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

Ghada N. Farhat, Steven R. Cummings, Rowan T. Chlebowski, Neeta Parimi, Jane A. Cauley, Thomas E. Rohan, Alison J. Huang, Mara Vitolins, F. Allan Hubbell, Joann E. Manson, Barbara B. Cochrane, Dorothy S. Lane, Jennifer S. Lee

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)562-570
Number of pages9
JournalJournal of the National Cancer Institute
Volume103
Issue number7
DOIs
StatePublished - Apr 6 2011

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Gonadal Steroid Hormones
Estrogen Receptors
Breast Neoplasms
Testosterone
Estradiol
Confidence Intervals
Odds Ratio
Neoplasms
Sex Hormone-Binding Globulin
Women's Health
Serum
Immunoassay
Radioimmunoassay
Observational Studies
Cohort Studies
Hormones

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers. / Farhat, Ghada N.; Cummings, Steven R.; Chlebowski, Rowan T.; Parimi, Neeta; Cauley, Jane A.; Rohan, Thomas E.; Huang, Alison J.; Vitolins, Mara; Hubbell, F. Allan; Manson, Joann E.; Cochrane, Barbara B.; Lane, Dorothy S.; Lee, Jennifer S.

In: Journal of the National Cancer Institute, Vol. 103, No. 7, 06.04.2011, p. 562-570.

Research output: Contribution to journalArticle

Farhat, GN, Cummings, SR, Chlebowski, RT, Parimi, N, Cauley, JA, Rohan, TE, Huang, AJ, Vitolins, M, Hubbell, FA, Manson, JE, Cochrane, BB, Lane, DS & Lee, JS 2011, 'Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers', Journal of the National Cancer Institute, vol. 103, no. 7, pp. 562-570. https://doi.org/10.1093/jnci/djr031
Farhat, Ghada N. ; Cummings, Steven R. ; Chlebowski, Rowan T. ; Parimi, Neeta ; Cauley, Jane A. ; Rohan, Thomas E. ; Huang, Alison J. ; Vitolins, Mara ; Hubbell, F. Allan ; Manson, Joann E. ; Cochrane, Barbara B. ; Lane, Dorothy S. ; Lee, Jennifer S. / Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers. In: Journal of the National Cancer Institute. 2011 ; Vol. 103, No. 7. pp. 562-570.
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abstract = "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.",
author = "Farhat, {Ghada N.} and Cummings, {Steven R.} and Chlebowski, {Rowan T.} and Neeta Parimi and Cauley, {Jane A.} and Rohan, {Thomas E.} and Huang, {Alison J.} and Mara Vitolins and Hubbell, {F. Allan} and Manson, {Joann E.} and Cochrane, {Barbara B.} and Lane, {Dorothy S.} and Lee, {Jennifer S.}",
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AU - Farhat, Ghada N.

AU - Cummings, Steven R.

AU - Chlebowski, Rowan T.

AU - Parimi, Neeta

AU - Cauley, Jane A.

AU - Rohan, Thomas E.

AU - Huang, Alison J.

AU - Vitolins, Mara

AU - Hubbell, F. Allan

AU - Manson, Joann E.

AU - Cochrane, Barbara B.

AU - Lane, Dorothy S.

AU - Lee, Jennifer S.

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N2 - 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.

AB - 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.

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