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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• 作者：Prof Garnet L Anderson ; PhD^a ; ^{garnet@whi.org} ; Prof Rowan T Chlebowski ; MD^b ; Aaron K Aragaki ; MS^a ; Prof Lewis H Kuller ; MD^c ; Prof JoAnn E Manson ; MD^d ; Prof Margery Gass ; MD^e ; Elizabeth Bluhm ; MD^f ; Prof Stephanie Connelly ; MD^g ; Prof F Allan Hubbell ; MD^h ; Prof Dorothy Lane ; MDⁱ ; Lisa Martin ; MD^j ; Prof Judith Ockene ; PhD^k ; Prof Thomas Rohan ; MBBS^l ; Prof Robert Schenken ; MD^m ; Prof Jean Wactawski-Wende ; PhDⁿ
• 刊名：Lancet Oncology
• 出版年：2012
• 期刊代码：184_14702045
• 类别：med
• 出版时间：May, 2012
• 卷：13
• 期：5
• 页码：476-486
• 文件大小：303 K

摘要

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Summary

Background

By contrast with many observational studies, women in the Women's Health Initiative (WHI) trial who were randomly allocated to receive oestrogen alone had a lower incidence of invasive breast cancer than did those who received placebo. We aimed to assess the influence of oestrogen use on longer term breast cancer incidence and mortality in extended follow-up of this cohort.

Methods

Between 1993 and 1998, the WHI enrolled 10鈥?39 postmenopausal women from 40 US clinical centres into a randomised, double-masked, placebo-controlled trial. Women aged 50-79 years who had undergone hysterectomy and had expected 3-year survival and mammography clearance were randomly allocated by a computerised, permuted block algorithm, stratified by age group and centre, to receive oral conjugated equine oestrogen (0路625 mg per day; n=5310) or matched placebo (n=5429). The trial intervention was terminated early on Feb 29, 2004, because of an adverse effect on stroke. Follow-up continued until planned termination (March 31, 2005). Consent was sought for extended surveillance from the 9786 living participants in active follow-up, of whom 7645 agreed. Using data from this extended follow-up (to Aug 14, 2009), we assessed long-term effects of oestrogen use on invasive breast cancer incidence, tumour characteristics, and mortality. We used Cox regression models to estimate hazard ratios (HRs) in the intention-to-treat population. This study is registered with , number .

Findings

After a median follow-up of 11路8 years (IQR 9路1-12路9), the use of oestrogen for a median of 5路9 years (2路5-7路3) was associated with lower incidence of invasive breast cancer (151 cases, 0路27%per year) compared with placebo (199 cases, 0路35%per year; HR 0路77, 95%CI 0路62-0路95; p=0路02) with no difference (p=0路76) between intervention phase (0路79, 0路61-1路02) and post-intervention phase effects (0路75, 0路51-1路09). In subgroup analyses, we noted breast cancer risk reduction with oestrogen use was concentrated in women without benign breast disease (p=0路01) or a family history of breast cancer (p=0路02). In the oestrogen group, fewer women died from breast cancer (six deaths, 0路009%per year) compared with controls (16 deaths, 0路024%per year; HR 0路37, 95%CI 0路13-0路91; p=0路03). Fewer women in the oestrogen group died from any cause after a breast cancer diagnosis (30 deaths, 0路046%per year) than did controls (50 deaths, 0路076%; HR 0路62, 95%CI 0路39-0路97; p=0路04).

Interpretation

Our findings provide reassurance for women with hysterectomy seeking relief of climacteric symptoms in terms of the effects of oestrogen use for about 5 years on breast cancer incidence and mortality. However, our data do not support use of oestrogen for breast cancer risk reduction because any noted benefit probably does not apply to populations at increased risk of such cancer.

Funding

US National Heart, Lung, and Blood Institute; Wyeth.