Kevin H Kensler1,2, Elizabeth M Poole3, Yujing J Heng4,5, Laura C Collins4,5, Benjamin Glass6, Andrew H Beck6, Aditi Hazra5,7, Bernard A Rosner2,5,8, A Heather Eliassen1,2,5, Susan E Hankinson1,2,5,9, Eric P Winer5,10, Myles Brown5,10, Rulla M Tamimi1,2,5. 1. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA. 2. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 3. Sanofi Genzyme, Cambridge, MA. 4. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA. 5. Harvard Medical School, Boston, MA. 6. PathAI, Cambridge, MA. 7. Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA. 8. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA. 9. Department of Biostatistics and Epidemiology, University of Massachusetts School of Public Health and Health Sciences, Amherst, MA. 10. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
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.
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: Rulla M Tamimi; A Heather Eliassen; Tengteng Wang; Yujing J Heng; Gabrielle M Baker; Vanessa C Bret-Mounet; Liza M Quintana; Lisa Frueh; Susan E Hankinson; Michelle D Holmes; Wendy Y Chen; Walter C Willett; Bernard Rosner Journal: Cancer Epidemiol Biomarkers Prev Date: 2022-10-04 Impact factor: 4.090
Authors: Kevin H Kensler; Meredith M Regan; Yujing J Heng; Gabrielle M Baker; Michael E Pyle; Stuart J Schnitt; Aditi Hazra; Roswitha Kammler; Beat Thürlimann; Marco Colleoni; Giuseppe Viale; Myles Brown; Rulla M Tamimi Journal: Breast Cancer Res Date: 2019-02-22 Impact factor: 6.466
Authors: Choong Man Lee; Il Yong Chung; Yangsoon Park; Keong Won Yun; Hwi Gyeong Jo; Hye Jin Park; Hee Jin Lee; Sae Byul Lee; Hee Jeong Kim; Beom Seok Ko; Jong Won Lee; Byung Ho Son; Sei Hyun Ahn; Jisun Kim Journal: J Breast Cancer Date: 2020-12-24 Impact factor: 3.588
Authors: Gabrielle M Baker; Michael E Pyle; Adam M Tobias; Richard A Bartlett; Jordana Phillips; Valerie J Fein-Zachary; Gerburg M Wulf; Yujing J Heng Journal: Transgend Health Date: 2019-11-19