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Age-related variation in the relationship between menopausal hormone therapy and the risk of dying from breast cancer.

ABSTRACT: Multiple past studies have reported a reduced risk of breast cancer-related mortality (BCM) in relation to pre-diagnostic use of hormone therapy (HT); however, the extent to which this reduction is due to heightened screening or tumor biology is unknown. Using a population-based cohort of 1,911 post-menopausal women diagnosed with invasive breast cancer at ages 45-79 from 1993 to 1999, we investigated the extent to which the reduced risk in BCM observed in relation to HT might be explained by screening patterns or tumor features. Estrogen-progestin therapy (EPT) use was associated with a decreased risk of BCM (after adjustment for age, study, mammography, stage, and treatment), but only among older women (ever use: ? 65 years: HR = 0.45 [95% CI 0.26-0.80]; <65 years: HR = 1.03 [95% CI 0.60-1.79]). Estrogen-alone therapy (ET) use was not associated with risk of BCM (ever use: ? 65 years: HR = 0.76 [95% CI 0.51-1.12]; <65 years: HR = 1.20 [95% CI 0.71-2.02]). HT users had a much greater frequency of mammography (P value <0.001). EPT use was associated with tumor characteristics related to improved prognosis in older women after adjustment for screening, including an inverse association with poorly differentiated tumors (OR = 0.57 [95% CI 0.38-0.85]) and an association with lobular tumors (OR = 1.68 [95% CI 1.07-2.65]). Beyond the influence of EPT use on screening uptake, these data indicate that the improved survival associated with pre-diagnostic EPT use may be due in part to the development of more favorable tumor characteristics.

SUBMITTER: Reding KW

PROVIDER: S-EPMC3059400 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Age-related variation in the relationship between menopausal hormone therapy and the risk of dying from breast cancer.

Reding Kerryn W KW Doody David R DR McTiernan Anne A Hsu Li L Davis Scott S Daling Janet R JR Porter Peggy L PL Malone Kathleen E KE

Breast cancer research and treatment 20100929 3

Multiple past studies have reported a reduced risk of breast cancer-related mortality (BCM) in relation to pre-diagnostic use of hormone therapy (HT); however, the extent to which this reduction is due to heightened screening or tumor biology is unknown. Using a population-based cohort of 1,911 post-menopausal women diagnosed with invasive breast cancer at ages 45-79 from 1993 to 1999, we investigated the extent to which the reduced risk in BCM observed in relation to HT might be explained by sc ...[more]

PMID: 20878463

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Project description:BackgroundMenopausal hormone therapy (MHT) is a risk factor for breast cancer (BC). Evidence suggests that its effect on BC risk could be partly mediated by mammographic density. The aim of this study was to investigate the relationship between MHT, mammographic density and BC risk using data from a prospective study.MethodsWe used data from a case-control study nested within the French cohort E3N including 453 cases and 453 matched controls. Measures of mammographic density, history of MHT use during follow-up and information on potential confounders were available for all women. The association between MHT and mammographic density was evaluated by linear regression models. We applied mediation modelling techniques to estimate, under the hypothesis of a causal model, the proportion of the effect of MHT on BC risk mediated by percent mammographic density (PMD) for BC overall and by hormone receptor status.ResultsAmong MHT users, 4.2% used exclusively oestrogen alone compared with 68.3% who used exclusively oestrogens plus progestogens. Mammographic density was higher in current users (for a 60-year-old woman, mean PMD 33%; 95% CI 31 to 35%) than in past (29%; 27 to 31%) and never users (24%; 22 to 26%). No statistically significant association was observed between duration of MHT and mammographic density. In past MHT users, mammographic density was negatively associated with time since last use; values similar to those of never users were observed in women who had stopped MHT at least 8 years earlier. The odds ratio of BC for current versus never MHT users, adjusted for age, year of birth, menopausal status at baseline and BMI, was 1.67 (95% CI, 1.04 to 2.68). The proportion of effect mediated by PMD was 34% for any BC and became 48% when the correlation between BMI and PMD was accounted for. These effects were limited to hormone receptor-positive BC.ConclusionsOur results suggest that, under a causal model, nearly half of the effect of MHT on hormone receptor-positive BC risk is mediated by mammographic density, which appears to be modified by MHT for up to 8 years after MHT termination.

Dataset Information

Age-related variation in the relationship between menopausal hormone therapy and the risk of dying from breast cancer.

Publications

Age-related variation in the relationship between menopausal hormone therapy and the risk of dying from breast cancer.

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