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Hereditary lobular breast cancer with an emphasis on E-cadherin genetic defect
  1. Giovanni Corso1,
  2. Joana Figueiredo2,3,
  3. Carlo La Vecchia4,
  4. Paolo Veronesi1,5,
  5. Gabriella Pravettoni5,6,
  6. Debora Macis7,
  7. Rachid Karam8,
  8. Roberto Lo Gullo9,
  9. Elena Provenzano10,11,12,
  10. Antonio Toesca1,
  11. Ketti Mazzocco5,6,
  12. Fátima Carneiro3,13,
  13. Raquel Seruca2,3,14,
  14. Soraia Melo2,3,14,
  15. Fernando Schmitt2,3,14,
  16. Franco Roviello15,
  17. Alessandra Margherita De Scalzi1,
  18. Mattia Intra1,
  19. Irene Feroce7,
  20. Elisa De Camilli16,
  21. Maria Grazia Villardita1,
  22. Chiara Trentin9,
  23. Francesca De Lorenzi17,
  24. Bernardo Bonanni7,
  25. Viviana Galimberti1
  1. 1 Division of Breast Surgery, European Institute of Oncology, Milano, Italy
  2. 2 EPIC Lab, Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal
  3. 3 Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal
  4. 4 Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
  5. 5 Oncology and Hematology, University of Milan, Milan, Italy
  6. 6 Applied Research Division for Cognitive and Psychological Science, European Institute of Oncology, Milan, Italy
  7. 7 Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy
  8. 8 Ambry Genetics, Aliso Viejo, California, USA
  9. 9 Division of Breast Imaging, European Institute of Oncology, Milan, Italy
  10. 10 NIHR Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, UK
  11. 11 Cambridge Breast Cancer Research Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  12. 12 Department of Histopathology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  13. 13 Division of Pathology, Hospital São Joao, Porto, Portugal
  14. 14 Medical Faculty of the University of Porto, Porto, Portugal
  15. 15 Departments of Surgery and Pathology, Le Scotte Hospital, University of Siena, Siena, Italy
  16. 16 Division of Pathology, European Institute of Oncology, Milan, Italy
  17. 17 Division of Plastic Surgery, European Institute of Oncology, Milan, Italy
  1. Correspondence to Dr Giovanni Corso, Division of Breast Surgery, European Institute of Oncology, Milano 20141, Italy; giovanni.corso{at}


Recent studies have reported germline CDH1 mutations in cases of lobular breast cancer (LBC) not associated with the classical hereditary diffuse gastric cancer syndrome. A multidisciplinary workgroup discussed genetic susceptibility, pathophysiology and clinical management of hereditary LBC (HLBC). The team has established the clinical criteria for CDH1 screening and results’ interpretation, and created consensus guidelines regarding genetic counselling, breast surveillance and imaging techniques, clinicopathological findings, psychological and decisional support, as well as prophylactic surgery and plastic reconstruction. Based on a review of current evidence for the identification of HLBC cases/families, CDH1 genetic testing is recommended in patients fulfilling the following criteria: (A) bilateral LBC with or without family history of LBC, with age at onset <50 years, and (B) unilateral LBC with family history of LBC, with age at onset <45 years. In CDH1 asymptomatic mutant carriers, breast surveillance with clinical examination, yearly mammography, contrast-enhanced breast MRI and breast ultrasonography (US) with 6-month interval between the US and the MRI should be implemented as a first approach. In selected cases with personal history, family history of LBC and CDH1 mutations, prophylactic mastectomy could be discussed with an integrative group of clinical experts. Psychodecisional support also plays a pivotal role in the management of individuals with or without CDH1 germline alterations. Ultimately, the definition of a specific protocol for CDH1 genetic screening and ongoing coordinated management of patients with HLBC is crucial for the effective surveillance and early detection of LBC.

  • lobular breast cancer
  • E-cadherin
  • hereditary cancer

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  • BB and VG contributed equally.

  • Contributors GC and JF contributed equally. Concept and design: GC, BB, DM, VG. Supervisor board: PV, VG, MI, FR, FC, RS, CLV, GP. Iconography and graphic design: FS, JF, SM, EDC. Acquisition of data, analysis and interpretation of data, critical revision of the manuscript for important intellectual content, final approval of manuscript: all authors. Drafting of the manuscript: GC, RLG, JF, CLV, AT, AMDS, IF, EP, CT, KM, RK, FDL with input of all authors. Editorial assistance: MGV, EP.

  • Funding This manuscript was supported by the Italian Ministry of Health (Understanding how CDH1 germline mutations affect hereditary lobular breast cancer).

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.