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Measuring cfDNA integrity as a biomarker for predicting neoadjuvant chemotherapy response in breast cancer patients: a pilot study

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Abstract

Purpose

Circulating cell-free DNA (cfDNA) is a promising biomarker for predicting treatment response and disease outcomes in Breast Cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC). To determine if cfDNA originates from tumors, matching tumor and cfDNA gene mutations are necessary, often requiring tumor DNA sequencing. We assessed plasma cfDNA integrity by measuring concentrations and ratios of larger-to-smaller Alu DNA fractions as a potential biomarker, eliminating the need for prior tumor sequencing.

Methods

We included patients with localized and/or locally advanced BC receiving standard NAC alone or in combination with immunotherapy and/or anti-HER2 targeted therapy. Blood samples were collected before treatment, every 2 weeks during treatment, and before surgery.

Results

Of the 38 evaluated patients, only 28 completed the protocol and underwent surgery after NAC. Seven patients (25%) achieved a pathologic complete response (pCR). We found that cfDNA integrity (cfDNAI) levels at 15 days after starting NAC were significantly higher in patients who achieved pCR (p = 0.045) and correlated significantly with Disease-Free Survival (DFS) in univariate analysis (p = 0.0371).

Conclusions

Evaluation of cfDNAI 2 weeks after NAC initiation appears to be an early biomarker for tumor pCR and DFS. Measuring Alu fragments of different lengths may replace techniques requiring prior tumor sequencing to measure ctDNA, reducing costs and complexity of cfDNA serial measurements in BC patients undergoing NAC.

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Data availability

Data will be made available under request.

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Instituto Brasileiro de Controle do Câncer (IBCC), São Paulo, SP, Brazil

    Camila Giro, Alayne M. T. D. Yamada, Felipe José S. M. Cruz & Lilian A. do R. Barros

  2. Departamento de Oncologia e Hematologia do Centro Universitário FMABC, Av. Príncipe de Gales, 821, Santo André, SP, 09060-650, Brazil

    Camila Giro, Felipe José S. M. Cruz & Auro del Giglio

  3. Laboratório de Análises Clínicas do Centro Universitário FMABC, Santo André, SP, Brazil

    Beatriz da C. A. Alves & Fernando L. A. Fonseca

  4. Instituto de Ciências Farmacêuticas, Universidade Federal de São Paulo (UNIFESP), Diadema, SP, Brazil

    Fernando L. A. Fonseca

Authors
  1. Camila Giro
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  2. Alayne M. T. D. Yamada
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  3. Felipe José S. M. Cruz
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  4. Lilian A. do R. Barros
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  5. Beatriz da C. A. Alves
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  6. Fernando L. A. Fonseca
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  7. Auro del Giglio
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Contributions

All authors contributed to the study conception and design. Conceptualization was performed by Fernando Luiz Affonso Fonseca, Lilian A. do R. Barros, and Auro del Giglio; methodology and validation were performed by Beatriz da Costa Aguiar Alves; formal analysis was performed by Camila Giro; investigation was performed by Alayne M. T. D. Yamada and Felipe José S. M. Cruz; resources were obtained by Auro del Giglio and Fernando Luiz Affonso Fonseca; the first draft of the manuscript was written by Auro del Giglio and Beatriz da Costa Aguiar Alves. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Auro del Giglio.

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Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethics Committee of Centro Universitário FMABC/ IBCC (protocol code 32158620.0.0000.0072, approved on July 2020) and we registered on ClinicalTrials.gov under the identifier NCT05050890. Informed consent was obtained from all subjects involved in the study.

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Giro, C., Yamada, A.M.T.D., Cruz, F.J.S.M. et al. Measuring cfDNA integrity as a biomarker for predicting neoadjuvant chemotherapy response in breast cancer patients: a pilot study. Breast Cancer Res Treat (2024). https://doi.org/10.1007/s10549-024-07366-y

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