BACKGROUND: Breast cancers with a triple negative tumor (TNT) subtype (as defined by lacking protein expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)) preclude the use of available targeted therapies and may contribute to poor outcome and to the historically poorest survival observed among African-American (AA) women. This study examines association of the ER/PR/HER2 subtypes with race and breast cancer survival. METHODS: Breast tumors from a population-based cohort of 116 AA and 360 white Atlanta women aged 20-54, diagnosed from 1990 to 1992 were centrally reviewed and tested by immunohistochemistry. Multivariate survival analyses within subtypes (TNT, ER-PR-HER2+, ER+/PR+HER2+, ER+/PR+HER2-) were conducted using weighted Cox regression and included socio-demographic, prognostic, and treatment factors. RESULTS: TNTs were more prevalent among young women and particularly among AA women (Odds Ratio [OR] = 1.9, 95% Confidence Interval [CI] 1.2-2.9), adjusting for age, stage, grade, and poverty index. Overall mortality was higher for AA women (Hazard Ratio [HR] = 1.9, 95% CI, 1.5-2.5) and differed by subtypes (P < 0.001). Within the TNT subtype, racial differences in survival persisted, after additional adjustment for treatment and comorbidities (HR = 2.0, 95% CI 1.0-3.7). TNTs were uniquely associated with high expression of p16, p53, and Cyclin E; and low Bcl-2 and Cyclin D1 expression. CONCLUSIONS: The high prevalence of TNTs among younger women and particularly younger AA women, along with unique protein expression patterns and poorer survival, suggests varying gene-environment etiologies with respect to age and race/ethnicity and a need for effective therapies.
BACKGROUND:Breast cancers with a triple negative tumor (TNT) subtype (as defined by lacking protein expression of estrogen receptor (ER), progesterone receptor (PR), and humanepidermal growth factor receptor 2 (HER2)) preclude the use of available targeted therapies and may contribute to poor outcome and to the historically poorest survival observed among African-American (AA) women. This study examines association of the ER/PR/HER2 subtypes with race and breast cancer survival. METHODS:Breast tumors from a population-based cohort of 116 AA and 360 white Atlanta women aged 20-54, diagnosed from 1990 to 1992 were centrally reviewed and tested by immunohistochemistry. Multivariate survival analyses within subtypes (TNT, ER-PR-HER2+, ER+/PR+HER2+, ER+/PR+HER2-) were conducted using weighted Cox regression and included socio-demographic, prognostic, and treatment factors. RESULTS:TNTs were more prevalent among young women and particularly among AA women (Odds Ratio [OR] = 1.9, 95% Confidence Interval [CI] 1.2-2.9), adjusting for age, stage, grade, and poverty index. Overall mortality was higher for AA women (Hazard Ratio [HR] = 1.9, 95% CI, 1.5-2.5) and differed by subtypes (P < 0.001). Within the TNT subtype, racial differences in survival persisted, after additional adjustment for treatment and comorbidities (HR = 2.0, 95% CI 1.0-3.7). TNTs were uniquely associated with high expression of p16, p53, and Cyclin E; and low Bcl-2 and Cyclin D1 expression. CONCLUSIONS: The high prevalence of TNTs among younger women and particularly younger AA women, along with unique protein expression patterns and poorer survival, suggests varying gene-environment etiologies with respect to age and race/ethnicity and a need for effective therapies.
Authors: Franca Podo; Lutgarde M C Buydens; Hadassa Degani; Riet Hilhorst; Edda Klipp; Ingrid S Gribbestad; Sabine Van Huffel; Hanneke W M van Laarhoven; Jan Luts; Daniel Monleon; Geert J Postma; Nicole Schneiderhan-Marra; Filippo Santoro; Hans Wouters; Hege G Russnes; Therese Sørlie; Elda Tagliabue; Anne-Lise Børresen-Dale Journal: Mol Oncol Date: 2010-04-24 Impact factor: 6.603
Authors: Christina A Clarke; Theresa H M Keegan; Juan Yang; David J Press; Allison W Kurian; Anish H Patel; James V Lacey Journal: J Natl Cancer Inst Date: 2012-07-05 Impact factor: 13.506
Authors: Jennifer A Crozier; Pooja P Advani; Betsy LaPlant; Timothy Hobday; Anthony J Jaslowski; Alvaro Moreno-Aspitia; Edith A Perez Journal: Clin Breast Cancer Date: 2015-08-19 Impact factor: 3.225
Authors: Christopher I Li; Justin E Mirus; Yuzheng Zhang; Arturo B Ramirez; Jon J Ladd; Ross L Prentice; Martin W McIntosh; Samir M Hanash; Paul D Lampe Journal: Breast Cancer Res Treat Date: 2012-08-19 Impact factor: 4.872
Authors: Katie M O'Brien; Stephen R Cole; Charles Poole; Jeannette T Bensen; Amy H Herring; Lawrence S Engel; Robert C Millikan Journal: Am J Epidemiol Date: 2013-11-10 Impact factor: 4.897
Authors: Larissa Belova; Bertha Delgado; Masha Kocherginsky; Amal Melhem; Olufunmilayo I Olopade; Suzanne D Conzen Journal: Breast Cancer Res Treat Date: 2008-07-31 Impact factor: 4.872
Authors: Amanda I Phipps; Kathleen E Malone; Peggy L Porter; Janet R Daling; Christopher I Li Journal: Cancer Epidemiol Biomarkers Prev Date: 2008-07-29 Impact factor: 4.254