The effect of denosumab on disseminated tumor cells (DTCs) of breast cancer patients with neoadjuvant treatment: a GeparX translational substudy

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Pauline Wimberger - , Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe (Autor:in)
  • Jens Uwe Blohmer - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Petra Krabisch - , Klinikum Chemnitz gGmbH (Autor:in)
  • Theresa Link - , Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe (Autor:in)
  • Marianne Just - , Onkologische Schwerpunktpraxis Bielefeld (Autor:in)
  • Bruno Valentin Sinn - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Eike Simon - , Kreiskrankenhaus Torgau (Autor:in)
  • Christine Solbach - , Universitätsklinikum Frankfurt (Autor:in)
  • Tanja Fehm - , Heinrich Heine Universität Düsseldorf (Autor:in)
  • Carsten Denkert - , Philipps-Universität Marburg (Autor:in)
  • Cristin Kühn - , Katharinen-Hospital Unna (Autor:in)
  • Kerstin Rhiem - , Universität zu Köln (Autor:in)
  • Hans Tesch - , Markus-Krankenhaus Frankfurt (Autor:in)
  • Sherko Kümmel - , Universität Duisburg-Essen (Autor:in)
  • Andrea Petzold - , Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe (Autor:in)
  • Oliver Stötzer - , Gemeinschaftspraxis Hämatologie/Intern. Onkologie (Autor:in)
  • Cornelia Meisel - , Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe (Autor:in)
  • Jan Dominik Kuhlmann - , Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe (Autor:in)
  • Valentina Nekljudova - , German Breast Group (Autor:in)
  • Sibylle Loibl - , German Breast Group (Autor:in)

Abstract

Background: Disseminated tumor cells (DTCs) in the bone marrow are observed in about 40% at primary diagnosis of breast cancer and predict poor survival. While anti-resorptive therapy with bisphosphonates was shown to eradicate minimal residue disease in the bone marrow, the effect of denosumab on DTCs, particularly in the neoadjuvant setting, is largely unknown. The recent GeparX clinical trial reported that denosumab, applied as an add-on treatment to nab-paclitaxel based neoadjuvant chemotherapy (NACT), did not improve the patient’s pathologic complete response (pCR) rate. Herein, we analyzed the predictive value of DTCs for the response to NACT and interrogated whether neoadjuvant denosumab treatment may eradicate DTCs in the bone marrow. Methods: A total of 167 patients from the GeparX trial were analyzed for DTCs at baseline by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Initially DTC-positive patients were re-analyzed for DTCs after NACT ± denosumab. Results: At baseline, DTCs were observed in 43/167 patients (25.7%) in the total cohort, however their presence did not predict response to nab-paclitaxel based NACT (pCR rates: 37.1% in DTC-negative vs. 32.6% DTC-positive; p = 0.713). Regarding breast cancer subtypes, the presence of DTCs at baseline was numerically associated with response to NACT in TNBC patients (pCR rates: 40.0% in DTC-positive vs. 66.7% in DTC-negative patients; p = 0.16). Overall, denosumab treatment did not significantly increase the given DTC-eradication rate of NACT (NACT: 69.6% DTC-eradication vs. NACT + denosumab: 77.8% DTC-eradication; p = 0.726). In TNBC patients with pCR, a numerical but statistically non-significant increase of DTC-eradication after NACT + denosumab was observed (NACT: 75% DTC-eradication vs. NACT + denosumab: 100% DTC-eradication; p = 1.00). Conclusion: This is the first study worldwide, demonstrating that neoadjuvant add-on denosumab over a short-term period of 24 months does not increase the DTC-eradication rate in breast cancer patients treated with NACT.

Details

OriginalspracheEnglisch
Aufsatznummer32
FachzeitschriftBreast cancer research
Jahrgang25
Ausgabenummer1
PublikationsstatusVeröffentlicht - Dez. 2023
Peer-Review-StatusJa

Externe IDs

PubMed 36978142

Schlagworte

Ziele für nachhaltige Entwicklung

ASJC Scopus Sachgebiete

Schlagwörter

  • Bone marrow, Denosumab, Disseminated tumor cells, GeparX trial, Neoadjuvant chemotherapy, Prognosis, Breast Neoplasms/pathology, Denosumab/therapeutic use, Triple Negative Breast Neoplasms, Humans, Neoplastic Cells, Circulating/pathology, Female, Neoadjuvant Therapy