Skip to main content

Advertisement

SpringerLink
Log in

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

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Speirs V, Shaaban AM (2009) The rising incidence of male breast cancer. Breast Cancer Res Treat 115(2):429–430

    Article  PubMed  Google Scholar 

  2. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics. CA Cancer J Clin 60(5):277–300

    Article  PubMed  Google Scholar 

  3. Anderson WF, Jatoi I, Tse J, Rosenberg PS (2010) Male breast cancer: a population-based comparison with female breast cancer. J Clin Oncol 28:232–239

    Article  PubMed  Google Scholar 

  4. Anderson WF, Althuis MD, Brinton LA, Devesa SS (2004) Is male breast cancer similar or different than female breast cancer? Breast Cancer Res Treat 83(1):77–86

    Article  PubMed  Google Scholar 

  5. Ottini L, Rizzolo P, Zanna I, Falchetti M, Masala G, Ceccarelli K, Vezzosi V, Gulino A, Giannini G, Bianchi S, Sera F, Palli D (2009) BRCA1/BRCA2 mutation status and clinical–pathologic features of 108 male breast cancer cases from Tuscany: a population-based study in central Italy. Breast Cancer Res Treat 116(3):577–586

    Article  PubMed  Google Scholar 

  6. Fentiman IS, Fourquet A, Hortobagyi GN (2006) Male breast cancer. Lancet 367:595–604

    Article  PubMed  Google Scholar 

  7. Vargas AC, Reis-Filho JS, Lakhani SR (2011) Phenotype-genotype correlation in familial breast cancer. J Mammary Gland Biol Neoplasia 16(1):27–40

    Article  PubMed  Google Scholar 

  8. Honrado E, Osorio A, Palacios J, Benitez J (2006) Pathology and gene expression of hereditary breast tumors associated with BRCA1, BRCA2 and CHEK2 gene mutations. Oncogene 25(43):5837–5845

    Article  PubMed  CAS  Google Scholar 

  9. Bane AL, Beck JC, Bleiweiss I, Buys SS, Catalano E, Daly MB, Giles G, Godwin AK, Hibshoosh H, Hopper JL, John EM, Layfield L, Longacre T, Miron A, Senie R, Southey MC, West DW, Whittemore AS, Wu H, Andrulis IL, O’Malley FP (2007) BRCA2 mutation-associated breast cancers exhibit a distinguishing phenotype based on morphology and molecular profiles from tissue microarrays. Am J Surg Pathol 31(1):121–128

    Article  PubMed  Google Scholar 

  10. Da Silva L, Lakhani SR (2010) Pathology of hereditary breast cancer. Mod Pathol 23(Suppl 2):S46–S51

    Article  PubMed  Google Scholar 

  11. Mavaddat N, Barrowdale D, Andrulis IL, Domchek SM, Eccles D, Nevanlinna H, Ramus SJ, Spurdle A, Robson M, Sherman M, Mulligan AM, Couch FJ, Engel C, McGuffog L, Healey S, Sinilnikova OM, Southey MC, Terry MB, Goldgar D, O’Malley F, John EM, Janavicius R, Tihomirova L, Hansen TV, Nielsen FC, Osorio A, Stavropoulou A, Benítez J, Manoukian S, Peissel B, Barile M, Volorio S, Pasini B, Dolcetti R, Putignano AL, Ottini L, Radice P, Hamann U, Rashid MU, Hogervorst FB, Kriege M, van der Luijt RB; for HEBON, Peock S, Frost D, Evans DG, Brewer C, Walker L, Rogers MT, Side LE, Houghton C; for EMBRACE, Weaver J, Godwin AK, Schmutzler RK, Wappenschmidt B, Meindl A, Kast K, Arnold N, Niederacher D, Sutter C, Deissler H, Gadzicki D, Preisler-Adams S, Varon-Mateeva R, Schönbuchner I, Gevensleben H, Stoppa-Lyonnet D, Belotti M, Barjhoux L; for GEMO Study Collaborators, Isaacs C, Peshkin BN, Caldes T, de la Hoya M, Cañadas C, Heikkinen T, Heikkilä P, Aittomäki K, Blanco I, Lazaro C, Brunet J, Agnarsson BA, Arason A, Barkardottir RB, Dumont M, Simard J, Montagna M, Agata S, D’Andrea E, Yan M, Fox S; for kConFab Investigators, Rebbeck TR, Rubinstein W, Tung N, Garber JE, Wang X, Fredericksen Z, Pankratz VS, Lindor NM, Szabo C, Offit K, Sakr R, Gaudet MM, Singer CF, Tea MK, Rappaport C, Mai PL, Greene MH, Sokolenko A, Imyanitov E, Toland AE, Senter L, Sweet K, Thomassen M, Gerdes AM, Kruse T, Caligo M, Aretini P, Rantala J, von Wachenfeld A, Henriksson K; for SWE-BRCA Collaborators, Steele L, Neuhausen SL, Nussbaum R, Beattie M, Odunsi K, Sucheston L, Gayther SA, Nathanson K, Gross J, Walsh C, Karlan B, Chenevix-Trench G, Easton DF, Antoniou AC; for the Consortium of Investigators of Modifiers of BRCA1/2 (2012) Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the consortium of investigators of modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomarkers Prev 21(1):134–147

    Google Scholar 

  12. Ge Y, Sneige N, Eltorky MA, Wang Z, Lin E, Gong Y, Guo M (2009) Immunohistochemical characterization of subtypes of male breast carcinoma. Breast Cancer Res 11:R28

    Article  PubMed  Google Scholar 

  13. Kornegoor R, Verschuur-Maes AH, Buerger H, Hogenes MC, de Bruin PC, Oudejans JJ, van der Groep P, Hinrichs B, van Diest PJ (2012) Molecular subtyping of male breast cancer by immunohistochemistry. Mod Pathol 25(3):398–404

    Article  PubMed  CAS  Google Scholar 

  14. Shaaban AM, Ball GR, Brannan RA, Cserni G, Benedetto AD, Dent J, Fulford L, Honarpisheh H, Jordan L, Jones JL, Kanthan R, Maraqa L, Litwiniuk M, Mottolese M, Pollock S, Provenzano E, Quinlan PR, Reall G, Shousha S, Stephens M, Verghese ET, Walker RA, Hanby AM, Speirs V (2011) A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences. Breast Cancer Res Treat. doi:10.1007/s10549-011-1856-9

    Google Scholar 

  15. Ottini L, Masala G, D’Amico C, Mancini B, Saieva C, Aceto G, Gestri D, Vezzosi V, Falchetti M, De Marco M, Paglierani M, Cama A, Bianchi S, Mariani-Costantini R, Palli D (2003) BRCA1 and BRCA2 mutation status and tumor characteristics in male breast cancer: a population-based study in Italy. Cancer Res 63:342–347

    PubMed  CAS  Google Scholar 

  16. Bianchi S, Palli D, Falchetti M, Saieva C, Masala G, Mancini B, Lupi R, Noviello C, Omerovic J, Paglierani M, Vezzosi V, Alimandi M, Mariani-Costantini R, Ottini L (2006) ErbB-receptors expression and survival in breast carcinoma: a 15-year follow-up study. J Cell Physiol 206:702–708

    Article  PubMed  CAS  Google Scholar 

  17. Papi L, Putignano AL, Congregati C, Zanna I, Sera F, Morrone D, Falchetti M, Turco MR, Ottini L, Palli D, Genuardi M (2009) Founder mutations account for the majority of BRCA1-attributable hereditary breast/ovarian cancer cases in a population from Tuscany,Central Italy. Breast Cancer Res Treat 117(3):497–504

    Article  PubMed  CAS  Google Scholar 

  18. Giordano SH, Cohen DS, Buzdar AU, Perkins G, Hortobagyi GN (2004) Breast carcinoma in men: a population-based study. Cancer 101(1):51–57

    Article  PubMed  Google Scholar 

  19. Satram-Hoang S, Ziogas A, Anton-Culver H (2007) Risk of second primary cancer in men with breast cancer. Breast Cancer Res 9(1):R10

    Article  PubMed  Google Scholar 

  20. Arslan UY, Oksüzoğlu B, Ozdemir N, Aksoy S, Alkış N, Gök A, Kaplan MA, Gümüş M, Berk V, Uncu D, Baykara M, Colak D, Uyetürk U, Türker I, Işıkdoğan A (2011) Outcome of non-metastatic male breast cancer: 118 patients. Med Oncol. doi:10.1007/s12032-011-9978-9

    Google Scholar 

  21. Nahleh ZA, Srikantiah R, Safa M, Jazieh AR, Muhleman A, Komrokji R (2007) Male breast cancer in the veterans affairs population: a comparative analysis. Cancer 109(8):1471–1477

    Article  PubMed  Google Scholar 

  22. Mitra AV, Bancroft EK, Barbachano Y, Page EC, Foster CS, Jameson C, Mitchell G, Lindeman GJ, Stapleton A, Suthers G, Evans DG, Cruger D, Blanco I, Mercer C, Kirk J, Maehle L, Hodgson S, Walker L, Izatt L, Douglas F, Tucker K, Dorkins H, Clowes V, Male A, Donaldson A, Brewer C, Doherty R, Bulman B, Osther PJ, Salinas M, Eccles D, Axcrona K, Jobson I, Newcombe B, Cybulski C, Rubinstein WS, Buys S, Townshend S, Friedman E, Domchek S, Ramon Y Cajal T, Spigelman A, Teo SH, Nicolai N, Aaronson N, Ardern-Jones A, Bangma C, Dearnaley D, Eyfjord J, Falconer A, Grönberg H, Hamdy F, Johannsson O, Khoo V, Kote-Jarai Z, Lilja H, Lubinski J, Melia J, Moynihan C, Peock S, Rennert G, Schröder F, Sibley P, Suri M, Wilson P, Bignon YJ, Strom S, Tischkowitz M, Liljegren A, Ilencikova D, Abele A, Kyriacou K, van Asperen C, Kiemeney L; IMPACT Study Collaborators, Easton DF, Eeles RA (2011) Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMCACT study. BJU Int 107(1):28–39

    Google Scholar 

Download references

Acknowledgments

The study was supported by a grant from Associazione Italiana per la Ricerca sul Cancro (AIRC IG 8713).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy

    Laura Ottini, Valentina Silvestri, Piera Rizzolo, Mario Falchetti & Giuseppe Giannini

  2. Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy

    Ines Zanna, Calogero Saieva, Giovanna Masala & Domenico Palli

  3. Division of Pathological Anatomy, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy

    Simonetta Bianchi

  4. Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Siranoush Manoukian

  5. Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy

    Monica Barile

  6. Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy

    Paolo Peterlongo & Paolo Radice

  7. Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Milan, Italy

    Paolo Peterlongo & Paolo Radice

  8. Unit of Hereditary Cancers, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

    Liliana Varesco

  9. Clinical Experimental Oncology Laboratory, National Cancer Centre of Bari, Bari, Italy

    Stefania Tommasi

  10. Section of Medical Oncology, Department of Surgical and Oncological Sciences, University of Palermo, Palermo, Italy

    Antonio Russo

  11. Department of Oncology and Haematology, University of Modena and Reggio Emilia, Modena, Italy

    Laura Cortesi

  12. Unit of Experimental Oncology I, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy

    Alessandra Viel

  13. Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto, IRCCS, Padua, Italy

    Marco Montagna

Authors
  1. Laura Ottini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Valentina Silvestri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Piera Rizzolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mario Falchetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ines Zanna
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Calogero Saieva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giovanna Masala
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Simonetta Bianchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Siranoush Manoukian
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Monica Barile
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Paolo Peterlongo
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Liliana Varesco
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Stefania Tommasi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Antonio Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Giuseppe Giannini
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Laura Cortesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Alessandra Viel
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Marco Montagna
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Paolo Radice
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Domenico Palli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laura Ottini.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 12 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ottini, L., Silvestri, V., Rizzolo, P. et al. Clinical and pathologic characteristics of BRCA-positive and BRCA-negative male breast cancer patients: results from a collaborative multicenter study in Italy. Breast Cancer Res Treat 134, 411–418 (2012). https://doi.org/10.1007/s10549-012-2062-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-012-2062-0

Keywords

Search

Navigation