Predictive factors for the effectiveness of neoadjuvant chemotherapy and prognosis in triple-negative breast cancer patients

Abstract

Triple-negative breast cancers (TNBCs) do not derive benefit from molecular-targeted treatments such as endocrine therapy or anti-HER2 therapy because they lack those molecular targets. On the other hand, TNBCs have been shown to respond to neoadjuvant chemotherapy (NAC). In this study, we analyzed TNBC patients who were treated with NAC at Osaka National Hospital over a recent 5-year period to clarify the predictive factors for NAC and prognostic factors. Thirty-three TNBC patients underwent sequential NAC with anthracycline (FEC100: 5FU 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2)/q3w, 4 courses) and taxanes (paclitaxel 80 mg/m(2)/qw, 12 courses or docetaxel 75 mg/m(2)/q3w, 4 courses) from May 2003 to July 2008. Pre-therapeutical and surgical specimens were studied for expressions of ER, PgR, HER-2, EGFR, cytokeratin 5/6, Ki-67, p53 and androgen receptor by immunohistochemistry (IHC). We analyzed clinicopathological factors and molecular markers in regard to the response to NAC and prognosis. Pathological complete response (pCR) was achieved in 12 TNBC patients (36%). The pCR rate in the basal-like phenotype was significantly lower than in the non-basal-like phenotype (23 vs. 64%, respectively: P = 0.02). High pre-operative expressions of Ki-67 (≥50%) and HER-2 (2+) were considered as predictive factors for a better response from NAC. Pre-operative Ki-67 expression showed a significant correlation with disease-free survival (DFS) and a lower expression of Ki-67 (<50%) after NAC was favorable for DFS among non-pCR patients. A non-basal-like phenotype and higher expressions of Ki-67 and HER-2 (2+) were favorable factors for NAC. However, a higher expression of Ki-67 on the surgical specimen after NAC was also a poor prognostic factor.