在妇女健康倡议（WHI）随机研究中，研究者发现雌激素联合黄体酮会增加女性乳腺癌发病率和死亡率。与之相反，绝大多数和雌激素联合黄体酮有关的观察性研究都指出这些乳腺癌患者的预后尚可。为了对上述问题进行进一步探讨，来自加利福尼亚州UCLA医学中心的Rowan T. Chlebowski等选择了与WHI临床研究中受试者具有相同特征的受试者组成了WHI观察性研究的受试者，并探讨了雌激素联合黄体酮对乳腺癌患者发病率和死亡率的影响，他们的研究结果发表在JNCI 3月的在线期刊上。
两组患者确诊后的生存时间
研究者纳入了41449名绝经后的女性作为受试者，她们既往没有接受过子宫切除术，并且在2年内她们的钼靶检查结果未见明显异常。在这些女性中，25328人不应用激素，另有16121名女性联合应用雌激素和黄体酮。研究者应用了多变量调整后的Cox风险比例回归模型来计算危险比和95%可信区间。所有的统计检验都在双侧进行。
在进行了约为111.3年的随访之后，研究者发现2236名女性成为了乳腺癌患者，与不应用激素的女性相比，联合应用雌激素和黄体酮的女性的乳腺癌发病率更高，分别为0.42%和0.60%，HR为1.55，95%可信区间为1.41至1.70，差异具有显著统计学意义。并且研究者发现在接近绝经期时才开始应用激素治疗的女性乳腺癌发病风险更高，随着开始激素治疗的时间距离绝经期的延长发病风险呈线性递减，结果同样具有显著统计学意义。乳腺癌确诊后的生存期（从确诊时间至死亡）在两组之间未有明显的差异，HR为1.03，95%可信区间为0.79至1.35。从人群的角度来看，与未使用激素的女性相比，联合应用雌激素和黄体酮组中的女性的死于乳腺癌的人数更多（HR为1.32，95%可信区间为0.90至1.93），并且总体死亡数也更高（HR为1.65，95%可信区间为1.29至2.12）。
与WHI随机研究的结果一致，本研究发现雌激素联合黄体酮会增加乳腺癌的发病率。虽然在确诊为乳腺癌之后，激素的应用并不会影响患者的预后，但是由于联合激素应用增加了患者的发病率，所以可以预期的是联合激素应用组中的死亡率也会相应的增加。(生物谷Bioon.com)
doi: 10.1093/jnci/djt043
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Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in the Women’s Health Initiative Observational Study
Rowan T. Chlebowski, JoAnn E. Manson, Garnet L. Anderson, Jane A. Cauley, Aaron K. Aragaki, Marcia L. Stefanick, Dorothy S. Lane, Karen C. Johnson, Jean Wactawski-Wende, Chu Chen, Lihong Qi, Shagufta Yasmeen, Polly A. Newcomb and Ross L. Prentice .
Background In the Women’s Health Initiative (WHI) randomized trial, estrogen plus progestin increased both breast cancer incidence and mortality. In contrast, most observational studies associate estrogen plus progestin with favorable prognosis breast cancers. To address differences, a cohort of WHI observational study participants with characteristics similar to the WHI clinical trial was studied.
Methods We identified 41 449 postmenopausal women with no prior hysterectomy and mammogram negative within 2 years who were either not hormone users (n = 25 328) or estrogen and progestin users (n = 16 121). Multivariable-adjusted Cox proportional hazard regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). All statistical tests were two-sided.
Results After a mean of 11.3 (SD = 3.1) years, with 2236 breast cancers, incidence was higher in estrogen plus progestin users than in nonusers (0.60% vs 0.42%, annualized rate, respectively; HR = 1.55, 95% CI = 1.41 to 1.70, P < .001). Women initiating hormone therapy closer to menopause had higher breast cancer risk with linear diminishing influence as time from menopause increased (P < .001). Survival after breast cancer, measured from diagnosis, was similar in combined hormone therapy users and nonusers (HR = 1.03, 95% CI = 0.79 to 1.35). On a population basis, there were somewhat more deaths from breast cancer, measured from cohort entry (HR = 1.32, 95% CI = 0.90 to 1.93, P = .15), and more all-cause deaths after breast cancer (HR = 1.65, 95% CI = 1.29 to 2.12, P < .001) in estrogen plus progestin users than in nonusers.
Conclusions Consistent with WHI randomized trial findings, estrogen plus progestin use is associated with increased breast cancer incidence. Because prognosis after diagnosis on combined hormone therapy is similar to that of nonusers, increased breast cancer mortality can be expected.
