Basal-Like Breast Cancer Defined by Five Biomarkers Has Superior Prognostic Value than Triple-Negative Phenotype
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...
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| Published in: | Clinical cancer research Vol. 14; no. 5; pp. 1368 - 1376 |
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| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Philadelphia, PA
American Association for Cancer Research
01-03-2008
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| 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. |
|---|---|
| AbstractList | 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. 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. 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. 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. 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. 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. PURPOSEBasal-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 DESIGNFour 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.RESULTSAmong 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.CONCLUSIONSThe 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. |
| Author | Maggie C.U. Cheang Charles M. Perou Chris Bajdik David Voduc Steven McKinney Stephen K. Chia Samuel Leung Torsten O. Nielsen |
| Author_xml | – sequence: 1 givenname: Maggie C. U surname: CHEANG fullname: CHEANG, Maggie C. U organization: Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia, Canada – sequence: 2 givenname: David surname: VODUC fullname: VODUC, David organization: Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia, Canada – sequence: 3 givenname: Chris surname: BAJDIK fullname: BAJDIK, Chris organization: Cancer Control Research Program, BC Cancer Agency, Canada – sequence: 4 givenname: Samuel surname: LEUNG fullname: LEUNG, Samuel organization: Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia, Canada – sequence: 5 givenname: Steven surname: MCKINNEY fullname: MCKINNEY, Steven organization: Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia, Canada – sequence: 6 givenname: Stephen K surname: CHIA fullname: CHIA, Stephen K organization: BC Cancer Agency, Vancouver, British Columbia, Canada – sequence: 7 givenname: Charles M surname: PEROU fullname: PEROU, Charles M organization: University of North Carolina, Chapel Hill, North Carolina, United States – sequence: 8 givenname: Torsten O surname: NIELSEN fullname: NIELSEN, Torsten O organization: Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia, Canada |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20192234$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/18316557$$D View this record in MEDLINE/PubMed |
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| Snippet | Purpose: Basal-like breast cancer is associated with high grade, poor prognosis, and younger patient age. Clinically, a triple-negative
phenotype definition... Basal-like breast cancer is associated with high grade, poor prognosis, and younger patient age. Clinically, a triple-negative phenotype definition [estrogen... Purpose: Basal-like breast cancer is associated with high grade, poor prognosis, and younger patient age. Clinically, a triple-negative phenotype definition... PURPOSEBasal-like breast cancer is associated with high grade, poor prognosis, and younger patient age. Clinically, a triple-negative phenotype definition... |
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| SubjectTerms | adjuvant systemic therapy Adult Aged Antineoplastic agents basal-like breast cancer Biological and medical sciences Biomarkers, Tumor - metabolism Breast Neoplasms - metabolism Breast Neoplasms - pathology Cohort Studies Female Follow-Up Studies Gynecology. Andrology. Obstetrics Humans Immunoenzyme Techniques In Situ Hybridization, Fluorescence Keratin-5 - metabolism Keratin-6 - metabolism Mammary gland diseases Medical sciences Middle Aged Neoplasm Invasiveness Pharmacology. Drug treatments Prognosis prognostic Receptor, Epidermal Growth Factor - metabolism Receptor, ErbB-2 - metabolism Receptors, Estrogen - metabolism Receptors, Progesterone - metabolism Tumors |
| Title | Basal-Like Breast Cancer Defined by Five Biomarkers Has Superior Prognostic Value than Triple-Negative Phenotype |
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