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Inherited breast-ovarian cancer was described in 1866. The underlying genetic defects in BRCA1/2 were demonstrated 128 years later. We now have 10 years of experience with genetic testing in BRCA kindreds. The majority of breast cancer kindreds (familial breast cancer) do not demonstrate ovarian cancer and are not associated with BRCA mutations. The effect of early diagnosis and treatment is monitored through international collaborations.BRCA1-associated breast cancer is biologically different from other breast cancers, including a worse prognosis. BRCA2-associated breast cancer is, beside early onset, in many ways similar to sporadic breast cancer. Mammography screening of the high risk groups aiming at early diagnosis and treatment, seems promising for familial breast cancer and for BRCA2-associated breast cancer, but numbers included for BRCA2 carriers are limited. BRCA1-carriers have worse prognosis, and the potential benefit of MRI for early diagnosis is now being explored. Early diagnosis and treatment of ovarian cancer does not substantially improve survival, and prophylactic oophorectomy at the end of childbearing ages is advocated. Prophylactic mastectomy is debated, and we may await the results of MRI trials before recommending this option. Familial breast cancer and BRCA2-associated breast cancers are often oestrogen receptor positive, and may be prevented by oestrogen blockers/inhibitors. Oophorectomy prevents ovarian cancer, and may possibly prevent both receptor positive and receptor negative breast cancer as well, also while using HRT. Oral contraceptives may reduce ovarian cancer risk and increase breast cancer risk, irrespective of initial risk and genetic subgroup.

Towards Evidence-Based Management of Inherited Breast and Breast-Ovarian Cancer