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Kotsopoulos J.,Familial Breast Cancer Unit | Lubinski J.,Pomeranian Medical University | Gronwald J.,Pomeranian Medical University | Cybulski C.,Pomeranian Medical University | And 11 more authors.
International Journal of Cancer | Year: 2015

The role of the lifetime number of ovulatory cycles has not been evaluated in the context of BRCA-associated ovarian cancer. Thus, we conducted a matched case-control study to evaluate the relationship between the cumulative number of ovulatory cycles (and contributing components) and risk of developing ovarian cancer in BRCA mutation carriers (1,329 cases and 5,267 controls). Information regarding reproductive and hormonal factors was collected from a routinely administered questionnaire. Conditional logistic regression was used to evaluate all associations. We observed a 45% reduction in the risk of developing ovarian cancer among women in the lowest vs. highest quartile of ovulatory cycles (OR=0.55; 95% CI 0.41-0.75, p=0.0001). Breastfeeding for more than 12 months was associated with a 38% (95% CI 0.48-0.79) and 50% (95% CI 0.29-0.84) reduction in risk among BRCA1 and BRCA2 mutation carriers, respectively. For oral contraceptive use, maximum benefit was seen with five or more years of use among BRCA1 mutation carriers (OR=0.50; 95% CI 0.40-0.63) and three or more years for BRCA2 mutation carriers (OR=0.42; 95% CI 0.22-0.83). Increasing parity was associated with a significant inverse trend among BRCA1 (OR=0.87; 95% CI 0.79-0.96; p-trend=0.005) but not BRCA2 mutation carriers (OR 0.98; 95% CI 0.81-1.19; p-trend=0.85). A later age at menopause was associated with an increased risk in women with a BRCA1 mutation (OR trend=1.18; 95% CI 1.03-1.35; p=0.02). These findings support an important role of breastfeeding and oral contraceptive use for the primary prevention of ovarian cancer among women carrying BRCA mutations. What's new? The number of ovulatory cycles a woman has in her lifetime may influence her risk for ovarian cancer, though how cancer-associated BRCA mutations factor into that relationship remains uncertain. Here, ovarian cancer risk was found to be significantly reduced among BRCA mutation carriers in the lowest quartile of ovulatory cycles. Likewise, risk was reduced in women with BRCA1 or BRCA2 mutations who used oral contraceptives for five or three years, respectively, or who breastfed for more than 12 months. The findings lend support to the idea that factors that suppress or interrupt ovulation protect against BRCA-associated ovarian cancer. © 2014 UICC. Source


Kotsopoulos J.,Familial Breast Cancer Unit | Lubinski J.,Pomeranian Medical University | Moller P.,University of Oslo | Lynch H.T.,Creighton University | And 18 more authors.
Breast Cancer Research and Treatment | Year: 2014

It is not clear if early oral contraceptive use increases the risk of breast cancer among young women with a breast cancer susceptibility gene 1 (BRCA1) mutation. Given the benefit of oral contraceptives for the prevention of ovarian cancer, estimating age-specific risk ratios for oral contraceptive use and breast cancer is important. We conducted a case-control study of 2,492 matched pairs of women with a deleterious BRCA1 mutation. Breast cancer cases and unaffected controls were matched on year of birth and country of residence. Detailed information about oral contraceptive use was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the odds ratios (OR) and 95 % confidence intervals (CI) for the association between oral contraceptive and breast cancer, by age at first use and by age at diagnosis. Among BRCA1 mutation carriers, oral contraceptive use was significantly associated with an increased risk of breast cancer for women who started the pill prior to age 20 (OR 1.45; 95 % CI 1.20-1.75; P = 0.0001) and possibly between ages 20 and 25 as well (OR 1.19; 95 % CI 0.99-1.42; P = 0.06). The effect was limited to breast cancers diagnosed before age 40 (OR 1.40; 95 % CI 1.14-1.70; P = 0.001); the risk of early-onset breast cancer increased by 11 % with each additional year of pill use when initiated prior to age 20 (OR 1.11; 95 % CI 1.03-1.20; P = 0.008). There was no observed increase for women diagnosed at or after the age of 40 (OR 0.97; 95 % CI 0.79-1.20; P = 0.81). Oral contraceptive use before age 25 increases the risk of early-onset breast cancer among women with a BRCA1 mutation and the risk increases with duration of use. Caution should be taken when advising women with a BRCA1 mutation to take an oral contraceptive prior to age 25. © 2014 Springer Science+Business Media New York. Source


Kotsopoulos J.,Familial Breast Cancer Unit | Lubinski J.,Pomeranian Medical University | Salmena L.,Familial Breast Cancer Unit | Lynch H.T.,Creighton University | And 18 more authors.
Breast Cancer Research | Year: 2012

Introduction: Breastfeeding has been inversely related to breast cancer risk in the general population. Clarifying the role of breastfeeding among women with a BRCA1 or BRCA2 mutation may be helpful for risk assessment and for recommendations regarding prevention. We present an updated analysis of breastfeeding and risk of breast cancer using a large matched sample of BRCA mutation carriers.Methods: We conducted a case-control study of 1,665 pairs of women with a deleterious mutation in either BRCA1 (n = 1,243 pairs) or BRCA2 (n = 422 pairs). Breast cancer cases and unaffected controls were matched on year of birth, mutation status, country of residence and parity. Information about reproductive factors, including breastfeeding for each live birth, was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the association between ever having breastfed, as well as total duration of breastfeeding, and the risk of breast cancer.Results: Among BRCA1 mutation carriers, breastfeeding for at least one year was associated with a 32% reduction in risk (OR = 0.68; 95% CI 0.52 to 0.91; P = 0.008); breastfeeding for two or more years conferred a greater reduction in risk (OR = 0.51; 95% CI 0.35 to 0.74). Among BRCA2 mutation carriers, there was no significant association between breastfeeding for at least one year and breast cancer risk (OR = 0.83; 95% CI 0.53 to 1.31; P = 0.43).Conclusions: These data extend our previous findings that breastfeeding protects against BRCA1-, but not BRCA2-associated breast cancer. BRCA mutation carriers should be advised of the benefit of breastfeeding in terms of reducing breast cancer risk. © 2012 Kotsopoulos et al.; licensee BioMed Central Ltd. Source


Kotsopoulos J.,Familial Breast Cancer Unit | Kotsopoulos J.,University of Toronto | Metcalfe K.,Familial Breast Cancer Unit | Metcalfe K.,55 College St | And 11 more authors.
BMC Cancer | Year: 2014

Background: We previously reported that women from high-risk families who tested negative for a BRCA1 or BRCA2 (BRCA1/2) mutation were four times more likely to develop breast cancer compared to women in the general population. Preventive measures and risk factors for breast cancer development in these high-risk women have not been evaluated to the same extent as BRCA1/2 positive women. Further, there is virtually no scientific evidence about best practices in their management and care. The proposed study will examine a role of genetic and non-genetic factors and develop the systems and parameters for the monitoring and surveillance necessary to help establish guidelines for the care of this high-risk population.Methods/Design: To achieve our goals, we will assemble and follow a Canadian cohort of 1,000 cancer-free women with a strong family history breast cancer (defined as two or more relatives affected by breast cancer under the age of 50, or three or more relatives diagnosed with breast cancer at any age from one side of the family and with no BRCA1/2 mutation in the family). All eligible participants will be mailed a study package including invitation to participate, consent form, a research questionnaire to collect data regarding family history, reproductive and lifestyle factors, as well as screening and surgery. Usual dietary intake will be assessed by a diet history questionnaire. Biological samples including toenail clippings, urine and blood samples will be collected. These women will be followed every two years by questionnaire to update exposure information, screening practices, surgical and chemoprevention, and disease development.Discussion: Findings from this study will serve to help establish clinical guidelines for the implementation of prevention, counseling, and treatment practices for women who face an elevated risk of breast cancer due to family history, but who do not carry a BRCA1/2 mutation. © 2014 Kotsopoulos et al.; licensee BioMed Central Ltd. Source

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