Basal-Like Breast Cancer Defined by Five Biomarkers Has Superior Prognostic Value than Triple-Negative Phenotype

• Published in: Clinical cancer research Vol. 14; no. 5; pp. 1368 - 1376
• Main Authors: CHEANG, Maggie C. U, VODUC, David, BAJDIK, Chris, LEUNG, Samuel, MCKINNEY, Steven, CHIA, Stephen K, PEROU, Charles M, NIELSEN, Torsten O
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-03-2008
• Subjects: 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; Mammary gland diseases; Phenotype; Breast disease; Prognosis; Biological marker; Breast cancer; Malignant tumor; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-07-1658

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.