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 ... -  《-》

Association of premenopausal risk-reducing salpingo-oophorectomy with breast cancer risk in BRCA1/2 mutation carriers: Maximising bias-reduction.

Whether risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 carriers reduces the breast cancer (BC) risk is conflicting, potentially due to methodological issues of prior analysis. We analysed the association between premenopausal RRSO and BC risk in BRCA1/2 carriers after adjusting for potential biases. We analysed data from 444 BRCA1 and 409 BRCA2 carriers under age 51 with no cancer prior to genetic testing or during first 6 months of surveillance (to avoid cancer-induced testing bias and prevalent-cancer bias). Observation started 6 months after genetic testing (to avoid event-free time bias), until BC diagnosis, risk-reducing mastectomy (RRM) or death. A multistate model with four states (non-RRSO, RRSO, RRM and BC) and five transitions was fitted to characterise outcomes and to calculate the BC risk reduction after premenopausal RRSO (before age 51). A systematic review was performed to assess the association between premenopausal RRSO and BC. During a mean follow-up of 4.3 years, 96 women (11.3%) developed BC (54 BRCA1, 42 BRCA2). The risk of BC after premenopausal RRSO decreased significantly in BRCA1 carriers (hazard ratio (HR) = 0.45 [95% confidence interval (CI):0.22-0.92]), but was not conclusive in BRCA2 carriers (HR = 0.77 [95%CI:0.35-1.67]). The systematic review suggested that premenopausal RRSO is associated with a decrease of BC risk in both BRCA1 and BRCA2 carriers. Premenopausal RRSO was associated with BC risk reduction in BRCA1 carriers, which can help guide cancer risk-reducing strategies in this population. Longer follow-up and larger sample size may be needed to estimate the potential benefit in BRCA2 carriers.

Stjepanovic N ，Villacampa G ，Nead KT ，Torres-Esquius S ，Melis GG ，Nathanson KL ，Teule A ，Brunet J ，Y Cajal TR ，Llort G ，Dienstmann R ，Rue M ，Domchek SM ，Balmaña J ... -  《-》

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 ... -  《-》

Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers.

Mavaddat N ，Antoniou AC ，Mooij TM ，Hooning MJ ，Heemskerk-Gerritsen BA ，GENEPSO ，Noguès C ，Gauthier-Villars M ，Caron O ，Gesta P ，Pujol P ，Lortholary A ，EMBRACE ，Barrowdale D ，Frost D ，Evans DG ，Izatt L ，Adlard J ，Eeles R ，Brewer C ，Tischkowitz M ，Henderson A ，Cook J ，Eccles D ，HEBON ，van Engelen K ，Mourits MJE ，Ausems MGEM ，Koppert LB ，Hopper JL ，John EM ，Chung WK ，Andrulis IL ，Daly MB ，Buys SS ，kConFab Investigators ，Benitez J ，Caldes T ，Jakubowska A ，Simard J ，Singer CF ，Tan Y ，Olah E ，Navratilova M ，Foretova L ，Gerdes AM ，Roos-Blom MJ ，Van Leeuwen FE ，Arver B ，Olsson H ，Schmutzler RK ，Engel C ，Kast K ，Phillips KA ，Terry MB ，Milne RL ，Goldgar DE ，Rookus MA ，Andrieu N ，Easton DF ，IBCCS ，kConFab ，BCFR ... -  《-》

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 ... -  《-》