αB-crystallin is a novel predictor of resistance to neoadjuvant chemotherapy in breast cancer

Aims alpha B-crystallin is an anti-apoptotic protein commonly expressed in poor prognosis basal-like breast tumors, which are largely triple (estrogen receptor (ER), progesterone receptor (PR), and HER2) negative. We examined whether alpha B-crystallin expression in breast cancer was associated with a poor response to neoadjuvant (preoperative) chemotherapy. Methods One hundred and twelve breast cancer patients who received neoadjuvant chemotherapy and who had post-chemotherapy tumor specimens available for analysis were included in the study. Forty-nine percent of patients were treated with doxorubicin and cyclophosphamide (AC), 37% received AC in combination with a taxane, and 14% received other regimens. Paired pre- and post-chemotherapy tumor specimens were available for 33 patients. alpha B-crystallin expression was determined by immunohistochemistry in tissue microarrays. Results Seventeen percent of tumors were alpha B-crystallin positive. alpha B-crystallin expression was identical in 32 of 33 cases for which both pre- and post-chemotherapy tumor tissue was available. alpha B-crystallin expression was associated with ER-negative (P = 0.0024) and triple negative status (P = 0.005). Overall response rates (ORR) defined as >= 50% reduction in tumor size after treatment were 53% (clinical ORR) and 61% (pathological ORR). Although tumor grade, size, ER, PR, HER2 or triple negative status was not associated with response, alpha B-crystallin-positive tumors had poorer overall response rates than alpha B-crystallin-negative tumors (clinical ORR, 21% vs. 59%, respectively, P = 0.0045; pathological ORR, 16% vs. 70%, respectively, P < 0.0001). Conclusion alpha B-crystallin is a novel biomarker expressed predominantly in triple negative breast tumors that identifies a subset of chemotherapy-resistant tumors, which may contribute to their poor prognosis.