HMGA2 expression and response to anthracycline-based preoperative chemotherapy in patients with operable breast cancer

Abstract

22035 Background: Preclinical data suggest that increased expression of high mobility group A2 (HMGA2) protein could enhance chemosensitivity towards doxorubicin in breast cancer cells. The present study investigated the predictive value of HMGA2 immunoreactivity in patients (pts) with operable breast cancer (BC) treated preoperatively with regimens including anthracyclines. Methods: We reviewed the pretreatment biopsies of 94 pts with large (> 2 cm) operable BC treated with preoperative anthracycline-based chemotherapy, performing immunohistochemistry for HMGA2 and other biological markers (ER, PgR, HER2, MIB1, topoisomerase II α). Characteristics of preoperative chemotherapy (i.e. number of courses, type of anthracycline or taxane) were also analyzed. Association between clinico-biological factors and pathological, clinical (by caliper) and radiological (by mammography, ultrasound and MRI) response was assessed. Results: In univariate analysis, high expression of HMGA2 was significantly associated with clinical complete response [odds ratio (OR) = 4.9, 95% CI 1.3–18.9] and with tumor shrinkage assessed by MRI (OR = 2.9, 95% CI 1.1–7.7). No statistically significant association was observed between HMGA2 and clinical or pathological response in multivariate analysis. Among the other variables, the following were associated with complete pathological response (pCR): ER (p = 0.005), MIB-1 (p = 0.01) and topoisomerase II alfa (p = 0.05). In multivariate analysis, ER was the only independent predictor of pCR (OR = 0.2, 95% CI 0.03–0.9). The number of chemotherapeutic courses was independently associated with tumor shrinkage assessed by caliper (OR = 9.9, 95% CI 2.4–40.5) and by mammography (OR = 4.02, 95% CI 1.4–11.3). MIB-1 expression was independently associated with tumor shrinkage assessed by ultrasound (OR = 3.8, 95% CI 1.1–13.4) and by MRI (OR = 3.6, 95% CI 1.2–11.3). Conclusions: Immunohistochemical evaluation ofHMGA2 significantly predicted clinical complete response and tumor shrinkage assessed by MRI in patients treated with preoperative anthracycline-based chemotherapy. Although no independent association with response was observed, the potential predictive role of this protein deserves further evaluation. No significant financial relationships to disclose.