Chlebowski Rowan T, Kuller Lewis H, Prentice Ross L, Stefanick Marcia L, Manson JoAnn E, Gass Margery, Aragaki Aaron K, Ockene Judith K, Lane Dorothy S, Sarto Gloria E, Rajkovic Aleksandar, Schenken Robert, Hendrix Susan L, Ravdin Peter M, Rohan Thomas E, Yasmeen Shagufta, Anderson Garnet
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
N Engl J Med. 2009 Feb 5;360(6):573-87. doi: 10.1056/NEJMoa0807684.
Following the release of the 2002 report of the Women's Health Initiative (WHI) trial of estrogen plus progestin, the use of menopausal hormone therapy in the United States decreased substantially. Subsequently, the incidence of breast cancer also dropped, suggesting a cause-and-effect relation between hormone treatment and breast cancer. However, the cause of this decrease remains controversial.
We analyzed the results of the WHI randomized clinical trial--in which one study group received 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily and another group received placebo--and examined temporal trends in breast-cancer diagnoses in the WHI observational-study cohort. Risk factors for breast cancer, frequency of mammography, and time-specific incidence of breast cancer were assessed in relation to combined hormone use.
In the clinical trial, there were fewer breast-cancer diagnoses in the group receiving estrogen plus progestin than in the placebo group in the initial 2 years of the study, but the number of diagnoses increased over the course of the 5.6-year intervention period. The elevated risk decreased rapidly after both groups stopped taking the study pills, despite a similar frequency of mammography. In the observational study, the incidence of breast cancer was initially about two times as high in the group receiving menopausal hormones as in the placebo group, but this difference in incidence decreased rapidly in about 2 years, coinciding with year-to-year reductions in combined hormone use. During this period, differences in the frequency of mammography between the two groups were unchanged.
The increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography.
2002年妇女健康倡议（WHI）雌激素加孕激素试验报告发布后，美国更年期激素疗法的使用大幅减少。随后，乳腺癌发病率也下降，这表明激素治疗与乳腺癌之间存在因果关系。然而，这种下降的原因仍存在争议。
我们分析了WHI随机临床试验的结果（其中一个研究组每天接受0.625毫克结合马雌激素加2.5毫克醋酸甲羟孕酮，另一组接受安慰剂），并研究了WHI观察性研究队列中乳腺癌诊断的时间趋势。我们评估了与联合激素使用相关的乳腺癌风险因素、乳房X线摄影频率以及特定时间的乳腺癌发病率。
在临床试验中，接受雌激素加孕激素的组在研究的最初两年中乳腺癌诊断数少于安慰剂组，但在5.6年的干预期内诊断数增加。两组停止服用研究药物后，尽管乳房X线摄影频率相似，但升高的风险迅速下降。在观察性研究中，接受更年期激素的组中乳腺癌发病率最初约为安慰剂组的两倍，但这种发病率差异在约2年内迅速下降，这与联合激素使用逐年减少相吻合。在此期间，两组之间乳房X线摄影频率的差异没有变化。
与使用雌激素加孕激素相关的乳腺癌风险在联合激素治疗停止后不久就显著下降，并且与乳房X线摄影频率的变化无关。
