21P - Expression of CD138 / syndecan-1 in triple-negative breast cancer – correlative study of GeparSixto

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Translational Research
Presenter Gunter von Minckwitz
Citation Annals of Oncology (2015) 26 (suppl_3): 6-9. 10.1093/annonc/mdv115
Authors G. von Minckwitz1, B.M. Pfitzner2, V. Müller3, P.A. Fasching4, T. Karn5, C. Schem6, K. Schönfeld7, T. Häder7, S. Loibl1, C. Denkert8
  • 1Medicine And Research, German Breast Group, GBG Forschungs GmbH, 63263 - Neu-Isenburg/DE
  • 2Institute Of Pathology, Charite Berlin Mitte, 10117 - Berlin/DE
  • 3Department Of Gynecology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg - Hamburg/DE
  • 4Department Of Obstetrics And Gynecology, Universitätsklinik Erlangen, Erlangen/DE
  • 5Obstetrics And Gynecology, Universitätsklinikum Frankfurt(Johannes-Wolfgang Goethe Institute), 60590 - Frankfurt am Main/DE
  • 6Klinik Für Gynäkologie Und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, 24105 - Kiel/DE
  • 7Research Immunology, Biotest AG, 63303 - Dreieich/DE
  • 8Institute Of Pathology, Charité Hospital, 10117 - Berlin/DE

Abstract

Body

Background: The cell adhesion molecule CD138/Syndecan-1 is a cell surface heparin sulphate proteoglycan receptor involved in cell differentiation, morphology, and migration and is primarily expressed in epithelial and plasma cells. Indatuximab-ravtansine is a monoclonal antibody conjugated to cytotoxic maytansinoids that showed selective cytotoxicity against CD138-positive multiple myeloma cells in-vitro and in-vivo. We evaluated expression of CD138 in a series of triple-negative breast cancers (TNBC) from a prospective trial to explore the potential use of indatuximab ravtansine in this disease entity.

Methods: We evaluated the CD138 expression on tumor cells and monocytes by immunohistochemistry using the CD138 antibody (clone: B-B4) on tissue microarrays (TMAs) constructed from formalin-fixed paraffin-embedded (FFPE) pre-treatment core biopsies from 234 patients with TNBC participating in the GeparSixto trial. The trial investigated the addition of carboplatin to non-pegylated liposomal doxorubicin, paclitaxel and bevacizumab. Response was assessed by histologic examination of resected breast and nodal tissue.

Results: Tumor cells in 73.9% and monocytes in 84.4% stained positive (immunoreactive score ≥3) for CD138. No staining of tumor cells was found in 7.3%. No correlation of tumor cell staining was found with age, body-mass-index, initial clinical tumor, histological type, grading, Ki67, tumor-infiltrating lymphocytes, PIK3CA, and p53 mutation status. Tumor cells of patients with clinically node-positive disease tend to be more frequently CD138 positive (p = 0.091). CD138 expression of tumor cells did not correlate with response of the breast tumor to neoadjuvant chemotherapy but was more frequently present in patients with residual nodal disease (ypN + ; p = 0.017). CD138 staining in monocytes was not correlated with any of these clinical markers.

Conclusions: CD138 is expressed in the majority of TNBC and approximately 3/4 of patients show expression considered sufficient for immunotargeted treatment with indatuximab ravtansine. Results do not suggest that CD138 plays a major role as prognostic or predictive marker in this aggressive breast cancer subtype.

Disclosure: G. von Minckwitz: GBG received research funds from Biotest AG.

K. Schönfeld and T. Häder: employee of Biotest AG.

All other authors have declared no conflicts of interest.