Taxanes have been established as one of the key drugs for breast cancer. In order to maximize its benefit, reliable prediction of the response is needed especially in the neoadjuvant setting. The aim of this study is to evaluate the efficacy and safety of neoadjuvant weekly nanoparticle albumin-bound paclitaxel (nab-PTX) for HER2-negative breast cancer and to explore the predictive factors.
Patients with Stage II to IV HER2-negative breast cancer received 12 cycles of weekly nab-PTX 100 mg/m2 as the first line treatment and response was assessed by imaging studies. Correlations between tumor response in the breast after nab-PTX regimen and positivity of ER, PgR, HER2, Ki67, Tau, FOXA1 and androgen receptor (AR) by immunohistochemistry (IHC) and mRNA expression of TS, DPD, SPARC, Tubulinß3, Ki67, MDR1 and TOPO IIα were evaluated. Correlations were investigated using the Spearman test and Mann-Whitney test.
From December 2012 to December 2014, we enrolled 66 patients, of whom 57 patients completed 12 cycles of nab-PTX treatment. The dose of nab-PTX was reduced 20% in one patient. Among all, 55 patients (83.3%) had hormone receptor-positive tumors and 11 patients (16.7%) had triple negative tumors. The response rate in the breast after nab-PTX regimen was 59.1% (95% CI, 47.2% to 71.0%); 63.6% in hormone receptor-positive tumor and 36.4% in triple negative tumor respectively (p = 0.090). The pathological complete response at the time of surgery was 15% (95% CI, 6.1% to 24.4%). Toxicity analysis showed that the incidence of grade 2 peripheral sensory neuropathy was 38 (57.6%), grade 2 or grade 3 leukocytopenia was 29 (43.9%), grade 2 or grade 3 neutropenia was 20 (30.4%) and grade 2 or grade 3 liver dysfunction was 5 (7.5%). Younger age, high Ki67 and low AR in IHC showed a statistically significantly higher tumor reduction rates in the breast. Low SPARC and high TOPO IIα in mRNA levels showed statistically significantly higher tumor reduction rates in the breast.
Weekly nab-PTX in the neoadjuvant setting was well tolerated, especially in the peripheral sensory neuropathy profile. Biomarker analysis suggested that high Ki67, low AR in IHC, low SPARC and high TOPO IIα in mRNA levels predict responses of weekly nab-PTX.
Clinical trial identification
Legal entity responsible for the study
Toho University Medical Center Ohashi Hospital
National Hospital Organization and Taiho Pharmaceutical Co.
A. Nagayama: owns stock options of Chugai, Inc.
A. Matsui: received from research grants from Taiho, Takeda, Chugai, Eisai and Daiichi-Sankyo. received lecture fees Taiho, Eisai, Kyowa-Kirin, Chugai and Daiichi-Sankyo.
Y. Okamoto: received research funding from Taiho and lecture fees from Eisai, Taiho, Chugai, Kyowa-Kirin, Takeda, Daiichi-Sankyo, AstraZeneca and Novartis.
All other authors have declared no conflicts of interest.