Genomic Characterization of Primary Invasive Lobular Breast Cancer - Aix-Marseille Université Access content directly
Journal Articles Journal of Clinical Oncology Year : 2016

Genomic Characterization of Primary Invasive Lobular Breast Cancer

Marco Fornili
Debora Fumagalli
  • Function : Author
David Brown
Françoise Rothé
  • Function : Author
Delphine Vincent
  • Function : Author
Naima Kheddoumi
  • Function : Author
Samira Majjaj
  • Function : Author
Sylvain Brohée
  • Function : Author
Ron Bose
  • Function : Author
Otto Metzger
  • Function : Author
Christine Galant
  • Function : Author
Martine Piccart-Gebhart
  • Function : Author
Giuseppe Viale
  • Function : Author
Elia Biganzoli
Peter Campbell
Christos Sotiriou


Purpose Invasive lobular breast cancer (ILBC) is the second most common histologic subtype after invasive ductal breast cancer (IDBC). Despite clinical and pathologic differences, ILBC is still treated as IDBC. We aimed to identify genomic alterations in ILBC with potential clinical implications. Methods From an initial 630 ILBC primary tumors, we interrogated oncogenic substitutions and insertions and deletions of 360 cancer genes and genome-wide copy number aberrations in 413 and 170 ILBC samples, respectively, and correlated those findings with clinicopathologic and outcome features. Results Besides the high mutation frequency of CDH1 in 65% of tumors, alterations in one of the three key genes of the phosphatidylinositol 3-kinase pathway, PIK3CA, PTEN, and AKT1, were present in more than one-half of the cases. HER2 and HER3 were mutated in 5.1% and 3.6% of the tumors, with most of these mutations having a proven role in activating the human epidermal growth factor receptor/ERBB pathway. Mutations in FOXA1 and ESR1 copy number gains were detected in 9% and 25% of the samples. All these alterations were more frequent in ILBC than in IDBC. The histologic diversity of ILBC was associated with specific alterations, such as enrichment for HER2 mutations in the mixed, nonclassic, and ESR1 gains in the solid subtype. Survival analyses revealed that chromosome 1q and 11p gains showed independent prognostic value in ILBC and that HER2 and AKT1 mutations were associated with increased risk of early relapse. Conclusion This study demonstrates that we can now begin to individualize the treatment of ILBC, with HER2, HER3, and AKT1 mutations representing high-prevalence therapeutic targets and FOXA1 mutations and ESR1 gains deserving urgent dedicated clinical investigation, especially in the context of endocrine treatment.


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Dates and versions

hal-03623737 , version 1 (29-03-2022)



Christine Desmedt, Gabriele Zoppoli, Gunes Gundem, Giancarlo Pruneri, Denis Larsimont, et al.. Genomic Characterization of Primary Invasive Lobular Breast Cancer. Journal of Clinical Oncology, 2016, 34 (16), pp.1872-1881. ⟨10.1200/jco.2015.64.0334⟩. ⟨hal-03623737⟩
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