Androgen Receptor Expression and Breast Cancer Survival: Results From the Nurses' Health Studies.

Abstract

BACKGROUND:

Hormone receptor signaling is critical in the progression of breast cancers, although the role of the androgen receptor (AR) remains unclear, particularly for estrogen receptor (ER)-negative tumors. This study assessed AR protein expression as a prognostic marker for breast cancer mortality.

METHODS:

This study included 4147 pre- and postmenopausal women with invasive breast cancer from the Nurses' Health Study (diagnosed 1976-2008) and Nurses' Health Study II (1989-2008) cohorts. AR protein expression was evaluated by immunohistochemistry and scored through pathologist review and as a digitally quantified continuous measure. Hazard ratios (HR) and 95% confidence intervals (CI) of breast cancer mortality were estimated from Cox proportional hazards models, adjusting for patient, tumor, and treatment covariates.

RESULTS:

Over a median 16.5 years of follow-up, there were 806 deaths due to breast cancer. In the 7 years following diagnosis, AR expression was associated with a 27% reduction in breast cancer mortality overall (multivariable HR = 0.73, 95% CI = 0.58 to 0.91) a 47% reduction for ER+ cancers (HR = 0.53, 95% CI = 0.41 to 0.69), and a 62% increase for ER- cancers (HR = 1.62, 95% CI = 1.18 to 2.22) (P heterogeneity < .001). A log-linear association was observed between AR expression and breast cancer mortality among ER- cancers (HR = 1.14, 95% CI = 1.02 to 1.26 per each 10% increase in AR), although no log-linear association was observed among ER+ cancers.

CONCLUSIONS:

AR expression was associated with improved prognosis in ER+ tumors and worse prognosis in ER- tumors in the first 5-10 years postdiagnosis. These findings support the continued evaluation of AR-targeted therapies for AR+/ER- breast cancers.

• Authors: Kevin H Kensler, Elizabeth M Poole, Yujing J Heng, Laura C Collins, Benjamin Glass, Andrew H Beck, Aditi Hazra, Bernard A Rosner, A Heather Eliassen, Susan E Hankinson, Eric P Winer, Myles Brown, Rulla M Tamimi
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 111 Issue 7 Pg. 700-708 (07 01 2019) ISSN: 1460-2105 [Electronic] United States
• PMID: 30445651 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].

Chemical References

• AR protein, human
• Biomarkers, Tumor
• Receptors, Androgen
• Receptors, Estrogen
• Receptors, Progesterone

Topics

• Adult
• Biomarkers, Tumor (genetics)
• Breast (metabolism, pathology)
• Breast Neoplasms (epidemiology, genetics, pathology)
• Cancer Survivors
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Prognosis
• Proportional Hazards Models
• Receptors, Androgen (genetics)
• Receptors, Estrogen (genetics)
• Receptors, Progesterone (genetics)