Gynecological-endocrinological aspects in women carriers of BRCA1/2 gene mutations

Abstract

Women carriers of mutations in the genes BRCA1 and BRCA2 coding for tumor suppressor proteins are at high risk of developing breast and ovarian cancers. Hereditary breast and ovarian cancers due to BRCA pathogenic mutations occur at earlier ages: mean age 43 years at diagnosis of breast cancer for BRCA1 mutations; onset of ovarian cancer up to 10-21% by age 50 years. Preventive strategies are then defined in the reproductive years. The National Comprehensive Cancer Network (NCCN) guidelines define that BRCA1/2 genetic testing should begin with the affected cancer individual (BRCA1/2 full sequencing); then, family members should be tested for the specific gene mutation found. A woman known to be a carrier needs a strict specific surveillance strategy to achieve early diagnosis. The NCCN proposes breast imageneological surveillance beginning at age 25 years; ovarian surveillance beginning at age 30-35 years. Concomitantly, risk-reducing strategies should be analyzed: surgical or pharmacological. When prophylactic bilateral salpingo-oophorectomy is performed before menopause, estrogen replacement therapy could be required. For BRCA, we review the risks of cancer in mutations carriers, criteria for genetic testing, surveillance and risk-reduction strategies, and the safety of prescribing hormone therapy when needed.

Keywords: BRCA mutation; estrogen therapy; genetic testing; hereditary breast cancer; hereditary ovarian cancer; hormonal therapy; risk-reducing strategies.