Abstract
BackgroundBRCA1/2 mutation carriers are generally exposed to early menopause due to risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 years. This risk-reducing intervention is based on a 10–40% life-time risk of ovarian cancer in this population. Although effective, premature and acute menopause induces non-cancer related morbidity in both the short and long term. Little is known about the impact of RRSO on the cardiovascular system. MethodsThis cross-sectional study explored the relationship between time since RRSO and signs of subclinical atherosclerosis, as measured by carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), in 165 BRCA1/2 mutation carriers. All participants, aged 40 to 63 years, underwent RRSO before the age of 45 years, and at least 5 years ago. Cardiovascular risk factors were assessed by questionnaires and a single screening visit. Data were analyzed using linear regression models. ResultsMean CIMT was 692.7 μm (SD 87.0), and mean central PWV 6.40 m/s (SD 1.42). After adjustment for age and several relevant cardiovascular risk factors, time since RRSO was not associated with CIMT (β=0.68 μm; 95% CI –4.02, 5.38) and PWV (β=44 mm/s; 95% CI –32, 120). Compared to women of a reference group from the general population, lower systolic blood pressure [mean difference 12 mmHg; 95% confidence interval (CI) 10, 14] was found in BRCA1/2 mutation carriers. ConclusionsWe found that, in BRCA1/2 mutation carriers, at 5 to 24 years follow-up, time since RRSO is not related to development of subclinical atherosclerosis. However, the follow-up period in these relatively young women might have been too short.
Highlights
BRCA1/2 mutation carriers have a lifetime risk for breast and ovarian cancer of 49–57% and 18–40%, respectively [1]
A possible role of deficient DNA repair mechanisms, as in BRCA1/2 mutation carriers, in the cardiovascular (CV) system is suggested in animal studies [10,11], but this is yet to be investigated in humans
The Cardiovascular Risk after risk-reducing salpingooophorectomy (RRSO) in BRCA1/2 Mutation Carriers (CARSOBRA) study was a single-center cohort study performed in the Radboud University Medical Center (Radboudumc) in the Netherlands between June and November 2015
Summary
BRCA1/2 mutation carriers have a lifetime risk for breast and ovarian cancer of 49–57% and 18–40%, respectively [1]. 2% and 15% of all women with respectively breast or ovarian cancer carry a germline mutation in the BRCA1 or BRCA2 gene [2]. To reduce ovarian cancer risk, BRCA1/2 mutation carriers are strongly advised to undergo a risk-reducing salpingooophorectomy (RRSO) around the age of 40 years, which is a highly effective strategy [3]. BRCA1/2 mutation carriers are generally exposed to early menopause due to risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 years. This risk-reducing intervention is based on a 10–40% life-time risk of ovarian cancer in this population. Little is known about the impact of RRSO on the cardiovascular system
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