Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype

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  • Cheang, Maggie C.U.
    • Other Affiliation: Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia
  • Voduc, David
    • Other Affiliation: Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia; BC Cancer Agency, Vancouver, British Columbia, Canada
  • Bajdik, Chris
    • Other Affiliation: Cancer Control Research Program, BC Cancer Agency
  • Leung, Samuel
    • Other Affiliation: Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia
  • McKinney, Steven
    • Other Affiliation: Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia
  • Chia, Stephen K.
    • Other Affiliation: BC Cancer Agency, Vancouver, British Columbia, Canada
  • Perou, Charles
  • Nielsen, Torsten O.
    • Other Affiliation: Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia
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 basallike 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 assembledinto tissuemicroarrays. Allhad staging, pathology, treatment, andoutcomeinformation;median follow-up was12.5 years. Cox regression analyses and likelihood ratio tests compared the prognostic significance for breast cancer death-specific survival (BCSS) of the twoimmunohistochemicalpanels. Results: Among3,744interpretable cases,17%werebasalusing the triple-negativedefinition(10- year BCSS, 6 7%) and 9% were basal using the five-marker method (10-year BCSS, 62%). Likelihood ratio tests ofmultivariable Coxmodelsincluding standard clinical variables show that the fivemarker 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-negativepatients treatedwithadjuvant anthracycline-based chemotherapy, theadditionalpositive basalmarkersidentified 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.
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  • Article
Rights statement
  • In Copyright
Journal title
  • Clinical Cancer Research
Journal volume
  • 14
Journal issue
  • 5
Page start
  • 1368
Page end
  • 1376
Language
  • English
Version
  • Postprint
ISSN
  • 1078-0432

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