Non-cancer endpoints in BRCA1/2 carriers after risk-reducing salpingo-oophorectomy

Abstract

Risk-reducing salpingo-oophorectomy (RRSO) significantly reduces the risk of ovarian cancer and breast cancer in pre-menopausal women with BRCA1 and BRCA2 (B1/2) mutations. Despite its clear benefits, little is known about non-cancer endpoints in this population. Medical records were examined in 226 B1/2 mutation carriers, who had previously undergone RRSO with a focus on bone health as well as the frequency of hypertension, hyperlipidemia, coronary artery disease (CAD), myocardial infarction (MI), diabetes, hypothyroidism and depression. From the medical records, DEXA scans, medications and medical conditions were recorded. Of the 226 patient records examined, 16% (36/226) had hypertension, 17% (39/226) hyperlipidemia, 2% (5/226) CAD or MI, 2% (4/226) diabetes, 13% (29/226) hypothyroidism and 14% (31/226) depression. DEXA results were available in 152 women. Of those DEXA scans, 71% (108/152) were abnormal (57% osteopenia and 14% osteoporosis). Among women who underwent RRSO prior to age 50, 71% (62/88) had osteopenia/osteoporosis. Although there was no difference in osteopenia/osteoporosis in women with RRSO prior to age 50 compared to those RRSO > 50, the age at follow up in these two groups differs greatly (mean age 44.7 vs. 60.6), suggesting that both current age and age at RRSO contribute to bone health assessment. In summary, here, we report the prevalence of non-cancer endpoints in a cohort of B1/2 mutation carriers and note a particularly high rate of osteopenia and osteoporosis in B1/2 with breast cancer undergoing RRSO prior to 50. Despite the risk reduction RRSO offers, attention should be paid to non-cancer endpoints, particularly bone health, in this population.

Osteoporosis risk and management in BRCA1 and BRCA2 carriers who undergo risk-reducing salpingo-oophorectomy

“…In this study, history of breast cancer, AI use, or chemotherapy had no significant effect on DXA result. Their study population was similar to ours in having a high rate of breast cancer (66%) but was distinct with a much lower rate of HRT use at 5% [15]. Since both our study and the Cohen et al study were unable to define a subset of women at greatest risk for bone disease, and the frequency of bone loss demonstrated in both cohorts was high, this underscores the recommendation that all women after RRSO should have screening with a DXA scan, regardless of additional risk factors.…”

Surgical Menopause

“…62,64,65 Overall, there is a growing body of evidence that bilateral oophorectomy, particularly before the natural menopause, is associated with greater bone loss and higher rates of osteoporosis and bone fractures. 52,[66][67][68][69][70][71][72] Cognition and central nervous system disease Although the evidence for the effect of menopause on cognition has been conflicting, the data suggest an age-dependent neuroprotective effect of estrogen. 73 For women undergoing surgical menopause before the age of natural menopause, it seems that use of estrogen replacement up until the age of natural menopause may be particularly important.…”

Bone mineral density and fractures after risk-reducing salpingo-oophorectomy in women at increased risk for breast and ovarian cancer

“…Others found a transient effect on fracture incidence or no effect at all [10,11]. Several studies reported a high risk of osteoporosis after RRSO; however, these studies were all prone to bias, due to retrospective study designs, selected study populations and in some cases lack of a control group [12][13][14][15].…”