Different menopausal hormone regimens and risk of breast cancer

Background: There are considerable knowledge gaps concerning different estrogen and progestin formulations, regimens, and modes of administration of menopausal hormone therapy (HT) and the risk of breast cancer. Our objective was to assess the different treatment options for menopausal HT and the risk of breast cancer. Patients and methods: This Swedish prospective nationwide cohort study included all women who received ≥1 HT prescription during the study period 2005-2012 (290 186 ever-users), group-level matched (1 : 3) to 870 165 never-users; respectively, 6376 (2.2%) and 18 754 (2.2%) developed breast cancer. HT, ascertained from the Swedish Prescribed Drug Register, was subdivided by estrogen and progestogen formulation types, regimens (continuous versus sequential) and modes of administration (oral versus transdermal). The risk of invasive breast cancer was presented as adjusted odds ratios (OR) and 95% confidence intervals. Results: Current use of estrogen-only therapy was associated with a slight excess breast cancer risk odds ratio (OR) = 1.08 (1.02-1.14). The risk for current estrogen plus progestogen therapy was higher OR = 1.77 (1.69-1.85) and increased with higher age at initiation OR = 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 OR = 2.18 (1.99-2.40) for progesterone-derived; OR = 2.66 (2.49-2.84) for testosterone-derived than sequential use OR = 1.37 (0.97-1.92) for progesterone-derived; OR = 1.12 (0.96-1.30) for testosterone-derived. The OR 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 HT showed similar associations. Conclusion: Different HT 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 HT is considered.