英国乳腺癌激素因素合作小组在研究中取得进展。他们的研究分析了更年期激素治疗（MHT）的类型和时间与乳腺癌风险的相关性。2019年8月30日，国际知名医学期刊《柳叶刀》发表了这一成果。
1992年1月1日到2018年1月1日，研究人员汇总了已发表和未发表的流行病学证据，在前瞻性随访中，108647名绝经后妇女平均在65岁时患上乳腺癌，其中55575人（51%）曾进行过MHT。在资料完整的女性中，当前使用者的平均MHT持续时间为10年，曾经使用者的平均MHT持续时间为7年，绝经的平均年龄为50岁， 开始MHT的平均年龄也是50岁。
除阴道用雌激素外，每一种类型的MHT都加大了患乳腺癌的风险，随着MHT持续时间的增加，风险逐渐增大，且使用雌激素-孕激素的风险比单用雌激素的风险更大。当前使用者在进行MHT的1-4年内，其超额风险也是确定的（雌激素-孕激素的风险比为1.60，单用雌激素的风险比为1.17），5-14年间风险是前者的两倍（雌激素-孕激素的风险比为2.08，单用雌激素的风险比为1.33）。
在5-14年期间，每天服用雌激素-孕激素的风险比不经常服用更大（风险比2.30 vs 1.93）。对于一种给定的制剂，当前使用者在5-14年患雌激素受体阳性肿瘤的风险大于雌激素受体阴性肿瘤，40-44岁开始MHT的女性，与45-49岁，50-54岁，55-59岁开始的女性相比风险差别不大，而60岁后开始MHT或肥胖的女性风险则显著降低。即便在停止MHT后，一些超额风险也持续了10多年，这取决于之前MHT的持续时间，而进行MHT不足一年则几乎没有超额风险。
如果这些关联很大程度上是因果关系，那么对于发达国家平均体重的女性来说，从50岁开始进行5年MHT，将显著增加50-69岁的乳腺癌发病率。每50个服用雌激素+每天服用孕激素的女性中就有1例患乳腺癌；每70个服用雌激素+间断服用孕激素的女性中就有1例患乳腺癌；每200个单用雌激素的女性中则仅有1例患乳腺癌。
Title: Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence
Author: Collaborative Group on Hormonal Factors in Breast Cancer
Issue&Volume: Volume 394 Number 10200,30 August 2019
Summary:
Background
Published findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence.
Methods
Principal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users.
Findings
During prospective follow-up, 108?647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55?575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1–4 (oestrogen-progestagen RR 1·60, 95% CI 1·52–1·69; oestrogen-only RR 1·17, 1·10–1·26), and were twice as great during years 5–14 (oestrogen-progestagen RR 2·08, 2·02–2·15; oestrogen-only RR 1·33, 1·28–1·37). The oestrogen-progestagen risks during years 5–14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21–2·40 vs 1·93, 1·84–2·01; heterogeneity p<0·0001). For a given preparation, the RRs during years 5–14 of current use were much greater for oestrogen-receptor-positive tumours than for oestrogen-receptor-negative tumours, were similar for women starting MHT at ages 40–44, 45–49, 50–54, and 55–59 years, and were attenuated by starting after age 60 years or by adiposity (with little risk from oestrogen-only MHT in women who were obese). After ceasing MHT, some excess risk persisted for more than 10 years; its magnitude depended on the duration of previous use, with little excess following less than 1 year of MHT use.
Interpretation
If these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great.
DOI: https://doi.org/10.1016/S0140-6736(19)31709-X
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31709-X/fulltext
LANCET：《柳叶刀》，创刊于1823年。隶属于爱思唯尔出版社，最新IF：202.731
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