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

doi:10.1158/1078-0432.CCR-08-2132

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 language	English
Pages (from-to)	2302-2310
Number of pages	9
Journal	Clinical Cancer Research
Volume	15
Issue number	7
DOIs	https://doi.org/10.1158/1078-0432.CCR-08-2132
Publication status	Published - 1 Apr 2009

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/1078-0432.CCR-08-2132

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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

@article{36eb3c9bece64f5596752938108d0dc9,

title = "Triple-Negative Breast Cancer: Distinguishing between Basal and Nonbasal Subtypes",

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.",

keywords = "GENE-EXPRESSION PROFILES, ESTROGEN-RECEPTOR, IMMUNOHISTOCHEMICAL MARKERS, PROGNOSTIC-SIGNIFICANCE, EPITHELIAL PHENOTYPE, MOLECULAR PORTRAITS, CARCINOMAS, TUMORS, BRCA1, CHEMOTHERAPY",

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

year = "2009",

month = apr,

day = "1",

doi = "10.1158/1078-0432.CCR-08-2132",

language = "English",

volume = "15",

pages = "2302--2310",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

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Rakha, EA, Elsheikh, SE, Aleskandarany, MA, Habashi, HO, Green, AR, Powe, DG, El-Sayed, ME, Benhasouna, A, Brunet, J-S, Akslen, LA, Evans, A, Blamey, R, Reis-Filho, JS, Foulkes, WD & Ellis, IO 2009, 'Triple-Negative Breast Cancer: Distinguishing between Basal and Nonbasal Subtypes', Clinical Cancer Research, vol. 15, no. 7, pp. 2302-2310. https://doi.org/10.1158/1078-0432.CCR-08-2132

TY - JOUR

T1 - Triple-Negative Breast Cancer

T2 - Distinguishing between Basal and Nonbasal Subtypes

AU - Rakha, Emad A.

AU - Elsheikh, Somaia E.

AU - Aleskandarany, Muhammed A.

AU - Habashi, Hany O.

AU - Green, Andrew R.

AU - Powe, Desmond G.

AU - El-Sayed, Maysa E.

AU - Benhasouna, Ahmed

AU - Brunet, Jean-Sebastien

AU - Akslen, Lars A.

AU - Evans, Andrew

AU - Blamey, Roger

AU - Reis-Filho, Jorge S.

AU - Foulkes, William D.

AU - Ellis, Ian O.

PY - 2009/4/1

Y1 - 2009/4/1

N2 - 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.

AB - 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.

KW - GENE-EXPRESSION PROFILES

KW - ESTROGEN-RECEPTOR

KW - IMMUNOHISTOCHEMICAL MARKERS

KW - PROGNOSTIC-SIGNIFICANCE

KW - EPITHELIAL PHENOTYPE

KW - MOLECULAR PORTRAITS

KW - CARCINOMAS

KW - TUMORS

KW - BRCA1

KW - CHEMOTHERAPY

U2 - 10.1158/1078-0432.CCR-08-2132

DO - 10.1158/1078-0432.CCR-08-2132

M3 - Article

C2 - 19318481

SN - 1078-0432

VL - 15

SP - 2302

EP - 2310

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 7

ER -

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

Abstract

Keywords

UN SDGs

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