Chlebowski Rowan T, Anderson Garnet, Pettinger Mary, Lane Dorothy, Langer Robert D, Gilligan Mary Ann, Walsh Brian W, Chen Chu, McTiernan Anne
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Arch Intern Med. 2008 Feb 25;168(4):370-7; quiz 345. doi: 10.1001/archinternmed.2007.123.
The effect of combined hormone therapy on breast cancer detection is not established.
We examined the effect of combined hormone therapy on breast cancer detection in the Women's Health Initiative trial, which randomized 16,608 postmenopausal women to receive conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo. Mammography and breast examinations were performed at baseline and annually per protocol, with breast biopsies based on clinical findings. The effects of conjugated equine estrogens plus medroxyprogesterone acetate on breast cancer detection was determined throughout 5.6 years of intervention using receiver operating characteristic analyses to evaluate mammography results.
Conjugated equine estrogens plus medroxyprogesterone acetate increased the cumulative frequency of mammograms with abnormalities vs placebo (35.0% vs 23.0%; P < .001), which had less sensitivity for cancer detection and increased cumulative breast biopsy frequency (10.0% vs 6.1%; P < .001). Although breast cancers were significantly increased and were diagnosed at higher stages in the combined hormone group, biopsies in that group less frequently diagnosed cancer (14.8% vs 19.6%; P = .006). After discontinuation of combined hormone therapy, its adverse effect on mammograms modulated but remained significantly different from that of placebo for at least 12 months (P < .001).
Use of conjugated equine estrogens plus medroxyprogesterone acetate for approximately 5 years resulted in more than 1 in 10 and 1 in 25 women having otherwise avoidable mammogram abnormalities and breast biopsies, respectively, and compromised the diagnostic performance of both. This adverse effect on breast cancer detection should be incorporated into risk-benefit discussions with women considering even short-term combined hormone therapy.
clinicaltrials.gov Identifier: NCT00000611.
联合激素疗法对乳腺癌检测的影响尚未明确。
我们在妇女健康倡议试验中研究了联合激素疗法对乳腺癌检测的影响，该试验将16608名绝经后妇女随机分为两组，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。在基线时以及按照方案每年进行乳房X光检查和乳房检查，并根据临床检查结果进行乳房活检。在5.6年的干预期间，使用受试者操作特征分析来评估乳房X光检查结果，以确定结合马雌激素加醋酸甲羟孕酮对乳腺癌检测的影响。
与安慰剂相比，结合马雌激素加醋酸甲羟孕酮增加了乳房X光检查出现异常的累积频率（35.0%对23.0%；P < 0.001），其对癌症检测的敏感性较低，且增加了乳房活检的累积频率（10.0%对6.1%；P < 0.001）。虽然联合激素组的乳腺癌显著增加且在更高分期被诊断出来，但该组活检诊断出癌症的频率较低（14.8%对19.6%；P = 0.006）。在停用联合激素疗法后，其对乳房X光检查的不良影响有所缓解，但至少在12个月内仍与安慰剂有显著差异（P < 0.001）。
使用结合马雌激素加醋酸甲羟孕酮约5年导致超过十分之一和二十五分之一的女性分别出现原本可避免的乳房X光检查异常和乳房活检，并且损害了两者的诊断性能。对于考虑即使是短期联合激素疗法的女性，这种对乳腺癌检测的不良影响应纳入风险效益讨论中。
clinicaltrials.gov标识符：NCT00000611
