National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Metabolic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Dr. rm 6E344, Bethesda, MD, 20892-9768, USA.
Breast Cancer Res. 2020 Nov 25;22(1):129. doi: 10.1186/s13058-020-01365-9.
Menopausal hormone therapy (MHT) increases breast cancer (BC) risk, but cohort studies largely consider use only at enrollment. Evidence is limited on how changes in MHT use alter the magnitude of risk, and whether risk varies between invasive and in situ cancer, by histology or by hormone receptor status.
We investigated the roles of estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT) on BC risk overall, by histology and estrogen receptor (ER) and progesterone receptor (PR) status, and on incidence of in situ disease, in the NIH-AARP cohort. Participants included 118,760 postmenopausal women (50-71 years), of whom 63.5% (n = 75,398) provided MHT use information at baseline in 1996 and in a follow-up survey in 2004, subsequent to the dissemination in 2002 of the Women's Health Initiative trial safety concerns regarding EPT. ET analyses included 50,476 women with hysterectomy (31,439 with follow-up data); EPT analyses included 68,284 women with intact uteri (43,959 with follow-up data). Adjusted hazard ratios (HRs) were estimated using Cox proportional hazards models using age as the time metric with follow-up through 2011.
Eight thousand three hundred thirty-three incident BC cases were accrued, 2479 in women with follow-up data. BC risk was not elevated in current ET users at baseline (HR = 1.05, 95% confidence interval [CI] CI = 0.95-1.16) but was higher in women continuing use through 2004 (HR = 1.35, 95% CI = 1.04-1.75). Ever EPT use at baseline was associated with elevated BC risk overall (HR = 1.54 (1.44-1.64), with a doubling in risk for women with 10 or more years of use, for in situ disease, and across subtypes defined by histology and ER/PR status (all p < 0.004). Risk persisted in women who continued EPT through 2004 (HR = 1.80, 95% CI = 1.39-2.32). In contrast, no association was seen in women who discontinued EPT before 2004 (HR = 1.14, 95% CI = 0.99-1.30).
ET use was not associated with BC risk in this cohort, although excess risk was suggested in women who continued use through 2004. EPT use was linked to elevated in situ and invasive BC risk, and elevated risk across invasive BC histologic and hormone receptor-defined subtypes, with the highest risk for women who continued use through the 2004 follow-up survey.
绝经后激素治疗（MHT）会增加乳腺癌（BC）的风险，但队列研究主要考虑的是在入组时的使用情况。关于 MHT 使用的变化如何改变风险的大小，以及风险是否因组织学或激素受体状态而在浸润性和原位癌之间、在不同类型的癌症之间存在差异，证据有限。
我们在 NIH-AARP 队列中研究了雌激素单独治疗（ET）和雌激素加孕激素治疗（EPT）对总体 BC 风险、组织学以及雌激素受体（ER）和孕激素受体（PR）状态的影响，以及对原位疾病发病率的影响。参与者包括 118760 名绝经后妇女（50-71 岁），其中 63.5%（n=75398）在 1996 年基线时和 2004 年后续随访调查中提供了 MHT 使用信息，后续在 2002 年发布了妇女健康倡议试验关于 EPT 的安全性担忧。ET 分析包括 50476 名子宫切除术患者（31439 名有随访数据）；EPT 分析包括 68284 名有完整子宫的患者（43959 名有随访数据）。使用 Cox 比例风险模型估计调整后的风险比（HR），使用年龄作为时间指标，随访至 2011 年。
共累积了 8333 例浸润性 BC 病例，其中 2479 例有随访数据。当前 ET 使用者在基线时的 BC 风险没有升高（HR=1.05，95%置信区间[CI]CI=0.95-1.16），但在 2004 年继续使用者的风险更高（HR=1.35，95% CI=1.04-1.75）。基线时曾使用过 EPT 与总体 BC 风险升高相关（HR=1.54（1.44-1.64），对于使用 10 年或更长时间的女性，风险增加一倍，对于原位疾病和根据组织学和 ER/PR 状态定义的亚型也是如此（所有 p<0.004）。在 2004 年继续使用 EPT 的女性中，风险持续存在（HR=1.80，95% CI=1.39-2.32）。相比之下，在 2004 年之前停止使用 EPT 的女性中未发现关联（HR=1.14，95% CI=0.99-1.30）。
在本队列中，ET 使用与 BC 风险无关，但在 2004 年继续使用的女性中，风险似乎有所增加。EPT 使用与原位和浸润性 BC 风险升高相关，与浸润性 BC 的组织学和激素受体定义亚型的风险升高相关，对于持续使用至 2004 年随访调查的女性，风险最高。
