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Residual cancer burden index and tumor-infiltrating lymphocyte subtypes in triple-negative breast cancer after neoadjuvant chemotherapy

  • Preclinical study
  • Published:
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Abstract

Purpose

There is a need to refine the prognosis of triple-negative breast cancer (TNBC) patients after neoadjuvant chemotherapy (NAC) and to study the influence of the tumor microenvironment. We evaluated the prognostic value of pathological and immune markers in TNBC with residual disease (RD) after NAC.

Methods

In a series of 186 TNBC patients treated by NAC, we assessed the prognostic value of the Residual Cancer Burden (RCB) index. In 109 patients with RD, we studied the impact of clinicopathological features and tumor immune response in the residual tumor on overall survival (OS) and distant recurrence-free interval (DRFI).

Results

In the whole group, the OS and DRFI, at 3 years, were statistically different between the different classes of RCB (P = 0.0004 and P < 0.0001, respectively). In univariate analysis of the RD group, low RCB index and high ratios of stromal tumor-infiltrating lymphocytes (TILs), CD3 + TILs, CD4 + TILs, CD8 + TILs, and IDO1-positive cells were significant favorable prognostic factors for DRFI at 3 years. In the final multivariate model, CD4 + TILs and RCB index showed a statistically independent prognostic significance for DRFI [Hazard Ratio (HR) 2.88 (95%CI 1.34–6.17), P = 0.007 and HR 12.04 (95%CI 2.78–52.23, P < 0.0001), respectively]. The CD4 + TIL levels influenced survival in the different RCB classes with a significant effect observed in RCB-II and RCB-III classes (P = 0.05 and P = 0.05, respectively).

Conclusions

These results suggest that the combination of pathological (RCB index) and tumor micro-environmental features (CD4 + TILs) help refining the prognosis of TNBC patients with RD following NAC.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We wish to thank patients for their support in the realization of this study. We thank Dr R. Nookala for the medical writing service and D. Quincy for manuscript submission. We also thank QuantacellTM, Image and data analysis company CRO (contract research organization) 2, Allée du Doyen Georges Brus, Pessac, France.

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Authors and Affiliations

  1. Department of Biopathology, Institut Bergonié, Comprehensive Cancer Center, 229 Cours de l’Argonne CS61283-33076, 33000, Bordeaux, Cedex, France

    Clémence Pinard, Houda Ben Rejeb, Valérie Velasco & Gaëtan MacGrogan

  2. University of Bordeaux, 33000, Bordeaux, France

    Clémence Pinard & Hervé Bonnefoi

  3. Department of Medical Oncology, Institut Bergonié, 33000, Bordeaux, France

    Marc Debled & Hervé Bonnefoi

  4. Department of Surgery, Institut Bergonié, 33000, Bordeaux, France

    Christine Tunon de Lara

  5. Department of Clinical Research and Medical Information, Institut Bergonié, 33000, Bordeaux, France

    Stéphanie Hoppe & Véronique Brouste

  6. INSERM U1218, 33000, Bordeaux, France

    Elodie Richard, Hervé Bonnefoi & Gaëtan MacGrogan

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  1. Clémence Pinard
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Correspondence to Gaëtan MacGrogan.

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This study was approved by the institutional review board of Institut Bergonié and data collection was in compliance with the Jardé law reference methodology 004(MR004).

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Pinard, C., Debled, M., Ben Rejeb, H. et al. Residual cancer burden index and tumor-infiltrating lymphocyte subtypes in triple-negative breast cancer after neoadjuvant chemotherapy. Breast Cancer Res Treat 179, 11–23 (2020). https://doi.org/10.1007/s10549-019-05437-z

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