Different menopausal hormone regimens and risk of breast cancer

ABSTRACT

Background

There are considerable knowledge gaps concerning different estrogen and progestin formulations, regimens, and modes of administration of menopausal hormone therapy and the risk of breast cancer. Our objective was to assess the different treatment options for menopausal hormone therapy and the risk of breast cancer.

Patients and methods

This Swedish prospective nationwide cohort study included all women who received ≥1 hormone therapy prescription during the study period 2005–2012 (290,186 ever–users), group–level matched (1:3) to 870,165 never–users; respectively 6,376 (2.2%) and 18,754 (2.2%) developed breast cancer. Hormone therapy, ascertained from the Swedish Prescribed Drug Register, was subdivided by estrogen and progestogen formulation types, regimens (continuous vs. sequential) and modes of administration (oral vs. transdermal). The risk of invasive breast cancer was presented as adjusted odds ratios and 95% confidence intervals.

Results

Current use of estrogen-only therapy was associated with a slight excess breast cancer risk (odds ratio=1.08 (1.02–1.14)). The risk for current estrogen plus progestogen therapy was higher (odds ratio=1.77 (1.69–1.85)) and increased with higher age at initiation (odds ratio=3.59 (3.30–3.91) in women 70+ years). In contrast, past use was associated with reduced breast cancer risk. Current continuous estrogen/progestin use was associated with higher risk (odds ratio=2.18 (1.99–2.40) for progesterone-derived; odds ratio=2.66 (2.49–2.84) for testosterone-derived) than sequential use (odds ratio=1.37 (0.97–1.92)) for progesterone-derived; odds ratio=1.12 (0.96–1.30) for testosterone-derived). The odds ratio for current use was 1.12 (1.04–1.20) for estradiol, 0.76 (0.69–0.84) for estriol, 4.47 (2.67–7.48) for conjugated estrogens, and 1.68 (1.51–1.87) for tibolone. Oral and cutaneous hormone therapy showed similar associations.

Conclusion

Different hormone therapy regimens have profoundly different effects on breast cancer risk. Because of registry limitations some confounders could not be assessed. This knowledge may guide clinical decision-making when hormone therapy is considered.