Breast Cancer Research and Treatment

, Volume 134, Issue 1, pp 411–418

Clinical and pathologic characteristics of BRCA-positive and BRCA-negative male breast cancer patients: results from a collaborative multicenter study in Italy

  • Laura Ottini
  • Valentina Silvestri
  • Piera Rizzolo
  • Mario Falchetti
  • Ines Zanna
  • Calogero Saieva
  • Giovanna Masala
  • Simonetta Bianchi
  • Siranoush Manoukian
  • Monica Barile
  • Paolo Peterlongo
  • Liliana Varesco
  • Stefania Tommasi
  • Antonio Russo
  • Giuseppe Giannini
  • Laura Cortesi
  • Alessandra Viel
  • Marco Montagna
  • Paolo Radice
  • Domenico Palli
Epidemiology

Abstract

Recently, the number of studies on male breast cancer (MBC) has been increasing. However, as MBC is a rare disease there are difficulties to undertake studies to identify specific MBC subgroups. At present, it is still largely unknown whether BRCA-related breast cancer (BC) in men may display specific characteristics as it is for BRCA-related BC in women. To investigate the clinical–pathologic features of MBC in association with BRCA mutations we established a collaborative Italian Multicenter Study on MBC with the aim to recruit a large series of MBCs. A total of 382 MBCs, including 50 BRCA carriers, were collected from ten Italian Investigation Centres covering the whole country. In MBC patients, BRCA2 mutations were associated with family history of breast/ovarian cancer (p < 0.0001), personal history of other cancers (p = 0.044) and contralateral BC (p = 0.001). BRCA2-associated MBCs presented with high tumor grade (p = 0.001), PR− (p = 0.026) and HER2+ (p = 0.001) status. In a multivariate logistic model BRCA2 mutations showed positive association with personal history of other cancers (OR 11.42, 95 % CI 1.79–73.08) and high tumor grade (OR 4.93, 95 % CI 1.02–23.88) and inverse association with PR+ status (OR 0.19, 95 % CI 0.04–0.92). Based on immunohistochemical (IHC) profile, four molecular subtypes of MBC were identified. Luminal A was the most common subtype (67.7 %), luminal B was observed in 26.5 % of the cases and HER2 positive and triple negative were represented by 2.1 % and 3.7 % of tumors, respectively. Intriguingly, we found that both luminal B and HER2 positive subtypes were associated with high tumor grade (p = 0.003 and 0.006, respectively) and with BRCA2 mutations (p = 0.016 and 0.001, respectively). In conclusion, our findings indicate that BRCA2-related MBCs represent a subgroup of tumors with a peculiar phenotype characterized by aggressive behavior. The identification of a BRCA2-associated phenotype might define a subset of MBC patients eligible for personalized clinical management.

Keywords

Male breast cancer BRCA1 BRCA2 Clinical–pathologic features Molecular subtypes 

Supplementary material

10549_2012_2062_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 12 kb)

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Laura Ottini
    • 1
  • Valentina Silvestri
    • 1
  • Piera Rizzolo
    • 1
  • Mario Falchetti
    • 1
  • Ines Zanna
    • 2
  • Calogero Saieva
    • 2
  • Giovanna Masala
    • 2
  • Simonetta Bianchi
    • 3
  • Siranoush Manoukian
    • 4
  • Monica Barile
    • 5
  • Paolo Peterlongo
    • 6
    • 7
  • Liliana Varesco
    • 8
  • Stefania Tommasi
    • 9
  • Antonio Russo
    • 10
  • Giuseppe Giannini
    • 1
  • Laura Cortesi
    • 11
  • Alessandra Viel
    • 12
  • Marco Montagna
    • 13
  • Paolo Radice
    • 6
    • 7
  • Domenico Palli
    • 2
  1. 1.Department of Molecular MedicineSapienza University of RomeRomeItaly
  2. 2.Molecular and Nutritional Epidemiology UnitCancer Research and Prevention Institute (ISPO)FlorenceItaly
  3. 3.Division of Pathological Anatomy, Department of Medical and Surgical Critical CareUniversity of FlorenceFlorenceItaly
  4. 4.Unit of Medical Genetics, Department of Preventive and Predictive MedicineFondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
  5. 5.Division of Cancer Prevention and GeneticsIstituto Europeo di OncologiaMilanItaly
  6. 6.Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive MedicineFondazione IRCCS Istituto Nazionale dei Tumori (INT)MilanItaly
  7. 7.Fondazione Istituto FIRC di Oncologia Molecolare (IFOM)MilanItaly
  8. 8.Unit of Hereditary CancersIstituto Nazionale per la Ricerca sul CancroGenoaItaly
  9. 9.Clinical Experimental Oncology LaboratoryNational Cancer Centre of BariBariItaly
  10. 10.Section of Medical Oncology, Department of Surgical and Oncological SciencesUniversity of PalermoPalermoItaly
  11. 11.Department of Oncology and HaematologyUniversity of Modena and Reggio EmiliaModenaItaly
  12. 12.Unit of Experimental Oncology I, Centro di Riferimento OncologicoIRCCSAvianoItaly
  13. 13.Immunology and Molecular Oncology UnitIstituto Oncologico Veneto, IRCCSPaduaItaly

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