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Genetic and non-genetic factors are believed to influence whether a woman with a BRCA1, BRCA2, and/or PALB2 mutation goes on to develop breast and/or ovarian cancer. The study is trying to identify which hormonal, reproductive, and lifestyle factors may increase cancer risk in this high-risk group.
The risk of breast cancer has been estimated to be up to 87% lifetime for women with a BRCA1 or BRCA2 mutation. Genetic testing is now established throughout Canada with the goal of preventing breast cancer in high risk women. The risks of breast and ovarian cancer in BRCA1 and BRCA2 carriers vary from woman to woman, based on age, family history, reproductive history and preventive surgeries. Preventive salpingo-oophorectomy reduces ovarian cancer risk by 80% and breast cancer risk by 50%. However, there is great interest in alternatives to surgery and in means of further reducing the risk of breast cancer after oophorectomy. Tamoxifen is approved for cancer prevention for pre- and post-menopausal women. Much evidence shows that tamoxifen can be used to prevent contralateral breast cancer in BRCA1 and BRCA2 carriers, but there is no direct evidence yet to support its use for primary prevention in BRCA mutation carriers and many women are reluctant to take it. We have recently shown, in a case-control study, that one year of tamoxifen reduces contralateral cancer in BRCA1 and BRCA2 carriers by up to 70%. It is important to establish the beneficial effect of tamoxifen chemoprevention on primary cancer risk in a large prospective study and to compare the risk reduction obtained with that of preventive mastectomy and oophorectomy.
1. To estimate the hazard ratio for first primary breast cancer associated with use of one or more years of preventive tamoxifen in women with a BRCA1 or BRCA2 mutation.
2. To compare the lifetime risks of breast cancer in carrier women who take tamoxifen with those who undergo preventive mastectomy or oophorectomy.
3. To create a user-friendly web-based interface for women with a BRCA1 or BRCA2 mutation to allow them to estimate their personal risks of breast and ovarian cancer and to estimate the expected impacts of tamoxifen and of preventive surgeries on breast and ovarian cancer risk.