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Benefit of adjuvant chemotherapy with or without trastuzumab in pT1ab node-negative human epidermal growth factor receptor 2-positive breast carcinomas: results of a national multi-institutional study

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Abstract

Purpose

Benefit of adjuvant trastuzumab-based chemotherapy for node-positive and/or >1 cm human epidermal growth factor receptor 2-positive (HER2+) breast carcinomas has been clearly demonstrated in randomized clinical trials. Yet, evidence that adjuvant chemotherapy with or without trastuzumab is effective in pT1abN0 HER2+ tumors is still limited. The primary objective of this study was to investigate the impact of adjuvant chemotherapy ± trastuzumab on outcome in this subpopulation.

Patients and methods

A total of 356 cases of pT1abN0M0 HER2 + breast cancers were retrospectively identified from a large cohort of 22,334 patients, including 1248 HER2+ patients who underwent primary surgery at 17 French centers, between December 1994 and January 2014. The primary end point was disease-free survival (DFS). A multivariate Cox model was built, including adjuvant chemotherapy, tumor size, hormone receptor status, and Scarff Bloom Richardson (SBR) grade.

Results

A total of 138 cases (39%) were treated with trastuzumab-based chemotherapy, 29 (8%) with chemotherapy alone, and 189 (53%) received neither trastuzumab nor chemotherapy. Adjuvant chemotherapy ± trastuzumab was associated with a significant DFS benefit (3-year 99 vs. 90%, and 5-year 96 vs. 84%, Hazard ratio, HR 0.26 [0.10–0.67]; p = 0.003, logrank test) which was maintained in multivariate analysis (HR 0.19 [0.07–0.52]; p = 0.001). Metastasis-free survival was also increased (HR 0.25 [0.07–0.86]; p = 0.018, logrank test) at 3-year (99 vs. 95%) and 5-year (98 vs. 89%) censoring. Exploratory subgroup analysis found DFS benefit to be significant in hormone receptor-negative, hormone receptor-positive, and pT1b tumors, but not in pT1a tumors.

Conclusions

Adjuvant chemotherapy ± trastuzumab is associated with a significantly reduced risk of recurrence in subcentimeter node-negative HER2+ breast cancers. Most of the benefit may be driven by pT1b tumors.

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Acknowledgements

Part of this work was originally presented at the Annual Meeting of American Society of Clinical Oncology, Chicago, IL, USA, June 3–7, 2016.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Author notes

    Authors and Affiliations

    1. Department of Medical Oncology, Institut Paoli Calmettes, CRCM, Marseille, France

      Alexandre de Nonneville, Anthony Gonçalves, Renaud Sabatier & François Bertucci

    2. Aix-Marseille University, Marseille, France

      Alexandre de Nonneville, Anthony Gonçalves, Eric Lambaudie, Renaud Sabatier, François Bertucci & Gilles Houvenaeghel

    3. Department of Clinical Research and Investigation, Biostatistics and Methodology UnitInstitut Paoli Calmettes, Marseille, France

      Christophe Zemmour & Jean M. Boher

    4. Department of Surgical Oncology, Institut Paoli Calmettes, CRCM, Marseille, France

      Monique Cohen, Eric Lambaudie & Gilles Houvenaeghel

    5. Institut René Gauducheau, St Herblain, France

      Jean M. Classe

    6. Institut Curie, Paris, France

      Fabien Reyal

    7. Pôle Santé République, Clermont-Ferrand, France

      Christophe Scherer

    8. Department of Radiotherapy, Hôpital de la Timone, Marseille, France

      Xavier Muracciole

    9. Department of Surgical Oncology, CRLC Val-d’Aurelle, Montpellier, France

      Pierre E. Colombo

    10. Centre Oscar Lambret, Lille, France

      Sylvia Giard

    11. Centre René Huguenin, Saint Cloud, France

      Roman Rouzier

    12. Hôpital des Diaconnesses, Paris, France

      Richard Villet

    13. Department of Surgical Oncology, Centre Léon Bérard, Lyon, France

      Nicolas Chopin

    14. Department of Gynecologic and Breast Cancers, Hôpital Tenon, Paris, France

      Emile Darai

    15. Department of Surgical Oncology, Gustave-Roussy, Villejuif, France

      Jean R. Garbay

    16. Department of Surgical Oncology, Centre Jean-Perrin, Clermont-Ferrand, France

      Pierre Gimbergues

    17. Department of Obstetrics Gynecology, Hôpital de la Conception, Marseille, France

      Laura Sabiani

    18. Department of Surgical Oncology, Centre Georges-François Leclerc, Dijon, France

      Charles Coutant

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    1. Alexandre de Nonneville
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    Correspondence to Alexandre de Nonneville.

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    Conflict of interest

    AG and RS have received consulting fees and travel accommodations from Roche. The other authors have no conflict of interest to disclose.

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    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. For this type of study, formal consent is not required. The research presented here complies with the current laws of the United States of America.

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    This article does not contain any studies with animals performed by any of the authors.

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    Alexandre de Nonneville and Anthony Gonçalves equally contributed to this work.

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    de Nonneville, A., Gonçalves, A., Zemmour, C. et al. Benefit of adjuvant chemotherapy with or without trastuzumab in pT1ab node-negative human epidermal growth factor receptor 2-positive breast carcinomas: results of a national multi-institutional study. Breast Cancer Res Treat 162, 307–316 (2017). https://doi.org/10.1007/s10549-017-4136-5

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