Short-term hormone replacement therapy in BRCA mutation carriers and risk of breast cancer: A nationwide study in Korea

초록

Objectives BRCA 1 and BRCA 2 gene mutations are well-known risk factors for breast and ovarian cancers in women, and risk-reducing salpingo-oophorectomy (RRSO) is the standard prophylactic treatment for the prevention of ovarian and fallopian tube carcinoma in women with BRCA mutations. Nevertheless, since most of the cases of RRSO are performed before menopause, those who receive RRSO suffer from postmenopausal syndrome (PMS) and adverse effects on cognition, mood, cardiovascular, bone, and sexual health. These symptoms can be comforted by hormone replacement therapy (HRT); however, the usage of HRT in carriers with BRCA mutations has been controversial due to concern that HRT increases the already high risk of breast cancer. We used the Korean National Health Insurance Service Database (KNHISD) to compare the risk of breast cancer in BRCA mutation carriers who received post-RRSO HRT with those who did not receive post-RRSO HRT. Methods A total of 151 carriers who received RRSO between 2013 and 2020 after the diagnosis of BRCA 1 or BRCA 2 mutations with no prior diagnosis of cancer were selected, and they were followed up for a mean of 2.2 years. They were divided into two groups, those who received HRT after RRSO (n = 33) and those who did not (n = 118). We compared the incidence of breast cancer over time in women who received HRT with those who did not. Results HRT did not increase the risk of breast cancer in carriers who received RRSO due to BRCA mutations (P = 0.229). When sorted by age 45, there were no significant differences in risk of breast cancer whether or not the patient received HRT both under age 45 (P = 0.8067) and above age 45 (P = 0.2534). We also classified the population according to the HRT medications they received, including progesterone, estrogen, tibolone, and progesterone-estrogen combination, and we found no increase in the risk of breast cancer in all medication groups (P = 0.9749). Conclusions We found no relationship between short-term post-RRSO HRT and breast cancer in the population with BRCA mutations in this study. Therefore, health caregivers should consider alleviation of symptoms of postmenopausal syndrome through HRT in patients who received RRSO. Further studies are needed for a longer follow-up period and to establish specific guidelines.