Dinger Juergen C, Heinemann Lothar A J, Möhner Sabine, Thai Do Minh, Assmann Anita
Centre for Epidemiology & Health Research Berlin, Invalidenstr, 115, 10115 Berlin, Germany.
BMC Womens Health. 2006 Sep 12;6:13. doi: 10.1186/1472-6874-6-13.
Previous epidemiological studies have inconsistently shown a modestly increased breast cancer risk associated with hormone replacement therapy (HRT). Limited information is available about different formulations--particularly concerning different progestins.
A case-control study was performed within Germany in collaboration with regional cancer registries and tumor centers. Up to 5 controls were matched breast cancer cases. Conditional logistic regression analysis was applied to estimate crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Stratified analyses were performed to compare the risk of different estrogens, progestins, and combinations.
A total of 3593 cases of breast cancer were identified and compared with 9098 controls. The adjusted overall risk estimate for breast cancer (BC) associated with current or past use of HRT was 1.2 (1.1-1.3), and almost identical for lag times from 6 months to 6 years prior to diagnosis. No significant trend of increasing BC risk was found with increasing duration of HRT use, or time since first or last use in aggregate. Many established BC risk factors significantly modified the effect of HRT on BC risk, particularly first-degree family history of BC, higher age, lower education, higher body mass index (BMI), and never having used oral contraceptives (OCs) during lifetime. Whereas the overall risk estimates were stable, the numbers in many of the sub-analyses of HRT formulation groups (estrogens, progestins, and combinations) were too small for strong conclusions. Nevertheless, the BC risk seems not to vary much across HRT formulation subgroups. In particular, no substantial difference in BC risk was observed between HRT containing conjugated equine estrogens (CEE) or medroxyprogesterone acetate (MPA) and other formulations more common in Europe.
The BC risk of HRT use is rather small. Low risk estimates for BC and a high potential for residual confounding and bias in this observational study do not permit causal conclusions. Apparently, there is not much variation of the BC risk across HRT formulations (estrogens, progestins). However, the small numbers and the overlapping nature of some of the subgroups suggest cautious interpretation.
以往的流行病学研究结果并不一致，显示激素替代疗法（HRT）与乳腺癌风险略有增加相关。关于不同制剂的信息有限，尤其是关于不同孕激素的信息。
在德国与地区癌症登记处和肿瘤中心合作开展了一项病例对照研究。每例乳腺癌病例匹配多达5名对照。应用条件逻辑回归分析来估计粗比值比（OR）和调整后的比值比以及95%置信区间（95%CI）。进行分层分析以比较不同雌激素、孕激素及其组合的风险。
共识别出3593例乳腺癌病例，并与9098名对照进行比较。当前或既往使用HRT与乳腺癌（BC）相关的调整后总体风险估计值为1.2（1.1 - 1.3），且在诊断前6个月至6年的滞后时间内几乎相同。未发现随着HRT使用时间的延长或首次或末次使用以来的总时间增加，BC风险有显著增加趋势。许多已确定的BC风险因素显著改变了HRT对BC风险的影响，特别是BC的一级家族史、较高年龄、较低教育水平、较高体重指数（BMI）以及一生中从未使用过口服避孕药（OCs）。虽然总体风险估计值稳定，但HRT制剂组（雌激素、孕激素及其组合）的许多亚分析中的病例数过少，无法得出有力结论。然而，BC风险在HRT制剂亚组之间似乎差异不大。特别是，含结合马雌激素（CEE）或醋酸甲羟孕酮（MPA）的HRT与欧洲更常见的其他制剂之间在BC风险上未观察到实质性差异。
使用HRT的BC风险相当小。在这项观察性研究中，BC风险估计值较低且存在残留混杂和偏倚的高可能性，不允许得出因果结论。显然，BC风险在HRT制剂（雌激素、孕激素）之间变化不大。然而，一些亚组的病例数较少且存在重叠性质，这表明解释时需谨慎。
