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

• Published in: Clinical cancer research Vol. 15; no. 7; pp. 2302 - 2310
• Main Authors: RAKHA, Emad A, ELSHEIKH, Somaia E, EVANS, Andy J, BLAMEY, Roger, REIS-FILHO, Jorge S, FOULKES, William D, ELLIS, Ian O, ALESKANDARANY, Muhammed A, HABASHI, Hany O, GREEN, Andrew R, POWE, Desmond G, EL-SAYED, Maysa E, BENHASOUNA, Ahmed, BRUNET, Jean-Sébastien, AKSLEN, Lars A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-04-2009
• Subjects: Antineoplastic agents; basal-like; Biological and medical sciences; Biomarkers - analysis; Biomarkers, Tumor - analysis; breast cancer; Breast Neoplasms - classification; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cell Cycle Proteins - analysis; Epithelial Cells - chemistry; Female; Genes, BRCA1; Gynecology. Andrology. Obstetrics; Humans; Immunophenotyping; Mammary gland diseases; Medical sciences; Middle Aged; Neoplasm Metastasis; Pharmacology. Drug treatments; Receptor, ErbB-2 - analysis; Receptors, Estrogen - analysis; Receptors, Progesterone - analysis; Survival Analysis; triple-negative; Tumors; Mammary gland diseases; Breast cancer; Breast disease; Malignant tumor; Subtype; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-2132

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.