3月7日,，Lancet Oncology雜志發(fā)表的一篇報告指出,，即使在停止雌激素治療最長達5年后，浸潤性乳腺癌的發(fā)生率仍然顯著降低,。
這是對婦女健康行動(WHI)中的7,645名參與者進行的一項延長隨訪研究,，由西雅圖市Fred Hutchinson腫瘤研究中心的Garnet L. Anderson博士及其同事進行。WHI是一項多中心,、隨機試驗,，共納入10,000例以上的婦女，將接受馬結合雌激素治療的受試者的預后與接受匹配安慰劑治療的受試者進行比較,。WHI的干預階段在平均隨訪7年后,，于2004年2月提前終止。接近78%的研究受試者（3,778名之前被隨機分配到接受雌激素治療組,，3,867名被分配到安慰劑組）同意繼續(xù)參與持續(xù)至2009年8月的延長隨訪研究,，總的中位隨訪時間為11.8年。
結果顯示,，在最終的評估中,，于干預階段接受雌激素治療中位時間為6年的婦女浸潤性乳腺癌的總發(fā)病率為每年0.27%（151例），而安慰劑組婦女年發(fā)病率為0.35%,，差異具有統(tǒng)計學意義,。 “雌激素對乳腺癌發(fā)生的這種持續(xù)性、干預后預防作用,，與其他經(jīng)證實可降低乳腺癌發(fā)病率的激素靶向藥物相似” (Lancet Oncol. 2012 March 7 [doi:10.1016/S1470-2045(12)70075-x]),，并且，在發(fā)生乳腺癌的受試者中,，雌激素組的全因死亡率（30例患者死亡,，年死亡率為0.046%）顯著低于安慰劑組（50例患者死亡，年死亡率為0.076%）,。接受雌激素治療者的乳腺癌特異性死亡率（6例患者死亡,，年死亡率為0.009%）也顯著低于安慰劑組（16例患者死亡,，年死亡率為0.024%）。從結果來看,，預防作用似乎局限于乳腺癌風險較低的婦女,，對于有良性乳腺疾病病史或有一級乳腺癌家族史的婦女并不適用。亞組分析發(fā)現(xiàn),，雌激素的保護作用與患者年齡,、體重指數(shù)、卵巢切除狀態(tài),、絕經(jīng)期開始后年數(shù),、既往雌激素使用情況或是否出現(xiàn)血管舒縮癥狀之間無相互作用。
研究者總結認為,，絕經(jīng)后婦女接受雌激素治療,，對乳腺癌具有長期預防作用。
WHI是由美國國立心肺血液研究所,、美國衛(wèi)生與公共服務部以及惠氏公司資助的,。Anderson 博士的一位合作者披露與阿斯利康、諾華,、安進和輝瑞公司之間存在利益關系。Anderson博士及其他研究者披露無相關利益沖突,。（生物谷Bioon.com）
doi:10.1016/S1470-2045(12)70075-X
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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
Prof Garnet L Anderson PhD a , 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 MD i, Lisa Martin MD j, Prof Judith Ockene PhD k, Prof Thomas Rohan MBBS l, Prof Robert Schenken MD m, Prof Jean Wactawski-Wende PhD
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 10 739 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 (0·625 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 ClinicalTrials.gov, number NCT00000611.
