Breast cancer
Bottom line
Combined MHT increases breast cancer risk, and duration matters. NICE describes very little or no increase with estrogen-only MHT. Claims that micronized progesterone has a lower breast cancer risk remain uncertain.
Current NICE guidance says the increase with combined MHT rises with duration and can persist for at least 10 years after stopping. Sequential combined MHT has a lower risk than continuous combined treatment, but a higher risk than no MHT. This applies to people without a personal history of breast cancer.
The WHI randomized trials tested specific formulations. In the 2020 long-term follow-up, conjugated equine estrogen alone in participants with a prior hysterectomy was associated with lower breast cancer incidence and mortality; combined conjugated equine estrogen plus medroxyprogesterone acetate increased incidence. Those results can't be extended to every estrogen product or used as a reason to prescribe HRT to prevent breast cancer.
A 2024 Norwegian cohort of 1,275,783 women still found associations with systemic oral and transdermal HRT, varying by formulation. A patch can have a lower blood-clot risk than a tablet without eliminating breast cancer risk. This was observational research, not proof of causation. The article was corrected in August 2025 without changing its overall conclusions.
Some observational studies suggest differences between progestogens. But NICE says evidence is insufficient to establish a lower breast cancer risk with micronized progesterone or dydrogesterone. The BMJ 2020 study assessed dydrogesterone, not micronized progesterone; it can't support a micronized-progesterone risk estimate.
The numbers
In the WHI long-term follow-up, annualized breast cancer incidence was 0.45% with conjugated equine estrogen plus MPA versus 0.36% with placebo: about 45 versus 36 cases per 10,000 participants per year. In the separate estrogen-only trial after hysterectomy, it was 0.30% versus 0.37%: about 30 versus 37 per 10,000 per year. These are trial-specific annualized rates over long-term follow-up, not personal predictions or rates for every MHT formulation. The trials involved different populations and shouldn't be compared directly.
Sources
- Chlebowski et al., JAMA 2020 — WHI 20-year follow-up of breast cancer incidence and mortality
- Collaborative Group on Hormonal Factors in Breast Cancer, Lancet 2019 — type and timing of MHT and breast cancer risk (meta-analysis)
- Vinogradova et al., BMJ 2020 — Use of HRT and breast cancer risk: nested case-control study in QResearch and CPRD (~98,000 cases)
- NICE NG23 (November 2024 update) — Menopause: diagnosis and management, including HRT and breast cancer risk tables
- Manson et al., JAMA 2024 — Menopausal hormone therapy: clinical recommendations (consolidated reframe of WHI in 2024)
- Fournier et al., Breast Cancer Res Treat 2008 — E3N cohort: micronized progesterone vs synthetic progestins
