Age-related variation in the relationship between menopausal hormone therapy and the risk of dying from breast cancer

Multiple past studies have reported a reduced risk of breast cancer-related mortality (BCM) in relation to pre-diagnostic use of hormone therapy (HT); however, the extent to which this reduction is due to heightened screening or tumor biology is unknown. Using a population-based cohort of 1,911 post-menopausal women diagnosed with invasive breast cancer at ages 45–79 from 1993 to 1999, we investigated the extent to which the reduced risk in BCM observed in relation to HT might be explained by screening patterns or tumor features. Estrogen–progestin therapy (EPT) use was associated with a decreased risk of BCM (after adjustment for age, study, mammography, stage, and treatment), but only among older women (ever use: ≥65 years: HR = 0.45 [95% CI 0.26–0.80]; <65 years: HR = 1.03 [95% CI 0.60–1.79]). Estrogen-alone therapy (ET) use was not associated with risk of BCM (ever use: ≥65 years: HR = 0.76 [95% CI 0.51–1.12]; <65 years: HR = 1.20 [95% CI 0.71–2.02]). HT users had a much greater frequency of mammography (P value <0.001). EPT use was associated with tumor characteristics related to improved prognosis in older women after adjustment for screening, including an inverse association with poorly differentiated tumors (OR = 0.57 [95% CI 0.38–0.85]) and an association with lobular tumors (OR = 1.68 [95% CI 1.07–2.65]). Beyond the influence of EPT use on screening uptake, these data indicate that the improved survival associated with pre-diagnostic EPT use may be due in part to the development of more favorable tumor characteristics.