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

Vinogradova, Yana; Coupland, Carol; Hippisley-Cox, Julia

Abstract

Objective: To assess breast cancer risks associated with different types and durations of hormone replacement therapy

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 hormone replacement therapy types, adjusted for: demographics; smoking status; alcohol consumption; comorbidities; family history; other prescribed drugs. Separate results from the two databases used were combined.

Results: Overall, 33,703 (34%) women diagnosed with breast cancer and 134,391 (31%) controls had used hormone replacement therapy before one year prior to the index date. Compared to never use, recent (within 5 years) long-term (5 years or more) use was associated with increased breast cancer risks for oestrogen-only therapy (adjusted odds ratio 1.15, 95% confidence interval 1.09 to 1.21) and oestrogen-progestogen therapy (1.79, 1.73 to 1.85). 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 (less than 5 years) use of oestrogen-progestogen were not associated with increased risk. However, the risk associated with past long-term oestrogen-progestogen use remained increased (1.16, 1.11 to 1.21).

Conclusion: This study has produced new generalisable estimates of the increased breast cancer risks associated with use of different hormone replacement preparations in the UK, and provided new data for widely used and rarer hormone replacement therapy treatments. These detailed findings will assist women and their doctors in choosing the most appropriate therapy and regime.

• Journal Article Type: Article
• Acceptance Date: Sep 17, 2020
• Online Publication Date: Oct 28, 2020
• Publication Date: Oct 28, 2020
• Deposit Date: Sep 21, 2020
• Publicly Available Date: Oct 28, 2020
• Journal: BMJ
• Print ISSN: 0959-8138
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 371
• Article Number: m3873
• DOI: https://doi.org/10.1136/bmj.m3873
• Keywords: menopausal, oestrogen, progestogen, tibolone, observational study, primary care
• Public URL: https://nottingham-repository.worktribe.com/output/4918377
• Publisher URL: https://www.bmj.com/content/371/bmj.m3873