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Mutational analysis of triple-negative breast cancers within the International Breast Cancer Study Group (IBCSG) Trial 22-00

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Abstract

Purpose

We investigated the occurrence and the prognostic and predictive relationship of a selected number of somatic mutations in triple-negative breast cancer (TNBC) patients having known clinical outcomes treated within the IBCSG Trial 22-00.

Methods

A matched case–control sampling selected patients enrolled in the IBCSG Trial 22-00 who had TNBC tumors, based on local assessment. Cases had invasive breast cancer recurrence (at local, regional, or distant site) according to the protocol definition. Matched controls had not recurred. Mutational analysis was performed with OncoCarta panel v1.0 using Mass Array System. The panel includes 19 genes belonging to different functional pathways as PI3K pathway, receptor tyrosine kinase, and cell cycle-metabolic group. Conditional logistic regression assessed the association of mutation status with breast cancer recurrence.

Results

Mutation assessment was successful for 135 patients (49 cases, 86 controls). A total of 37 (27.4%) of the 135 patients had at least one mutation in the selected genes. PIK3CA was the most common mutated gene (18/135; 13.3%), followed by BRAF, KIT and PDGFRA (each 4/135, 3.0%) and AKT1 (3/135; 2.2%). TNBC patients with at least one mutation had increased odds of recurrence compared with those with wild-type tumors (odds ratio (OR) 2.28; 95% CI 0.88–5.92), though this difference was not statistically significant (p = 0.09). We found no evidence that these mutations were predictive for the value of maintenance metronomic chemotherapy.

Conclusions

Mutations in the tested oncogenes were not associated with breast cancer recurrence in this TNBC subset of patients. The question of whether any of these mutated genes (e.g., PIK3CA) may represent a useful therapeutic target in TNBC may be answered by ongoing clinical trials and/or larger dataset analysis.

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Acknowledgements

We thank the patients, physicians, nurses, and data managers who participated in the International Breast Cancer Study Group (IBCSG) Trial 22-00, which was supported by the IBCSG and participating centers. Support for Trial 22-00 central coordination, data management and statistics was provided by the Swedish Cancer League; The Cancer Council Australia; Australia & New Zealand Breast Cancer Trials Group; the Frontier Science and Technology Research Foundation; the Swiss Group for Clinical Cancer Research; the Swiss Cancer League/Oncosuisse. Funding for this study was provided by Italian Ministry of Health, Ricerca Finalizzata, RF-2009-1536545.

Author information

Authors and Affiliations

  1. Division of Medical Senology, European Institute of Oncology, Milan, Italy

    Elisabetta Munzone

  2. International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, and Harvard T.H Chan School of Public Health, Boston, MA, USA

    Kathryn P. Gray

  3. Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy

    Caterina Fumagalli

  4. Division of Pathology and Laboratory Medicine, Department of Oncology and Hemato-oncology, European Institute of Oncology and University of Milan, Milan, Italy

    Elena Guerini-Rocco

  5. National Institute of Oncology, Budapest, Hungary

    István Láng

  6. Breast Center St. Gallen, Switzerland, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland

    Thomas Ruhstaller

  7. Divisione di Oncologia, Ospedale degli Infermi, Rimini, Dipartimento di Oncologia ed Ematologia, AUSL della Romagna, Rimini, Italy

    Lorenzo Gianni

  8. Translational Research Coordination and Central Pathology Office, International Breast Cancer Study Group Coordinating Center, Bern, Switzerland

    Roswitha Kammler

  9. Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan and International Breast Cancer Study Group Central Pathology Office, Milan, Italy

    Giuseppe Viale

  10. Hospital of Prato-AUSL Toscana Centro, Istituto Toscano Tumori, and International Breast Cancer Study Group, Prato, Italy

    Angelo Di Leo

  11. International Breast Cancer Study Group and University of Sydney, Sydney, Australia

    Alan S. Coates

  12. International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, Harvard T.H. Chan School of Public Health, Harvard Medical School and Frontier Science & Technology Research Foundation, Boston, MA, USA

    Richard D. Gelber

  13. International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA

    Meredith M. Regan

  14. Scientific & Clinical Evaluation Board, European Institute of Oncology and International Breast Cancer Study Group, Milan, Italy

    Aron Goldhirsch

  15. Division of Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan, Milan, Italy

    Massimo Barberis

  16. Division of Medical Senology, European Institute of Oncology, and International Breast Cancer Study Group, Milan, Italy

    Marco Colleoni

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  1. Elisabetta Munzone
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Corresponding author

Correspondence to Elisabetta Munzone.

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Munzone, E., Gray, K.P., Fumagalli, C. et al. Mutational analysis of triple-negative breast cancers within the International Breast Cancer Study Group (IBCSG) Trial 22-00. Breast Cancer Res Treat 170, 351–360 (2018). https://doi.org/10.1007/s10549-018-4767-1

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  • DOI: https://doi.org/10.1007/s10549-018-4767-1

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