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CD73 expression and pathologic response to neoadjuvant chemotherapy in triple negative breast cancer

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Abstract

The immune system plays a key role in tumor surveillance and escape. Recently, CD73 has been proposed as a prognostic biomarker associated with disease-free survival and overall survival in triple negative breast cancer (TNBC). In this study, we investigated the role of both CD73 expression and stromal tumor–infiltrating lymphocytes (TILs) in predicting the pathologic response of TNBC to neoadjuvant chemotherapy (NACT). We retrospectively analyzed CD73 immunohistochemical expression and stromal TILs on 61 consecutive biopsies from patients who received standard NACT. Twenty-three patients (38%) achieved pathologic complete response (pCR). TILs were present in the majority of biopsies (93%) with percentages ranging from 2 to 80%. High TILs (≥ 50%) were found in 30% of cases, and in this group, pCR was achieved in 76.5% of cases. Levels of TILs were associated with a better pathologic response only at univariate analysis (p = 0.037). The median value of CD73 expression on tumor cells was 40%. In 32 (52.5%) basal biopsies, CD73 expression was below or equal to median value (“low CD73”). A pCR was obtained in 53% of cases with “low CD73” and in 21% with high CD73, and this was statistically different both at univariate (p = 0.011) and multivariate (p = 0.014) analysis.

Our results suggest that CD73 expression better predicts the response to NACT than TILs in TNBC. Characterization of both TILs and microenvironment could be a promising approach to personalize treatment.

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Contributions

Cerbelli Bruna contributed to design of work, data analysis, and manuscript writing;

Botticelli Andrea contributed to design of work, data analysis, and manuscript writing;

Pisano Annalinda contributed to acquisition and analysis of data;

Pernazza Angela contributed to interpretation of data;

Campagna Domenico contributed to acquisition of data;

De Luca Alessandro contributed to acquisition of data;

Ascierto Paolo Antonio revised the work critically for important intellectual content;

Pignataro Maria Gemma contributed to acquisition and analysis of data;

Pelullo Maria contributed to analysis of data;

Della Rocca Carlo revised the work critically for important intellectual content;

Marchetti Paolo revised and approved the final version manuscript;

Fortunato Lucio contributed to the conception of the work and critically revised it;

Costarelli Leopoldo contributed to the conception of the work and critically revised it;

d’Amati Giulia contributed to the design of the work, data analysis, and manuscript writing.

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Author notes

  1. Bruna Cerbelli and Andrea Botticelli contributed equally to this work.

Authors and Affiliations

  1. Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100, Latina, Italy

    Bruna Cerbelli, Angelina Pernazza & Carlo Della Rocca

  2. Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy

    Andrea Botticelli & Paolo Marchetti

  3. Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, 00161, Rome, Italy

    Annalinda Pisano, Maria Gemma Pignataro & Giulia d’Amati

  4. Department of Pathology, San Giovanni-Addolorata Hospital, 00184, Rome, Italy

    Domenico Campagna & Leopoldo Costarelli

  5. Department of Surgical Sciences, Sapienza University of Rome, 00161, Rome, Italy

    Alessandro De Luca

  6. Istituto Nazionale Tumori-Istituto di Ricovero e Cura a Carattere Scientifico, Fondazione G. Pascale, 80131, Naples, Italy

    Paolo Antonio Ascierto

  7. Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, 00161, Rome, Italy

    Maria Pelullo

  8. Breast Unit, San Giovanni Addolorata Hospital, 00184, Rome, Italy

    Lucio Fortunato

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  1. Bruna Cerbelli
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Correspondence to Giulia d’Amati.

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The study complies with ethical standards with both Institutions. All patients gave their informed consent.

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Cerbelli, B., Botticelli, A., Pisano, A. et al. CD73 expression and pathologic response to neoadjuvant chemotherapy in triple negative breast cancer. Virchows Arch 476, 569–576 (2020). https://doi.org/10.1007/s00428-019-02722-6

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  • DOI: https://doi.org/10.1007/s00428-019-02722-6

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