Breast tumours following combined hormone replacement therapy express favourable prognostic factors

Abstract

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 (ERa, ERb 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 nonusers. 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 ERa-, ERb-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. ' 2007 Wiley-Liss, Inc.

Common variants in the UBC9 gene encoding the SUMO‐conjugating enzyme are associated with breast tumor grade

“…In agreement with data previously reported by others, [25][26][27] we found an underrepresentation of grade 3 tumors and overrepresentation of grade 1 tumors among women who had used HT. Even after adjustment for HT use, women homozygous for the rare allele of rs7187167 tend to develop low grade tumors.…”

Age at first childbirth and oral contraceptive use are associated with risk of androgen receptor-negative breast cancer: the Malmö Diet and Cancer Cohort

“…Previously, we have shown an increased risk of breast cancer among cHRT users in the MDCS (28). The same pattern was seen in this study, the risk increment for women using HRT being irrespective of AR status.…”

“…Representative areas of invasive cancer from the donating tumor block were selected for tissue microarray (TMA) construction as described in detail previously (28). in ISH analysis.…”

“…Menopausal status at baseline was defined as pre-, peri-or postmenopausal as described in detail previously (28). Use of hormonal replacement therapy (HRT) was categorized as current use or non-use and as type of HRT, coded according to the Anatomic Therapeutic Chemical classification (ATC) system (28).…”

Menopausal Hormone Therapy and Risk of Clinical Breast Cancer Subtypes

“…Hormone therapy has been found to confer greater risk on invasive lobular, tubular, and mixed ductal-lobular histologic types (5-7)-types associated with better outcomes in some but not all studies-than for invasive ductal cancers. In addition, hormone therapy -associated tumors have been shown to be smaller (8)(9)(10)(11), hormone receptor positive (12)(13)(14), of lower grade (14)(15)(16)(17)(18), and to have fewer affected nodes (9,19) than tumors not associated with hormone therapy use. However, due to the strong correlation between histologic type and clinical characteristics, in particular estrogen receptor/ progesterone receptor (ER/PR) status (20)(21)(22)(23)(24), it is unclear which tumor subtypes are most strongly associated with hormone therapy use.…”