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Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers

Farhat, GN and Cummings, SR and Chlebowski, RT and Parimi, N and Cauley, JA and Rohan, TE and Huang, AJ and Vitolins, M and Hubbell, FA and Manson, JE and Cochrane, BB and Lane, DS and Lee, JS (2011) Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers. Journal of the National Cancer Institute, 103 (7). 562 - 570. ISSN 0027-8874

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BackgroundEndogenous sex hormone levels are associated with risks of breast cancer overall and estrogen receptor (ER)-positive breast tumors; however, their associations with ER-negative tumors remain unclear.MethodsIn a case-cohort study within the Women's Health Initiative Observational Study among postmenopausal women aged 50-79 years, we examined associations between endogenous testosterone and estradiol levels and the risks of ER-negative and ER-positive breast cancers. Serum levels of bioavailable testosterone and estradiol were assessed at the baseline visit in 317 invasive breast cancer case subjects and in a subcohort of 594 women. Bioavailable sex hormone levels were calculated using the total hormone level and the sex hormone-binding globulin concentration (measured by radioimmunoassays and a chemiluminescent immunoassay, respectively). Cox proportional hazards regression was used for statistical analysis. All statistical tests were two-sided.ResultThe unadjusted absolute rates of ER-negative breast cancer for testosterone quartiles 1-4 were 0.34, 0.20, 0.23, and 0.21 per 10000 person-years, respectively. Compared with women in the lowest quartile of testosterone level, those in quartile 2 had a 56% lower risk of ER-negative cancer (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.23 to 0.85), those in quartile 3 had a 45% lower risk (HR = 0.55, 95% CI = 0.30 to 1.01), and those in quartile 4 had a 49% lower risk (HR = 0.51, 95% CI = 0.28 to 0.94), independent of other risk factors. Estradiol level was not associated with ER-negative breast cancer. ER-positive breast cancer risk increased with higher testosterone levels (Ptrend =. 04), but this trend was not statistically significant after adjustment for estradiol (Ptrend =. 15). ER-positive cancer risk was approximately twofold higher in women with estradiol levels in quartiles 2-4 compared with women in quartile 1, independent of risk factors.ConclusionHigher serum levels of bioavailable testosterone are associated with lower risks of ER-negative breast cancer in postmenopausal women. © 2011 The Author.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Farhat, GN
Cummings, SR
Chlebowski, RT
Parimi, N
Cauley, JAJCauley@edc.pitt.eduJCAULEY
Rohan, TE
Huang, AJ
Vitolins, M
Hubbell, FA
Manson, JE
Cochrane, BB
Lane, DS
Lee, JS
Date: 6 April 2011
Date Type: Publication
Journal or Publication Title: Journal of the National Cancer Institute
Volume: 103
Number: 7
Page Range: 562 - 570
DOI or Unique Handle: 10.1093/jnci/djr031
Schools and Programs: Graduate School of Public Health > Epidemiology
Refereed: Yes
ISSN: 0027-8874
Date Deposited: 03 Apr 2015 16:40
Last Modified: 02 Feb 2019 21:55


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