Department of Epidemiology and Biostatistics, School of Public Health-Bloomington, Indiana University, Bloomington, IN, USA.
Breast Cancer Res Treat. 2013 Feb;137(3):915-25. doi: 10.1007/s10549-012-2402-0. Epub 2013 Jan 12.
Post-menopausal hormone therapy with estrogen plus progestin is consistently reported to be associated with an increased risk of invasive breast cancer. However, findings on an association between hormone use and ductal carcinoma in situ of the breast (DCIS), a possible precursor lesion of invasive breast cancer, are sparse and inconsistent. Women's Health Initiative data were used to assess the effects of hormone therapy on the risk of DCIS in two clinical trials of hormone therapy (16,276 women enrolled in the trial of daily conjugated equine estrogens plus medroxyprogesterone acetate (CEE + MPA) vs placebo; 10,187 women enrolled in the trial of CEE-alone vs placebo). The effects of hormone therapy on DCIS in clinical trial participants were assessed during the intervention, post-intervention, and entire followup periods, and in the observational study (OS; 30,421 CEE + MPA users and non-users and 18,657 CEE-alone users and non-users who met eligibility criteria similar to the clinical trial). Compared to placebo, CEE + MPA was non-significantly associated with higher risk of DCIS over approximate average of 11 years of follow-up (HR = 1.23; 95 % CI: 0.91-1.64). No statistical difference was detected between intervention and post-intervention phases (p = 0.32). Corresponding OS results supported an increased risk for DCIS in CEE + MPA users compared to women who were non-users (HR = 1.65; 95 % CI: 1.25-2.19) after adjusting for potential confounders. There was no clear association between CEE-alone use and risk of DCIS. CEE-alone trial data showed that the risk of DCIS was non-significantly lower in the treatment than in the placebo group, while analysis of the corresponding OS showed a non-significantly higher risk of DCIS in the CEE-alone users than non-users. Our analysis suggests that combined estrogen plus progestin use in post-menopausal women may increase risk of DCIS. Whether estrogen-alone use is associated with DCIS requires further investigation.
绝经后激素治疗（雌激素加孕激素）一直被报道与侵袭性乳腺癌的风险增加有关。然而，关于激素使用与乳腺导管原位癌（DCIS）之间的关联的发现很少且不一致，DCIS 是侵袭性乳腺癌的一个可能的前期病变。妇女健康倡议（Women's Health Initiative）的数据被用于评估激素治疗对两项激素治疗临床试验（16276 名接受每日结合雌激素加醋酸甲羟孕酮（CEE+MPA）治疗的试验参与者与安慰剂组相比；10187 名接受 CEE 单药治疗的试验参与者与安慰剂组相比）中 DCIS 风险的影响。在干预期间、干预后和整个随访期间，以及在观察性研究（OS；30421 名 CEE+MPA 使用者和非使用者以及 18657 名 CEE 单药使用者和非使用者符合与临床试验相似的入选标准）中评估了激素治疗对 DCIS 的影响。与安慰剂相比，CEE+MPA 与 DCIS 风险增加相关，但在平均约 11 年的随访中无统计学意义（HR=1.23；95%CI：0.91-1.64）。干预期和干预后阶段之间未检测到统计学差异（p=0.32）。OS 的相应结果支持 CEE+MPA 使用者与非使用者相比，DCIS 风险增加（调整潜在混杂因素后 HR=1.65；95%CI：1.25-2.19）。CEE 单药使用与 DCIS 风险之间没有明确的关联。CEE 单药试验数据显示，治疗组 DCIS 风险显著低于安慰剂组，而 OS 分析显示 CEE 单药使用者的 DCIS 风险显著高于非使用者。我们的分析表明，绝经后妇女联合使用雌激素加孕激素可能会增加 DCIS 的风险。雌激素单药使用是否与 DCIS 相关，需要进一步研究。
