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

Aims To evaluate the clinicopathological associations and predictive value of the transcription factor NF-kappa B in a large series of breast cancer patients treated with neoadjuvant chemotherapy. Methods A retrospective search of a prospectively maintained database was performed to identify patients. Immunohistochemistry was used to assess the p65 subunit of NF-kappa B, using nuclear staining as a surrogate of activation. Results Nuclear NF-kappa B expression was found in 26.3% (35/133) of cases. Nuclear NF-kappa B staining was associated with high histological grade (p=0.05), oestrogen receptor (ER) negativity (p=0.01) and higher Ki67 index (p=0.002). Patients with nuclear NF-kappa B staining had a higher pathological complete response (pCR) rate than those without (26.5% vs 6.0% respectively, p=0.004); there was no significant association with clinical response or outcome. In an exploratory hypothesis-generating analysis, in the ER+/HER2- subgroup (n=43) a significantly lower clinical response rate was observed in those with nuclear NF-kappa B staining compared with those who had no nuclear NF-kappa B staining (14.3% vs 61.0%, p=0.038). There were no pCRs in ER+/HER2- tumours. Conclusions Nuclear NF-kappa B expression is associated with ER negativity, higher Ki67 index and tumour grade. It was also found to be significantly associated with increased pCR but not clinical response to neoadjuvant chemotherapy.