Triple-Negative Breast Cancer: Distinguishing between Basal and Nonbasal Subtypes

Emad A. Rakha, Somaia E. Elsheikh, Muhammed A. Aleskandarany, Hany O. Habashi, Andrew R. Green, Desmond G. Powe, Maysa E. El-Sayed, Ahmed Benhasouna, Jean-Sebastien Brunet, Lars A. Akslen, Andrew Evans, Roger Blamey, Jorge S. Reis-Filho, William D. Foulkes, Ian O. Ellis

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    Abstract

    Purpose: Triple-negative (TN; estrogen receptor, progesterone receptor, and HER-2 negative) cancer and basal-like breast cancer (BLBC) are associated with poor outcome and lack the benefit of targeted therapy. It is widely perceived that BLBC and TN tumors are synonymous and BLBC can be defined using a TN definition without the need for the expression of basal markers.

    Experimental Design: We have used two well-defined cohorts of breast cancers with a large panel of biomarkers, BRCA1 mutation status, and follow-up data to compare the clinicopathologic and immunohistochemical features of TN tumors expressing one or more of the specific basal markers (CK5/6, CK17, CK14, and epidermal growth factor receptor; BLBC) with those TN tumors that express none of these markers (TN3BKE-).

    Results: Here, we show that although the morphologic features of BLBC are not significantly different from that of TN3BKE- tumors, BLBC showed distinct clinical and immunophenotypic differences. BLBC showed a statistically significant association with the expression of the hypoxia-associated factor (CA9), neuroendocrine markers, and other markers of poor prognosis such as p53. A difference in the expression of cell cycle-associated proteins and biomarkers involved in the immunologic portrait of tumors was seen. Compared with TN3BKE- tumors, BLBC was positively associated with BRCA1 mutation status and showed a unique pattern of distant metastasis, better response to chemotherapy, and shorter survival.

    Conclusion: TN breast cancers encompass a remarkably heterogeneous group of tumors. Expression of basal markers identifies a biologically and clinically distinct subgroup of TN tumors, justifying the use of basal markers (in TN tumors) to define BLBC.

    Original languageEnglish
    Pages (from-to)2302-2310
    Number of pages9
    JournalClinical Cancer Research
    Volume15
    Issue number7
    DOIs
    Publication statusPublished - 1 Apr 2009

    Keywords

    • GENE-EXPRESSION PROFILES
    • ESTROGEN-RECEPTOR
    • IMMUNOHISTOCHEMICAL MARKERS
    • PROGNOSTIC-SIGNIFICANCE
    • EPITHELIAL PHENOTYPE
    • MOLECULAR PORTRAITS
    • CARCINOMAS
    • TUMORS
    • BRCA1
    • CHEMOTHERAPY

    Cite this

    Rakha, E. A., Elsheikh, S. E., Aleskandarany, M. A., Habashi, H. O., Green, A. R., Powe, D. G., El-Sayed, M. E., Benhasouna, A., Brunet, J-S., Akslen, L. A., Evans, A., Blamey, R., Reis-Filho, J. S., Foulkes, W. D., & Ellis, I. O. (2009). Triple-Negative Breast Cancer: Distinguishing between Basal and Nonbasal Subtypes. Clinical Cancer Research, 15(7), 2302-2310. https://doi.org/10.1158/1078-0432.CCR-08-2132