Chlebowski Rowan T, Hendrix Susan L, Langer Robert D, Stefanick Marcia L, Gass Margery, Lane Dorothy, Rodabough Rebecca J, Gilligan Mary Ann, Cyr Michele G, Thomson Cynthia A, Khandekar Janardan, Petrovitch Helen, McTiernan Anne
Harbor-UCLA Research and Education Institute, Torrance 90502, USA.
JAMA. 2003 Jun 25;289(24):3243-53. doi: 10.1001/jama.289.24.3243.
The Women's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Outstanding issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography.
To determine the relationship among estrogen plus progestin use, breast cancer characteristics, and mammography recommendations.
DESIGN, SETTING, AND PARTICIPANTS: Following a comprehensive breast cancer risk assessment, 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were randomly assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40 clinical centers. Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter.
Breast cancer number and characteristics, and frequency of abnormal mammograms by estrogen plus progestin exposure.
In intent-to-treat analyses, estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001) and invasive (199 vs 150 cases; HR, 1.24; weighted P =.003) breast cancers compared with placebo. The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P =.04) and were at more advanced stage (regional/metastatic 25.4% vs 16.0%, respectively; P =.04) compared with those diagnosed in the placebo group. After 1 year, the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration.
Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms. These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.
女性健康倡议组织关于雌激素加孕激素联合用药的试验提前终止，因为包括浸润性乳腺癌在内的总体健康风险超过了益处。此前未解决的突出问题包括使用激素的女性中观察到的乳腺癌特征，以及诊断是否可能受到激素对乳房X光检查影响。
确定雌激素加孕激素的使用、乳腺癌特征和乳房X光检查建议之间的关系。
设计、地点和参与者：在进行全面的乳腺癌风险评估后，1993年至1998年期间，40个临床中心将16608名年龄在50至79岁、子宫完整的绝经后女性随机分配，分别接受结合马雌激素（0.625毫克/天）加醋酸甲羟孕酮（2.5毫克/天）或安慰剂。在基线时以及此后每年进行乳房X光筛查和临床乳房检查。
乳腺癌的数量和特征，以及根据雌激素加孕激素暴露情况出现乳房X光检查异常的频率。
在意向性分析中，与安慰剂相比，雌激素加孕激素增加了乳腺癌总数（245例对185例；风险比[HR]，1.24；加权P<.001）和浸润性乳腺癌（199例对150例；HR，1.24；加权P =.003）。雌激素加孕激素组诊断出的浸润性乳腺癌在组织学和分级上相似，但与安慰剂组相比更大（平均[标准差]分别为1.7厘米[1.1]对1.5厘米[0.9]；P =.04），且处于更晚期阶段（区域/转移分别为25.4%对16.0%；P =.04）。1年后，雌激素加孕激素组乳房X光检查异常的女性百分比（7656名中的716名[9.4%]）显著高于安慰剂组（7310名中的398名[5.4%]；P<.00），这种模式在研究期间持续存在。
相对短期使用雌激素加孕激素会增加乳腺癌发病率，与使用安慰剂相比，这些乳腺癌在更晚期被诊断出来，并且还会大幅增加乳房X光检查异常的女性百分比。这些结果表明雌激素加孕激素可能刺激乳腺癌生长并阻碍乳腺癌诊断。
