Nuclear NF-kb/p65 expression and response to neoadjuvant chemotherapy in breast cancer.

Abstract

611 Background: NF-kB is a potential therapeutic target in breast cancer and other tumor types. However, studies assessing its significance in a clinical setting are as yet limited. The aim of this study was to evaluate clinicopathological associations and predictive value of the transcription factor NF-kB in a large series of breast cancer patients that received neoadjuvant systemic treatment. Methods: A retrospective search of a prospectively maintained database was performed to identify patients. Immunohistochemistry was employed to asses the p65 subunit of NF-kB using nuclear staining, as a surrogate of activation. Results: Nuclear NF-kB expression (n = 133) was found in 26.3% (n = 35) of cases. Nuclear NF-kB staining was associated with high histological grade (p = 0.05), ER negativity (p = 0.01) and high Ki67 index (p = 0.002). Patients with nuclear NF-kB staining had a higher pathological complete response (pCR) rate compared to those without (26.5% vs. 6.0% respectively, p = 0.004); there were no significant associations with clinical response or outcome. In a subset analysis, in HER2+ and/or ER- tumors combined (n = 42) there was no significant association between nuclear NF-kB staining and pCR rate (p = 014) and clinical response (p = 0.39). In contrast, in ER+/HER2- tumors (n = 43), those with nuclear NF-kB staining had a significantly less clinical responses compared to negative cases (14.3% vs. 61%; p = 0.038). There were no pCRs in ER+/ HER2- tumors. Conclusions: Nuclear NF-kB/p65 expression is associated with ER negativity, high Ki67 index and tumor grade. In the entire series, it was associated to increased pCRs but not to clinical response to neoadjuvant chemotherapy. A subset analysis revealed that nuclear NF-kB/p65 expression was linked to chemoresistance in ER+/HER2- tumors. No significant financial relationships to disclose.