激素补充疗法与乳腺癌风险大数据分析
激素补充疗法可减少老年女性绝经期症状、预防骨质疏松。不过，关于激素补充疗法对乳腺癌发病风险的影响，既往研究结果存在分歧。
2020年10月28日，国际四大医学期刊之一、英国医学会《英国医学杂志》正刊发表诺丁汉大学、牛津大学的研究报告，根据对55.6万女性的20年随访数据，分析了激素补充疗法不同类型和持续时间对乳腺癌发病风险的影响。
该病例对照嵌套研究首先将英国全科医师两大数据库QResearch和CPRD的医院、死亡登记、社会影响因素和癌症登记数据进行关联，随后按年龄、全科医师、入组日期，将1998～2018年首次确诊乳腺癌的9万8611例年龄50～79岁女性患者与45万7498女性对照者进行匹配。乳腺癌诊断来自全科医师、死亡登记、医院或癌症登记记录。对个人特征、吸烟与否、酒精摄入量、合并症、家族史以及其他处方药进行校正后，计算激素补充疗法不同类型的乳腺癌发病比值比。对来自两大数据库的单独结果进行合并分析。
结果，其中3万3703例（34%）乳腺癌女性和13万4391例（31%）对照组女性在入组日期前用过激素补充疗法。
与从未用过激素补充疗法的女性相比，近5年内长期（≥5年）用过：
仅雌激素：乳腺癌发病比例高15%（校正后比值比：1.15，95%置信区间：1.09～1.21）
雌孕激素：乳腺癌发病比例高79%（校正后比值比：1.79，95%置信区间：1.73～1.85）
联合雌激素的4种孕激素相比：
炔诺孕酮：乳腺癌发病比例高88%（校正比值比：1.88，95%置信区间：1.79～1.99）
甲羟孕酮：乳腺癌发病比例高87%（校正比值比：1.87，95%置信区间：1.71～2.05）
左炔孕酮：乳腺癌发病比例高79%（校正比值比：1.79，95%置信区间：1.68～1.90）
地屈孕酮：乳腺癌发病比例高24%（校正比值比：1.24，95%置信区间：1.03～1.48）
长期（≥5年）仅用过雌激素、短期（<5年）用过雌孕激素的女性，与从未用过激素补充疗法的女性相比，乳腺癌发病比例相似。
长期（≥5年）用过雌孕激素的女性，与从未用过激素补充疗法的女性相比，乳腺癌发病比例高16%（校正比值比：1.16，95%置信区间：1.11～1.21）。
近5年内短期（<5年）仅用过雌激素，与从未用过激素补充疗法相比，每1万例女性：
50～59岁：乳腺癌多3例
60～69岁：乳腺癌多4例
70～79岁：乳腺癌多8例
近5年内短期（<5年）用过雌孕激素，与从未用过激素补充疗法相比，每1万例女性：
50～59岁：乳腺癌多9例
60～69岁：乳腺癌多15例
70～79岁：乳腺癌多19例
近5年内长期（≥5年）用过雌孕激素，与从未用过激素补充疗法相比，每1万例女性：
50～59岁：乳腺癌多15例
60～69岁：乳腺癌多26例
70～79岁：乳腺癌多36例
近5年前短期（<5年）用过雌孕激素，与从未用过激素补充疗法相比，每1万例女性：
60～69岁：乳腺癌多2例
70～79岁：乳腺癌多5例
近5年前长期（≥5年）用过雌孕激素，与从未用过激素补充疗法相比，每1万例女性：
60～69岁：乳腺癌多5例
70～79岁：乳腺癌多8例
因此，该研究结果表明，激素补充疗法不同类型和持续时间，对乳腺癌发病风险的影响不同：雌孕激素高于仅雌激素、长期高于短期、近期高于远期、年老高于年轻。
相关链接
BMJ. 2020 Oct 28;371:m3873.
Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases.
Vinogradova Y, Coupland C, Hippisley-Cox J.
University of Nottingham, Nottingham, UK; University of Oxford, Oxford, UK.
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: 98 611 women aged 50-79 with a primary diagnosis of breast cancer between 1998 and 2018, matched by age, general practice, and index date to 457 498 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, 33 703 (34%) women with a diagnosis of breast cancer and 134 391 (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 10 000 women years would be expected, and in oestrogen-progestogen users between nine and 36 extra cases per 10 000 women years. For past oestrogen-progestogen users, the results would suggest between two and eight extra cases per 10 000 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.
PMID: 33115755
DOI: 10.1136/bmj.m3873