Unopposed Estrogen Therapy and the Risk of Invasive Breast Cancer

Department of Nutrition , Harvard University, Cambridge, Massachusetts, United States
Archives of Internal Medicine (Impact Factor: 17.33). 06/2006; 166(9):1027-32. DOI: 10.1001/archinte.166.9.1027
Source: PubMed

ABSTRACT Although short-term unopposed estrogen use does not seem to increase breast cancer risk, the effect of longer-term estrogen use remains unclear. We sought to assess the relationship between longer-term use of unopposed estrogen and the risk of invasive breast cancer over an extended follow-up period.
Within the Nurses' Health Study, a prospective cohort study, we observed 11 508 postmenopausal women who had a hysterectomy and reported information on estrogen use at baseline (1980). The study population was expanded every 2 years to include women who subsequently became postmenopausal and had a hysterectomy, so that 28 835 women were included in the final follow-up period (2000-2002). Estrogen use was assessed from self-reported data on biennial questionnaires. The main outcome was invasive breast cancer.
A total of 934 invasive breast cancers were included in the analysis. Breast cancer risk increased with duration of unopposed estrogen use among longer-term users with the highest risk seen in cancers positive for estrogen receptor (ER+) and progesterone receptor (PR+). The multivariate relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer with current use of unopposed estrogen for less than 5 years, 5 to 9.9 years, 10 to 14.9 years, 15 to 19.9 years, and 20 years or longer were, respectively, 0.96 (95% CI, 0.75-1.22), 0.90 (95% CI, 0.73-1.12), 1.06 (95% CI, 0.87-1.30), 1.18 (95% CI, 0.95-1.48), and 1.42 (95% CI, 1.13-1.77) (P for trend <.001). The risk of ER+/PR+ breast cancers was noted to be statistically significant after 15 years of current use (RR, 1.48; 95% CI, 1.05-2.07).
Users of unopposed estrogen were at increased risk of breast cancer but only after longer-term use.

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    • "In one study, short-term use of estrogen-only HRT did not increase the risk of breast cancer [29]. In the Nurses Health Study, the risk of breast cancer was increased significantly in women with prior hysterectomy after 20 years or more of HRT, and the relative risk was higher for estrogen receptor (ER)+/progesterone receptor (PR)+ cancers [30]. One prospective study reported that combined use of estrogen and testosterone HRT in postmenopausal women increases the risk of breast cancer by 17% per year [31]. "
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    • "When one considers the rapidity at which excess risk appears, plus the fact that this risk increase disappears rapidly when the treatment is stopped, plus the absence of in situ cancers increase, it is likely that there is a promotion phenomenon and not of initiation [1] [2]. The arm estrogens only of WHI, as well as numerous other studies of the cohort, do not show any increase with estrogens only (RR=0,77 (0,57–1,06) [7] [8]. One study with a very long follow-up is the only one to show a very late risk increase (more than 15 years) with estrogens only [9]. "
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    • "More recently, the WHI trial reported that about 7 years of treatment with exogenous oestrogen did not raise the risk of breast cancer in 11 000 women who had previously undergone hysterectomy (Stefanick et al. 2006). The prospective cohort Nurses Health Study observed that the risk of breast cancer positive for oestrogen and progesterone receptors increased only after 15 years of oestrogen treatment, and all breast cancers after 20 years (Chen et al. 2006). Although this studies clarify the risks of oestrogen use, the role of progesterone appear more ambiguous. "
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