Risk of Breast Cancer After Ovarian Cancer in Women With a Pathogenic/Likely Pathogenic Variant in <i>BRCA1</i> or <i>BRCA2</i>.

Abstract

<i>BRCA</i> carriers face high risks of developing both breast and ovarian/fallopian tube cancers (hereafter referred to as <i>ovarian</i>). Among <i>BRCA</i> carriers with ovarian cancer, it is not clear whether the risk of breast cancer is sufficiently high that risk-reducing mastectomy should be offered. This study aimed to assess the risk of breast cancer <i>BRCA</i> carriers after a diagnosis of ovarian cancer. We included women with a pathogenic/likely pathogenic variant in <i>BRCA1</i> or <i>BRCA2</i>, a diagnosis of ovarian cancer, and no other cancer history and no risk-reducing bilateral mastectomy. Women were followed for incident breast cancer from the date of ovarian cancer diagnosis or the date of baseline questionnaire, whichever came last. The 5-, 10-, and 15-year cumulative risks of breast cancer were compared for women with ovarian cancer and an age-matched set of control women without ovarian cancer. A total of 960 participants with ovarian cancer were identified (814 <i>BRCA1</i> and 146 <i>BRCA2</i> carriers). After a mean follow-up of 4.9 years, 41 women (4.3%) developed breast cancer, at a mean age at diagnosis of 57.5 years (range, 39-74). Actuarial cumulative breast cancer risks after ovarian cancer were 4.4%, 8.9%, and 11.5% at 5, 10, and 15 years, respectively. Only three breast cancer-related deaths occurred. Among 741 age-matched <i>BRCA</i> carriers <i>without</i> ovarian cancer, actuarial cumulative risks of breast cancer were 20.9%, 38.6%, and 47.2% at 5, 10, and 15 years, respectively. The hazard ratio for breast cancer, after an ovarian cancer diagnosis, compared with no ovarian cancer, was 0.18 ([95% CI, 0.12 to 0.27]; <i>P</i> < .0001). After ovarian cancer, <i>BRCA</i> carriers have a relatively low risk of breast cancer. Risk-reducing mastectomy should not be recommended routinely, but might be considered for long-term survivors. Magnetic resonance imaging surveillance and/or mammography is a realistic alternative.