Menopausal hormone therapy and breast cancer: what is the true size of the increased risk?

Abstract

Background:Menopausal hormone therapy (MHT) increases breast cancer risk; however, most cohort studies omit MHT use after enrolment and many infer menopausal age.Methods:We used information from serial questionnaires from the UK Generations Study cohort to estimate hazard ratios (HRs) for breast cancer among post-menopausal women with known menopausal age, and examined biases induced when not updating data on MHT use and including women with inferred menopausal age.Results:Among women recruited in 2003–2009, at 6 years of follow-up, 58 148 had reached menopause and 96% had completed a follow-up questionnaire. Among 39 183 women with known menopausal age, 775 developed breast cancer, and the HR in relation to current oestrogen plus progestogen MHT use (based on 52 current oestrogen plus progestogen MHT users in breast cancer cases) relative to those with no previous MHT use was 2.74 (95% confidence interval (CI): 2.05–3.65) for a median duration of 5.4 years of current use, reaching 3.27 (95% CI: 1.53–6.99) at 15+ years of use. The excess HR was underestimated by 53% if oestrogen plus progestogen MHT use was not updated after recruitment, 13% if women with uncertain menopausal age were included, and 59% if both applied. The HR for oestrogen-only MHT was not increased (HR=1.00; 95% CI: 0.66–1.54).Conclusions:Lack of updating MHT status through follow-up and inclusion of women with inferred menopausal age is likely to result in substantial underestimation of the excess relative risks for oestrogen plus progestogen MHT use in studies with long follow-up, limited updating of exposures, and changing or short durations of use.

Association between lifestyle, menstrual/reproductive history, and histological factors and risk of breast cancer in women biopsied for benign breast disease

“…Nonetheless, findings from our study are consistent with those from previous studies which indicate a greater risk of breast cancer among HRT users than non-users (34–36). Unlike the Collaborative Group on Hormonal Factors in Breast Cancer study and more recent studies (34,37,38), which have reported that longer duration of HRT use is associated with increased risk of breast, we did not observe any association between duration of use and breast cancer. Nonetheless, the positive association observed in this study between HRT use and breast cancer risk is in accord with biologically plausible evidence which suggests that hormones such as estrogen may induce breast carcinogenesis by promoting tumor cell proliferation and migration (39–41).…”

Best practice for HRT: unpicking the evidence

“…10 As shown with other studies, there was no increased risk of breast cancer seen for users of oestrogen-only therapy.…”

Study of Known Risk Factors in Breast Cancer Patients in the Regional Population

“…The Hazard Ratio for oestrogen-only HRT was not increased (HR=1.00; 95% CI: 0.66-1.54). 13 In our study, none of the patients had ever taken menopausal hormone replacement therapy.…”