Menopausal hormone therapy and risk of breast cancer: a meta-analysis of epidemiological studies and randomized controlled trials

Abstract

We conducted meta-analyses to assess the impact of menopausal hormone therapy (MHT) on the risk of incident invasive breast cancer (BC) in cohort studies (CS), case-control studies (CCS) and randomized controlled trials (RCTs) published 1989-2004. We used published data providing information upon unopposed estrogen therapy (ET), estrogen-progestin therapy (EPT) or all MHT combined. Major outcomes were MHT-associated overall risk of BC and change of risk per year used. There is a linear increase of overall risk by midterm year of case ascertainment based upon data of all study types for MHT and to a larger extent for EPT, not for ET. Effects are larger in CS than in CCS. Meta-analyses stratified by <1992 versus > or =1992 as midterm year of case ascertainment indicate larger summary risks for the latter period for all MHT analysed, in particular for EPT. Annual increases in BC risk for EPT across study types are 0-9%, for ET 0-3%. In conclusion, there is evidence that relative risks for BC risks by MHT, in particular EPT, have been increasing in recent years. Given the widespread use of MHT, and often long duration, more detailed knowledge about differential BC risks of both estrogens and progestins are necessary to minimize BC risk in symptomatic women who consider MHT.

Oral progestagens before menopause and breast cancer risk

“…The hormonal dependence of breast cancer has been clearly demonstrated (Dunn et al, 2005) and risk factors include early age at menarche, nulliparity, late age at first birth, late age at menopause (Rosner et al, 1994) and the use of oral contraceptives (OCs) (Collaborative Group on Hormonal Factors in Breast Cancer, 1996) and hormone replacement therapy (HRT) (Greiser et al, 2005).…”

Vaginal estrogen therapy in postmenopausal breast cancer patients treated with aromatase inhibitors

“…Several metaanalysis and randomized controlled trials have shown that the use of combined estrogen progestin therapy (EPT) increases the risk of breast cancer [10][11][12][13][14][15][16][17][18][19][20][21]. In the Women's Health Initiative (WHI) the relative risk of EPT was 1.26, which is equivalent to 8 additional invasive breast cancer cases per 10,000 women after 5.2 years of use [22,23].…”

Pharmacology of Hormone Replacement Therapy in Menopause

“…The risk of developing breast cancer increases with longer duration of HRT use (Beral, 2003;Fournier et al, 2008). One meta-analysis assessing the impact of HRT on the risk of invasive breast cancer in epidemiological studies and RCTs reported an increased annual risk for breast cancer varying between 0-9% in the case of E+P regimens and 0-3% in oestrogen-only administration (Greiser et al, 2005).…”