Menopausal hormone therapy and breast cancer: risk and management

Menopausal hormone therapy remains the most effective treatment for vasomotor symptoms and genitourinary syndrome of menopause (GSM), yet concerns about breast cancer risk continue to limit its use. This review summarizes contemporary evidence regarding breast safety in healthy women and breast cancer survivors, with attention to emerging therapies and special populations.

Long-term data show that estrogen-alone therapy after hysterectomy does not increase breast cancer incidence and is associated with reduced mortality, while combined estrogen-progestogen therapy carries a small, duration-dependent increase in risk. Risk varies by progestogen, with micronized progesterone demonstrating a more favorable profile than synthetic progestins. Conjugated estrogens with bazedoxifene improve symptoms and bone density without increasing mammographic density, though long-term oncologic outcomes are unknown. In breast cancer survivors, evidence of harm comes from randomized trials of combined estrogen-progestogen therapy and tibolone; estrogen-alone therapy has not been tested in randomized trials in this population. For GSM, low-dose vaginal estrogen is effective and has not been associated with higher recurrence or mortality in most survivors; aromatase inhibitor users warrant shared decision-making. Nonhormonal therapies, including neurokinin-3 receptor antagonists, offer effective systemic alternatives when hormone therapy is contraindicated or declined.

Most healthy women can use hormone therapy safely with individualized counseling, attention to timing, and progestogen selection. Among survivors, low-dose vaginal estrogen remains appropriate for refractory GSM with oncology involvement.