Hormone replacement therapy and risk of benign proliferative epithelial disorders of the breast

Use of hormone replacement therapy (HRT) has been associated with increased risk of breast cancer, and it is possible that this reflects a positive association between HRT use and risk of proliferative forms of benign breast disease (BBD), conditions which are thought to have pre- malignant potential. The purpose of the present investigation was to study the association between HRT use and risk of benign proliferative epithelial disorders of the breast (BPED). The study was undertaken using the 56,837 women within the Canadian National Breast Screening Study (NBSS) who completed self-administered lifestyle and dietary questionnaires. (The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40-59 at recruitment.) During the course of the follow-up period, a total of 691 women in the dietary cohort were diagnosed with biopsy-confirmed incident BPED. For comparative purposes, a sub-cohort consisting of a random sample of 5681 women (including 65 of the subjects with BPED) was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 691 cases and 5443 non-cases. In postmenopausal women, in whom most of the reported use occurred, there was a positive association between duration of HRT use and risk of BPED, the adjusted incidence rate ratio (95% confidence interval) in those who had used HRT for more than 8 years being 1.70 (1.06-2.72). There were too few cases of atypical BPED for meaningful analysis, but results for those whose BPED showed no atypia were similar to the overall results. Further analyses conducted separately in the screened and control arms of the NBSS were similar to those observed overall, as were those conducted separately for screen-detected and interval-detected BPED.