The aim of the present study was to evaluate the association between different types of hormone replacement therapy (HRT) and risk of specific breast cancer subgroups. A population-based prospective cohort study including 12,583 peri- or postmenopausal women were followed using record-linkage with national cancer registries. During an average follow-up of 4.5 years, 332 cases of invasive breast cancer were diagnosed. Tumour samples were available from 283 cases. These tumours were re-evaluated according to histological type, grade, and mitotic index. Evaluation of tumours included estrogen and progesterone receptor status (ERalpha, ERbeta and PgR), as well as expression of Ki67, HER2, cyclin D1 and p27. The incidence of breast cancer in current users of combined HRT (CHRT) was significantly higher than in non-users. The difference corresponded to an adjusted relative risk (95% confidence interval) of 3.01 (2.35-3.84) as obtained using a Cox's proportional hazards analysis. CHRT was associated with lobular tumours (3.48:1.99-6.10), grade 1 tumours (4.46:2.79-7.13) and tumours with a low mitotic index (4.35:2.99-6.34). CHRT was not related to any specific subgroup in terms of ERalpha-, ERbeta- or PgR-expression. CHRT was associated with low proliferating tumours, defined by the Ki67 index (3.58:2.60-4.93), HER2 amplified tumours (4.40:1.93-10.06), low expression of the oncogene cyclin D1 (3.14:2.32-4.23) and high expression of the tumour suppressor gene p27 (3.47:2.40-5.01). Use of estrogen-alone HRT (ERT) was not associated with any statistically significant risk of breast cancer. We conclude that the use of CHRT is associated with an increased incidence of breast tumours with comparatively favourable prognostic factors.
(c) 2007 Wiley-Liss, Inc.