Postmenopausal Hormone Use and Breast Cancer Associations Differ by Hormone Regimen and Histologic Subtype
ABSTRACT 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.
Full-textDOI: · Available from: Janet S Hildebrand, Mar 24, 2015
- SourceAvailable from: Mélanie Bourque
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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). "
ABSTRACT: Finasteride and Dutasteride are 5α-reductase inhibitors used in the clinic to treat endocrine conditions and were recently found to modulate brain dopamine (DA) neurotransmission and motor behaviour. We investigated if Finasteride and Dutasteride have a neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) male mice as a model of Parkinson's disease (PD). Experimental groups included saline treated controls and mice treated with saline, Finasteride (5 and 12.5 mg/kg) or Dutasteride (5 and 12.5 mg/kg) for 5 days before and 5 days after MPTP administration (4 MPTP injections, 6.5 mg/kg on day 5 inducing a moderate DA depletion) and then they were euthanized. MPTP administration decreased striatal DA contents measured by HPLC while serotonin contents remained unchanged. MPTP mice treated with Dutasteride 5 and 12.5 mg/kg had higher striatal DA and metabolites (DOPAC and HVA) contents with a decrease of metabolites/DA ratios compared to saline-treated MPTP mice. Finasteride had no protective effect on striatal DA contents. Tyrosine hydroxylase (TH) mRNA levels measured by in situ hybridization in the substantia nigra pars compacta were unchanged. Dutasteride at 12.5 mg/kg reduced the effect of MPTP on specific binding to striatal DA transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) measured by autoradiography. MPTP reduced compared to controls plasma testosterone (T) and dihydrotestosterone (DHT) concentrations measured by liquid chromatography-tandem mass spectrometry; Dutasteride and Finasteride increased plasma T levels while DHT levels remained low. In summary, our results showed that a 5α-reductase inhibitor, Dutasteride has neuroptotective activity preventing in male mice the MPTP-induced loss of several dopaminergic markers. Copyright © 2015. Published by Elsevier Ltd.Neuropharmacology 05/2015; 97. DOI:10.1016/j.neuropharm.2015.05.015 · 5.11 Impact Factor
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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]. "
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.Breast cancer research: BCR 12/2010; 12(6):R106. DOI:10.1186/bcr2790 · 5.49 Impact Factor
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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. "
ABSTRACT: Background Correlation between circulating sex steroid levels and breast cancer has been controversial, with measurement of free, or bioavailable hormone rarely available. Salivary hormone levels represent the bioavailable fraction. To further elucidate the role of endogenous hormones in breast cancer, we aimed to assess correlation between salivary sex steroid levels and breast cancer prevalence. Methods Salivary hormone levels of testosterone (T), Estradiol (E2), Progesterone (P), Estriol (E3), Estrone (E1), DHEAS and Cortisol (C) were measured by Enzyme Immunoassay (EIA) in 357 women with histologically verified breast cancer and 184 age-matched control women. Results Salivary T and DHEAS levels were significantly lower in breast cancer cases vs. controls (27.2+13.9 vs. 32.2+17.5 pg/ml, p < 0.001 for T and 5.3+4.3 vs. 6.4+4.5 ng/ml, p = 0.007 for DHEAS). E2 and E1 levels were elevated and E3 levels were lowered in cases vs. controls. Conclusions Salivary T levels, representing the bioavailable hormone, are significantly lower in women with breast cancer compared to age-matched control women. These findings support the protective role of biovailable testosterone in counteracting the proliferative effects of estrogens on mammary tissue.BMC Cancer 10/2010; 10(1):547. DOI:10.1186/1471-2407-10-547 · 3.36 Impact Factor