Hormone Replacement Therapy Does Not Increase Risk for Ovarian Cancer in Women with BRCAmutations
Ovarian Cancer Risk
Using hormone therapy (HT) does not appear to increase the risk of developing ovarian cancer in BRCA mutation carriers, according to this case-control study of 162 matched sets of women with the mutations. Women with a diagnosis of ovarian cancer were matched to controls by mutation type, year of birth, and age at menopause. Cases had a history of invasive ovarian, fallopian tube, or peritoneal cancer. Controls had never had cancer but were carriers of the BRCA1 or BRCA2 mutation. One or more controls were selected for each case (162 cases and 375 controls); ages ranged from 48 to 86 years (mean, 61.2-62.7). Information on HT use was derived from questionnaires routinely given to mutation carriers. The study sought to determine by logistic regression analysis the association between HT use and risk of developing ovarian cancer among women with BRCA1 or BRCA2 mutations. Risk was stratified by mutation and HT type.
Compared with those who had never used HT, the odds ratio (OR) associated with HT use was 0.93 (95% CI, 0.56-1.56). When the data were stratified by mutation type, HT use was not associated with the risk of BRCA1- or BRCA2associated ovarian cancer. Although not significant, women who had used estrogen (either as estrogen alone or estrogen plus progestin) had a modest increase in risk (OR, 1.50; 95% CI, 0.73-3.11). In contrast, ever using progestin (progestin alone or estrogen plus progestin) appeared to diminish risk (OR, 0.57; 95% CI, 0.24-1.35). These associations, however, were lessened after adjustment for covariates.
The authors conclude that HT use has little impact on risk for ovarian cancer among women who carry the BRCA1 or BRCA2 mutations. They note that this is in accordance with other studies that report no association between HT use and the development of ovarian cancer among women in general.
Comment. Studies of the relationship between HT and ovarian cancer risk have yielded inconsistent results, but the strongest data in support of an association with increased risk are with long-term use of unopposed estrogen. The present paper suggests that HT does not increase ovarian cancer risk in women who carry BRCA1 or BRCA2 mutations, but the relatively small size of the study and short median duration of hormone use did not allow for definitive examination of "duration of use" effects or the risk with unopposed estrogen. These limitations aside, the longer median duration of use in controls compared to cases is supportive of the conclusion that HT does not increase ovarian cancer risk in BRCA1/2 carriers. The finding that use of progestin appeared to be protective is intriguing in view of observational and biological evidence that progestins may act as chemopreventives in the ovarian epithelium.
From a practical clinical standpoint, only those BRCA1/2 carriers who have not already had breast cancer and have undergone prophylactic mastectomy are likely to consider HT because of their exceedingly high risk of breast cancer. Furthermore, because of their considerable risk of ovarian cancer and its high lethality, women who carry BRCA1/2 mutations and have completed childbearing would be best advised to undergo prophylactic salpinoophorectomy, which essentially eliminates the risk of ovarian cancer. The Society of Gynecologic Oncologists and other professional societies and experts have issued opinions strongly supporting this practice. It is our hope that the issue of whether HT affects ovarian cancer risk in BRCA1/2 mutation carriers will become an increasingly moot issue as prophylactic salpingoophorectomy becomes adopted as the standard of care.