英国诺丁汉大学Yana Vinogradova团队研究了使用激素替代疗法与乳腺癌风险的相关性。2020年10月28日，该研究发表在《英国医学杂志》上。

为了评估与激素替代疗法（HRT）不同类型和持续时间相关的乳腺癌风险，研究组进行了两个嵌套的病例对照研究。研究组使用英国QResearch或临床实践研究数据链（CPRD），并与住院、死亡率、社会剥夺和癌症登记（仅QResearch）数据相关联。

1998-2018年间，研究组招募了98611名年龄在50-79岁之间，初步诊断为乳腺癌的女性，按年龄、全科医学和索引日期与457498名女性对照者相匹配。根据常规实践、死亡率、医院或癌症登记记录对乳腺癌进行诊断。

总体而言，在开始索引的前一年，有33703例（34％）被诊断为乳腺癌的女性和134391例（31％）对照者使用了HRT。与从不使用相比，在最近使用（<5年）且长期使用（≥5年）的参与者中，仅雌激素疗法以及雌激素-孕激素联合疗法均会增加患乳腺癌的风险，校正比值比分别为1.15和1.79。

对于联合孕激素而言，炔诺酮的风险最高（1.88），而地屈孕酮的风险最低（1.24）。过去长期仅使用雌激素疗法和过去短期（<5年）使用雌激素-孕激素与风险增加无关。但过去长期使用雌激素和孕激素的相关风险仍然增加（1.16）。

在近期雌激素使用者中，每1万女性年预期新增3名（年轻女性）至8名（老年女性）乳腺癌患者；在近期雌激素-孕激素使用者中，则分别增加9名至36名；而在过去雌激素-孕激素使用者中，则分别增加2名至8名。

研究结果表明，乳腺癌风险水平因HRT类型而异，联合治疗和使用时间更长的风险更高。

附：英文原文

Title: Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases

Author: Yana Vinogradova, Carol Coupland, Julia Hippisley-Cox

Issue&Volume: 2020/10/28

Abstract:

Objective To assess the risks of breast cancer associated with different types and durations of hormone replacement therapy (HRT).

Design Two nested case-control studies.

Setting UK general practices contributing to QResearch or Clinical Practice Research Datalink (CPRD), linked to hospital, mortality, social deprivation, and cancer registry (QResearch only) data.

Participants 98611 women aged 50-79 with a primary diagnosis of breast cancer between 1998 and 2018, matched by age, general practice, and index date to 457498 female controls.

Main outcome measures Breast cancer diagnosis from general practice, mortality, hospital, or cancer registry records. Odds ratios for HRT types, adjusted for personal characteristics, smoking status, alcohol consumption, comorbidities, family history, and other prescribed drugs. Separate results from QResearch or CPRD were combined.

Results Overall, 33703 (34%) women with a diagnosis of breast cancer and 134391 (31%) controls had used HRT prior to one year before the index date. Compared with never use, in recent users (<5 years) with long term use (≥5 years), oestrogen only therapy and combined oestrogen and progestogen therapy were both associated with increased risks of breast cancer (adjusted odds ratio 1.15 (95% confidence interval 1.09 to 1.21) and 1.79 (1.73 to 1.85), respectively). For combined progestogens, the increased risk was highest for norethisterone (1.88, 1.79 to 1.99) and lowest for dydrogesterone (1.24, 1.03 to 1.48). Past long term use of oestrogen only therapy and past short term (<5 years) use of oestrogen-progestogen were not associated with increased risk. The risk associated with past long term oestrogen-progestogen use, however, remained increased (1.16, 1.11 to 1.21). In recent oestrogen only users, between three (in younger women) and eight (in older women) extra cases per 10000 women years would be expected, and in oestrogen-progestogen users between nine and 36 extra cases per 10000 women years. For past oestrogen-progestogen users, the results would suggest between two and eight extra cases per 10000 women years.

Conclusion This study has produced new generalisable estimates of the increased risks of breast cancer associated with use of different hormone replacement preparations in the UK. The levels of risks varied between types of HRT, with higher risks for combined treatments and for longer duration of use.

DOI: 10.1136/bmj.m3873

Source: https://www.bmj.com/content/371/bmj.m3873