Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial.
Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial.
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共轭性雌激素和乳腺癌的发病率和乳腺癌的死亡率以及子宫切除术后妇女：妇女健康计划的扩展随访随机性安慰剂对照试验。
DOI：
10.1016/s1470-2045(12)70075-x
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发表时间：
2012-05
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通讯作者：
Wactawski-Wende J
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作者：
Anderson GL;Chlebowski RT;Aragaki AK;Kuller LH;Manson JE;Gass M;Bluhm E;Connelly S;Hubbell FA;Lane D;Martin L;Ockene J;Rohan T;Schenken R;Wactawski-Wende J
与许多观察性研究不同的是，在妇女健康倡议(WHI)试验中，随机服用雌激素的女性侵袭性乳腺癌的发病率比那些分配了安慰剂的女性低。雌激素的使用对乳腺癌死亡率的影响尚未见报道。在1993至1998年间，WHI招募了来自40个美国中心的10,739名绝经后妇女参加了一项随机、双盲、安慰剂对照试验，评估口服结合马雌激素(0.625 mg/d)。年龄在50-79岁之间、有子宫切除史、预期3年存活期和乳房X光检查合格的妇女，通过计算机化的排列区块算法随机分组，按年龄组和中心分层，接受雌激素或匹配的安慰剂。这项试验于2004年因对中风的不良影响而提前终止。在截至2009年8月的长期随访中，我们评估了雌激素使用对浸润性乳腺癌发病率、肿瘤特征和死亡率的长期影响。用COX回归模型估计意向治疗风险比[HR]。经过中位数11.8年(四分位数范围[IQR]，9.1至12.9年)的随访，与安慰剂(151对199乳腺癌；年化率，0.27%对0.35%；HR，0.77；95%可信区间[CI]，0.62至0.95；P=0.02)相比，与安慰剂相比，单独使用结合雌激素的中位数为5.9年(IQR，2.5至7.3)与较低的浸润性乳腺癌发病率相关(P=0.76)。95%CI，0.61~1.02)和干预后效果(HR，0.75；95%CI：0.51~1.09)。观察良性乳腺疾病(P=0·01)和乳腺癌家族史(P=0·02)的潜在影响。在单独服用雌激素的组中，死于乳腺癌的女性较少(6例死亡，16例死亡；年化死亡率0.09%vs.0.024%；HR，0.37；95%CI，0.13至0.91；P=0.03)；乳腺癌确诊后死于各种原因的女性较少(30例死亡vs.50例；年化死亡率0.046%vs.0.076%；HR 0.62；95%CI，0.39至0.9；P=0.04)。寻求缓解更年期症状的子宫切除患者可以得到保证，雌激素的使用对乳腺癌的影响与本试验中观察到的持续时间一致。然而，这些发现并不支持雌激素用于降低乳腺癌风险，因为这一益处可能不适用于高危人群。美国国家心肺血液研究所。惠氏提供了研究药物。
In contrast to many observational studies, women in the Women’s Health Initiative (WHI) trial randomised to oestrogen-alone had lower invasive breast cancer incidence than those assigned placebo. Influence of oestrogen use on breast cancer mortality has not been reported. Between 1993 and 1998, the WHI enrolled 10,739 postmenopausal women from 40 US centres into a randomized, double-masked, placebo-controlled trial evaluating oral conjugated equine oestrogen (0·625 mg/d). Women aged 50–79 years with prior hysterectomy, anticipated 3-year survival, and mammography clearance were randomized by a computerized, permuted block algorithm, stratified by age group and centre, to receive oestrogen or matching placebo. The trial was terminated early, in 2004, for an adverse effect on stroke. In extended follow-up through August 2009, we assessed long-term effects of oestrogen use on invasive breast cancer incidence, tumor characteristics, and mortality. Cox regression models were used to estimate intention-to-treat hazard ratios [HRs]. After a median 11.8 (interquartile range [IQR], 9·1 to 12·9) years of follow-up, conjugated equine oestrogen-alone use for a median of 5·9 (IQR, 2·5 to 7·3) years was associated with lower invasive breast cancer incidence compared to placebo (151 vs. 199 breast cancers; annualized rates, 0·27% vs. 0·35%; HR, 0·77; 95% confidence interval [CI], 0·62 to 0·95; P=0·02) with no difference (P=0·76) between intervention-phase (HR, 0·79; 95% CI, 0·61 to 1·02) and post-intervention effects (HR, 0·75; 95% CI: 0·51 to 1·09) ). Potential effect modification by benign breast disease (P=0·01) and family history of breast cancer (P=0·02) was observed. In the oestrogen-alone group fewer women died from breast cancer (6 vs.16 deaths; annualized rates 0·009% vs. 0·024%; HR, 0·37; 95% CI, 0·13 to 0·91; P=0.03) and fewer died from all causes after a breast cancer diagnosis (30 vs. 50 deaths; annualized rates, 0·046% vs. 0·076%; HR, 0·62; 95% CI, 0·39 to 0·9;, P=0·04). Women with hysterectomy seeking relief of climacteric symptoms may be given reassurance regarding breast cancer influence of oestrogen use consistent with durations observed in this trial. However, these findings do not support oestrogen use for breast cancer risk reduction since this benefit may not apply to populations at higher risk. US National Heart, Lung and Blood Institute. Wyeth provided study medications.