Hormone therapy and breast cancer: what factors modify the association?

To determine factors that may modify the association between hormone therapy (HT) and breast cancer risk.

Prospective cohort study (the Melbourne Collaborative Cohort Study) of 24,479 women aged 40 to 69 years. History of HT use was collected at baseline and 4 years later by questionnaire. By June 2002, 336 cases of breast cancer were diagnosed among 13,444 women postmenopausal at baseline. Association of breast cancer risk with history of HT use was analyzed using proportional hazards models.

The hazard ratio (HR) for recent HT use (current or stopped within the last year) was elevated (HR 1.51; 95% CI, 1.16-1.98) but was not significantly increased for past HT users (HR 1.19; 95% CI, 0.86-1.64). Recent HT use was associated with better differentiated tumors but was not more likely to be associated with estrogen receptor-positive / progesterone receptor-positive tumors. There was little evidence of interactions between recent HT use and body mass index, alcohol intake, parity, and smoking, although the HR for recent HT use in categories of alcohol consumption was greatest in women consuming the most alcohol (HR 2.37; 95% CI, 1.45-3.88 for those consuming > or = 10 g/d versus HR 1.33; 95% CI, 0.85-2.08 for nondrinkers, P interaction = 0.32).

The risk of breast cancer for recent users of HT in this Australian population is increased by approximately 50%. Our results suggest that any potential modifying effect of the association between HT and breast cancer risk by factors such as alcohol intake and body mass index is likely to be modest.