Stem Cells Inhibition by Bevacizumab in Combination with Neoadjuvant Chemotherapy for Breast Cancer

Autor: Emmanuelle Charafe-Jauffret, Patrick Sfumato, Jean-Yves Pierga, Renaud Sabatier, Hervé Curé, Christophe Ginestier, Patrice Viens, Gilles Houvenaeghel, Dominique Genre, Jean-Marc Extra, Anthony Gonçalves, Eric Lambaudie, François Bertucci
Přispěvatelé: Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département d'Oncologie Médicale [Paris], Institut Curie [Paris], CRLCC Jean Godinot, Service d'Oncologie Chirurgicale, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département de chirurgie Paoli Calmette (Paoli Calmette), Service d'Oncologie Médicale, Unité de Biostatistiques [Institut Paoli-Calmettes] (Département de la Recherche clinique et de l'Innovation), Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Bidaut, Ghislain, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Institut Curie, Cancérologie expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Oncology
cancer stem cells
medicine.medical_specialty
Bevacizumab
[SDV]Life Sciences [q-bio]
medicine.medical_treatment
lcsh:Medicine
[SDV.CAN]Life Sciences [q-bio]/Cancer
bevacizumab
early breast cancer
neoadjuvant chemotherapy
ALDH1
Article
03 medical and health sciences
0302 clinical medicine
Breast cancer
[SDV.CAN] Life Sciences [q-bio]/Cancer
Cancer stem cell
Internal medicine
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
medicine
Clinical endpoint
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
0303 health sciences
Chemotherapy
business.industry
lcsh:R
General Medicine
medicine.disease
3. Good health
Clinical trial
030220 oncology & carcinogenesis
Concomitant
[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Stem cell
business
medicine.drug
Zdroj: Journal of Clinical Medicine Research
Journal of Clinical Medicine Research, Elmer Press, 2019, 8 (5), pp.612. ⟨10.3390/jcm8050612⟩
Journal of Clinical Medicine, Vol 8, Iss 5, p 612 (2019)
Journal of Clinical Medicine
Journal of Clinical Medicine Research, 2019, 8 (5), pp.612. ⟨10.3390/jcm8050612⟩
Journal of Clinical Medicine; Volume 8; Issue 5; Pages: 612
ISSN: 1918-3003
1918-3011
DOI: 10.3390/jcm8050612⟩
Popis: Preclinical works have suggested cytotoxic chemotherapies may increase the number of cancer stem cells (CSC) whereas angiogenesis inhibition may decrease CSC proliferation. We developed a proof of concept clinical trial to explore bevacizumab activity on breast CSC. Breast cancer patients requiring preoperative chemotherapy were included in this open-label, randomized, prospective, multicenter phase II trial. All received FEC-docetaxel combination, and patients randomized in the experimental arm received concomitant bevacizumab. The primary endpoint was to describe ALDH1 (Aldehyde dehydrogenase 1) positive tumor cells rate before treatment and after the fourth cycle. Secondary objectives included safety, pathological complete response (pCR) rate, disease-free survival (DFS), relapse-free survival (RFS), and overall survival (OS). Seventy-five patients were included. ALDH1+ cells rate increase was below the predefined 5% threshold in both arms for the 32 patients with two time points available. Grade 3 or 4 adverse events rates were similar in both arms. A non-significant increase in pCR was observed in the bevacizumab arm (42.6% vs. 18.2%, p = 0.06), but survival was not improved (OS: p = 0.89; DFS: p = 0.45; and RFS: p = 0.68). The increase of ALDH1+ tumor cells rate after bevacizumab-based chemotherapy was less than 5%. However, as similar results were observed with chemotherapy alone, bevacizumab impact on breast CSC cells cannot be confirmed.
Databáze: OpenAIRE
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