Cancer Patients: Analysis on Incidence, Risk Factors and Serum Hormone Profiles

Science.gov (United States)

Liem, Giok S.; Mo, Frankie K. F.; Pang, Elizabeth; Suen, Joyce J. S.; Tang, Nelson L. S.; Lee, Kun M.; Yip, Claudia H. W.; Tam, Wing H.; Ng, Rita; Koh, Jane; Yip, Christopher C. H.; Kong, Grace W. S.; Yeo, Winnie

2015-01-01

Purpose In this prospective cross-sectional study on young premenopausal breast cancer patients, the objectives were to: determine the incidences of chemotherapy-related amenorrhea (CRA) and menopause (CRM); identify associated factors; and assess plasma levels of estradiol (E2) and follicular stimulating hormone (FSH) among patients who developed menopause. Methods Eligibility criteria include Chinese stage I-III breast cancer patients, premenopausal, age ≤45 at breast cancer diagnosis, having received adjuvant chemotherapy, within 3–10 years after breast cancer diagnosis. Detailed menstrual history prior to and after adjuvant treatment was taken at study entry. Patients’ background demographics, tumor characteristics and anti-cancer treatments were collected. The rates of CRA and CRM were determined. Analysis was conducted to identify factors associated with CRM. For postmenopausal patients, levels of E2 and FSH were analyzed. Results 286 patients were recruited; the median time from breast cancer diagnosis to study entry was 5.0 years. 255 patients (91.1%) developed CRA. Of these, 66.7% regained menstruation. At the time of study entry, 137 (48.9%) had developed CRM, amongst whom 84 were age ≤45. On multivariate analysis, age was the only associated factor. Among patients with CRM, the median FSH was 41.0 IU/L; this was significantly lower in those who were taking tamoxifen compared to those who were not (20.1 vs. 59.7 IU/L, p<0.0001). The E2 level was <40 pmol/L; there was no difference between those who were still on tamoxifen or not. Conclusion After adjuvant chemotherapy, the majority of young Chinese breast cancer patients developed CRA; ~50% developed CRM, with 61% at age ≤45. Age at diagnosis is the only factor associated with CRM. FSH level may be affected by tamoxifen intake. PMID:26485568

Risk of breast cancer by type of menopausal hormone therapy: a case-control study among post-menopausal women in France.

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Emilie Cordina-Duverger

Full Text Available BACKGROUND: There is extensive epidemiological evidence that menopausal hormone therapy (MHT increases breast cancer risk, particularly combinations of estrogen and progestagen (EP. We investigated the effects of the specific formulations and types of therapies used by French women. Progestagen constituents, regimen (continuous or sequential treatment by the progestagen, and time interval between onset of menopause and start of MHT were examined. METHODS: We conducted a population-based case-control study in France in 1555 menopausal women (739 cases and 816 controls. Detailed information on MHT use was obtained during in-person interviews. Odds ratios and 95% confidence interval adjusted for breast cancer risk factors were calculated. RESULTS: We found that breast cancer risk differed by type of progestagen among current users of EP therapies. No increased risk was apparent among EP therapy users treated with natural micronized progesterone. Among users of EP therapy containing a synthetic progestin, the odds ratio was 1.57 (0.99-2.49 for progesterone-derived and 3.35 (1.07-10.4 for testosterone-derived progestagen. Women with continuous regimen were at greater risk than women treated sequentially, but regimen and type of progestagen could not be investigated independently, as almost all EP combinations containing a testosterone-derivative were administered continuously and vice-versa. Tibolone was also associated with an increased risk of breast cancer. Early users of MHT after onset of menopause were at greater risk than users who delayed treatment. CONCLUSION: This study confirms differential effects on breast cancer risk of progestagens and regimens specifically used in France. Formulation of EP therapies containing natural progesterone, frequently prescribed in France, was not associated with increased risk of breast cancer but may poorly protect against endometrial cancer.

PET and Hormone Receptor Ligands in Breast Cancer

National Research Council Canada - National Science Library

Gemignani, Mary

2006-01-01

.... To investigate this further, this project's objectives are: To evaluate the use of estrogen-like ligands labeled with positron emitters in preoperatively determining the ER status of breast cancer using PET...

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

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Robertson John FR

2011-09-01

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

Second primary in the contralateral breast after treatment of breast cancer

International Nuclear Information System (INIS)

Yadav, Budhi Singh; Sharma, Suresh C.; Patel, Firuza D.; Ghoshal, Shushmita; Kapoor, Rakesh K.

2008-01-01

Purpose: To study the potential risk factors for contralateral breast cancer (CBC) in women after treatment of the primary breast cancer. Patients and methods: Between January 1985 and December 1995, records of 1084 breast cancer patients at our institution were analyzed for incidence of CBC. In all the patients a detailed analysis was carried out with respect to age, disease stage, radiation therapy technique, dose, the use of chemotherapy or hormone therapy, and other clinical and/or pathologic characteristics. The Kaplan-Meier method was used to estimate the acturial rate of CBC. The Cox proportional hazard regression model was used to estimate the relative risk (RR) of CBC. Results: Up to December 2005, the median follow up was 12 years. Overall incidence of CBC was 4%. The 10 and 20 year acturial rate of CBC was 5.6% and 11.3%, respectively. The CBC rate at 10 and 20 year was 5.4% and 10.2%, respectively, for patients with mastectomy only and 5.1% and 9.7%, respectively, in the mastectomy plus RT group (p = 0.3). In the subset of patients <45 years of age at the time of treatment, 10 and 20 year acturial rate of CBC was 5% and 9%, respectively, for patients who underwent mastectomy only and 6.3% and 11%, respectively, for patients treated with mastectomy plus RT (RR = 1.4, 95% CI: 1.14-1.45, p = 0.003). There was statistically significant lower rate of CBC in patients given adjuvant hormonal therapy (8.5%) as compared to those without hormonal therapy (14.3%, p = 0.004) at 20 year. Women with family history of breast cancer had highest rate (15.3%) of CBC (RR = 1.6, 95% CI: 1.12-1.27) at 20 years. The adjuvant use of chemotherapy did not significantly affect the risk of second malignancy. Conclusion: There seems to be little risk of second malignancies in patients treated with mastectomy plus RT using modern techniques, compared with mastectomy only, that was only prevalent in patients <45 years of age. Family history of breast cancer seems to be the highest

Mammary Ductal Environment Is Necessary for Faithful Maintenance of Estrogen Signaling in ER⁺ Breast Cancer.

Science.gov (United States)

Haricharan, Svasti; Lei, Jonathan; Ellis, Matthew

2016-03-14

In this issue of Cancer Cell, Sflomos et al. (2016) describe a robust preclinical animal model of ER⁺ breast cancer. The authors identify the critical role of the breast microenvironment in determining hormone response of ER⁺ breast cancer cells and in driving the luminal phenotype of breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Breast and gastrointestinal cancer updates from ASCO 2015.

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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.

Targeting the NFκB signaling pathways for breast cancer prevention and therapy.

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Wang, Wei; Nag, Subhasree A; Zhang, Ruiwen

2015-01-01

The activation of nuclear factor-kappaB (NFκB), a proinflammatory transcription factor, is a commonly observed phenomenon in breast cancer. It facilitates the development of a hormone-independent, invasive, high-grade, and late-stage tumor phenotype. Moreover, the commonly used cancer chemotherapy and radiotherapy approaches activate NFκB, leading to the development of invasive breast cancers that show resistance to chemotherapy, radiotherapy, and endocrine therapy. Inhibition of NFκB results in an increase in the sensitivity of cancer cells to the apoptotic effects of chemotherapeutic agents and radiation and restoring hormone sensitivity, which is correlated with increased disease-free survival in patients with breast cancer. In this review article, we focus on the role of the NFκB signaling pathways in the development and progression of breast cancer and the validity of NFκB as a potential target for breast cancer prevention and therapy. We also discuss the recent findings that NFκB may have tumor suppressing activity in certain cancer types. Finally, this review also covers the state-of-the-art development of NFκB inhibitors for cancer therapy and prevention, the challenges in targeting validation, and pharmacology and toxicology evaluations of these agents from the bench to the bedside.

The mammographic correlations of a new immunohistochemical classification of invasive breast cancer

Energy Technology Data Exchange (ETDEWEB)

Taneja, S. [Nottingham Breast Institute, City Hospital, Hucknall Road, Nottingham NG5 1PB (United Kingdom)], E-mail: sheeba_taneja@yahoo.co.uk; Evans, A.J. [Nottingham Breast Institute, City Hospital, Hucknall Road, Nottingham NG5 1PB (United Kingdom); Rakha, E.A.; Green, A.R. [Division of Pathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham (United Kingdom); Ball, G. [Nottingham Trent University, School of Biomedical and Natural Sciences, Nottingham (United Kingdom); Ellis, I.O. [Division of Pathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham (United Kingdom)

2008-11-15

Aim: Recent protein expression profiling of breast cancer has identified specific subtypes with clinical, biological, and therapeutic implications. The aim of this study was to identify the mammographic correlates of these novel molecular classes of invasive breast cancer. Materials and methods: The mammographic findings of 415 patients with operable breast cancer were correlated with the previously described protein expression classes identified by our group using immunohistochemical (IHC) assessment of a large series of breast cancer cases prepared as tissue microarrays (TMAs). Twenty-five proteins of known relevance in breast cancer were assessed, including hormone receptors, HER-2 status, basal and luminal markers, p53 expression, and E-cadherin. Results: The mammographic background pattern and proportion of lesions that were mammographically occult were similar in all groups. Groups characterized by luminal and hormone receptor positivity had significantly more spiculate lesions at mammography. Groups characterized by HER-2 overexpression, basal characteristics, and E-cadherin positivity had a significantly higher proportion of ill-defined masses. These findings were independent of histological grade. Conclusion: The mammographic features of breast cancer show significant correlation with molecular classes of invasive breast cancer identified by protein expression IHC analysis. The biological reasons for the findings and implications of these regarding imaging protocols require further study and may provide mechanisms for improvement of detection of these lesions.

Hormonal regulation of epithelial organization in a three-dimensional breast tissue culture model.

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Speroni, Lucia; Whitt, Gregory S; Xylas, Joanna; Quinn, Kyle P; Jondeau-Cabaton, Adeline; Barnes, Clifford; Georgakoudi, Irene; Sonnenschein, Carlos; Soto, Ana M

2014-01-01

The establishment of hormone target breast cells in the 1970's resulted in suitable models for the study of hormone control of cell proliferation and gene expression using two-dimensional (2D) cultures. However, to study mammogenesis and breast tumor development in vitro, cells must be able to organize in three-dimensional (3D) structures like in the tissue. We now report the development of a hormone-sensitive 3D culture model for the study of mammogenesis and neoplastic development. Hormone-sensitive T47D breast cancer cells respond to estradiol in a dose-dependent manner by forming complex epithelial structures. Treatment with the synthetic progestagen promegestone, in the presence of estradiol, results in flat epithelial structures that display cytoplasmic projections, a phenomenon reported to precede side-branching. Additionally, as in the mammary gland, treatment with prolactin in the presence of estradiol induces budding structures. These changes in epithelial organization are accompanied by collagen remodeling. Collagen is the major acellular component of the breast stroma and an important player in tumor development and progression. Quantitative analysis of second harmonic generation of collagen fibers revealed that collagen density was more variable surrounding budding and irregularly shaped structures when compared to more regular structures; suggesting that fiber organization in the former is more anisotropic than in the latter. In sum, this new 3D model recapitulates morphogenetic events modulated by mammogenic hormones in the breast, and is suitable for the evaluation of therapeutic agents.

Hormone replacement therapy dependent changes in breast cancer-related gene expression in breast tissue of healthy postmenopausal women.

Science.gov (United States)

Sieuwerts, Anieta M; De Napoli, Giuseppina; van Galen, Anne; Kloosterboer, Helenius J; de Weerd, Vanja; Zhang, Hong; Martens, John W M; Foekens, John A; De Geyter, Christian

2011-12-01

Risk assessment of future breast cancer risk through exposure to sex steroids currently relies on clinical scorings such as mammographic density. Knowledge about the gene expression patterns in existing breast cancer tumors may be used to identify risk factors in the breast tissue of women still free of cancer. The differential effects of estradiol, estradiol together with gestagens, or tibolone on breast cancer-related gene expression in normal breast tissue samples taken from postmenopausal women may be used to identify gene expression profiles associated with a higher breast cancer risk. Breast tissue samples were taken from 33 healthy postmenopausal women both before and after a six month treatment with either 2mg micronized estradiol [E2], 2mg micronized estradiol and 1mg norethisterone acetate [E2+NETA], 2.5mg tibolone [T] or [no HRT]. Except for [E2], which was only given to women after hysterectomy, the allocation to each of the three groups was randomized. The expression of 102 mRNAs and 46 microRNAs putatively involved in breast cancer was prospectively determined in the biopsies of 6 women receiving [no HRT], 5 women receiving [E2], 5 women receiving [E2+NETA], and 6 receiving [T]. Using epithelial and endothelial markers genes, non-representative biopsies from 11 women were eliminated. Treatment of postmenopausal women with [E2+NETA] resulted in the highest number of differentially (pbreast tissue with a change in the expression of genes putatively involved in breast cancer. Our data suggest that normal mammary cells triggered by [E2+NETA] adjust for steroidogenic up-regulation through down-regulation of the estrogen-receptor pathway. This feasibility study provides the basis for whole genome analyses to identify novel markers involved in increased breast cancer risk. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Hormonal therapy and risk of breast cancer in mexican women.

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Amina Amadou

Full Text Available The use of hormonal therapies, including hormonal contraceptives (HC and postmenopausal hormone replacement therapy (HRT have been shown to influence breast cancer (BC risk. However, the variations of these effects among populations and ethnic groups are not completely documented, especially among Hispanic women. We evaluated the association between HC and premenopausal BC risk, and between HRT and postmenopausal BC risk in Mexican women. Data from a Mexican multi-center population-based case-control study ofwomen aged 35 to 69 years were analysed. A total of 1000 cases and 1074 matched controls were recruited between 2004 and 2007. Information on hormonal therapy was collected through a structured questionnaire. Results were analysed using conditional logistic regression models. Overall, HC were used by 422/891 (47.3% premenopausal women and HRT was used by 220/1117 (19.7% postmenopausal women. For HC, odds ratios (ORs for BC were 1.11 (95% confidence interval (CI: 0.82, 1.49 for current users and 1.68 (95% CI: 0.67, 4.21 for ever-users. No clear effect of duration of use was observed. For HRT, the OR for BC was significantly increased in ever users (OR: 1.45; 95% CI: 1.01, 2.08. A non-significant increased risk was observed for combined estrogen/progestin, (OR =  1.85; 95% CI: 0.84, 4.07 whereas no effect was observed for the use of estrogen alone (OR = 1.14; 95% CI: 0.68, 1.91. Our results indicate that, HC had a non-significant effect on the risk of pre-menopausal BC, but suggested that injected contraceptives may slightly increase the risk, whereas HRT had a significant effect on post-menopausal BC in this population. This study provides new information about the effects of HC and HRT on BC risk in a Mexican population, which may be of relevance for the population of Latin America as a whole.

Does fasting during Ramadan trigger non-adherence to oral hormonal therapy in breast cancer patients?

International Nuclear Information System (INIS)

Zeeneldin, A.A.; Gaber, A.A.; Taha, F.M.

2012-01-01

Purpose: To estimate the effect of fasting during Ramadan (the ninth lunar month) on adherence to oral hormonal therapies (OHT) among breast cancer (BC) patients. Patients and Methods: During Ramadan 2010, 139 BC patients were interviewed at the Egyptian National Cancer Institute. They were asked about fasting as well as intake of OHT in Ramadan and in the preceding month. Results: The median age was 50 years and most patients were postmenopausal with good performance status and non-metastatic disease. The median number of fasting days was 18% and 93% of patients were fasting 80% or more of Ramadan. Tamoxifen and aromatase inhibitors were used in 64% and 36%, respectively. Adherence to OHT during Ramadan and its preceding month were 94.2% and 95.7%, respectively (p = 0.77). In univariate analysis, non-adherence prior to Ramadan and shorter duration of OHT were predictors of non-adherence during Ramadan (P < 0.001, 0.003, respectively). Fasting, age, performance status, presence of metastases and type of hormonal therapy were not good predictors of adherence. Conclusions: While most of patients receiving OHT for BC are fasting during Ramadan, this does not negatively impact compliance with treatment

The genesis of breast cancer is a two-step phenomenon. II. Dissociation of two biomarkers in cancer patients from a low risk area of Japan.

Science.gov (United States)

Kodama, M; Kodama, T; Murakami, M; Kobayashi, S; Akita, T; Nakamura, Y

1992-01-01

The association of dual steroidal disorders with breast cancer, as proposed on the basis of a case-control study in a high risk area of Japan, was tested for its validity in breast cancer patients from a low risk area of Japan. A state of glucocorticoid excess, the first hormonal trait of a breast cancer patient, was assessed using a urinary steroid parameter (a reduction of the androsterone to tetrahydrocortisol ratio by definition), and/or using a physical parameter (an elevation of the waist to hip circumference ratio by definition). Inclination to ovulation failure, the second hormonal trait, was tested using another urinary steroid parameter (a specified disorder of progestin metabolism by definition), and/or a demographic parameter (a reduction in the number of live births by definition). Results obtained are as follows: 1) premenopausal breast cancer patients from a low risk area were found to have the second trait but not the first trait, as tested using 2 parameters for each trait. 2) Postmenopausal cancer patients from a low risk area as well as pre- and post-menopausal cancer patients from a high risk area had both the 2 hormonal traits. 3) There was no discrepancy of results between any 2 test systems with the identification of 2 hormonal traits in 4 cancer patient groups. The significance of the dissociation of 2 hormonal traits, as observed in premenopausal cancer patients from a low risk area, is discussed in favor of the two-step carcinogenesis theory. Possible interaction of heredity and environment in the genesis of breast cancer is also taken into consideration.

Everolimus-associated acute kidney injury in patients with metastatic breast cancer

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A Chandra

2017-01-01

Full Text Available Recently, everolimus (Evl has been introduced in the management of hormone receptor-positive metastatic breast cancer, in combination with aromatase inhibitors. Evl-induced acute kidney injury has hitherto been described in other malignancies, especially renal cell cancer, but only once before in a patient with breast cancer. We describe two cases of Evl-associated nephrotoxicity in patients with breast cancer, one of whom underwent a renal biopsy showing acute tubular necrosis. Both our patients improved after withdrawal of the offending agent and have normal renal functions on follow-up.

Estrogens and women's health: interrelation of coronary heart disease, breast cancer and osteoporosis.

Science.gov (United States)

Kuller, L H; Matthews, K A; Meilahn, E N

2000-11-30

The determinants of blood levels of estrogen, estrogen metabolites, and relation to receptors and post-transitional effects are the likely primary cause of breast cancer. Very high risk women for breast cancer can now be identified by measuring bone mineral density and hormone levels. These high risk women have rates of breast cancer similar to risk of myocardial infarction. They are candidates for SERM therapies to reduce risk of breast cancer. The completion of the Women's Health Initiative and other such trials will likely provide a definite association of risk and benefit of both estrogen alone and estrogen-progesterone therapy, coronary heart disease, osteoporotic fracture, and breast cancer. The potential intervention of hormone replacement therapy, obesity, or weight gain and increased atherogenic lipoproteinemia may be of concern and confound the results of clinical trials. Estrogens, clearly, are important in the risk of bone loss and osteoporotic fracture. Obesity is the primary determinant of postmenopausal estrogen levels and reduced risk of fracture. Weight reduction may increase rates of bone loss and fracture. Clinical trials that evaluate weight loss should monitor effects on bone. The beneficial addition of increased physical activity, higher dose of calcium or vitamin D, or use of bone reabsorption drugs in coordination with weight loss should be evaluated. Any therapy that raises blood estrogen or metabolite activity and decreases bone loss may increase risk of breast cancer. Future clinical trials must evaluate multiple endpoints such as CHD, osteoporosis, and breast cancer within the study. The use of surrogate markers such as bone mineral density, coronary calcium, carotid intimal medial thickness and plaque, endothelial function, breast density, hormone levels and metabolites could enhance the evaluation of risk factors, genetic-environmental intervention, and new therapies.

Current state and controversies in fertility preservation in women with breast cancer.

Science.gov (United States)

Taylan, Enes; Oktay, Kutluk H

2017-06-10

On average, over 25000 women are diagnosed with breast cancer under the age of 45 annually in the United States. Because an increasing number of young women delay childbearing to later life for various reasons, a growing population of women experience breast cancer before completing childbearing. In this context, preservation of fertility potential of breast cancer survivors has become an essential concept in modern cancer care. In this review, we will outline the currently available fertility preservation options for women with breast cancer of reproductive age, discuss the controversy behind hormonal suppression for gonadal protection against chemotherapy and highlight the importance of timely referral by cancer care providers.

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

DEFF Research Database (Denmark)

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

2015-01-01

To determine whether CYP19A1 polymorphisms are associated with abnormal activity of aromatase and with musculoskeletal and bone side effects of aromatase inhibitors. DNA was isolated from tumor specimens of 4861 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1...

Role of endogenous hormones in premenopausal females with ...

African Journals Online (AJOL)

The objective of this study is to evaluate hormone levels in premenopausal females with breast cancer at the time of diagnosis and to predict their role as a risk factor of breast cancer in females. Circulating hormone levels were measured in 345 previously untreated premenopausal breast cancer patients during luteal ...

Polymorphic repeat in AIB1 does not alter breast cancer risk

International Nuclear Information System (INIS)

Haiman, Christopher A; Hankinson, Susan E; Spiegelman, Donna; Colditz, Graham A; Willett, Walter C; Speizer, Frank E; Brown, Myles; Hunter, David J

2000-01-01

We assessed the association between a glutamine repeat polymorphism in AIB1 and breast cancer risk in a case-control study (464 cases, 624 controls) nested within the Nurses' Health Study cohort. We observed no association between AIB1 genotype and breast cancer incidence, or specific tumor characteristics. These findings suggest that AIB1 repeat genotype does not influence postmenopausal breast cancer risk among Caucasian women in the general population. A causal association between endogenous and exogenous estrogens and breast cancer has been established. Steroid hormones regulate the expression of proteins that are involved in breast cell proliferation and development after binding to their respective steroid hormone receptors. Coactivator and corepressor proteins have recently been identified that interact with steroid hormone receptors and modulate transcriptional activation [1]. AIB1 (amplified in breast 1) is a member of the steroid receptor coactivator (SRC) family that interacts with estrogen receptor (ER)α in a ligand-dependent manner, and increases estrogen-dependent transcription [2]. Amplification and overexpression of AIB1 has been observed in breast and ovarian cancer cell lines and in breast tumors [2,3]. A polymorphic stretch of glutamine amino acids, with unknown biologic function, has recently been described in the carboxyl-terminal region of AIB1 [4]. Among women with germline BRCA1 mutations, significant positive associations were observed between AIB1 alleles with 26 or fewer glutamine repeats and breast cancer risk [5] To establish whether AIB1 repeat alleles are associated with breast cancer risk and specific tumor characteristics among Caucasian women. We evaluated associations prospectively between AIB1 alleles and breast cancer risk in the Nurses' Health Study using a nested case-control design. The Nurses' Health Study was initiated in 1976, when 121 700 US-registered nurses between the ages of 30 and 55 years returned an

Management of breast cancer following Hodgkin's disease

International Nuclear Information System (INIS)

Wolden, Suzanne L.; Carlson, Robert W.; Jeffrey, Stefanie S.; Hancock, Steven L.

1997-01-01

because of prior radiation. Two patients received a lumpectomy with breast irradiation. In one case, the breast irradiation overlapped the prior mantle field for a cumulative dose of 89.6 Gy. This patient suffered severe fat necrosis. Of 48 patients who had axillary dissections, 31% had involved nodes. One patient presented with bilateral disease and two others developed subsequent invasive cancers in the opposite breast. Three patients had prophylactic contralateral mastectomies. The patient with LCIS was followed after biopsy and Tamoxifen only. Adjuvant chemotherapy was given to 55% and hormonal therapy to 36% of women with invasive breast cancer. Adriamycin containing regimens were used infrequently due to concerns about prior cardiotoxic chemotherapy and radiation. Ten year, disease specific actuarial survival was 100% for patients with carcinoma in situ, 71% for those with stage I or II breast cancer, and 43% for stages III and IV. Two women died from third cancers (lung and bladder) and two from myocardial infarction (ages 45 and 60). Conclusion: The risk of breast cancer is increased in patients treated for Hodgkin's disease. Our data suggested that mammography may be underutilized, as most cases in this series were detected by the patient. Histology and tumor grade do not appear to differ from that expected in the general breast cancer population. Generally, breast cancer following Hodgkin's disease is most appropriately treated with mastectomy because of prior radiation. One of two patients in this series had an unacceptable complication following breast conserving therapy. Axillary node dissection is possible after mantle radiotherapy and as many as 31% of patients may have involved nodes. Prophylactic contralateral mastectomy is not recommended because the incidence of bilateral breast cancer is relatively low. Adjuvant chemotherapy and hormonal therapy should be used according to general guidelines, but adriamycin is relatively contraindicated in patients

Breast Cancer Vaccines: New Insights

OpenAIRE

Benedetti, Rosaria; Dell’Aversana, Carmela; Giorgio, Cristina; Astorri, Roberta; Altucci, Lucia

2017-01-01

Breast cancer (BC) is a persistent global challenge for its high frequency in women (although it seldom occurs in men), due to the large diffusion of risk factors and gene mutations, and for its peculiar biology and microenvironment. To date, BC can benefit from different therapeutic strategies involving surgery, ablation, chemotherapy, radiotherapy, and more specific approaches such as hormone therapy and the administration of various substances impairing cancer growth, aggressivity, and rec...

Phytotherapy and Nutritional Supplements on Breast Cancer

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C. M. Lopes

2017-01-01

Full Text Available Breast cancer is the most frequent type of nonskin malignancy among women worldwide. In general, conventional cancer treatment options (i.e., surgery, radiotherapy, chemotherapy, biological therapy, and hormone therapy are not completely effective. Recurrence and other pathologic situations are still an issue in breast cancer patients due to side effects, toxicity of drugs in normal cells, and aggressive behaviour of the tumours. From this point of view, breast cancer therapy and adjuvant methods represent a promising and challenging field for researchers. In the last few years, the use of some types of complementary medicines by women with a history of breast cancer has significantly increased such as phytotherapeutic products and nutritional supplements. Despite this, the use of such approaches in oncologic processes may be problematic and patient’s health risks can arise such as interference with the efficacy of standard cancer treatment. The present review gives an overview of the most usual phytotherapeutic products and nutritional supplements with application in breast cancer patients as adjuvant approach. Regardless of the contradictory results of scientific evidence, we demonstrated the need to perform additional investigation, mainly well-designed clinical trials in order to establish correlations and allow for further validated outcomes concerning the efficacy, safety, and clinical evidence-based recommendation of these products.

Endocrinology and hormone therapy in breast cancer: Endocrine therapy in premenopausal women

International Nuclear Information System (INIS)

Pritchard, Kathleen

2005-01-01

Endocrine therapy remains important in premenopausal women with hormone receptor positive breast cancer. Ovarian ablation, used alone, is effective in delaying recurrence and increasing survival in such women. When added to chemotherapy, it is less clear that it is effective perhaps because of the endocrine ablative effect of chemotherapy. Trials comparing ovarian ablation with or without tamoxifen to CMF-type chemotherapy suggest that the endocrine therapy is equivalent to or better than this chemotherapy in women whose tumors have estrogen and/or progesterone receptor. Tamoxifen is also effective in preventing recurrence and prolonging survival in the adjuvant setting in premenopausal women. While most of the available data deals with tamoxifen given alone, it appears to have a similar beneficial effect when added to chemotherapy in the premenopausal adjuvant setting. Adjuvant aromatase inhibitors should not be used in premenopausal women

Light deficiency confers breast cancer risk by endocrine disorders.

Science.gov (United States)

Suba, Zsuzsanna

2012-09-01

North-America and northern European countries exhibit the highest incidence rate of breast cancer, whereas women in southern regions are relatively protected. Immigrants from low cancer incidence regions to high-incidence areas might exhibit similarly higher or excessive cancer risk as compared with the inhabitants of their adoptive country. Additional cancer risk may be conferred by incongruence between their biological characteristics and foreign environment. Many studies established the racial/ethnic disparities in the risk and nature of female breast cancer in United States between African-American and Caucasian women. Mammary tumors in black women are diagnosed at earlier age, and are associated with higher rate of mortality as compared with cancers of white cases. Results of studies on these ethnic/racial differences in breast cancer incidence suggest that excessive pigmentation of dark skinned women results in a relative light-deficiency. Poor light exposure may explain the deleterious metabolic and hormonal alterations; such as insulin resistance, deficiencies of estrogen, thyroxin and vitamin-D conferring excessive cancer risk. The more northern the location of an adoptive country the higher the cancer risk for dark skinned immigrants. Recognition of the deleterious systemic effects of darkness and excessive melatonin synthesis enables cancer protection treatment for people living in light-deficient environment. Recent patents provide new methods for the prevention of hormonal and metabolic abnormities.

Associations between breast cancer risk factors and religious practices in Utah.

Science.gov (United States)

Daniels, Melissa; Merrill, Ray M; Lyon, Joseph L; Stanford, Joseph B; White, George L

2004-01-01

Utah has the lowest female malignant breast cancer incidence rates in the United States, due in part to low rates among women who are members of the Church of Jesus Christ of Latter-day Saints (LDS or Mormon). Several established reproductive and non-reproductive breast cancer risk factors may be lower among LDS women because of their religious doctrine related to marriage, family, and health. This paper investigates the association between selected breast cancer risk factors and religious preference and religiosity in Utah. A 37-item anonymous cross-sectional telephone survey was developed and conducted during March and April 2002. Results are based on 848 non-Hispanic white female respondents. Number of births (parity), prevalence of breastfeeding, and lifetime total duration of breastfeeding were highest among LDS women who attended church weekly. Average months of breastfeeding per child were greatest among weekly church attendees, regardless of religious preference. Oral contraceptive use and total duration of hormone replacement therapy use were greatest for individuals of any religion attending church less than weekly and for individuals with no religious preference. Comparisons of divergent reproductive behaviors between LDS and non-LDS, and between weekly and less than weekly church goers, provide strong support for the relatively low breast cancer incidence rates previously identified among LDS and, therefore, in Utah. High parity and breastfeeding coincide with comparatively low breast cancer incidence rates among LDS and are consistent with recent findings of the Collaborative Group on Hormonal Factors in Breast Cancer, showing the primary role parity and breastfeeding play in reducing breast cancer.

A Comprehensive Nuclear Receptor Network for Breast Cancer Cells

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Ralf Kittler

2013-02-01

Full Text Available In breast cancer, nuclear receptors (NRs play a prominent role in governing gene expression, have prognostic utility, and are therapeutic targets. We built a regulatory map for 24 NRs, six chromatin state markers, and 14 breast-cancer-associated transcription factors (TFs that are expressed in the breast cancer cell line MCF-7. The resulting network reveals a highly interconnected regulatory matrix where extensive crosstalk occurs among NRs and other breast -cancer-associated TFs. We show that large numbers of factors are coordinately bound to highly occupied target regions throughout the genome, and these regions are associated with active chromatin state and hormone-responsive gene expression. This network also provides a framework for stratifying and predicting patient outcomes, and we use it to show that the peroxisome proliferator-activated receptor delta binds to a set of genes also regulated by the retinoic acid receptors and whose expression is associated with poor prognosis in breast cancer.

The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

International Nuclear Information System (INIS)

Osin, Pinchas P; Lakhani, Sunil R

1999-01-01

Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried out in the few years since the identification of these familial breast cancer predisposing genes. The morphological studies suggest that BRCA1 tumours differ from BRCA2 tumours and from sporadic breast cancers. Recent progress in immunohistochemistry and molecular biology techniques has enabled in-depth investigation of molecular pathology of these tumours. Studies to date have investigated issues such as steroid hormone receptor expression, mutation status of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell cycle proteins p21, p27 and cyclin D 1 . Despite relative paucity of data, strong evidence of unique biological characteristics of BRCA1-associated breast cancer is accumulating. BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors. Further studies of larger number of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify and confirm these observations

PAM50 Risk of Recurrence Score Predicts 10-Year Distant Recurrence in a Comprehensive Danish Cohort of Postmenopausal Women Allocated to 5 Years of Endocrine Therapy for Hormone Receptor–Positive Early Breast Cancer

DEFF Research Database (Denmark)

Lænkholm, Anne Vibeke; Jensen, M.B.; Eriksen, J O

2018-01-01

with hormone receptor-positive early breast cancer treated with 5 years of endocrine therapy alone. Patients and Methods Using the population-based Danish Breast Cancer Cooperative Group database, follow-up data were collected on all patients diagnosed from 2000 through 2003 who, by nationwide guidelines, were...... treated with endocrine therapy for 5 years. Primary tumor blocks from 2,740 patients were tested with Prosigna and, after determination of human epidermal growth factor receptor 2 (HER2) status, data from 2,558 hormone receptor-positive/HER2-negative samples were analyzed, including 1,395 node...

Cycling Towards Progress: Ribociclib, CDK 4/6 inhibitor for Breast Cancer.

Science.gov (United States)

Spring, Laura; Bardia, Aditya

2018-04-23

Ribociclib is an orally active, highly selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6. It is the second CDK 4/6 inhibitor approved for hormone receptor-positive breast cancer. The addition of ribociclib to an aromatase inhibitor has resulted in marked improvements in progression-free survival for patients with metastatic breast cancer. Copyright ©2018, American Association for Cancer Research.

Radiation as a cause of breast cancer

International Nuclear Information System (INIS)

Simon, N.; Silverstone, S.M.

1976-01-01

The possible role of radiation as a factor in the causation of breast cancer was investigated. Some variables said to be associated with a high risk of breast cancer include genetic factors, pre-existing breast disease, artificial menopause, family history of breast cancer, failure to breast feed, older than usual age at time of first pregnancy, high socioeconomic status, specific blood groups, fatty diet, obesity, and hormonal imbalances. To this list we must add ionizing radiation as an additional and serious risk factor in the causation of breast cancer. Among the irradiated groups which have an increase in the incidence of cancer of the breast are: tuberculous women subjected to repeated fluoroscopy; women who received localized x-ray treatments for acute post-partum mastitis; atom-bomb survivors; other x-ray exposures involving the breast, including irradiation in children and in experimental animals; and women who were treated with x rays for acne or hirsuitism. The dose of radiation received by the survivors of the atom bomb who subsequently developed cancer of the breast ranged from 80 to 800 rads, the tuberculous women who were fluoroscoped received an estimated 50 to 6,000 rads, the women who were treated for mastitis probably were exposed to 30 to 700 rads, and the patients with acne received 100 to 6,000 rads. These imprecise estimates are compared with mammographic doses in the range of 10s of rads to the breast at each examination, an imprecise estimate depending on technique and equipment. However imprecise these estimates may be, it is apparent that younger women are more likely than older women to develop cancer from exposure to radiation. It is pointed out that the American Cancer Society advises that women under 35 years should have mammography only for medical indication, not for so-called screening

Modifiable risk factors and survival in women diagnosed with primary breast cancer

DEFF Research Database (Denmark)

Hellmann, Sophie Sell; Thygesen, Lau Caspar; Tolstrup, Janne Schurmann

2010-01-01

This study examines the impact of smoking, body mass index, alcohol consumption, hormone replacement therapy, and physical activity on all-cause mortality among 528 Danish women diagnosed with primary breast cancer. Participants were women enrolled in the Copenhagen City Heart Study. Prospective...... intake, smoking, physical activity, body mass index, and hormone replacement therapy. The study shows that smoking for total mortality [hazard ratio, 1.16; 95% confidence interval, 1.05-1.29] and obesity for both total mortality (1.61; 1.12-2.33) and breast cancer-specific mortality (1.82; 1...

Night Shift Work and Risk of Breast Cancer.

Science.gov (United States)

Hansen, Johnni

2017-09-01

Night work is increasingly common and a necessity in certain sectors of the modern 24-h society. The embedded exposure to light-at-night, which suppresses the nocturnal hormone melatonin with oncostatic properties and circadian disruption, i.e., misalignment between internal and external night and between cells and organs, are suggested as main mechanisms involved in carcinogenesis. In 2007, the International Agency for Research on Cancer (IARC) classified shift work that involves circadian disruption as probably carcinogenic to humans based on limited evidence from eight epidemiologic studies on breast cancer, in addition to sufficient evidence from animal experiments. The aim of this review is a critical update of the IARC evaluation, including subsequent and the most recent epidemiologic evidence on breast cancer risk after night work. After 2007, in total nine new case-control studies, one case-cohort study, and eight cohort studies are published, which triples the number of studies. Further, two previous cohorts have been updated with extended follow-up. The assessment of night shift work is different in all of the 26 existing studies. There is some evidence that high number of consecutive night shifts has impact on the extent of circadian disruption, and thereby increased breast cancer risk, but this information is missing in almost all cohort studies. This in combination with short-term follow-up of aging cohorts may explain why some cohort studies may have null findings. The more recent case-control studies have contributed interesting results concerning breast cancer subtypes in relation to both menopausal status and different hormonal subtypes. The large differences in definitions of both exposure and outcome may contribute to the observed heterogeneity of results from studies of night work and breast cancer, which overall points in the direction of an increased breast cancer risk, in particular after over 20 years of night shifts. Overall, there is a

The Breast-Thyroid Cancer Link: A Systematic Review and Meta-Analysis

Science.gov (United States)

Nielsen, Sarah M.; White, Michael G.; Hong, Susan; Aschebrook-Kilfoy, Briseis; Kaplan, Edwin L.; Angelos, Peter; Kulkarni, Swati A.; Olopade, Olufunmilayo I.; Grogan, Raymon H.

2015-01-01

Rates of thyroid cancer in women with a history of breast cancer are higher than expected. Similarly, rates of breast cancer in those with a history of thyroid cancer are increased. Explanations for these associations include detection bias, shared hormonal risk factors, treatment effect, and genetic susceptibility. With increasing numbers of breast and thyroid cancer survivors clinicians should be particularly cognizant of this association. Here we perform a systematic review and meta-analysis of the literature utilizing PubMed and Scopus search engines to identify all publications studying the incidence of breast cancer as a secondary malignancy following a diagnosis of thyroid cancer or thyroid cancer following a diagnosis of breast cancer. This demonstrated an increased risk of thyroid cancer as a secondary malignancy following breast cancer (OR=1.55, 95% CI [1.44,1.67]) and an increased risk of breast cancer as a secondary malignancy following thyroid cancer (OR= 1.32, 95% CI [1.23,1.42]). There is a clear increase in the odds of developing either thyroid or breast cancer as a secondary malignancy after diagnosis with the other. Here we review this association and current hypothesis as to the cause of this correlation. PMID:26908594

Perinatal factors and breast cancer risk among Hispanics

Directory of Open Access Journals (Sweden)

Maureen Sanderson

2013-06-01

Conclusions: The results tended to differ slightly from previous studies of this topic perhaps owing to the different hormonal milieu among Hispanics relative to Caucasians, African Americans and Asians in whom all previous studies of this topic have been conducted. Confirmation of these findings in larger studies may assist in determining how hormonal mechanisms responsible for breast cancer differ by ethnicity.

Understanding breast cancer - The long and winding road.

Science.gov (United States)

Lukong, Kiven Erique

2017-06-01

Despite a remarkable increase in the depth of our understanding and management of breast cancer in the past 50 years, the disease is still a major public health problem worldwide and poses significant challenges. The palpability of breast tumors has facilitated diagnosis and documentation since ancient times. The earliest descriptions of breast cancer date back to around 3500 BCE. For centuries to follow, theories by Hippocrates (460 BCE) and Galen (200 CE), attributing the cause of breast cancer to an "excess of black bile" and treatment options including the use of opium and castor oil, prevailed. Surgical resection was introduced in the 18th century. The advent of modern medicine led to the development of novel treatment options that include hormonal, targeted and chemo-therapies. There are still several therapeutic challenges including the treatment of triple negative breast cancer (TNBC), and overcoming drug resistance. The increased incidence and awareness of breast cancer has led to significant changes in diagnosis and treatment in recent decades. But, mankind has come a long way. Herein, I have traced how our understanding of breast cancer has evolved from the early description of the disease around 460 BCE as "black bile-containing crab-like tumors" to the conventional as a heterogeneous disease with high degree of diversity between and within tumors, as well as among breast cancer patients. How is breast cancer treated today and how do risk factors, breast cancer subtype and drug resistance contribute to the therapeutic challenges at the turn of the 21st century? Breast cancer remains a serious public health issue worldwide. However, appreciable growth in our understanding of breast cancer in the past century has led to remarkable progress in the early detection, treatment and prevention of the disease. The clinical focus is shifting more towards tailored therapy as more targets are characterized and novel highly innovative approaches are developed

FDG-PET in monitoring therapy of breast cancer

Energy Technology Data Exchange (ETDEWEB)

Biersack, H J; Bender, H; Palmedo, H [Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn (Germany)

2004-06-01

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been used successfully for the staging and re-staging of breast cancer. Another significant indication is the evaluation of therapy response. Only limited data are available on the use of FDG-PET in breast cancer after radiation therapy. The same holds true for chemotherapy. Only the therapy response in locally advanced breast cancer after chemotherapy has been investigated thoroughly. Histopathological response could be predicted with an accuracy of 88-91% after the first and second courses of therapy. A quantitative evaluation is, of course, a prerequisite when FDG-PET is used for therapy monitoring. Only a small number of studies have focussed on hormone therapy. In this context, a flare phenomenon with increasing standardised uptake values after initiation of tamoxifen therapy has been observed. More prospective multicentre trials will be needed to make FDG-PET a powerful tool in monitoring chemotherapy in breast cancer. (orig.)

FDG-PET in monitoring therapy of breast cancer

International Nuclear Information System (INIS)

Biersack, H.J.; Bender, H.; Palmedo, H.

2004-01-01

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been used successfully for the staging and re-staging of breast cancer. Another significant indication is the evaluation of therapy response. Only limited data are available on the use of FDG-PET in breast cancer after radiation therapy. The same holds true for chemotherapy. Only the therapy response in locally advanced breast cancer after chemotherapy has been investigated thoroughly. Histopathological response could be predicted with an accuracy of 88-91% after the first and second courses of therapy. A quantitative evaluation is, of course, a prerequisite when FDG-PET is used for therapy monitoring. Only a small number of studies have focussed on hormone therapy. In this context, a flare phenomenon with increasing standardised uptake values after initiation of tamoxifen therapy has been observed. More prospective multicentre trials will be needed to make FDG-PET a powerful tool in monitoring chemotherapy in breast cancer. (orig.)

Receptor conversion in distant breast cancer metastases

NARCIS (Netherlands)

Hoefnagel, L.D.C.

2013-01-01

The routine pathological work-up of breast cancer includes the evaluation of the estrogen receptor (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) which reveals biological information about the tumour as well as provides predictive biomarkers regarding hormonal

Estrogens in breast cancer

International Nuclear Information System (INIS)

Terzieff, V.; Vázquez, A.

2004-01-01

The prolonged exposure to estrogen increases the risk of cancer breast, the precise role of estrogen in the carcinogenesis process is unclear. They are capable of inducing cell proliferation through different channels receptor Estrogen (ER) known, for example through MAPkinasa sensitivity the promoter of proliferation effect depends on the level of RE, or type to â, integrity (mutations may alter its function) and ligand. The different types of estrogens and related compounds have different profile of affinity for RE and effect end. The modulatory role of progestogens proliferation is very complex, and the interaction between the effector pathways of progestin’s, estrogens, EGF and IGF family - maybe others - determines the final effect .. Estrogens are mutagenic per se weak, but is now known for its hepatic metabolism occur highly reactive species such as quinones, and catechol, powerful mutagens in vitro. Direct or indirect genotoxicity probably explains Part of the effects of estrogen on tumor cells. The use of hormone replacement (HTR) increases the risk of CM, as proportional to the time of use. The combination with progestin seems to be increased risk (R R 2). It is unclear the role of phyto estrogens in the prevention the CM. In the male breast is known that the proliferative response to parenchymal different hormonal maneuvers is different. The effect is minimal castration are and maximum with the combination of estrogen and progesterone. It is unclear, however, the risk of the population exposed to hormone therapy for cancer prostate or otherwise

Novel Approaches to Breast Cancer Prevention and Inhibition of Metastases

Science.gov (United States)

2016-10-01

Using mouse genetics, we showed that RANKL and its receptor RANK are critical regulators of sex hormone and BRCA1 mutation-driven breast cancer...into breast cancer patients and controls due to self reporting and histological examination. We have tested differences in RANKL, OPG and RANKL/OPG...cohort, we determined RANKL and OPG serum levels of participants from the Bruneck study [28, 29], that allowed us to analyse matched patient samples

Effects of omega-3 fatty acids on progestin stimulation of invasive properties in breast cancer.

Science.gov (United States)

Moore, Michael R; King, Rebecca A

2012-12-01

Clinical studies have shown that progestins increase breast cancer risk in hormone replacement therapy, while we and others have previously reported that progestins stimulate invasive properties in progesterone receptor (PR)-rich human breast cancer cell lines. Based on others' reports that omega-3 fatty acids inhibit metastatic properties of breast cancer, we have reviewed the literature for possible connections between omega-3 fatty-acid-driven pathways and progestin-stimulated pathways in an attempt to suggest theoretical mechanisms for possible omega-3 fatty acid inhibition of progestin stimulation of breast cancer invasion. We also present some data suggesting that fatty acids regulate progestin stimulation of invasive properties in PR-rich T47D human breast cancer cells, and that an appropriate concentration of the omega-3 fatty acid eicosapentaenoic acid inhibits progestin stimulation of invasive properties. It is hoped that focus on the inter-relationship between pathways by which omega-3 fatty acids inhibit and progestins stimulate breast cancer invasive properties will lead to further in vitro, in vivo, and clinical studies testing the hypothesis that omega-3 fatty acids can inhibit progestin stimulation of invasive properties in breast cancer, and ameliorate harmful effects of progestins which occur in combined progestin-estrogen hormone replacement therapy.

Adaptive Randomization of Neratinib in Early Breast Cancer.

Science.gov (United States)

Park, John W; Liu, Minetta C; Yee, Douglas; Yau, Christina; van 't Veer, Laura J; Symmans, W Fraser; Paoloni, Melissa; Perlmutter, Jane; Hylton, Nola M; Hogarth, Michael; DeMichele, Angela; Buxton, Meredith B; Chien, A Jo; Wallace, Anne M; Boughey, Judy C; Haddad, Tufia C; Chui, Stephen Y; Kemmer, Kathleen A; Kaplan, Henry G; Isaacs, Claudine; Nanda, Rita; Tripathy, Debasish; Albain, Kathy S; Edmiston, Kirsten K; Elias, Anthony D; Northfelt, Donald W; Pusztai, Lajos; Moulder, Stacy L; Lang, Julie E; Viscusi, Rebecca K; Euhus, David M; Haley, Barbara B; Khan, Qamar J; Wood, William C; Melisko, Michelle; Schwab, Richard; Helsten, Teresa; Lyandres, Julia; Davis, Sarah E; Hirst, Gillian L; Sanil, Ashish; Esserman, Laura J; Berry, Donald A

2016-07-07

The heterogeneity of breast cancer makes identifying effective therapies challenging. The I-SPY 2 trial, a multicenter, adaptive phase 2 trial of neoadjuvant therapy for high-risk clinical stage II or III breast cancer, evaluated multiple new agents added to standard chemotherapy to assess the effects on rates of pathological complete response (i.e., absence of residual cancer in the breast or lymph nodes at the time of surgery). We used adaptive randomization to compare standard neoadjuvant chemotherapy plus the tyrosine kinase inhibitor neratinib with control. Eligible women were categorized according to eight biomarker subtypes on the basis of human epidermal growth factor receptor 2 (HER2) status, hormone-receptor status, and risk according to a 70-gene profile. Neratinib was evaluated against control with regard to 10 biomarker signatures (prospectively defined combinations of subtypes). The primary end point was pathological complete response. Volume changes on serial magnetic resonance imaging were used to assess the likelihood of such a response in each patient. Adaptive assignment to experimental groups within each disease subtype was based on Bayesian probabilities of the superiority of the treatment over control. Enrollment in the experimental group was stopped when the 85% Bayesian predictive probability of success in a confirmatory phase 3 trial of neoadjuvant therapy reached a prespecified threshold for any biomarker signature ("graduation"). Enrollment was stopped for futility if the probability fell to below 10% for every biomarker signature. Neratinib reached the prespecified efficacy threshold with regard to the HER2-positive, hormone-receptor-negative signature. Among patients with HER2-positive, hormone-receptor-negative cancer, the mean estimated rate of pathological complete response was 56% (95% Bayesian probability interval [PI], 37 to 73%) among 115 patients in the neratinib group, as compared with 33% among 78 controls (95% PI, 11 to 54

Breast cancer and menopause: perceptions of diagnosis, menopausal therapies and health behaviors.

Science.gov (United States)

Sayakhot, P; Vincent, A; Teede, H

2012-02-01

The aim of this study was to investigate the perception and experience of menopause diagnosis and therapies, the information provided and health behaviors in younger women with breast cancer. The questionnaire study was completed by 114 women, aged 40-51 years, with non-metastatic breast cancer. Women were recruited from outpatient clinics and the community. Descriptive statistics were completed. Most women were satisfied with the manner in which they were informed of the breast cancer (69%) and the menopause (59%) diagnoses. Although 80% of women were given breast cancer information, only 54% were given menopause information at diagnosis. Women were least satisfied (26%) with information regarding the long-term complications of menopause. Women perceived exercise (68%) and improving lifestyle (61%) as most effective in alleviating symptoms of menopause. The majority of women reported that they did not understand the risks/benefits of 'bioidentical' hormones (79%) and herbal therapies (78%), while 58% perceived hormone replacement therapies as associated with an increased risk of breast cancer. Most women reported weight gain (68%) and osteoporosis (67%) as the most common problems/fears regarding menopause. However, regarding health behaviors, only 56% reported having relevant tests including a blood sugar test or a bone density test. While information needs regarding breast cancer appear well met in younger women, unmet information needs regarding menopause after breast cancer persist. Further education and support are required for these women to optimize health screening and prevention behaviors and to ensure informed decision-making regarding menopause treatment options.

Nonbreast Second Malignancies After Treatment of Primary Breast Cancer

International Nuclear Information System (INIS)

Yadav, Budhi S.; Sharma, Suresh C.; Patel, Firuza D.; Ghoshal, Sushmita; Kapoor, Rakesh; Kumar, Rajinder

2009-01-01

Purpose: To determine the incidence and risk factors for nonbreast second malignancies (NBSMs) in women after treatment for primary breast cancer. Methods and Materials: Between January 1985 and December 1995, a total of 1,084 breast cancer patients were analyzed for NBSMs. Detailed analysis was carried out for age, family history, disease stage, radiation therapy, chemotherapy, hormone therapy, other clinical/pathologic characteristics, and site of NBSMs. The Cox proportional hazard regression model was used to estimate the relative risk of NBSMs. Results: Median follow-up was 12 years. In total, 33 cases of NBSMs were noted in 29 patients. The overall incidence of NBSM was 3%, and the median time for NBSMs was 7 years. The most common NBSMs were gynecologic (22 patients), gastrointestinal (4 patients), head and neck (3 patients), hematologic (2 patients), lung (1 patient), and thyroid (1 patient). The NBSMs rate at 12 years was 2.4% for both mastectomy and radiation therapy groups. In the subset of patients less than 45 years of age at the time of treatment, the NBSMs rate was 0.7% as compared with 4.6% in patients more than 45 years of age (p = 0.001). Statistically significant higher incidences of endometrial and ovarian cancer were seen in patients with hormonal therapy (5.2%) as compared with patients without hormonal therapy (1.8%, p = 0.002). Women with a family history of breast cancer had a higher incidence (6%) of endometrial and ovarian malignancy compared with women without such a history (2.1%, p = 0.003). Chemotherapy did not affect the risk of second malignancy. Conclusion: The most common NBSMs in this study were gynecologic. Family history of breast cancer was a high risk factor for NBSMs. No risk of NBSMs with radiotherapy was observed.

Bilateral Salpingo-Oophorectomy Versus GnRH Analogue in the Adjuvant Treatment of Premenopausal Breast Cancer Patients: Cost-Effectiveness Evaluation of Breast Cancer Outcome, Ovarian Cancer Prevention and Treatment.

Science.gov (United States)

Ferrandina, Gabriella; Amadio, Giulia; Marcellusi, Andrea; Azzolini, Elena; Puggina, Anna; Pastorino, Roberta; Ricciardi, Walter; Scambia, Giovanni

2017-11-01

BACKGROUND AND OBJECTIVE: There is no available evidence to recommend gonadotropin-releasing hormone (GnRH) analogue-based ovarian suppression versus bilateral salpingo-oophorectomy (BSO) in the adjuvant treatment of early breast cancer, since the two approaches are considered equivalent in terms of oncologic outcome. The role of surgical ovarian ablation has been revitalized based on the advances of minimally invasive surgery, and a better understanding of clinical and molecular basis of hereditary breast/ovarian cancer syndromes. The aim of this study is to analyze the cost-effectiveness of laparoscopic BSO and GnRH analogue administration in patients aged 40-49 years with hormone-sensitive breast cancer. A probabilistic decision tree model was developed to evaluate costs and outcomes of ovarian ablation through laparoscopic BSO, or ovarian suppression through monthly injections of GnRH analogue. Results were expressed as incremental costs per quality-adjusted life years (QALYs) gained. Laparoscopic BSO strategy was associated with a lower mean total cost per patient than GnRH treatment, and considering the difference in terms of QALYs, the incremental effectiveness did not demonstrate a notable difference between the two approaches. From the National Health Service perspective, and for a time horizon of 5 years, laparoscopic BSO was the dominant option compared to GnRH treatment; laparoscopic BSO was less expensive than GnRH, €2385 [95% confidence interval (CI) = 2044, 2753] vs €7093 (95% CI = 3409, 12,105), respectively, and more effective. Surgical ovarian ablation is more cost-effective than GnRH administration in the adjuvant treatment of hormone-sensitive breast cancer patients aged 40-49 years, and the advantage of preventing ovarian cancer through laparoscopic BSO should be considered.

Breast Tissue Composition and Immunophenotype and Its Relationship with Mammographic Density in Women at High Risk of Breast Cancer.

Directory of Open Access Journals (Sweden)

Jia-Min B Pang

Full Text Available To investigate the cellular and immunophenotypic basis of mammographic density in women at high risk of breast cancer.Mammograms and targeted breast biopsies were accrued from 24 women at high risk of breast cancer. Mammographic density was classified into Wolfe categories and ranked by increasing density. The histological composition and immunophenotypic profile were quantified from digitized haematoxylin and eosin-stained and immunohistochemically-stained (ERα, ERβ, PgR, HER2, Ki-67, and CD31 slides and correlated to mammographic density.Increasing mammographic density was significantly correlated with increased fibrous stroma proportion (rs (22 = 0.5226, p = 0.0088 and significantly inversely associated with adipose tissue proportion (rs (22 = -0.5409, p = 0.0064. Contrary to previous reports, stromal expression of ERα was common (19/20 cases, 95%. There was significantly higher stromal PgR expression in mammographically-dense breasts (p=0.026.The proportion of stroma and fat underlies mammographic density in women at high risk of breast cancer. Increased expression of PgR in the stroma of mammographically dense breasts and frequent and unexpected presence of stromal ERα expression raises the possibility that hormone receptor expression in breast stroma may have a role in mediating the effects of exogenous hormonal therapy on mammographic density.

Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone

International Nuclear Information System (INIS)

Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V.

1989-01-01

Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer and prostate cancer cell lines in vitro. Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides

Dietary flavonoid and lignan intake and breast cancer risk according to menopause and hormone receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study

DEFF Research Database (Denmark)

Zamora-Ros, Raul; Ferrari, Pietro; González, Carlos A.

2013-01-01

Evidence on the association between dietary flavonoids and lignans and breast cancer (BC) risk is inconclusive, with the possible exception of isoflavones in Asian countries. Therefore, we investigated prospectively dietary total and subclasses of flavonoid and lignan intake and BC risk according...... to menopause and hormonal receptor status in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 334,850 women, mostly aged between 35 and 70 years from ten European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid...

Tumor-suppressor activity of RRIG1 in breast cancer

International Nuclear Information System (INIS)

Zhang, Guihong; Brewster, Abenaa; Guan, Baoxiang; Fan, Zhen; Brown, Powel H; Xu, Xiao-Chun

2011-01-01

Retinoid receptor-induced gene-1 (RRIG1) is a novel gene that has been lost in several types of human cancers. The aim of this study was to determine whether RRIG1 plays a role in breast cancer, such as in the suppression of breast cancer cell growth and invasion. Immunohistochemistry was used to detect RRIG1 expression in breast tissue specimens. Gene transfection was used to restore or knock down RRIG1 expression in breast cancer cell lines for analysis of cell viability, colony formation, and migration/invasion potential. Reverse-transcription polymerase chain reaction and western blot assays were used to detect the changes in gene expression. The RhoA activation assay was used to assess RRIG1-induced inhibition of RhoA activity. The immunohistochemical data showed that RRIG1 expression was reduced in breast cancer tissues compared with normal and atypical hyperplastic breast tissues. RRIG1 expression was inversely correlated with lymph node metastasis of breast cancer but was not associated with the status of hormone receptors, such as estrogen receptor, progesterone receptor, or HER2. Furthermore, restoration of RRIG1 expression inhibited proliferation, colony formation, migration, and invasion of breast cancer cells. Expression of RRIG1 also reduced phosphorylated Erk1/2 and Akt levels; c-Jun, MMP9, and Akt expressions; and RhoA activity. In contrast, knockdown of RRIG1 expression promoted breast cancer cell proliferation, colony formation, migration, and invasion potential. The data from the current study indicated that RRIG1 expression was reduced or lost in breast cancer and that restoration of RRIG1 expression suppressed breast cancer cell growth and invasion capacity. Future studies will determine the underlying molecular mechanisms and define RRIG1 as a tumor-suppressor gene in breast cancer

Interrelationships of Prenatal and Postnatal Growth, Hormones, Diet, and Breast Cancer

National Research Council Canada - National Science Library

Sanderson, Maureen

2006-01-01

... activity would modify the effect of insulin resistance on breast cancer. Specific aims were: 1) to undergo intensive training in cancer biology, and nutritional, molecular and genetic epidemiology, 2...

Night shift work and prolactin as a breast cancer risk factor

Directory of Open Access Journals (Sweden)

Agnieszka Bukowska

2013-04-01

Full Text Available Prolactin - a hormone secreted in a circadian rhythm acts as a regulator of growth and development of the mammary glands. It has been observed that working at night increases breast cancer risk in women. Night shift work, probably carcinogenic to humans (Group 2A IARC, can disrupt a circadian rhythm, and thus potentially alter the rhythm of prolactin secretion. The aim of our work was to review epidemiological evidence on the association between prolactin and the risk of breast cancer and the influence of work at night on prolactin secretion. Search was done in the Medline database by keywords (shift work, work at night, risk of breast cancer and prolactin. The increased proliferation of breast cells activated by prolactin can promote the development of cancer. The results of the largest epidemiological prospective studies suggest the association between prolactin levels and the risk of breast cancer in women. So far, only seven studies have investigated the association between work at night and prolactin secretion. In three studies lower concentrations of prolactin have been observed in night shift workers. No relationship between the night shift work duration and prolactin level in women have been reported. Night shift work can modify the profile of prolactin secretion in night workers, probably decreasing the secretion of this hormone at night. It is therefore unlikely that prolactin plays an important role in the development of breast cancer in women working at night. This conclusion is based on the results of a few epidemiological studies. Med Pr 2013;64(2:245–257

Pregnancy hormone concentrations across ethnic groups: implications for later cancer risk.

Science.gov (United States)

Potischman, Nancy; Troisi, Rebecca; Thadhani, Ravi; Hoover, Robert N; Dodd, Kevin; Davis, William W; Sluss, Patrick M; Hsieh, Chung-Cheng; Ballard-Barbash, Rachel

2005-06-01

A variety of in utero factors have been associated with risk of adult cancers, particularly birth weight, toxemia, and gestational age. These factors are thought to reflect hormonal exposures during pregnancy. We hypothesized that the prenatal hormonal milieu may explain part of the variation in cancer rates across ethnic groups, for example, the higher incidence of breast cancer in the Caucasian compared with Hispanic women and the higher incidence of prostate and lower incidence of testicular cancers among African-Americans compared with Caucasians. We measured hormones in early pregnancy blood samples from three ethnic groups in a health care plan in Boston, MA. Mean levels of androstenedione, testosterone, estrone, and prolactin were significantly lower in Caucasian women compared with Hispanic women. Although not statistically significant, estradiol levels were lower in Caucasian compared with Hispanic or African-American women. Concentrations of androstenedione, testosterone, and progesterone were notably higher in African-American compared with Caucasian or Hispanic women. These data are consistent with hypotheses that in utero hormonal exposures may explain some of the ethnic group differences in cancer risk.

PPARgamma-PGC-1alpha activity is determinant of alcohol related breast cancer

DEFF Research Database (Denmark)

Koefoed Petersen, Rasmus; Benzon Larsen, Signe; Jensen, Ditte Marie

2012-01-01

Alcohol is a risk factor for postmenopausal breast cancer. One of several proposed mechanisms is that alcohol-related breast cancer is caused by increased sex hormone levels. PPARγ inhibits aromatase transcription in breast adipocytes. We reproduced previously found allele-specific effects...... of the wildtype Pro-allele of PPARG Pro12Ala in alcohol related breast cancer. In transiently transfected cells, transcriptional activation by PPARγ and the PPARγ-PGC-1α complex was inhibited by ethanol. PPARγ 12Ala-mediated transcription activation was not enhanced by PGC-1α, resulting in allele......-specific transcription activation by the PPARγ 12Pro-PGC-1α complex. Our results suggest that PPARγ and PGC-1α activity is an important determinant of alcohol related breast cancer....

The normal breast microenvironment of premenopausal women differentially influences the behavior of breast cancer cells in vitro and in vivo

Directory of Open Access Journals (Sweden)

Ginsburg Erika

2010-05-01

Full Text Available Abstract Background Breast cancer studies frequently focus on the role of the tumor microenvironment in the promotion of cancer; however, the influence of the normal breast microenvironment on cancer cells remains relatively unknown. To investigate the role of the normal breast microenvironment on breast cancer cell tumorigenicity, we examined whether extracellular matrix molecules (ECM derived from premenopausal African-American (AA or Caucasian-American (CAU breast tissue would affect the tumorigenicity of cancer cells in vitro and in vivo. We chose these two populations because of the well documented predisposition of AA women to develop aggressive, highly metastatic breast cancer compared to CAU women. Methods The effects of primary breast fibroblasts on tumorigenicity were analyzed via real-time PCR arrays and mouse xenograft models. Whole breast ECM was isolated, analyzed via zymography, and its effects on breast cancer cell aggressiveness were tested in vitro via soft agar and invasion assays, and in vivo via xenograft models. Breast ECM and hormone metabolites were analyzed via mass spectrometry. Results Mouse mammary glands humanized with premenopausal CAU fibroblasts and injected with primary breast cancer cells developed significantly larger tumors compared to AA humanized glands. Examination of 164 ECM molecules and cytokines from CAU-derived fibroblasts demonstrated a differentially regulated set of ECM proteins and increased cytokine expression. Whole breast ECM was isolated; invasion and soft agar assays demonstrated that estrogen receptor (ER-, progesterone receptor (PR/PR- cells were significantly more aggressive when in contact with AA ECM, as were ER+/PR+ cells with CAU ECM. Using zymography, protease activity was comparatively upregulated in CAU ECM. In xenograft models, CAU ECM significantly increased the tumorigenicity of ER+/PR+ cells and enhanced metastases. Mass spectrometry analysis of ECM proteins showed that only 1

Interaction between common breast cancer susceptibility variants, genetic ancestry, and nongenetic risk factors in Hispanic women.

Science.gov (United States)

Fejerman, Laura; Stern, Mariana C; John, Esther M; Torres-Mejía, Gabriela; Hines, Lisa M; Wolff, Roger K; Baumgartner, Kathy B; Giuliano, Anna R; Ziv, Elad; Pérez-Stable, Eliseo J; Slattery, Martha L

2015-11-01

Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population. We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions. We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74-1.20), 1.20 (0.94-1.53), and 1.49 (1.28-1.75) for current, former, and never hormone therapy users, respectively, Pinteraction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72-1.42), 1.19 (0.98-1.45), and 1.69 (1.26-2.26) for never, 12 months breastfeeding, respectively, Pinteraction 0.014]. The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women. These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and nongenetic risk factors and their contribution to breast cancer risk. ©2015 American Association for Cancer Research.

Pizza consumption and the risk of breast, ovarian and prostate cancer.

Science.gov (United States)

Gallus, Silvano; Talamini, Renato; Bosetti, Cristina; Negri, Eva; Montella, Maurizio; Franceschi, Silvia; Giacosa, Attilio; La Vecchia, Carlo

2006-02-01

Pizza has been favourably related to the risk of prostate cancer in North America. Scanty information, however, is available on sex hormone-related cancer sites. We therefore studied the role of pizza consumption on the risk of breast, ovarian and prostate cancers using data from three hospital-based case-control studies conducted in Italy between 1991 and 2002. These included 2569 women with breast cancer, 1031 with ovarian cancer, 1294 men with prostate cancer, and a total of 4864 controls. Compared with non-pizza eaters, the multivariate odds ratios for eaters were 0.97 (95% confidence interval (CI) 0.86-1.10) for breast, 1.06 (95% CI 0.89-1.26) for ovarian and 1.04 (95% CI 0.88-1.23) for prostate cancer. Corresponding estimates for regular eaters (i.e. > or =1 portion per week) were 0.92 (95% CI 0.78-1.08), 1.00 (95% CI 0.80-1.25) and 1.12 (95% CI 0.88-1.43), respectively. Our results do not show a relevant role of pizza on the risk of sex hormone-related cancers. The difference with selected studies from North America suggests that dietary and lifestyle correlates of pizza eating vary between different populations and social groups.

Characterization of hormonal receptors and human epidermal growth factor receptor-2 in tissues of women with breast cancer at Muhimbili National Hospital, Dar es salaam, Tanzania.

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Mwakigonja, Amos Rodger; Lushina, Nyanda Elias; Mwanga, Ally

2017-01-01

Breast cancer is a leading cause of morbidity and deaths among women worldwide. In Tanzania there is no published data on human epidermal growth receptor-2 (HER2/neu) expression in breast carcinoma. Hormonal receptors and HER2/neu status reportedly influence post-mastectomy adjuvant therapy and predict treatment outcome and prognosis. Here we evaluate hormonal receptors and HER-2 status in biopsies of women with breast cancer at Muhimbili National Hospital (MNH). A cross-sectional study of female breast post-modified radical mastectomy (MRM)/incisional biopsies confirmed to be carcinoma at the Histopathology Unit (January-December 2013). Tissue blocks having poor morphology, without tumor, secondary tumors, cases outside the study period and male patients were excluded. Routine staining was done followed by immunohistochemistry for estrogen (ER), and progesterone (PgR) receptors and HER2. Data analyzed using Statistical Package for Social Sciences (SPSS). A total of 218 cases were confirmed to be carcinoma including 70 meeting inclusion criteria. Age at diagnosis ranged 18-75 years and mean age was 48.36 years. Majority (64.3%) were in the 36-55 years age-group. Histologically, most (88.6%) women had invasive ductal carcinoma including 43.1% of intermediate grade. A great majority (78%) were stage three. Due to logistical constrains, 75.7% ( n  = 53/70) cases where immunostained for hormones including 43.4% (ER+), 26.4% (PgR+), and 28% (ER+/PgR+). Furthermore, 65.7% ( n  = 46/70) cases were immunostained for HER-2 and 15.2% ( n  = 7/46) were positive, 45.6% were triple negative (ER-,PgR-,HER2-), 23.9% (ER+,PgR+,HER2-) or luminal B, 2.2% (ER+,PgR-,HER2+),13% (ER-,PgR-,HER2+) and 15% (ER+,PgR-,HER2-) with none being triple positive. Hormonal receptors and HER2 expression at MNH appears to be comparable to previous Africans/African Americans reports but not with studies among Caucasians and the current proportion of triple negative breast carcinomas (TNBC) is

Characterization of hormonal receptors and human epidermal growth factor receptor-2 in tissues of women with breast cancer at Muhimbili National Hospital, Dar es salaam, Tanzania

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Amos Rodger Mwakigonja

2017-11-01

Full Text Available Abstract Background Breast cancer is a leading cause of morbidity and deaths among women worldwide. In Tanzania there is no published data on human epidermal growth receptor-2 (HER2/neu expression in breast carcinoma. Hormonal receptors and HER2/neu status reportedly influence post-mastectomy adjuvant therapy and predict treatment outcome and prognosis. Here we evaluate hormonal receptors and HER-2 status in biopsies of women with breast cancer at Muhimbili National Hospital (MNH. Methods A cross-sectional study of female breast post-modified radical mastectomy (MRM/incisional biopsies confirmed to be carcinoma at the Histopathology Unit (January–December 2013. Tissue blocks having poor morphology, without tumor, secondary tumors, cases outside the study period and male patients were excluded. Routine staining was done followed by immunohistochemistry for estrogen (ER, and progesterone (PgR receptors and HER2. Data analyzed using Statistical Package for Social Sciences (SPSS. Results A total of 218 cases were confirmed to be carcinoma including 70 meeting inclusion criteria. Age at diagnosis ranged 18–75 years and mean age was 48.36 years. Majority (64.3% were in the 36–55 years age-group. Histologically, most (88.6% women had invasive ductal carcinoma including 43.1% of intermediate grade. A great majority (78% were stage three. Due to logistical constrains, 75.7% (n = 53/70 cases where immunostained for hormones including 43.4% (ER+, 26.4% (PgR+, and 28% (ER+/PgR+. Furthermore, 65.7% (n = 46/70 cases were immunostained for HER-2 and 15.2% (n = 7/46 were positive, 45.6% were triple negative (ER-,PgR-,HER2-, 23.9% (ER+,PgR+,HER2- or luminal B, 2.2% (ER+,PgR-,HER2+,13% (ER-,PgR-,HER2+ and 15% (ER+,PgR-,HER2- with none being triple positive. Conclusions Hormonal receptors and HER2 expression at MNH appears to be comparable to previous Africans/African Americans reports but not with studies among Caucasians and the current proportion

Dietary acrylamide intake and estrogen and progesterone receptor-defined postmenopausal breast cancer risk

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Pedersen, Grete S; Hogervorst, Janneke G F; Schouten, Leo J

2010-01-01

and risk of postmenopausal breast cancer stratified by estrogen and progesterone receptor status. This study was embedded within the Netherlands Cohort Study on diet and cancer, which was initiated in 1986 enrolling 62,573 women aged 55-69 years at baseline. After 13.3 years of follow-up, 2225 incident...... breast cancer cases were ascertained, with hormone receptor status information for 43%. Cox proportional hazards analysis was applied to determine hazard ratios in quintiles of dietary acrylamide intake stratifying on estrogen receptor (ER) and progesterone receptor (PR) and smoking status....... No association was observed for overall breast cancer or receptor-negative breast cancer risk, irrespective of smoking status. A statistically non-significantly increased risk of ER positive, PR positive and joint receptor-positive breast cancer was found in never-smoking women. The multivariable-adjusted hazard...

Diabetes and Breast Cancer Subtypes.

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Heleen K Bronsveld

, treated with or without insulin, develop different breast cancer subtypes than women without diabetes. However, premenopausal women with diabetes tended to develop breast tumors that do not express hormonal receptors, which are typically associated with poor prognosis.

Diabetes and Breast Cancer Subtypes.

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Bronsveld, Heleen K; Jensen, Vibeke; Vahl, Pernille; De Bruin, Marie L; Cornelissen, Sten; Sanders, Joyce; Auvinen, Anssi; Haukka, Jari; Andersen, Morten; Vestergaard, Peter; Schmidt, Marjanka K

2017-01-01

with or without insulin, develop different breast cancer subtypes than women without diabetes. However, premenopausal women with diabetes tended to develop breast tumors that do not express hormonal receptors, which are typically associated with poor prognosis.

Health care factors associated with survival among women with breast cancer on hormone therapy in Rio de Janeiro, Brazil, 2004 – 2010

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Cláudia de Brito

Full Text Available ABSTRACT Objectives To better understand the role that health care plays in breast cancer survival by investigating the effects that hormone therapy adherence and other select health care variables, adjusted for clinical and sociodemographic factors, had among a population of women in Rio de Janeiro, Brazil. Methods This was a longitudinal study based on secondary data of 5 861 women treated with hormone therapy (tamoxifen or aromatase inhibitors at the National Cancer Institute of Brazil (INCA, from 1 January 2004 – 29 October 2010. Four different sources of data were integrated for analysis: INCA Pharmacy Sector Dispensation System; Hospital-based Cancer Registry; Integrated Hospital System and INCA Absolute System; and Mortality Information System. Analyses explored the effects of adherence to hormone therapy, disease care aspects, and sociodemographic, behavioral, and clinical variables, on the time of survival, using Kaplan-Meier and Cox proportional hazards models. Results The general survival rate was 94% in the first year after initiation of hormone therapy, and 71% in the fifth year. The Cox model indicated a higher hazard of death among women smokers, with more hospitalizations, more exams, and, among those who used, who used only aromatase inhibitors, as hormone therapy modality. The hazard was lower among women with a partner (stable relationship, a high school or college education a family history of cancer, and those who were treated by a mastologist, oncologist, and/or psychotherapist, who underwent surgery, and who adhered to hormone therapy. Conclusions The study indicated more vulnerable sub-groups and the aspects of care that provide best results, bringing new knowledge to improve assistance to this group of women.

Treating ER+ Breast Cancer with CDK4/6 Inhibitors.

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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.

Screening and prevention of breast cancer in primary care.

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Tice, Jeffrey A; Kerlikowske, Karla

2009-09-01

Mammography remains the mainstay of breast cancer screening. There is little controversy that mammography reduces the risk of dying from breast cancer by about 23% among women between the ages of 50 and 69 years, although the harms associated with false-positive results and overdiagnosis limit the net benefit of mammography. Women in their 70s may have a small benefit from screening mammography, but overdiagnosis increases in this age group as do competing causes of death. While new data support a 16% reduction in breast cancer mortality for 40- to 49-year-old women after 10 years of screening, the net benefit is less compelling in part because of the lower incidence of breast cancer in this age group and because mammography is less sensitive and specific in women younger than 50 years. Digital mammography is more sensitive than film mammography in young women with similar specificity, but no improvements in breast cancer outcomes have been demonstrated. Magnetic resonance imaging may benefit the highest risk women. Randomized trials suggest that self-breast examination does more harm than good. Primary prevention with currently approved medications will have a negligible effect on breast cancer incidence. Public health efforts aimed at increasing mammography screening rates, promoting regular exercise in all women, maintaining a healthy weight, limiting alcohol intake, and limiting postmenopausal hormone therapy may help to continue the recent trend of lower breast cancer incidence and mortality among American women.

Prolactin promotes breast cancer cell migration through actin cytoskeleton remodeling

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Priscilla Ludovico da Silva

2015-12-01

Full Text Available The role of prolactin on breast cancer development and progression is debated. Breast cancer progression largely depends on cell movement and on the ability to remodel the actin cytoskeleton. In this process, actin-binding proteins are requested to achieve fibrillar actin de-polymerization and relocation at the cell membrane. Kinases such as focal adhesion kinase (FAK are later required to form actin/vinculin-enriched structures called focal adhesion complexes, which mediate firm adhesion to the extracellular matrix. These controllers are regulated by c-Src, which forms multiprotein signaling complexes with membrane receptors and is regulated by a number of hormones, including prolactin. We here show that breast cancer cells exposed to prolactin display an elevated c-Src expression and phosphorylation. In parallel, increased moesin and FAK expression and phosphorylation are found. These molecular changes are associated to relocation to the plasma membrane of cytoskeletal actin fibers and to increased horizontal cell movement. In conclusion, prolactin regulates actin remodeling and enhances breast cancer cell movement. This finding broadens the understanding of prolactin actions on breast cancer cells, highlighting new pathways that may be relevant to on breast cancer progression.

Phytochemicals for breast cancer therapy: current status and future implications.

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Siddiqui, Jawed Akhtar; Singh, Aru; Chagtoo, Megha; Singh, Nidhi; Godbole, Madan Madhav; Chakravarti, Bandana

2015-01-01

Breast cancer is one of the most common malignancies among women, representing nearly 30% of newly diagnosed cancers every year. Till date, various therapeutic interventions, including surgery, chemotherapy, hormonal therapy, and radiotherapy are available and are known to cause a significant decline in the overall mortality rate. However, therapeutic resistance, recurrence and lack of treatment in metastasis are the major challenges that need to be addressed. Increasing evidence suggests the presence of cancer stem cells (CSCs) in heterogeneous population of breast tumors capable of selfrenewal and differentiation and is considered to be responsible for drug resistance and recurrence. Therefore, compound that can target both differentiated cancer cells, as well as CSCs, may provide a better treatment strategy. Due to safe nature of dietary agents and health products, investigators are introducing them into clinical trials in place of chemotherapeutic agents.This current review focuses on phytochemicals, mainly flavonoids that are in use for breast cancer therapy in preclinical phase. As phytochemicals have several advantages in breast cancer and cancer stem cells, new synthetic series for breast cancer therapy from analogues of most potent natural molecule can be developed via rational drug design approach.

Does fasting during Ramadan trigger non-adherence to oral hormonal therapy in breast cancer patients?

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Zeeneldin, Ahmed Abdelmabood; Gaber, Ayman Abdelsamee; Taha, Fatma Mohamed

2012-09-01

To estimate the effect of fasting during Ramadan (the ninth lunar month) on adherence to oral hormonal therapies (OHT) among breast cancer (BC) patients. During Ramadan 2010, 139 BC patients were interviewed at the Egyptian National Cancer Institute. They were asked about fasting as well as intake of OHT in Ramadan and in the preceding month. The median age was 50years and most patients were postmenopausal with good performance status and non-metastatic disease. The median number of fasting days was 18% and 93% of patients were fasting 80% or more of Ramadan. Tamoxifen and aromatase inhibitors were used in 64% and 36%, respectively. Adherence to OHT during Ramadan and its preceding month were 94.2% and 95.7%, respectively (p=0.77). In univariate analysis, non-adherence prior to Ramadan and shorter duration of OHT were predictors of non-adherence during Ramadan (PRamadan, this does not negatively impact compliance with treatment. Copyright © 2012. Published by Elsevier B.V.

Healthy lifestyle and risk of breast cancer among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition cohort study.

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McKenzie, Fiona; Ferrari, Pietro; Freisling, Heinz; Chajès, Veronique; Rinaldi, Sabina; de Batlle, Jordi; Dahm, Christina C; Overvad, Kim; Baglietto, Laura; Dartois, Laureen; Dossus, Laure; Lagiou, Pagona; Trichopoulos, Dimitrios; Trichopoulou, Antonia; Krogh, Vittorio; Panico, Salvatore; Tumino, Rosario; Rosso, Stefano; Bueno-de-Mesquita, H B As; May, Anne; Peeters, Petra H; Weiderpass, Elisabete; Buckland, Genevieve; Sanchez, Maria-Jose; Navarro, Carmen; Ardanaz, Eva; Andersson, Anne; Sund, Malin; Ericson, Ulrika; Wirfält, Elisabet; Key, Tim J; Travis, Ruth C; Gunter, Marc; Riboli, Elio; Vergnaud, Anne-Claire; Romieu, Isabelle

2015-06-01

Breast cancer is the most common cancer among women and prevention strategies are needed to reduce incidence worldwide. A healthy lifestyle index score (HLIS) was generated to investigate the joint effect of modifiable lifestyle factors on postmenopausal breast cancer risk. The study included 242,918 postmenopausal women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, with detailed information on diet and lifestyle assessed at baseline. The HLIS was constructed from five factors (diet, physical activity, smoking, alcohol consumption and anthropometry) by assigning scores of 0-4 to categories of each component, for which higher values indicate healthier behaviours. Hazard ratios (HR) were estimated by Cox proportional regression models. During 10.9 years of median follow-up, 7,756 incident breast cancer cases were identified. There was a 3% lower risk of breast cancer per point increase of the HLIS. Breast cancer risk was inversely associated with a high HLIS when fourth versus second (reference) categories were compared [adjusted HR = 0.74; 95% confidence interval (CI): 0.66-0.83]. The fourth versus the second category of the HLIS was associated with a lower risk for hormone receptor double positive (adjusted HR = 0.81, 95% CI: 0.67-0.98) and hormone receptor double negative breast cancer (adjusted HR = 0.60, 95% CI: 0.40-0.90). Findings suggest having a high score on an index of combined healthy behaviours reduces the risk of developing breast cancer among postmenopausal women. Programmes which engage women in long term health behaviours should be supported. © 2014 UICC.

Reduced risk of axillary lymphatic spread in triple-negative breast cancer

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Holm-Rasmussen, Emil Villiam; Jensen, Maj-Britt; Balslev, Eva

2015-01-01

We examined the association between the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status of women with primary breast cancer and the risk of axillary lymph node (ALN) involvement at the time of diagnosis. Information on 20,009 women diagnosed with primary breast...... cancer between 2008 and 2012 was retrieved from the Danish Breast Cancer Cooperative Group database. The associations between clinical and pathological variables and ALN involvement at the time of diagnosis were evaluated in univariate and multivariate regression analyses, as well as the significance......-negative breast cancer (TNBC) patients showed a significantly reduced risk of ALN involvement at the time of diagnosis compared to patients with HR-positive/HER2-negative tumors (OR 0.55; 95 % CI 0.49-0.62; P

Primary hypothyroidism in breast cancer patients with irradiated supraclavicular lymph nodes

International Nuclear Information System (INIS)

Bruning, P.; Bonfrer, J.; Jong-Bakker, M. de; Nooyen, W.; Burgers, M.

1985-01-01

Since the treatment of postmenopausal breast cancer patients with aminoglutethimide caused hypothyroidism with an unexpectedly high frequency previous treatment was suspected to contribute to hypofunction of the thyroid. Serum thyrotropin, triiodothyronine and free thyroxine index were compared between breast cancer patients who had undergone irradiation of regional lymph nodes and non-irradiated breast cancer patients, as well as patients having endometrial or colorectal carcinoma. Subclinical and clinical primary hypothyroidism was significantly more frequent in breast cancer patients who had previously received irradiation on supraclavicular lymph nodes comprising a minor part of the thyroid. Testing for the presence of autoantibodies against thyroid tissue components gave no evidence for radiation-induced autoimmune thyroiditis. Drugs suppressing thyroid hormone synthesis like aminoglutethimide may frequently cause myxedema in such irradiated women, especially at postmenopausal age. (author)

[Survival rate for breast cancer in Rabat (Morocco) 2005-2008].

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Mechita, Nada Bennani; Tazi, Mohammed Adnane; Er-Raki, Abdelouahed; Mrabet, Mustapha; Saadi, Asma; Benjaafar, Noureddine; Razine, Rachid

2016-01-01

Breast cancer is a public health problem in Morocco. This study aims to estimate the survival rate for patients with breast cancer living in Rabat. We conducted a prognostic study of female patients with breast cancer diagnosed during 2005-2008, living in Rabat and whose data were recorded in the Rabat Cancer Registry. The date of inclusion in this study corresponded with the date on which cancer was histologically confirmed. Survival rate was estimated using the Kaplan-Meier method and the comparison between the different classes of a variable was made using the log rank test. The study of factors associated with survival was performed using the Cox model. During the study period 628 cases of breast cancer were collected. Mortality rate was 19.9%. Overall 1-year survival rate was 97.1%, 89.2% at 3 years and 80.6% at 5 years. In multivariate analysis, breast cancer survival was statistically lower in patients over 70 years of age (p <0.001) with large tumor size (p < 0.001), advanced-stage adenopathies (p = 0.007), metastases (p < 0.001) and not using hormone therapy (p = 0.002). Large tumor size and metastases are poor prognostic factors in breast cancer, hence the need to strengthen screening programs.

Oestrogen receptors in tumors of breast cancer patients

Energy Technology Data Exchange (ETDEWEB)

Levin, J; Kay, G; Da Fonseca, M [University of the Witwatersrand, Johannesburg (South Africa). Department of Nuclear Medicine; Lange, M [University of the Witwatersrand, Johannesburg (South Africa). Dept. of Surgery; De Moor, N G [University of the Witwatersrand, Johannesburg (South Africa). Department of Radiation Therapy; Savage, N [University of the Witwatersrand, Johannesburg (South Africa). Department of Physiological Chemistry

1978-04-15

Oestrogen receptors were measured in the cytoplasmic fraction of tumors from patients with breast cancer. Receptors were detected in 48% of patients, and 52% showed no receptors. A follow-up study of a small group of patients on hormone therapy is reported.

Covering women's greatest health fear: breast cancer information in consumer magazines.

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Walsh-Childers, Kim; Edwards, Heather; Grobmyer, Stephen

2011-04-01

Women identify consumer magazines as a key source of information on many health topics, including breast cancer, which continues to rank as women's greatest personal health fear. This study examined the comprehensiveness and accuracy of breast cancer information provided in 555 articles published in 17 consumer magazines from 2002 through 2007. Accuracy of information was determined for 33 key breast cancer facts identified by an expert panel as important information for women to know. The results show that only 7 of 33 key facts were mentioned in at least 5% of the articles. These facts all dealt with breast cancer risk factors, screening, and detection; none of the key facts related to treatment or outcomes appeared in at least 5% of the articles. Other topics (not key facts) mentioned centered around controllable risk factors, support for breast cancer patients, and chemotherapy treatment. The majority of mentions of key facts were coded as fully accurate, although as much as 44% of mentions of some topics (the link between hormone replacement therapy and breast cancer) were coded as inaccurate or only partially accurate. The magazines were most likely to emphasize family history of breast cancer or genetic characteristics as risk factors for breast cancers; family history was twice as likely to be discussed as increasing age, which is in fact the most important risk factor for breast cancer other than being female. Magazine coverage may contribute to women's inaccurate perceptions of their breast cancer risk.

The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress

International Nuclear Information System (INIS)

Kim, Hyun-Ah; Ahn, Sei Hyun; Nam, Seok Jin; Park, Seho; Ro, Jungsil

2016-01-01

Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event. This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy

Role of MicroRNA Regulation in Obesity-Associated Breast Cancer: Nutritional Perspectives.

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Kasiappan, Ravi; Rajarajan, Dheeran

2017-11-01

Breast cancer is the most common malignancy diagnosed in women, and the incidence of breast cancer is increasing every year. Obesity has been identified as one of the major risk factors for breast cancer progression. The mechanisms by which obesity contributes to breast cancer development is not yet understood; however, there are a few mechanisms counted as potential producers of breast cancer in obesity, including insulin resistance, chronic inflammation and inflammatory cytokines, adipokines, and sex hormones. Recent emerging evidence suggests that alterations in microRNA (miRNA) expressions are found in several diseases, including breast cancer and obesity; however, miRNA roles in obesity-linked breast cancer are beginning to unravel. miRNAs are thought to be potential noninvasive biomarkers for diagnosis and prognosis of cancer patients with comorbid conditions of obesity as well as therapeutic targets. Recent studies have evidenced that nutrients and other dietary factors protect against cancer and obesity through modulation of miRNA expressions. Herein, we summarize a comprehensive overview of up-to-date information related to miRNAs and their molecular targets involved in obesity-associated breast cancer. We also address the mechanisms by which dietary factors modulate miRNA expression and its protective roles in obesity-associated breast cancer. It is hoped that this review would provide new therapeutic strategies for the treatment of obesity-associated breast cancer to reduce the burden of breast cancer. © 2017 American Society for Nutrition.

RANKL/RANK: from bone loss to the prevention of breast cancer.

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Sigl, Verena; Jones, Laundette P; Penninger, Josef M

2016-11-01

RANK and RANKL, a receptor ligand pair belonging to the tumour necrosis factor family, are the critical regulators of osteoclast development and bone metabolism. Besides their essential function in bone, RANK and RANKL have also been identified as the key factors for the formation of a lactating mammary gland in pregnancy. Mechanistically, RANK and RANKL link the sex hormone progesterone with stem cell expansion and proliferation of mammary epithelial cells. Based on their normal physiology, RANKL/RANK control the onset of hormone-induced breast cancer through the expansion of mammary progenitor cells. Recently, we and others were able to show that RANK and RANKL are also critical regulators of BRCA1-mutation-driven breast cancer. Currently, the preventive strategy for BRCA1-mutation carriers includes preventive mastectomy, associated with wide-ranging risks and psychosocial effects. The search for an alternative non-invasive prevention strategy is therefore of paramount importance. As our work strongly implicates RANK and RANKL as key molecules involved in the initiation of BRCA1-associated breast cancer, we propose that anti-RANKL therapy could be a feasible preventive strategy for women carrying BRCA1 mutations, and by extension to other women with high risk of breast cancer. © 2016 The Authors.

Polymorphisms of the SIPA1 gene and sporadic breast cancer susceptibility

International Nuclear Information System (INIS)

Hsieh, Szu-Min; Smith, Robert A; Lintell, Nicholas A; Hunter, Kent W; Griffiths, Lyn R

2009-01-01

The novel breast cancer metastasis modulator gene signal-induced proliferation-associated 1 (Sipa1) underlies the breast cancer metastasis efficiency modifier locus Mtes 1 and has been shown to influence mammary tumour metastatic efficiency in the mouse, with an ectopically expressing Sipa1 cell line developing 1.5 to 2 fold more surface pulmonary metastases. Sipa1 encodes a mitogen-inducible GTPase activating (GAP) protein for members of the Ras-related proteins; participates in cell adhesion and modulates mitogen-induced cell cycle progression. Germline SIPA1 SNPs showed association with positive lymph node metastasis and hormonal receptor status in a Caucasian cohort. We hypothesized that SIPA1 may also be correlated to breast carcinoma incidence as well as prognosis. Therefore, this study investigated the potential relationship of SIPA1 and human breast cancer incidence by a germline SNP genotype frequency association study in a case-control Caucasian cohort in Queensland, Australia. The SNPs genotyped in this study were identified in a previous study and the genotyping assays were carried out using TaqMan SNP Genotyping Assays. The data were analysed with chi-square method and the Monte Carlo style CLUMP analysis program. Results indicated significance with SIPA1 SNP rs3741378; the CC genotype was more frequently observed in the breast cancer group compared to the disease-free control group, indicating the variant C allele was associated with increased breast cancer incidence. This observation indicates SNP rs3741378 as a novel potential sporadic breast cancer predisposition SNP. While it showed association with hormonal receptor status in breast cancer group in a previous pilot study, this exonic missense SNP (Ser (S) to Phe (F)) changes a hydrophilic residue (S) to a hydrophobic residue (F) and may significantly alter the protein functions of SIPA1 in breast tumourgenesis. SIPA1 SNPs rs931127 (5' near gene), and rs746429 (synonymous (Ala (A) to Ala (A

Polymorphisms of the SIPA1 gene and sporadic breast cancer susceptibility

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Lintell Nicholas A

2009-09-01

Full Text Available Abstract Background The novel breast cancer metastasis modulator gene signal-induced proliferation-associated 1 (Sipa1 underlies the breast cancer metastasis efficiency modifier locus Mtes 1 and has been shown to influence mammary tumour metastatic efficiency in the mouse, with an ectopically expressing Sipa1 cell line developing 1.5 to 2 fold more surface pulmonary metastases. Sipa1 encodes a mitogen-inducible GTPase activating (GAP protein for members of the Ras-related proteins; participates in cell adhesion and modulates mitogen-induced cell cycle progression. Germline SIPA1 SNPs showed association with positive lymph node metastasis and hormonal receptor status in a Caucasian cohort. We hypothesized that SIPA1 may also be correlated to breast carcinoma incidence as well as prognosis. Therefore, this study investigated the potential relationship of SIPA1 and human breast cancer incidence by a germline SNP genotype frequency association study in a case-control Caucasian cohort in Queensland, Australia. Methods The SNPs genotyped in this study were identified in a previous study and the genotyping assays were carried out using TaqMan SNP Genotyping Assays. The data were analysed with chi-square method and the Monte Carlo style CLUMP analysis program. Results Results indicated significance with SIPA1 SNP rs3741378; the CC genotype was more frequently observed in the breast cancer group compared to the disease-free control group, indicating the variant C allele was associated with increased breast cancer incidence. Conclusion This observation indicates SNP rs3741378 as a novel potential sporadic breast cancer predisposition SNP. While it showed association with hormonal receptor status in breast cancer group in a previous pilot study, this exonic missense SNP (Ser (S to Phe (F changes a hydrophilic residue (S to a hydrophobic residue (F and may significantly alter the protein functions of SIPA1 in breast tumourgenesis. SIPA1 SNPs rs931127 (5

Mode of detection: an independent prognostic factor for women with breast cancer.

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Hofvind, Solveig; Holen, Åsne; Román, Marta; Sebuødegård, Sofie; Puig-Vives, Montse; Akslen, Lars

2016-06-01

To investigate breast cancer survival and risk of breast cancer death by detection mode (screen-detected, interval, and detected outside the screening programme), adjusting for prognostic and predictive tumour characteristics. Information about detection mode, prognostic (age, tumour size, histologic grade, lymph node status) and predictive factors (molecular subtypes based on immunohistochemical analyses of hormone receptor status (estrogen and progesterone) and Her2 status) were available for 8344 women in Norway aged 50-69 at diagnosis of breast cancer, 2005-2011. A total of 255 breast cancer deaths were registered by the end of 2011. Kaplan-Meier method was used to estimate six years breast cancer specific survival and Cox proportional hazard model to estimate hazard ratio (HR) for breast cancer death by detection mode, adjusting for prognostic and predictive factors. Women with screen-detected cancer had favourable prognostic and predictive tumour characteristics compared with interval cancers and those detected outside the screening programme. The favourable characteristics were present for screen-detected cancers, also within the subtypes. Adjusted HR of dying from breast cancer was two times higher for women with symptomatic breast cancer (interval or outside the screening), using screen-detected tumours as the reference. Detection mode is an independent prognostic factor for women diagnosed with breast cancer. Information on detection mode might be relevant for patient management to avoid overtreatment. © The Author(s) 2015.

Breast Cancer Prevention

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... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Prevention (PDQ®)–Patient Version What is prevention? Go ... from starting. Risk-reducing surgery . General Information About Breast Cancer Key Points Breast cancer is a disease in ...

Breast Cancer Treatment

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... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer Go to Health Professional Version Key Points Breast ...

Association Between Imaging Characteristics and Different Molecular Subtypes of Breast Cancer.

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Wu, Mingxiang; Ma, Jie

2017-04-01

Breast cancer can be divided into four major molecular subtypes based on the expression of hormone receptor (estrogen receptor and progesterone receptor), human epidermal growth factor receptor 2, HER2 status, and molecular proliferation rate (Ki67). In this study, we sought to investigate the association between breast cancer subtype and radiological findings in the Chinese population. Medical records of 300 consecutive invasive breast cancer patients were reviewed from the database: the Breast Imaging Reporting and Data System. The imaging characteristics of the lesions were evaluated. The molecular subtypes of breast cancer were classified into four types: luminal A, luminal B, HER2 overexpressed (HER2), and basal-like breast cancer (BLBC). Univariate and multivariate logistic regression analyses were performed to assess the association between the subtype (dependent variable) and mammography or 15 magnetic resonance imaging (MRI) indicators (independent variables). Luminal A and B subtypes were commonly associated with "clustered calcification distribution," "nipple invasion," or "skin invasion" (P cancers showed association with persistent enhancement in the delayed phase on MRI and "clustered calcification distribution" on mammography (P breast tumor, which are potentially useful tools in the diagnosis and subtyping of breast cancer. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Cancer related antigens with special reference to casein in breast cancer

International Nuclear Information System (INIS)

Henrick, J.C.; Reuter, A.; Franchimont, P.

1976-01-01

It has been known for more than 15 years that various tumours can secrete polypeptide hormones such as acth, parathormone, calcitonin...However, the presence of these hormones has no specificity as far as the presence of the tumor is concerned. On the other hand, it has been shown that tumor cells regain the property of synthesizing casein, this product of the exocrine secretion of the breast is only present during lactation under physiological circumstances. It can, however, be found in the serum of patients with breast cancer and also in a significant percentage of the sera of subjects with gastrointestinal and pulmonary neoplasms. This fact indicates the existence of ectopic exocrine secretion which has a greater specificity for the presence of a neoplasm. (G.C.)

Cancer related antigens with special reference to casein in breast cancer

Energy Technology Data Exchange (ETDEWEB)

Henrick, J C; Reuter, A; Franchimont, P [Institut National des Radioelements, Brussels (Belgium)

1976-01-01

It has been known for more than 15 years that various tumours can secrete polypeptide hormones such as ACTH, parathormone, and calcitonin. However, the presence of these hormones has no specificity as far as the presence of the tumor is concerned. On the other hand, it has been shown that tumor cells regain the property of synthesizing casein. This product of the exocrine secretion of the breast is only present during lactation under physiological circumstances. It can, however, be found in the serum of patients with breast cancer and also in a significant percentage of the sera of subjects with gastrointestinal and pulmonary neoplasms. This fact indicates the existence of ectopic exocrine secretion which has a greater specificity for the presence of a neoplasm.

The implications of breast cancer molecular phenotype for radiation oncology

Directory of Open Access Journals (Sweden)

Shirin eSioshansi

2011-06-01

Full Text Available The identification of distinct molecular subtypes of breast cancer has advanced the understanding and treatment of breast cancer by providing insight into prognosis, patterns of recurrence and effectiveness of therapy. The prognostic significance of molecular phenotype with regard to distant recurrences and overall survival are well established in the literature and has been readily incorporated into systemic therapy management decisions. However, despite the accumulating data suggesting similar prognostic significance for locoregional recurrence, integration of molecular phenotype into local management decision making has lagged. Although there are some conflicting reports, collectively the literature supports a low risk of local recurrence in the hormone receptor positive luminal subtypes compared to hormone receptor negative subtypes (triple negative and HER2-enriched. The development of targeted therapies, such as trastuzumab for the treatment of HER2-enriched subtype, has been shown to mitigate the increased risk of local recurrence. Unfortunately, no such remedy exists to address the increased risk of local recurrence for patients with triple negative tumors, making it a clinical challenge for radiation oncologists. In this review we discuss the correlation between molecular subtype and local recurrence following either breast conservation therapy or mastectomy. We also explore the possible mechanisms for increased local recurrence in triple negative breast cancer and radiotherapeutic implications for this population, such as the safety of breast conservation, consideration of dose escalation and the appropriateness of accelerated partial breast irradiation.

Breast Cancer Treatment Practices in Elderly Women in a Community Hospital

International Nuclear Information System (INIS)

Wang, H.; Singh, A.P.; Luce, S.A.St.; Go, A.R.

2011-01-01

Background. Elderly women with breast cancer are considered under diagnosed and under treated, and this adversely affects their overall survival. Methods. A total of 393 female breast cancer patients aged 70 years and older, diagnosed within the years 1989-1999, were identified from the tumor registry of The Brooklyn Hospital Center. Comparisons between the 3 different subgroups 70-74, 75-79, and 80 years and older were made using the Pearson Chi Square test. Results. Lumpectomy was performed in 42% of all patients, while mastectomy was done in 46% of patients. Adjuvant therapy such as chemotherapy, radiation therapy, and hormonal therapy were done in 12%, 25%, and 38%, respectively. Forty-seven percent of patients with positive lymph nodes received chemotherapy. Eighty-six percent of patients who were estrogen receptor-positive received adjuvant hormonal therapy. Overall five-year survival was only 14% for the =80 age group, compared to that of 32% and 35% for the 70-74 and the 75-79 age groups, respectively. Conclusions. Surgery was performed in majority of these patients, about half received lumpectomy, the other half mastectomy. Adjuvant therapies were frequently excluded, with only hormonal therapy being the most commonly used. Overall five-year survival is significantly worse in patients =80 years with breast cancer

Breast cancer screening

Science.gov (United States)

Mammogram - breast cancer screening; Breast exam - breast cancer screening; MRI - breast cancer screening ... is performed to screen women to detect early breast cancer when it is more likely to be cured. ...

The knowledge of risk factors and prevention of breast cancer in Polish women.

Science.gov (United States)

Chmaj-Wierzchowska, K; Jurczyk, M U; Czech-Szczapa, B; Wilczak, M

2017-01-01

Currently, breast cancer is one of the most common malignancies among women and it constitutes a significant medical, economic, and social problem. The study was conducted in a group of 600 healthy women (aged 18 to 88 years) between September 2011 and February 2015 living in the region of Wielkopolska (Poland) in a private gynecological practice. A survey questionnaire designed specifically for purposes of the study was a tool used to conduct the study. With regards to risk factors for breast cancer: 93% - familial history of breast cancer, 46% - use of hormone treatment, and 40.16% - taking contraceptive pills. A significant component of breast cancer prevention should be providing information regarding prevention tests and increasing accessibility to medical services.

Standard and Low-dose Hormone Therapy for Postmenopausal Women—Focus on the Breast

Directory of Open Access Journals (Sweden)

Peng-Hui Wang

2007-06-01

Full Text Available Menopause occurs naturally when the ovary ceases folliculogenesis, or artificially by surgical and/or medical ablation of the ovarian function. Menopause is a hypoestrogenic state, which may adversely affect estrogen target tissues, such as the brain, skeleton and skin, as well as the cardiovascular and genitourinary systems, with resultant frequency and severity of climacteric symptoms. The climacteric symptoms, however, vary significantly among women. For decades, hormone therapy (HT has been the mainstay and is considered the most effective for managing menopausal symptoms. The prolonged use of either single estrogen therapy or a combination therapy of estrogen and progestogen (EPT might be associated with a slightly increased risk of breast cancer and many resultant adverse events, such as coronary heart disease, stroke and venous thromboembolism. Perhaps because the clear benefits are limited to these end points of HT in treating menopausal women, the relatively significant adverse event profiles of these women may not be enough to trigger primary care physicians to be more aggressive than they have been to date in treating climacteric symptoms of postmenopausal women. However, severe climacteric symptoms really disturb the woman's life. Some epidemiologic studies have shown that the increased risk for breast cancer after 5 years of combined EPT is similar in magnitude to other lifestyle variables, such as 10-year delayed menopause, fewer pregnancies and reduced breastfeeding, postmenopausal obesity, excessive alcohol or cigarette use, and lack of regular exercise. Furthermore, elevated serum concentrations of either endogenous or exogenous (replaced by HT sex hormone in either pre- or postmenopausal women are associated with an increased risk of breast cancer. Finally, the increased breast cancer risk diminishes soon after discontinuing hormones, and largely disappears by 5 years after cessation. Taken together, low-dose conventional HT

Breast Milk Hormones and Their Protective Effect on Obesity

Directory of Open Access Journals (Sweden)

Fissore MariaF

2009-11-01

Full Text Available Data accumulated over recent years have significantly advanced our understanding of growth factors, cytokines, and hormones in breast milk. Here we deal with leptin, adiponectin, IGF-I, ghrelin, and the more recently discovered hormones, obestatin, and resistin, which are present in breast milk and involved in food intake regulation and energy balance. Little is known about these compounds in infant milk formulas. Nutrition in infancy has been implicated in the long-term tendency to obesity, and a longer duration of breastfeeding appears to protect against its development. Diet-related differences in serum leptin and ghrelin values in infancy might explain anthropometric differences and differences in dietary habits between breast-fed and formula-fed infants also later in life. However, there are still gaps in our understanding of how hormones present in breast milk affect children. Here we examine the data related to hormones contained in mother's milk and their potential protective effect on subsequent obesity.

Natural history of breast cancers detected in the Swedish mammography screening programme: a cohort study

DEFF Research Database (Denmark)

Zahl, Per-Henrik; Gøtzsche, Peter C; Mæhlen, Jan

2011-01-01

The natural history of screen-detected breast cancers is not well understood. A previous analysis of the incidence change during the introduction of the Norwegian screening programme in the late 1990s suggested that the natural history of many screen-detected invasive breast cancers is to regress...... spontaneously but the study was possibly confounded by use of hormone replacement therapy in the population. We did a similar analysis of data collected during an earlier period when few women were exposed to hormone replacement therapy....

A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women.

Science.gov (United States)

Secreto, Giorgio; Sieri, Sabina; Agnoli, Claudia; Grioni, Sara; Muti, Paola; Zumoff, Barnett; Sant, Milena; Meneghini, Elisabetta; Krogh, Vittorio

2016-08-01

Minimizing endogenous estrogen production and activity in women at high risk for breast cancer is a prominent approach to prevention of the disease. A number of clinical trials have shown that the administration of selective-estrogen receptor modulators or aromatase inhibitors significantly reduces the incidence of breast cancer in healthy women. Unfortunately, these drugs often produce adverse effects on the quality of life and are, therefore, poorly accepted by many women, even those who are at high risk for breast cancer. We propose a novel alternative approach to decreasing estrogen production: suppression of ovarian synthesis of the androgen precursors of estrogens by administration of long-acting gonadotropin-releasing hormone analogs to women with ovarian stromal hyperplasia. The specific target population would be elderly postmenopausal women, at increased risk of breast cancer, and with high blood levels of testosterone, marker of ovarian hyperandrogenemia, and recognized factor of risk for breast cancer. Testosterone levels are measured at baseline to identify women at risk and during the follow-up to evaluate the effectiveness of therapy. The postmenopausal ovary is an important source of excessive androgen production which originates from the ovarian interstitial cell hyperplasia frequently present in breast cancer patients. We propose to counter the source of androgen excess in women with ovarian stromal hyperplasia, thus reducing the substrate for estrogen formation without completely inhibiting estrogen synthesis. Available evidence indicates that gonadotropin-releasing hormone analogs can be safely used for breast cancer prevention in postmenopausal women.