Triple negative breast cancer: molecular profiling and prognostic impact in adjuvant anthracycline-treated patients.
BACKGROUND
We analysed the clinical features, distribution of basal markers, prevalence of oncogene amplification, and outcome of triple negative (TN) compared to those of non-TN cancers in a series of adjuvant-anthracycline treated breast cancer patients.


METHODS
We examined the prognostic impact of the TN and BL phenotype in 245 breast cancer patients uniformly treated with adjuvant anthracycline-based chemotherapy following primary surgery, with regards to local relapse-free (LRFS), metastasis free (MFS), and breast cancer specific survival (BCSS). A comparative analysis of the clinicopathological characteristics, expression of basal markers (cytokeratins (Cks) 5/6, 14, 17, EGFR, and caveolin 1 and 2), MIB-1, p53 and topoisomerase II alpha, and prevalence of CCND1, MYC and TOP2A amplification in TN and non-TN breast tumours was performed.


RESULTS
TN cancers were significantly associated with the expression of basal markers (all P < 0.0001). However 19.4% of TN tumours were negative for basal markers, whilst 7.3% of non-TN tumours expressed basal markers. TN phenotype was significantly associated with p53, MIB-1 and topoisomerase II alpha (all, P < 0.01) expression. No TN cancer harboured amplification of CCND1 or TOP2A. In univariate analysis, TN and BL phenotype were significantly associated with shorter MFS (both, P < 0.01) and BCSS (both, P < 0.005) but not LRFS.


CONCLUSIONS
Despite treatment with standard dose anthracycline-based chemotherapy, the clinical outcome of TN and BL cancers remains poor. Alternative chemotherapeutic regimens and/or novel therapeutic approaches are warranted. Although a significant phenotypic overlap exists between TN and basal-like tumours, the TN phenotype is not an ideal surrogate marker for basal-like breast cancers.
Tan
David S P
DS
The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK.
Marchió
Caterina
C
Jones
Robin L
RL
Savage
Kay
K
Smith
Ian E
IE
Dowsett
Mitch
M
Reis-Filho
Jorge S
JS
D018943:Anthracyclines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D010641:Phenotype; D011379:Prognosis; D046888:Tissue Array Analysis
D018943:Anthracyclines; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor