Department of Gynecology, Shaare Zedek Medical Center, Jerusalem, Israel; Medical Genetics Unit, Shaare Zedek Medical Center, Jerusalem, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Israel.
Faculty of Medicine, Hebrew University of Jerusalem, Israel.
Eur J Cancer. 2021 May;148:95-102. doi: 10.1016/j.ejca.2021.02.007. Epub 2021 Mar 17.
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.
BRCA1/BRCA2 突变携带者通常在自然绝经前进行降低风险的输卵管卵巢切除术 (RRSO)，这引发了激素替代治疗 (HRT) 使用的问题。关于 HRT 对乳腺癌 (BC) 风险的影响存在相互矛盾的证据，并且基于暴露年龄的数据有限。在普通人群中，HRT 使用者的 BC 风险增加（风险比=1.34）。我们评估了短期 HRT 使用对健康的 BRCA1/2 突变携带者的 BC 风险的影响，重点关注暴露于 HRT 的年龄。
对 306 例连续的接受 RRSO 的健康 BRCA1/2 突变携带者进行了回顾性队列研究，平均随访 7.26 年。我们比较了接受 HRT 和未接受 HRT 的携带者的 BC 发病率随时间的变化。
36 名携带者被诊断为 BC，HRT 组 148 名患者中的 20 名（13.5%）与非 HRT 组 155 名患者中的 16 名（10.3%）相比（比值比 [OR] = 1.4，95%置信区间 [CI] = 0.7-2.7）。在 RRSO 时年龄为 45 岁或以下的女性中，HRT 并未影响 BC 发生率。然而，在 RRSO 时年龄大于 45 岁的女性中，HRT 使用者的 BC 发生率明显高于非使用者（OR = 3.43，p<0.05，95%CI = 1.2-9.8）。
在本研究中，BRCA1/BRCA2 携带者 RRSO 后短期使用 HRT 与 45 岁以上携带者的 BC 风险增加三倍相关。这些结果表明，风险可能与 HRT 暴露时间有关，即使在 BRCA1/2 携带者中也是如此，这与自然绝经年龄有关。需要进一步的研究来验证并指导未来的建议。
