228P - Development of a novel quantitative assay for predicting ADCC, antibody dependent cell mediated cytotoxicity, and prediction of pathological complet...

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Biomarkers
Breast Cancer
Presenter Kenji Tamura
Authors K. Tamura1, M. Yunokawa2, H. Yamamoto3, M. Kodaira4, C. Shimizu2, K. Yonemori4, Y. Fujiwara5, F. Koizumi6
  • 1Outpatient Treatment Center, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 2Department Of Breast And Medical Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 3Breast And Medical Oncology Division, National Cancer Center Hospital, JP-104-0045 - Tokyo/JP
  • 4Breast And Medical Oncology Division, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 5Medical Oncology, National Cancer Center, Tokyo/JP
  • 6Shien-lab, National Cancer Center Hospital, Tokyo/JP

Abstract

Background

Antibody-dependent cell-mediated cytotoxicity (ADCC) has been shown to be one of the modes of action for trastuzumab. We have previously reported that FcγRIIIa-158 V/V and FcγRIIa-131 H/H genotypes predicted clinical outcome of trastuzumab in both neoadjuvant and metastatic setting in patients with HER-2 positive breast cancer. The purpose of this study is to directly measure an inter-individual ADCC and to develop a new system for predicting to a clinical effectiveness of trastuzumab.

Materials and methods

The stability of the inter-individual differences has been confirmed using peripheral blood mononuclear cells (PBMCs) of 11 healthy volunteers (HVs). Next, we adopted an ex vivo gene expression analysis to identify the molecules which correlate with ADCC activity. We examined the expression change of 14 candidate genes in the 8 HVs after ex vivo exposure to heat-aggregated IgG1 for 4 hr using Hem A (+) system. After identification of the molecules predicting ADCC, we evaluated prospectively whether values of fold increase (FIs) of these the molecules are associated with a pathological complete response (pCR) in 18 patients with HER2 positive breast cancer, who received trastuzumab-based neoadjuvant chemotherapy.

Results

FI in expressions of TNFSF15, IL-6, and CxCL3 are significantly correlated with ADCC activity (R = 0.74, R = 0.85, R = 0.87, respectively). Eligible criteria of the prospective comfort include HER2 positive breast cancer, chemotherapy-naïve, measurable disease, PS 0-2 and adequate organ functions. Patients received standard FEC (5-fluorouracil/epirubicin/cyclophosphamide) q3w for 4cycles followed by weekly paclitaxel/trastuzumab for 12 weeks. Patients who achieved a pCR had a higher FI of CXCL-1, CXCL-3, TNFSF-2, and TNFSF-15 than those who did not (p = 0.004, 0.015, =0.0495, and =0.014, respectively).

Conclusions

These results suggest the novel quantitative ADCC assay have a potential to predict pCR to trastuzumab-based neoadjuvant chemotherapy.

Disclosure

All authors have declared no conflicts of interest.