Hormone replacement therapy after prophylactic risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A meta-analysis.

Hormone replacement therapy (HRT) has been tested in women with BRCA1 and BRCA2 mutations who underwent risk-reducing salpingo-oophorectomy (RRSO), but its effect on breast cancer (BC) risk has never been appraised using meta-analysis comparison. We performed the first meta-analysis aimed to clarify whether HRT after RRSO could negatively impact on BC risk in women carriers of BRCA1 and BRCA2 mutations. Pubmed and Scopus databases were searched to retrieve articles written in the English language. Trials comparing RRSO with or without HRT were identified and only those trials with available BC events were included. BC risk was the main endpoint. Three trials with 1100 patients were included. There was not a significantly higher BC risk in BRCA1 and BRCA2 mutation carriers receiving HRT after RRSO (HR = 0.98; 95% CI 0.63-1.52). There was a slightly but not significantly, benefit in BC risk reduction in favor of estrogen alone HRT versus estrogen plus progesterone HRT formulation (OR = 0.53; 95% CI 0.25-1.15). HRT use after RRSO in BRCA 1 and BRCA2 mutation carries does not affect BC risk. Comparison of the different HRT types suggests that estrogen alone should be related to lowest BC risk.

Marchetti C ，De Felice F ，Boccia S ，Sassu C ，Di Donato V ，Perniola G ，Palaia I ，Monti M ，Muzii L ，Tombolini V ，Benedetti Panici P ... -  《-》

Breast cancer risk and hormone replacement therapy among BRCA carriers after risk-reducing salpingo-oophorectomy.

BRCA1/BRCA2 mutation carriers often undergo risk-reducing salpingo-oophorectomy (RRSO) before natural menopause, raising the issue of hormonal replacement treatment (HRT) use. There is conflicting evidence on the effect of HRT on breast cancer (BC) risk, and there are limited data on risk based on age at exposure. In the general population, HRT users have an increased BC risk (hazard ratio = 1.34). We assessed the impact of short-term HRT use on BC risk among healthy BRCA1/2 mutation carriers, with emphasis on age at exposure to HRT. A retrospective cohort of 306 consecutive healthy BRCA1/2 mutation carriers who had undergone RRSO was followed up for a mean of 7.26 years. We compared BC incidence over time in carriers who received HRT with that in those who did not receive. Thirty-six of the carriers were diagnosed with BC, 20 of 148 patients (13.5%) in the HRT group compared with 16 of 155 (10.3%) in the non-HRT group (odds ratio [OR] = 1.4, 95% confidence interval [CI] = 0.7-2.7). In women who were aged 45 years or younger at RRSO, HRT did not affect BC rates. However, in those older than 45 years at RRSO, BC rates were significantly higher in HRT users than in non-users (OR = 3.43, p < 0.05, 95% CI = 1.2-9.8). In BRCA1/BRCA2 carriers in this study, short-term post-RRSO HRT use was associated with a threefold risk of BC in carriers older than 45 years. These results suggest that risk may be related to time of exposure to HRT around the natural age of menopause, even among BRCA1/2 carriers. Further studies are needed for validation and to guide future recommendations.

Michaelson-Cohen R ，Gabizon-Peretz S ，Armon S ，Srebnik-Moshe N ，Mor P ，Tomer A ，Levy-Lahad E ，Paluch-Shimon S ... -  《-》

Hormone replacement therapy after risk reducing salpingo-oophorectomy in patients with BRCA1 or BRCA2 mutations; a systematic review of risks and benefits.

Women with germline BRCA1 or BRCA2 (BRCA) mutations, are recommended risk-reducing salpingo-oophorectomy (RRSO) prior to menopause. Surgical menopause has significant impact on patients' health and well-being. Subsequently, concerns about surgical menopause influence uptake of RRSO in high risk women. The role of hormone replacement therapy (HRT) in BRCA mutation carriers undergoing RRSO has been controversial. In the general population, premature surgical menopause is associated with worse quality of life and cognitive function, and increased risk of bone and cardiovascular disease; HRT continued until the natural age of menopause is shown to alleviate a number of these effects. Conflicting information has been published on HRT and breast cancer risk. For BRCA mutation carriers, potential augmentation of already elevated breast cancer risk is of great concern. In this article, we provide a review of the literature on HRT in this high-risk population, including effects on quality of life, cardiovascular, bone, and brain health. We also review impact of HRT on breast cancer risk, with a discussion of HRT formulation and surgical approach. Though evidence is limited, HRT after RRSO has a number of reported benefits and does not appear to impact breast cancer risk reduction in BRCA mutation carriers. This information is critical when discussing RRSO with patients, as providers should review risks of early menopause and treatment options. This review provides information to assist with counseling this specific population.

Gordhandas S ，Norquist BM ，Pennington KP ，Yung RL ，Laya MB ，Swisher EM ... -  《-》

Risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1 or BRCA2 mutation carriers: A systematic review and meta-analysis.

BRCA mutation carriers have a high lifetime risk of developing breast cancer (BC) and ovarian cancer (OC). Risk-reducing salpingo-oophorectomy (RRSO) has been shown to reduce OC risk. This meta-analysis was aim to analyze the effect of RRSO on the BC risk among BRCA1/2 mutation carriers. Embase, PubMed, Web of Science, and Cochrane databases were searched for all studies investigating the effect of RRSO on BC risk. The pooled results were used to evaluate the association between RRSO and BC risk. This meta-analysis included 13,965 BRCA1 and 7,057 BRCA2 mutation carriers from 14 observational studies. The pooled results showed that RRSO lowered BC risk among BRCA1 mutation carriers [hazard ratio (HR) = 0.63, 95% confidence interval (CI): 0.49-0.81, P < 0.01] and BRCA2 mutation carriers (HR = 0.51, 95% CI: 0.34-0.75, P < 0.01). RRSO reduced BC risk in younger women with BRCA1 mutation (HR = 0.48, 95% CI: 0.30-0.77, P < 0.01) and BRCA2 mutation (HR = 0.22, 95% CI: 0.08-0.65, P < 0.01). Analysis of the efficacy of RRSO at different time intervals after surgery showed a reduction of BC risk at <5 years after surgery in BRCA1 mutation carriers (HR = 0.60, 95% CI: 0.40-0.89, P = 0.01) and BRCA2 mutation carriers (HR = 0.42, 95% CI: 0.20-0.86, P = 0.02). RRSO is an effective way to reduce BC risk among women with BRCA1/2 mutation, especially in younger women. BRCA1/2 mutation carriers could benefit from RRSO in the immediate 5 years after surgery.

Wang Y ，Song Z ，Zhang S ，Wang X ，Li P ... -  《-》

Risk-reducing bilateral salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations.

Eleje GU ，Eke AC ，Ezebialu IU ，Ikechebelu JI ，Ugwu EO ，Okonkwo OO ... -  《Cochrane Database of Systematic Reviews》