Basal-Like Breast Cancer Defined by Five Biomarkers Has Superior Prognostic Value than Triple-Negative Phenotype
Top Cited Papers
- 1 March 2008
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 14 (5), 1368-1376
- https://doi.org/10.1158/1078-0432.ccr-07-1658
Abstract
Purpose: Basal-like breast cancer is associated with high grade, poor prognosis, and younger patient age. Clinically, a triple-negative phenotype definition [estrogen receptor, progesterone receptor, and human epidermal growth factor receptor (HER)-2, all negative] is commonly used to identify such cases. EGFR and cytokeratin 5/6 are readily available positive markers of basal-like breast cancer applicable to standard pathology specimens. This study directly compares the prognostic significance between three- and five-biomarker surrogate panels to define intrinsic breast cancer subtypes, using a large clinically annotated series of breast tumors. Experimental Design: Four thousand forty-six invasive breast cancers were assembled into tissue microarrays. All had staging, pathology, treatment, and outcome information; median follow-up was 12.5 years. Cox regression analyses and likelihood ratio tests compared the prognostic significance for breast cancer death-specific survival (BCSS) of the two immunohistochemical panels. Results: Among 3,744 interpretable cases, 17% were basal using the triple-negative definition (10-year BCSS, 6 7%) and 9% were basal using the five-marker method (10-year BCSS, 62%). Likelihood ratio tests of multivariable Cox models including standard clinical variables show that the five-marker panel is significantly more prognostic than the three-marker panel. The poor prognosis of triple-negative phenotype is conferred almost entirely by those tumors positive for basal markers. Among triple-negative patients treated with adjuvant anthracycline-based chemotherapy, the additional positive basal markers identified a cohort of patients with significantly worse outcome. Conclusions: The expanded surrogate immunopanel of estrogen receptor, progesterone receptor, human HER-2, EGFR, and cytokeratin 5/6 provides a more specific definition of basal-like breast cancer that better predicts breast cancer survival.Keywords
This publication has 35 references indexed in Scilit:
- Descriptive analysis of estrogen receptor (ER)‐negative, progesterone receptor (PR)‐negative, and HER2‐negative invasive breast cancer, the so‐called triple‐negative phenotypeCancer, 2007
- Prognostic markers in triple‐negative breast cancerCancer, 2006
- Concordance among Gene-Expression–Based Predictors for Breast CancerThe New England Journal of Medicine, 2006
- Race, breast cancer subtypes, and survival in the Carolina Breast Cancer StudyJAMA, 2006
- Phenotypic evaluation of the basal-like subtype of invasive breast carcinomaLaboratory Investigation, 2005
- Hallmarks of 'BRCAness' in sporadic cancersNature Reviews Cancer, 2004
- Expression of luminal and basal cytokeratins in human breast carcinomaThe Journal of Pathology, 2004
- Repeated observation of breast tumor subtypes in independent gene expression data setsProceedings of the National Academy of Sciences of the United States of America, 2003
- Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implicationsProceedings of the National Academy of Sciences of the United States of America, 2001
- Proportional hazards tests and diagnostics based on weighted residualsBiometrika, 1994