Abstract
PurposeBRCA mutation carriers have an increased risk of developing breast or ovarian cancer. Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is associated with a decrease in risk for tubal and ovarian cancer. Hormone replacement therapy (HRT) may increase breast, ovarian, and endometrial cancer risk in the general population. This review analyses the published data on HRT and risk of cancer in BRCA mutation carriers with and without RRBSO.MethodsWe included all relevant articles published in English from 1995 to October 2020. Sources were identified through a search on PubMed and Cochrane Library.ResultsWe included one case–control and one retrospective cohort study on ovarian and one case–control study on endometrial cancer risk and HRT in BRCA mutation carriers. Regarding breast cancer risk, one case–control study on BRCA mutation carriers with and without RRBSO and one case–control study, one Markov chain decision model, two prospective cohort studies, and one metaanalysis on carriers after RRBSO were included. For ovarian cancer, results were ambiguous. For breast cancer, most studies did not find an adverse effect associated with HRT. However, some of the studies found a risk modification associated with different formulations and duration of use.ConclusionAlthough data are limited, HRT does not seem to have a relevant effect on cancer risk in BRCA mutation carriers. RRBSO should not be postponed to avoid subsequent HRT in this population. Adequate HRT after RRBSO should be offered to avoid chronic diseases resulting from low estrogen levels. However, further data on the safety of different formulations are needed.
Highlights
Hormone replacement therapy (HRT) is the most effective treatment for climacteric symptoms
A case–control study by Kotsopoulos et al from 2006 found no increase in ovarian cancer risk associated with use of HRT in BRCA1/2 mutation carriers (OR = 0.93; 95% CI 0.56–1.56; P = 0.79) (Kotsopoulos et al 2006)
When the type of HRT was examined, the study found a modest increase in ovarian cancer risk associated with ever use of estrogen (OR = 1.5; 95% CI 0.73–3,11) and a decrease in risk associated with ever use of progestin (OR = 0.57; 95% CI 0.24–1.35) compared with never use of HRT
Summary
Hormone replacement therapy (HRT) is the most effective treatment for climacteric symptoms. A recent metaanalysis shows a significant time dependent increase in breast cancer risk associated with HRT. The increase in risk was higher for combined estrogen–progestin therapy (EPT) than for estrogen-only therapy (ET). (Collaborative Group on Hormonal Factors in Breast Cancer 2019) In hysterectomized women, ET is, recommended, when HRT is needed. Recent metaanalyses show an increased ovarian cancer risk in HRT users. The observed increase in risk was associated with ET and EPT. An increased risk was observed after a duration of less than 5 years. (S3-Leitlinie Peri 2020) Regarding endometrial cancer, ET is associated with an increase in risk in non-hysterectomized women.
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