A phase II neoadjuvant trial of concurrent trastuzumab and paclitaxel without anthracycline in women with HER2-positive operable breast cancer.

Abstract

e11070 Background: Neoadjuvant paclitaxel plus trastuzumab followed by 5-fluorouracil, epirubicin, and cyclophosphamide plus trastuzumab revealed the high pathologic complete response (pCR) rate of up to 60% in patients with HER-2-positive breast cancer. However, combination of trastuzumab and anthracycline has been associated with an increased incidence of cardiac dysfunction. The objective of this study was to determine the efficacy of concurrent administration of trastuzumab and paclitaxel without anthracycline as neoadjuvant chemotherapy. Predictive factors of pCR including deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway were also investigated. Methods: Patients with HER2-positive operable breast cancer received 12 cycles of weekly paclitaxel (80 mg/m2 IV) plus weekly trastuzumab (4mg/kg loading dose followed by 2 mg/kg IV) before surgery. PTEN status was evaluated by IHC with PTEN antibody (Thermo Scientific, CA). PTEN expression level was scored semiquantitatively based on staining intensity (0; no staining , 1+; reduced staining, and 2+; equal staining as compared to the internal control). PIK3CA mutation status was evaluated by sequencing of PIK3CA exons 9 and 20 using PCR amplification and direct sequencing. pCR was defined as no residual invasive carcinoma in the breast. Results: Among 37 patients enrolled, ER and PgR were positive in 18 (48.6%) and 16 (43.2%) patients, respectively. The overall response rate was 86.5% (32/37) and the pCR rate was 48.6% (18/37). pCR rate was significantly correlated with PgR negativity (p=0.004) and higher Ki67 (p=0.01). PTEN loss was observed in 33.3% (8/24) of the tumor examined. PIK3CA sequence analysis of the 13 tumors identified 2 mutations in exon 20 and 2 mutations in exon 9, corresponding to a PIK3CA mutation frequency of 30.8%. PTEN loss and/or PIK3CA mutation were not significantly associated with pCR rate. Conclusions: These data indicate that the combination of trastuzumab and paclitaxel without anthracycline is effective neoadjuvant chemotherapy with high pCR rate. PTEN loss and/or PIK3CA mutation were not useful predictors of resistance to trastuzumab.