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Tumor-infiltrating lymphocytes and molecular response after neoadjuvant therapy for HR+/HER2− breast cancer: results from two prospective trials

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An Erratum to this article was published on 03 April 2017

Abstract

Purpose

The aim was to evaluate the role of tumor-infiltrating lymphocytes (TIL) in predicting molecular response after preoperative endocrine or cytotoxic treatment for HR+/HER2− patients who do not achieve a pathological complete response.

Methods

Stromal (Str) TIL were centrally evaluated on samples from diagnostic core-biopsies of HR+/HER2− patients included in two prospective randomized trials: the LETLOB trial (neoadjuvant endocrine-based treatment) and the GIOB trial (neoadjuvant chemotherapy-based treatment). Pre- and post-treatment Ki67 was centrally assessed.

Results

StrTIL were evaluable in 111 cases (n = 73 from the LETLOB trial and n = 38 from the GIOB trial). Median StrTIL was 2%. Patients with high StrTIL (StrTIL ≥10%, n = 28) had more frequently breast cancer of ductal histology (p = 0.02), high grade (p = 0.049), and high Ki67 (p = 0.02). After neoadjuvant endocrine treatment (LETLOB cohort), a significant Ki67 suppression (p < 0.01) from pre- to post-treatment was observed in both the low and high StrTIL groups. High StrTIL patients achieve more frequently a relative Ki67 suppression ≥50% from baseline as compared to low StrTIL patients (55 vs. 35%, p non significant). After neoadjuvant chemotherapy (GIOB cohort), a significant Ki67 suppression was observed only for low StrTIL patients (Wilcoxon p = 0.001) and not in the high StrTIL group (p = 0.612). In this cohort, the rate of patients achieving a relative Ki67 suppression ≥50% from baseline was significantly higher in the high vs low StrTIL group (64 vs. 10%, p = 0.003). Geometric mean Ki67 suppression was evaluated in each cohort according to StrTIL: the lowest value (−41%) was observed for high StrTIL cases treated with chemotherapy.

Conclusions

This hypothesis-generating study suggests that in HR+/HER2− breast cancer StrTIL at baseline may influence the achievement of a molecular response after neoadjuvant treatment. Further evaluation in large studies is needed, and interaction with the type of treatment warrants to be explored.

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Author information

Authors and Affiliations

  1. Department of Surgery, Oncology and Gastroenterology, University of Padova, via Giustiniani 2, 35128, Padua, Italy

    M. V. Dieci, G. Griguolo, Pierfranco Conte & V. Guarneri

  2. Division of Medical Oncology 2, Istituto Oncologico Veneto IRCCS, via Gattamelata 64, 35128, Padua, Italy

    M. V. Dieci, G. Griguolo, Pierfranco Conte & V. Guarneri

  3. Division of Clinical Oncology, S. Anna University Hospital, via Moro 8, 44100, Cona, Ferrara, Italy

    A. Frassoldati

  4. Breast UnitASST Cremona, viale Concordia 1, 26100, Cremona, Italy

    D. Generali

  5. Department of Medical, Surgery & Health Sciences, University of Trieste, Piazza Ospitale 1, 34129, Trieste, Italy

    D. Generali

  6. Division of Medical Oncology, Azienda Ospedaliera ASMN, IRCSS, Viale Umberto I 50, 42123, Reggio Emilia, Italy

    G. Bisagni

  7. Department of Medical and Surgical Sciences of Mother, Child and Adult, University of Modena and Reggio Emilia, Modena, Italy

    F. Piacentini

  8. Division of Medical Oncology, Modena University Hospital, via del Pozzo 71, 41124, Modena, Italy

    F. Piacentini

  9. Division of Oncology, “Guglielmo da Saliceto” Hospital, via Taverna 49, 29121, Piacenza, Italy

    L. Cavanna

  10. Division of Medical Oncology, “B.Ramazzini” Hospital, Via Molinari 2, 41012, Carpi, Italy

    K. Cagossi

  11. Department of Medical and Biological Sciences, University of Udine, Udine, Italy

    F. Puglisi

  12. Department of Oncology, University Hospital of Udine, Piazzale Santa Maria della Misericordia 15, 33010, Udine, Italy

    F. Puglisi

  13. UO Oncologia Medica I, Azienda Ospedaliera Universitaria Pisana, Santa Chiara Hospital, via Roma 67, 56126, Pisa, Italy

    F. Puglisi

  14. Division of Medical Oncology, Università Politecnica delle Marche, Ospedali Riuniti Umberto I, via Conca 71, 60126, Ancona, Italy

    A. Michelotti & R. Berardi

  15. Division of Medical Oncology, Cannizzaro Hospital, via Messina 829, 95126, Catania, Italy

    G. Banna

  16. ICR Clinical Trials and Statistics Unit, 15 Cotswold Road, Sutton, SM2 5NG, UK

    A. Goubar

  17. Division of Pathology, Modena University Hospital, via del Pozzo 71, 41124, Modena, Italy

    G. Ficarra

Authors
  1. M. V. Dieci
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  2. A. Frassoldati
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  9. A. Michelotti
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  15. Pierfranco Conte
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  16. V. Guarneri
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Corresponding author

Correspondence to Pierfranco Conte.

Ethics declarations

Funding

The LETLOB study was sponsored and funded by GlaxoSmithKline; the GIOB study was sponsored and funded by Astrazeneca. Moreover, authors acknowledge the following fundings: Istituto Oncologico Veneto project L02P38; University of Padova project 60A07-7808/13.

Conflict of interest

The authors declare that they have no conflict of interest.

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.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s10549-017-4219-3.

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Dieci, M.V., Frassoldati, A., Generali, D. et al. Tumor-infiltrating lymphocytes and molecular response after neoadjuvant therapy for HR+/HER2− breast cancer: results from two prospective trials. Breast Cancer Res Treat 163, 295–302 (2017). https://doi.org/10.1007/s10549-017-4191-y

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