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Original Research| Volume 185, P119-130, May 2023

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Evolution of biological features of invasive lobular breast cancer: Comparison between primary tumour and metastases

  • Pamela Trillo
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, 20141 Milan, Italy

    Department of Oncology and Hematology, University of Milan, 20122 Milan, Italy
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  • Josè Sandoval
    Affiliations
    Unit of Population Epidemiology, Division and Department of Primary Care Medicine, 1205 Geneva University Hospitals, Geneva, Switzerland

    Department of Oncology, Geneva University Hospitals, 1205 Geneva, Switzerland
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  • Dario Trapani
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, 20141 Milan, Italy

    Department of Oncology and Hematology, University of Milan, 20122 Milan, Italy
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  • Eleonora Nicolò
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, 20141 Milan, Italy

    Department of Oncology and Hematology, University of Milan, 20122 Milan, Italy
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  • Paola Zagami
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, 20141 Milan, Italy

    Department of Oncology and Hematology, University of Milan, 20122 Milan, Italy
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  • Federica Giugliano
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, 20141 Milan, Italy

    Department of Oncology and Hematology, University of Milan, 20122 Milan, Italy
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  • Paolo Tarantino
    Affiliations
    Breast Oncology Program, Dana-Farber Cancer Institute, 02115 Boston, USA

    Harvard Medical School, 02115 Boston, USA
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  • Grazia Vivanet
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, 20141 Milan, Italy

    Department of Oncology and Hematology, University of Milan, 20122 Milan, Italy
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  • Liliana Ascione
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, 20141 Milan, Italy

    Department of Oncology and Hematology, University of Milan, 20122 Milan, Italy
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  • Alex Friedlaender
    Affiliations
    Department of Oncology, Geneva University Hospitals, 1205 Geneva, Switzerland
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  • Angela Esposito
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, 20141 Milan, Italy
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  • Carmen Criscitiello
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, 20141 Milan, Italy

    Department of Oncology and Hematology, University of Milan, 20122 Milan, Italy
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  • Author Footnotes
    1 Department of Oncology and Hematology (DIPO), University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy.
    ,
    Author Footnotes
    2 Twitter: @curijoey.
    Giuseppe Curigliano
    Correspondence
    Corresponding author: Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milan, Italy.
    Footnotes
    1 Department of Oncology and Hematology (DIPO), University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy.
    2 Twitter: @curijoey.
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, 20141 Milan, Italy

    Department of Oncology and Hematology, University of Milan, 20122 Milan, Italy
    Search for articles by this author
  • Author Footnotes
    1 Department of Oncology and Hematology (DIPO), University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy.
    2 Twitter: @curijoey.
Published:March 07, 2023DOI:https://doi.org/10.1016/j.ejca.2023.02.028

      Highlights

      • We report the change of the hormone receptors (HRs) and HER2 in lobular breast cancer.
      • We describe the discordance in HR and HER2 between primary cancer and metastasis.
      • The majority of discordances regarded a reduced expression or loss of HR.
      • We observed a shift from luminal-like to triple-negative and to HER2-low cancers.
      • HR but not HER2-low changes have prognostic implications.

      Abstract

      Background

      Invasive lobular carcinoma (ILC) has unique clinical-biological features. Phenotypical differences between primary tumours (PTs) and metastases (M) have been described for invasive ductal carcinoma, but data on ILC are limited.

      Methods

      We retrospectively analysed patients with recurrent ILC from our institution from 2013 to 2020. We evaluated the discordance of the oestrogen receptor (ER), progesterone receptor (PgR) and HER2 between PT and M, to understand prognostic and therapeutic implications.

      Results

      Thirteen percent (n = 91) of all patients had ILC. We observed 15%, 44% and 5% of ER, PgR and HER2 status discordance between PT and M. ER/PgR discordance was related to receptor loss and HER2 mainly due to gain. PT presented a luminal-like phenotype (93%); 6% and 1% were triple-negative (TNBC) and HER2-positive. In M, there was an increase in TNBC (16%) and HER2-positive (5%). Metastasis-free survival and overall survival (OS) were different according to clinical phenotype, with poorer prognosis for HER2+ and TNBC (p < 0.001); OS after metastatic progression did not differ across phenotypes (p = 0.079). In luminal-like ILC (n = 85) at diagnosis, we found that OS after relapse was poorer in patients experiencing a phenotype switch to TNBC but improved in patients with HER2 gain (p = 0.0028). Poorer survival was reported in patients with a PgR and/or ER expression loss of ≥25%. There was HER2-low enrichment in M1 (from 37% to 58%): this change was not associated with OS (p > 0.05).

      Conclusion

      Our results suggest that phenotype switch after metastatic progression may be associated with patients’ outcomes. Tumour biopsy in recurrent ILC could drive treatment decision-making, with prognostic implications.

      Keywords

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