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Computed tomography-based analyses of baseline body composition parameters and changes in breast cancer patients under treatment with CDK 4/6 inhibitors

  • Epidemiology
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Abstract

Purpose

Body composition parameters including muscle and adipose tissue measurements have emerged as prognostic factors in cancer patients. Besides cell cycle regulation, CDK 4 and 6 also control metabolic processes (lipid synthesis, glycolysis, and mitochondrial function). We studied the impact of baseline body composition parameters on response to CDK 4/6 inhibition and changes on body composition during treatment.

Methods

Retrospective study of 50 patients treated at Institut Jules Bordet between December 2016 and August 2019 with endocrine therapy and CDK 4/6 inhibitor as first or second-line treatment for metastatic breast cancer (BC). CT-based body composition analysis was performed at 3 time points. Cox regression and Kaplan–Meier method were used for the association with Progression-free survival (PFS). Changes in body composition parameters were described in means and compared using paired sampled T test.

Results

Baseline sarcopenia was present in 40% of patients and associated with a significantly worse PFS compared to patients without sarcopenia (20.8 vs 9.6 months, HR 2.52; 95% CI 1.02–6.19, p = 0.037). Patients with higher visceral fat index and higher visceral fat density had better PFS (20.8 vs 10.4 months, HR 0.40; 95% CI 0.16–0.99 p = 0.041-stratified for treatment line). No significant alterations in body composition parameters during treatment were observed.

Conclusion

Sarcopenia is a potential early marker of poor prognosis among patients with metastatic BC treated with CDK 4/6 inhibitors. CT scan evaluation of sarcopenia and adiposity revealed significant prognostic information. Visceral fat could also play an important role in response to CDK 4/6 inhibitors, deserving further investigation.

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Funding

This study has received no funding.

Author information

Author notes

  1. Maria Alice Franzoi and Caroline Vandeputte have contributed equally to this manuscript.

Authors and Affiliations

  1. Academic Trials Promoting Team, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B), Rue Héger-Bordet, 1, 1000, Brussels, Belgium

    Maria Alice Franzoi, Daniel Eiger, Rafael Caparica, Mariana Brandão, Claudia De Angelis & Evandro de Azambuja

  2. GUTS Research Group, Medical Oncology, Institut Jules Bordet, Brussels, Belgium

    Caroline Vandeputte & Alain Hendlisz

  3. Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium

    Ahmad Awada, Martine Piccart & Evandro de Azambuja

Authors
  1. Maria Alice Franzoi
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  2. Caroline Vandeputte
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Contributions

MA and CV: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Software, Validation, Visualization, writing original draft and writing-review & editing. DE, RC, CDA and AH: Investigation, Validation, Visualization, writing original draft and writing review & editing. MB: Formal analysis, Investigation, Methodoloy, Sotware, Validation, Visualization, writing original draft and writing review & editing. AA and MP: Resources, Project administration, Supervision, Writing – review & editing. EA: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Software, Validation, Visualization, Supervision, Project administration, writing- original draft and writing-review & editing. All authors have read and approved this manuscript and ensure this submission is not under consideration elsewhere.

Corresponding author

Correspondence to Maria Alice Franzoi.

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Conflict of interest

MAF, CV, AH and CDA: none. DE: Funding for his ESMO fellowship: Novartis. RC: speaker honoraria from Boehringer Ingelheim, AstraZeneca and Janssen, travel grants from AstraZeneca and Pfizer. MB: travel grant and speaker honoraria from Roche/GNE. AA: Advisory role, speaker fees and research funding for his institute from: Roche, Lilly, Amgen, EISAI, BMS, Pfizer, Novartis, MSD, Genomic Health, Ipsen, AstraZeneca, Bayer, Leo Pharma. M.P.: Board Member (Scientific Board): Oncolytics, Radius; Consultant (honoraria): AstraZeneca, Camel-IDS, Crescendo Biologics, Debiopharm, G1 Therapeutics, Genentech, Huya, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Oncolytics, Periphagen, Pfizer, Roche, Seattle Genetics; Research grants to her Institute: AstraZeneca, Lilly, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier, Synthon; Speakers bureau/stock ownership: none. EA: honoraria and advisory board: Roche/GNE, Novartis, Seatle Genetics; travel grants: Roche/GNE, GSK/Novartis; co-principal investigator of the LORELEI trial (NCT02273973). Research grant for his institute: Roche/GNE, Astra-Zeneca, Novartis, and Servier.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.This study was approved by an internal ethics committee (EC3048), and informed consent was not required as patient’s information was retrieved from retrospective review of medical records only. The identity of the patients was kept always anonymously.

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Franzoi, M.A., Vandeputte, C., Eiger, D. et al. Computed tomography-based analyses of baseline body composition parameters and changes in breast cancer patients under treatment with CDK 4/6 inhibitors. Breast Cancer Res Treat 181, 199–209 (2020). https://doi.org/10.1007/s10549-020-05617-2

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