The Influence of Receptor Status on Locoregional Recurrence Risk Among Breast Cancer Patients With Positive Lymph Nodes Following Neoadjuvant Chemotherapy and Mastectomy

Abstract

ER, PR, and HER2 expression defines the triple negative phenotype and serves as a surrogate marker for basal-like carcinoma. Phosphorylation of the epithelial intermediate filament protein keratin 8 at serine 73 (phosphoK8) occurs during mitosis, cellular stress and apoptosis, and inversely correlates with colorectal cancer progression. In this study, we aimed to determine the prognostic value of phospho-K8 in triple negative breast cancer (TNBC). Materials/Methods: Tumor specimens from 369 women with breast cancer (patient age range 25-89 years) and a median follow-up of 7.02 years were constructed into a tissue microarray. The array was stained for ER, PR, HER2, and phospho-K8. Among these, 90 specimens were of the triple negative phenotype and were the focus of this study. The results were correlated with overall, local, and distant relapse-free survival. Using multivariate analysis, the relationship between phospho-K8, other co-variables, and outcome was evaluated. Results: Positive expression of ER, PR, HER2, and phospho-K8 was detected in 61.5%, 58.3%, 12.7%, and 62.9% of all tumor specimens, respectively. In total, 35 local and 55 distant recurrences were observed. Among TNBC patients only, there were 15 local and 19 distant recurrences. In univariate analysis, among these triple negative patients, lack of phospho-K8 expression correlated with higher local recurrence and higher distant metastasis rates. At 10 years, 89.1% of women with phospho-K8 positive tumors and 70.9% of women with phospho-K8 negative tumors were local recurrence-free, respectively. At 10 years, 82.6% of women with phospho-K8 positive tumors and 60.4% of women with phospho-K8 negative tumors were distant metastasis-free, respectively. In multivariate analysis, which included T stage, nodal status, margins, and age, lack of phospho-K8 expression in triple negative phenotype patients remained a significant predictor of poor local (RR Z 3.4; 95% CI Z 1.1110.1; p Z 0.032) and distant recurrence rates (RRZ 3.7; 95% CI Z 1.409.80; p Z 0.008), but not overall survival (RR Z 1.4; 95% CI Z 0.5963.20; p Z 0.452). Conclusions: Lack of phospho-K8 expression distinguishes a set of triple negative phenotype patients at higher risk for local and distant recurrences. This data suggests that TNBC patients with phospho-K8 negative tumors may benefit from more aggressive local and systemic therapy. Further evaluation and validation of these findings in larger data sets is warranted. Author Disclosure: R. Garg: None. N. Housri: None. S. Kongara: None. H. Wu: None. D. Schiff: None. M. Moran: None. V. Karantza: None. B. Haffty: None.