The breast: lactation and breast cancer as an endocrine disease

2011 ◽  
pp. 1305-1318 ◽  
Author(s):  
R. Santen
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Hormonal Treatment ◽  
Cancer Development ◽  
Breast Lesions ◽  
Breast Cancers ◽  
Benign Breast Lesions ◽  
Hormonal Treatments

This chapter discusses both benign breast lesions and those that associated with an increased risk of breast cancer development, as well as the aetiology, clinical and pathologic prognosis, and hormonal treatment of breast cancers. Clinical observations in women suggest that hormones play a role in the aetiology of benign lesions. In postmenopausal women receiving oestrogens (with or without progestins) for more than 8 years, the prevalence of benign breast lesions is increased 1.7-fold; whilst the anti-oestrogen, tamoxifen, is associated with a 28 % reduction in prevalence of benign breast lesions. Cyclic and non-cyclic breast pain, nipple discharge and breast lumps are all clinical features of benign breast lesions. A practical classification, based primarily on degree of proliferation, distinguishes benign breast lesions with no associated increase in breast cancer risk from those with a small or moderate (i.e. 1.1–2.0- fold), or high risk (higher than 2.0-fold). Women considered at high risk of developing breast cancer can be treated with selective oestrogen receptor modulators (SERMS) including tamoxifen and raloxifene, which have been shown to decrease breast cancer risk by approximately 50 % when compared to placebo. The aetiology of breast cancer includes the accumulation of mutations of key genes involved in cell proliferation, DNA repair, vasculogenesis, invasion, metastasis, and apoptosis; dietary, environmental, and lifestyle factors also play a key role. The majority of risk factors for breast cancer relate to the duration or intensity of a woman’s exposure to endogenous or exogenous oestrogens; mitogenic and mutagenic effects of oestradiol probably act in concert to initiate and promote the breast cancer development. In this chapter, a variety of established and newer methods for classifying established breast cancers and predicting their prognosis and response to hormonal treatment strategies are discussed. The mechanisms (blockade of oestrogen synthesis or function) of hormonal treatments are described, as is the development of resistance to these treatments. An overview of the clinical efficacy of different hormonal treatments for breast cancer is given, as are recommended approaches to hormonal treatment of breast cancer in pre- and post-menopausal women, and in advanced disease states.

Effectiveness of Breast Cancer Surveillance in BRCA1/2 Gene Mutation Carriers and Women With High Familial Risk

2001 ◽  
Vol 19 (4) ◽  
pp. 924-930 ◽  
Author(s):  
C.T.M. Brekelmans ◽  
C. Seynaeve ◽  
C.C.M. Bartels ◽  
M.M.A. Tilanus-Linthorst ◽  
E.J. Meijers-Heijboer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Average Risk ◽  
Breast Cancers ◽  
Risk Population ◽  
Detection Rates ◽  
High Risk Women ◽  
Mutation Carriers

PURPOSE: Women with a high breast cancer risk due to a familial predisposition may choose between preventive surgery and regular surveillance. The effectiveness of surveillance in high-risk women and especially BRCA1/2 mutation carriers is unknown. We present first results from a single large family cancer clinic. PATIENTS AND METHODS: Women with breast cancer risk over 15% were examined by physical examination every 6 months and mammography every year. Detection rates and screening parameters were calculated for the total group and separately for different age and genetic risk groups. RESULTS: At least one examination was performed in 1,198 women: 449 moderate and 621 high-risk women and 128 BRCA1/2 mutation carriers. Within a median follow-up of 3 years, 35 breast cancers were detected (four ductal carcinoma-in-situ; 31 invasive tumors); the average detection rate was 9.7 per 1,000. Detection rates (95% confidence interval) for moderate and high-risk women and BRCA1/2 carriers were 3.3 (1.1 to 8.6), 8.4 (5.4 to 13.2), and 33 (17 to 63) per 1,000 person-years, respectively. The ratio of observed cases versus breast cancers expected in an average-risk population of comparable age was 2.7, 7.0 and 23.7 respectively. Overall, node negativity was 65%; 34% of primary tumors were less than 10 mm; sensitivity was 74%. Results with respect to tumor stage and sensitivity were less favorable in BRCA1/2 carriers and in women under the age of 40. CONCLUSION: It is possible to identify young women at high risk for breast cancer. The number of cancers detected was significantly greater than expected in an age-matched average-risk population and related to the risk category. Overall, screening parameters were comparable to population screening data, with less favorable results in the youngest age group (< 40) and BRCA1/2 carriers.

scholarly journals Addressing Barriers to Uptake of Breast Cancer Chemoprevention for Patients and Providers

2015 ◽  
pp. e50-e58 ◽  
Author(s):  
Katherine D. Crew
Keyword(s):  
Breast Cancer ◽  
Primary Prevention ◽  
High Risk ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Chemoprevention ◽  
The United States ◽  
Cancer Risk Assessment ◽  
Breast Cancer Risk Assessment ◽  
Breast Cancer Chemoprevention

Breast cancer is the most common malignancy among women in the United States, and the primary prevention of this disease is a major public health issue. Because there are relatively few modifiable breast cancer risk factors, pharmacologic interventions with antiestrogens have the potential to significantly affect the primary prevention setting. Breast cancer chemoprevention with selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene, and with aromatase inhibitors (AIs) exemestane and anastrozole, is underutilized despite several randomized controlled trials demonstrating up to a 50% to 65% relative risk reduction in breast cancer incidence among women at high risk. An estimated 10 million women in the United States meet high-risk criteria for breast cancer and are potentially eligible for chemoprevention, but less than 5% of women at high risk who are offered antiestrogens for primary prevention agree to take it. Reasons for low chemoprevention uptake include lack of routine breast cancer risk assessment in primary care, inadequate time for counseling, insufficient knowledge about antiestrogens among patients and providers, and concerns about side effects. Interventions designed to increase chemoprevention uptake, such as decision aids and incorporating breast cancer risk assessment into clinical practice, have met with limited success. Clinicians can help women make informed decisions about chemoprevention by effectively communicating breast cancer risk and enhancing knowledge about the risks and benefits of antiestrogens. Widespread adoption of chemoprevention will require a major paradigm shift in clinical practice for primary care providers (PCPs). However, enhancing uptake and adherence to breast cancer chemoprevention holds promise for reducing the public health burden of this disease.

scholarly journals Perceptions of Breast Cancer Risk, Psychological Adjustment and Behaviors in Adolescent Girls at High-risk and Population-risk for Breast Cancer

2014 ◽  
Vol 54 (2) ◽  
pp. S87
Author(s):  
Angela R. Bradbury ◽  
Linda Patrick-Miller ◽  
Brian Egleston ◽  
Lisa Schwartz ◽  
Lisa Tuchman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Psychological Adjustment ◽  
Adolescent Girls ◽  
And Behaviors

Toward robust mammography-based models for breast cancer risk

2021 ◽  
Vol 13 (578) ◽  
pp. eaba4373 ◽  
Author(s):  
Adam Yala ◽  
Peter G. Mikhael ◽  
Fredrik Strand ◽  
Gigin Lin ◽  
Kevin Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Deep Learning ◽  
High Risk ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Massachusetts General Hospital ◽  
The United States ◽  
University Hospital ◽  
Chang Gung Memorial Hospital ◽  
Risk Models

Improved breast cancer risk models enable targeted screening strategies that achieve earlier detection and less screening harm than existing guidelines. To bring deep learning risk models to clinical practice, we need to further refine their accuracy, validate them across diverse populations, and demonstrate their potential to improve clinical workflows. We developed Mirai, a mammography-based deep learning model designed to predict risk at multiple timepoints, leverage potentially missing risk factor information, and produce predictions that are consistent across mammography machines. Mirai was trained on a large dataset from Massachusetts General Hospital (MGH) in the United States and tested on held-out test sets from MGH, Karolinska University Hospital in Sweden, and Chang Gung Memorial Hospital (CGMH) in Taiwan, obtaining C-indices of 0.76 (95% confidence interval, 0.74 to 0.80), 0.81 (0.79 to 0.82), and 0.79 (0.79 to 0.83), respectively. Mirai obtained significantly higher 5-year ROC AUCs than the Tyrer-Cuzick model (P < 0.001) and prior deep learning models Hybrid DL (P < 0.001) and Image-Only DL (P < 0.001), trained on the same dataset. Mirai more accurately identified high-risk patients than prior methods across all datasets. On the MGH test set, 41.5% (34.4 to 48.5) of patients who would develop cancer within 5 years were identified as high risk, compared with 36.1% (29.1 to 42.9) by Hybrid DL (P = 0.02) and 22.9% (15.9 to 29.6) by the Tyrer-Cuzick model (P < 0.001).

scholarly journals Circulating carotenoids and breast cancer among high-risk individuals

2020 ◽  
Author(s):  
Cheng Peng ◽  
Chi Gao ◽  
Donghao Lu ◽  
Bernard A Rosner ◽  
Oana Zeleznik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Genetic Risk ◽  
Case Control Study ◽  
Case Control ◽  
Polygenic Risk Score ◽  
Nested Case Control ◽  
Control Study

ABSTRACT Background Carotenoids represent 1 of few modifiable factors to reduce breast cancer risk. Elucidation of interactions between circulating carotenoids and genetic predispositions or mammographic density (MD) may help inform more effective primary preventive strategies in high-risk populations. Objectives We tested whether women at high risk for breast cancer due to genetic predispositions or high MD would experience meaningful and greater risk reduction from higher circulating levels of carotenoids in a nested case-control study in the Nurses’ Health Studies (NHS and NHSII). Methods This study included 1919 cases and 1695 controls in a nested case-control study in the NHS and NHSII. We assessed both multiplicative and additive interactions. RR reductions and 95% CIs were calculated using unconditional logistic regressions, adjusting for matching factors and breast cancer risk factors. Absolute risk reductions (ARR) were calculated based on Surveillance, Epidemiology, and End Results incidence rates. Results We showed that compared with women at low genetic risk or low MD, those with higher genetic risk scores or high MD had greater ARRs for breast cancer as circulating carotenoid levels increase (additive P-interaction = 0.05). Among women with a high polygenic risk score, those in the highest quartile of circulating carotenoids had a significant ARR (28.6%; 95% CI, 14.8–42.1%) compared to those in the lowest quartile of carotenoids. For women with a high percentage MD (≥50%), circulating carotenoids were associated with a 37.1% ARR (95% CI, 21.7–52.1%) when comparing the highest to the lowest quartiles of circulating carotenoids. Conclusions The inverse associations between circulating carotenoids and breast cancer risk appeared to be more pronounced in high-risk women, as defined by germline genetic makeup or MD.

scholarly journals Considerations When Using Breast Cancer Risk Models for Women with Negative BRCA1/BRCA2 Mutation Results

2019 ◽  
Vol 112 (4) ◽  
pp. 418-422
Author(s):  
Robert J MacInnis ◽  
Yuyan Liao ◽  
Julia A Knight ◽  
Roger L Milne ◽  
Alice S Whittemore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Invasive Breast Cancer ◽  
Disease Incidence ◽  
Brca2 Mutation ◽  
Estimation Algorithm ◽  
Breast Cancers ◽  
Risk Models ◽  
Replication Studies

Abstract The performance of breast cancer risk models for women with a family history but negative BRCA1 and/or BRCA2 mutation test results is uncertain. We calculated the cumulative 10-year invasive breast cancer risk at cohort entry for 14 657 unaffected women (96.1% had an affected relative) not known to carry BRCA1 or BRCA2 mutations at baseline using three pedigree-based models (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm, BRCAPRO, and International Breast Cancer Intervention Study). During follow-up, 482 women were diagnosed with invasive breast cancer. Mutation testing was conducted independent of incident cancers. All models underpredicted risk by 26.3%–56.7% for women who tested negative but whose relatives had not been tested (n = 1363; 63 breast cancers). Although replication studies with larger sample sizes are needed, until these models are recalibrated for women who test negative and have no relatives tested, caution should be used when considering changing the breast cancer risk management intensity of such women based on risk estimates from these models.

scholarly journals Polygenic risk score for the prediction of breast cancer is related to lesser terminal duct lobular unit involution of the breast

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Clara Bodelon ◽  
Hannah Oh ◽  
Andriy Derkach ◽  
Joshua N. Sampson ◽  
Brian L. Sprague ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Intermediate Step ◽  
Breast Cancers ◽  
Tissue Samples ◽  
Polygenic Risk ◽  
Age Related

Abstract Terminal duct lobular units (TDLUs) are the predominant anatomical structures where breast cancers originate. Having lesser degrees of age-related TDLU involution, measured as higher TDLUs counts or more epithelial TDLU substructures (acini), is related to increased breast cancer risk among women with benign breast disease (BBD). We evaluated whether a recently developed polygenic risk score (PRS) based on 313-common variants for breast cancer prediction is related to TDLU involution in the background, normal breast tissue, as this could provide mechanistic clues on the genetic predisposition to breast cancer. Among 1398 women without breast cancer, higher values of the PRS were significantly associated with higher TDLU counts (P = 0.004), but not with acini counts (P = 0.808), in histologically normal tissue samples from donors and diagnostic BBD biopsies. Mediation analysis indicated that TDLU counts may explain a modest proportion (≤10%) of the association of the 313-variant PRS with breast cancer risk. These findings suggest that TDLU involution might be an intermediate step in the association between common genetic variation and breast cancer risk.

scholarly journals Epigenetic Biomarkers for Environmental Exposures and Personalized Breast Cancer Prevention

2020 ◽  
Vol 17 (4) ◽  
pp. 1181 ◽  
Author(s):  
Hannah Lui Park
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Alcohol Consumption ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Hormone Therapy ◽  
Environmental Exposures ◽  
Breast Cancers ◽  
Prevention Strategies ◽  
Epigenetic Biomarkers

Environmental and lifestyle factors are believed to account for >80% of breast cancers; however, it is not well understood how and when these factors affect risk and which exposed individuals will actually develop the disease. While alcohol consumption, obesity, and hormone therapy are some known risk factors for breast cancer, other exposures associated with breast cancer risk have not yet been identified or well characterized. In this paper, it is proposed that the identification of blood epigenetic markers for personal, in utero, and ancestral environmental exposures can help researchers better understand known and potential relationships between exposures and breast cancer risk and may enable personalized prevention strategies.

Breast cancer epidemiologic risk factors by HER2/neu status

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 585-585
Author(s):  
W. Y. Chen ◽  
G. A. Colditz ◽  
B. Rosner
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Risk Factor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Benign Breast Disease ◽  
Breast Disease ◽  
Breast Cancers ◽  
Cancer Risk Factors ◽  
Breast Cancer Risk Factors

585 Background: Although breast cancers categorized by estrogen receptor (ER) and progesterone receptor (PR) status are recognized to differ in their associations with standard breast cancer risk factors, little data exist on differences by HER2/neu status. Methods: The Nurses’ Health Study is a prospective cohort study of 121,700 registered nurses aged 30–55 in 1976 who answered biennial questionnaires to update medical and lifestyle factors and disease occurrence. Medical record review was used to confirm invasive breast cancer and abstract ER, PR, and HER2/neu status. Statistical analyses included both proportional hazards models to estimate relative risks and control for potential confounders and polytomous logistic regression to compare the effects. Only cases diagnosed from return of the 1998 questionnaire until June 2002 were included in the analysis since HER2/neu was only routinely assessed beginning with the 1998 follow-up cycle. Results: 211 HER2/neu positive and 770 HER2/neu negative cases were included in the analysis. In this predominantly postmenopausal group aged 52–77 in 1998, HER2neu negative cancers were more likely to be ER+/PR+ (72%) and less likely to be ER-/PR- (11%) than HER2/neu positive ones (58% ER+/PR+ and 24% ER-/PR-), but the majority of cancers were still ER+/PR+. In multivariate models, risk factor associations by HER2/neu status were similar with positive associations seen for family history, benign breast disease, body mass index, current postmenopausal hormone use, and cumulative alcohol consumption. However, when the subgroup of ER-/PR-/HER2/neu negative cancers were evaluated separately (N=83), most of these risk factor associations disappeared with the only significant risk factor being a prior history of benign breast disease. Conclusions: This is the first prospective data study to report on risk factor association by HER2/neu status. For the standard epidemiologic breast cancer risk factors, ER and PR status appear to better represent separate etiologic pathways, rather than HER2/neu status. However, the subgroup of ER/PR/HER2neu negative breast cancers appears to be distinct, although power was limited and HER2/neu status was not confirmed by central review. Additional analyses stratified by ER/PR status will also be presented. No significant financial relationships to disclose.

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