Neoadjuvant chemotherapy (NAC) has become as the preferred initial therapy for locally advanced breast cancer (LABC) patients. A pathologic complete response (pCR) following NAC correlates strongly with both prolonged disease-free survival and overall survival especially for patients with HER2+ or triple negative breast cancer (TNBC). A lot of modalities and molecular markers for assessing chemotherapy response have been evaluated; however, they have demonstrated only limited predictive value.
Plasma samples have been collected from 167 patients diagnosed with LABC and received NAC from month, year to month, year prospectively. Samples were collected three times from each patient, prior to NAC (pre-treatment), prior to second cycle of NAC (on-treatment), and after breast surgery (post-treatment). Samples were assayed by multiplex immunoassays for 45 biomarkers. Plasma biomarker levels using Cytokine/Chemokine/Growth Factor 45-Plex Human ProcartaPlexTM Panel were compared with pathologic treatment responses. pCR was defined as the absence of residual tumor both in breast and axillary lymph nodes. This study was approved by the Institutional Review Board of Samsung Medical Center (SMC 2014-11-015-017).
A median age at diagnosis of the 167 patients was 42 (range, 23-68 years). Most of the patients were treated with anthracycline and taxane-based regimen including adriamycin with cyclophosphamide plus docetaxel (AC-T), or AC-T plus trastuzumab. The patients were divided into the following four groups: HR+/HER2- (n = 46, 28%), HR+/HER2 + (n = 26, 16%), HR-/HER2 + (n = 32, 19%), and TNBC (n = 63, 38%). Thirty four patients (20%) achieving a pCR were compared with 133 patients (80%) demonstrating no pCR. Several groups of biomarker expression, BDNF, bNGF, HGF, IFN-gamma, IL-18, IP-10, MCP-1, RANTES, and SCF, were significantly different among pre-treatment, on-treatment and post-treatment. Multivariate analysis on pCR showed that analysis using the multiplex panel has predictive power.
Plasma biomarkers including immune-cytokine may have a role to predict treatment response in the neoadjuvant setting.
Samsung Medical Center.
Has not received any funding.
All authors have declared no conflicts of interest.