The relationship between hormone replacement treatment (HRT) and breast cancer risk was considered in age-specific groups of women, combining data from two case-control studies conducted between 1983 and 1994 in six Italian centers. Cases were comprised of 5984 women, below age 75 years, with histologically confirmed breast cancer, and controls were comprised of 5504 women admitted to the hospital for a wide spectrum of acute, nonneoplastic, nonhormone-related diseases. Ever-use of HRT was reported by 6.1% of the cases and 5.5% of the controls, corresponding to a multivariate odds ratio (OR) of 1.2 [95% confidence interval (CI), 1.0-1.4]. A significant trend in risk with duration of use was observed. Separate analysis for women < 55, 55-64, and 65-74 years old at diagnosis showed that the excess risk of breast cancer associated with ever-use of HRT was not observed in the youngest age group (OR, 0.9) and increased with age at diagnosis to 1.2 (95% CI, 0.9-1.5) for women 55-64 years old and 1.6 (95% CI, 1.2-2.3) for those 65-74 years old at diagnosis. A significant trend in risk with duration was observed only in the oldest group (65-74 years old), with ORs of 1.6 (95% CI, 1.1-2.3) and 2.2 (95% CI, 1.1-4.7), respectively, for < 60 and > or = 60 months of use. Thus, this study suggests that the relationship between HRT and breast cancer risk is influenced by age at diagnosis and that any risk-benefit assessment is particularly critical for women using HRT several years after menopause.

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