Expression of CK5 Better Correlates with Shorter Survival and Poor Prognosis in Triple-Negative Breast Cancer
M De Brot, FA Soares, H Gobbi. Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Hospital AC Camargo, Sao Paulo, Brazil
Background: Triple-negative breast cancer (ER, PR, and HER2-negative) is a high risk breast cancer that lacks the benefit of specific therapy that targets these proteins. There is a great deal of overlap between triple-negative and basal-like breast cancers (BLC), but this overlap is by no means complete. The aim of our study was to investigate basal phenotype in a series of triple-negative invasive mammary carcinomas; to assess the expression of different biomarkers associated with basal phenotype; and to evaluate their relationship with prognosis.
Design: We selected 140 previously tested triple-negative tumors. Clinical, histopathological and survival data were obtained. A TMA containing 2 cylinders from each tumor was constructed and immunohistochemistry for ER, PR, HER2, CK5, CK14, EGFR, p63, caveolin, and p53 was performed. We considered BLC to be any tumor ER/PR/HER2-negative, CK5- and/or CK14-positive.
Results: We found 105 cases of BLC among the 140 triple-negative tumors (frequency=75.0%). The mean age at diagnosis was 54.8 years-old and 34.3% were premenopausal women. The majority of tumors were high grade (83.7%) and of ductal/no-special-type (80.8%). Triple-negative tumors showed immunoreactivity for CK5 (75.0%), CK14 (29.0%), EGFR (28.6%), p63 (28.6%), caveolin (14.3%), and p53 (67.1%). CK14 expression always coexisted with CK5 expression. Tumor size larger than 5cm was observed in 41 cases (39.0%) and axillary metastases were detected in 61 patients (59.2%). Follow-up was obtained for 89 patients (mean=51 months): 45 patients (50.5%) with no evidence of disease; 6 patients (6.7%) were alive with disease; and 38 patients (42.6%) died of the disease. Relapse was detected in 42 women (47.1%), lungs, brain, and bones being the most commom sites of metastases. The mean overall survival (OS) was 36 months and the mean disease-free interval was 28 months. OS in patients with triple-negative CK5-positive/basal tumors was shorter than OS in those with triple-negative CK5-negative/non basal tumors (RR=2.4). In contrast, positivity for CK14, EGFR, p63, or caveolin was not associated with poorer outcome.
Conclusions: Our findings confirmed that BLC have a poor prognosis and are high-frequent carcinomas among triple-negative tumors. Compared to other basal markers, CK5 expression was the most prevalent and the only one that improved recognition of patients with shorter survival in triple-negative breast cancer.
Monday, March 9, 2009 1:15 PM
Platform Session: Section B, Monday Afternoon