Abstract

Abstract Background Peri-menopausal women commonly experience hot flashes and night sweats. Hormone replacement therapy (HRT) containing estrogen only or estrogen plus progesterone can alleviate these symptoms. Women with menopausal symptoms have been found to have reduced risk of breast cancer, possibly reflecting low endogenous hormone levels. However, use of estrogen plus progesterone is associated with increased risk of breast cancer in postmenopausal women. The effects of HRT on breast cancer may vary according to timing of exposure relative to menopause. We examined the associations between menopausal symptoms, HRT and young-onset breast cancer. Methods Women with breast cancer (n=1422), whose breast-cancer-free sister (n=1669) had previously enrolled in the prospective Sister Study, were eligible if they were under 50 at diagnosis and still within 4 years of diagnosis at enrollment. Use of HRT and menopause-associated symptoms (hot flashes, poor sleeping, night sweats, etc) were assessed using computer-assisted telephone interviews. Conditional logistic regression was used to account for sister matching. To ensure comparable opportunity for exposures, we assessed them in relation to an index age, defined as the minimum of the age at diagnosis of the case and the age at interview of her sister(s). Analyses adjusted for birth order and menopausal status at index age. Results Women who had experienced menopause-associated symptoms (n=706) prior to the index age were less likely to have young-onset breast cancer (odds ratio (OR), 0.49; 95% confidence interval (CI), 0.40 to 0.61). Compared to never-use of HRT, history of use of estrogen only was associated with reduced risk, after adjustment for birth order, menopausal status and menopause-associated symptoms (OR=0.55; 95% CI 0.35 to 0.87); the reduction was more pronounced in current users (use within the year preceding index age), long-term users (≥ 3 years) and users with first use after menopause. Women using estrogen plus progesterone had non-statistically significantly reduced risk, and the association was statistically significant for women who had used both for more than 3 years (OR=0.34; 95% CI 0.12 to 0.95). There was no evidence of effect measure modification by current use or age at first use. Associations with menopause-associated symptoms remained strong but the association with HRT was attenuated when analysis was limited to invasive, estrogen-positive cancers. Conclusions Menopause-associated symptoms and use of estrogen only were associated with reduced risk of young-onset breast cancer. Use of both estrogen and progesterone was not associated with increased risk. These results provide some reassurance regarding HRT use in women < 50 years and the risk of young-onset breast cancer, but further investigations and follow-up studies are needed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5493. doi:1538-7445.AM2012-5493

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