Postmenopausal Hormone Use and Breast Cancer Associations Differ by Hormone Regimen and Histologic Subtype

Department of Epidemiology and Surveillance Research, American Cancer Society, 250 Williams Street, NW, Atlanta, GA 30303, USA.
Cancer (Impact Factor: 4.89). 03/2009; 115(5):936-45. DOI: 10.1002/cncr.24101
Source: PubMed


Data from large prospective studies are needed to fully characterize the impact of exogenous hormones on breast cancer incidence by type of hormone preparation and histology of the cancer.
In a prospective cohort of 67,754 postmenopausal women in the US, 1821 cases of invasive ductal cancer and 471 cases of invasive lobular or mixed lobular cancer occurred during 13 years of follow-up. The authors computed age-adjusted rates, as well as age-adjusted and multivariate-adjusted rate ratios (RR) for ductal and lobular breast cancer and for the use of estrogen only (E-only) and estrogen and progesterone (E + P) for current and former hormone users by duration of use and years since last use.
Current use of E + P was associated with an increased risk of both ductal (RR of 1.75; 95% confidence interval [95% CI], 1.53-2.01) and lobular (RR of 2.12; 95% CI, 1.62-2.77) breast cancer. Risk increased within the first 2 to 3 years of use and attenuated 2 years after cessation. In contrast, current use of E-only was not associated with an overall increased risk of invasive ductal cancer. The only exceptions to this finding were in lean (body mass index <25) women and for ductal cancers diagnosed at the regional/distant stage, where in both cases the use of E-only was associated with an increased risk. E-only use was associated with a 50% increased risk of invasive lobular cancer after >or=10 years of use.
Use of E + P is more detrimental to the breast than E-only use, in terms of both ductal and lobular cancer. The findings from the current study suggest a window of 2 to 3 years for the risks of E + P both to become apparent after initial use and to attenuate after cessation.

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Available from: Janet S Hildebrand, Mar 24, 2015
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    • "Hormone therapy has also been associated with a reduced risk of developing the disease (Currie et al., 2004). However, the beneficial effects of estrogen in the brain could be offset by adverse side effects; chronic use of steroid hormones has been associated with increased risk to develop breast and ovarian cancer (Calle et al., 2009). Furthermore, in men, elevated circulating estradiol levels may have unwanted side-effects such as enlarged breasts, weight gain, emotional disturbances as well as infertility (Lund et al., 1999; Rozati et al., 2002). "
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    Full-text · Article · May 2015 · Neuropharmacology
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    • "Of these, all but two cohort studies reported a stronger increased risk for lobular compared with ductal carcinoma [27,28]. In general, most studies have shown that combined E+P was more strongly related to risk of lobular vs. ductal carcinoma than use of E alone [7,29]. Lobular cancers are more likely to be ER-positive and/or PR-positive than ductal tumors [30,31]. "
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    ABSTRACT: Ductal and lobular carcinomas are the two most common types of invasive breast cancer. Whether well-established risk factors are differentially associated with risk on the basis of histologic subtype is not clear. We prospectively investigated the association between a number of hormonal and nonhormonal exposures and risk defined by histologic subtype among 4,655 ductal and 659 lobular cases of postmenopausal breast cancer from the Nurses' Health Study. Multivariate Cox proportional hazards regression stratified by histologic subtype and time period was used to examine the association between risk factors and the incidence of ductal and lobular subtypes. For each exposure, we calculated the P value for heterogeneity using a likelihood ratio test comparing models with separate estimates for the two subtypes versus a single estimate across subtypes. The associations with age at menarche (P-heterogeneity (het) = 0.03), age at first birth (P-het < 0.001) and postmenopausal hormone use (P-het < 0.001) were more strongly associated with lobular cancers. The associations with age, nulliparity, parity, age at menopause, type of menopause, alcohol intake, adult body mass index (BMI), BMI at age 18, family history of breast cancer and personal history of benign breast disease did not vary by subtype (P-het ≥ 0.08). Results were similar when we restricted the analyses to estrogen receptor-positive and progesterone receptor-positive tumors. These data indicate that breast cancer is a heterogeneous disease, and the differential association with a number of risk factors is suggestive of etiologically distinct tumors. Epidemiological analyses should continue to take into account a modifying role of histology.
    Full-text · Article · Dec 2010 · Breast cancer research: BCR
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    • "Unlike other studies [27,28], no correlation was found between tumor histology and hormone levels. Testosterone and estrogen levels did not differ between in-situ and invasive carcinoma. "
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    Full-text · Article · Oct 2010 · BMC Cancer
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