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An updated review of epidemiology, risk factors, and management of male breast cancer

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Abstract

Unlike female breast cancer, male breast cancer (MBC) is rare and not very well understood. Prospective data in the management of MBC are lacking and majority of treatment strategies are adopted from the established guidelines for breast cancer in women. The understanding of biology, clinical presentation, genetics, and management of MBC is evolving but there still remains a large knowledge gap due to the rarity of this disease. Older age, high estradiol levels, klinefelter syndrome, radiation exposure, gynecomastia, family history of breast cancer, BRCA2 and BRCA1 mutation are some of the known risk factors for MBC. Routine screening mammography is not recommended for asymptomatic men. Diagnostic mammogram with or without ultrasound should be considered if there is a suspicion for breast mass. Majority of men with early-stage breast cancer undergo mastectomy whereas breast conserving surgery (BCS) with sentinel lymph node biopsy (SLNB) remains an alternative option in selected cases. Since the majority of MBC are hormone receptor positive (HR+), adjuvant hormonal therapy is required. Tamoxifen for a total of 5 to 10 years is the mainstay adjuvant hormonal therapy. The role of neoadjuvant and adjuvant chemotherapy for early-stage breast cancer is uncertain and not commonly used. The role of gene recurrence scores like oncotype Dx and mammaprint is evolving and can be used as an aid for adjuvant chemotherapy. Majority of metastatic MBC are treated with hormonal therapy with either tamoxifen, gonadotropin-releasing hormone agonist (GnRH) with aromatase inhibitors (AI), or fulvestrant. Chemotherapy is reserved for patients with visceral crisis or rapidly growing tumors.

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References

  1. Cancer Statistics Center. American Cancer Society. 2020. Breast Statistics | American Cancer Society - Cancer Facts & Statistics. https://cancerstatisticscenter.cancer.org/cancer-site/Breast/91Q4dqjU

  2. Surveillance, Epidemiology, and End Results Program. SEER cancer statistics review (CSR) 1975–2016. https://seer.cancer.gov/csr/1975_2016/. Accessed 24 Oct 2019

  3. Giordano SH, Cohen DS, Buzdar AU, Perkins G, Hortobagyi GN. Breast carcinoma in men: a population-based study. Cancer. 2004;101(1):51–7.

    PubMed  Google Scholar 

  4. Brinton LA, Richesson DA, Gierach GL, Lacey JV Jr, Park Y, Hollenbeck AR, Schatzkin A. Prospective evaluation of risk factors for male breast cancer. J Natl Cancer Inst. 2008;100(20):1477–81.

    PubMed  PubMed Central  Google Scholar 

  5. Newcomb PA, Trentham-Dietz A, Egan KM, Titus-Ernstoff L, Baron JA, Storer BE, Willett WC, Stampfer MJ. Fracture history and risk of breast and endometrial cancer. Am J Epidemiol. 2001;153(11):1071–8.

    CAS  PubMed  Google Scholar 

  6. Brinton LA, Carreon JD, Gierach GL, McGlynn KA, Gridley G. Etiologic factors for male breast cancer in the US Veterans affairs medical care system database. Breast Cancer Res Treat. 2010;119(1):185–92.

    PubMed  Google Scholar 

  7. Hultborn R, Hanson C, Köpf I, Verbiene I, Warnhammar E, Weimarck A. Prevalence of Klinefelter’s syndrome in male breast cancer patients. Anticancer Res. 1997;17(6D):4293–7.

    CAS  PubMed  Google Scholar 

  8. Swerdlow AJ, Schoemaker MJ, Higgins CD, Wright AF, Jacobs PA. Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study. J Natl Cancer Inst. 2005;97(16):1204–10.

    PubMed  Google Scholar 

  9. Thomas DB, Rosenblatt K, Jimenez LM, McTiernan A, Stalsberg H, Stemhagen A, Thompson WD, Curnen MG, Satariano W, Austin DF, Greenberg RS. Ionizing radiation and breast cancer in men (United States). Cancer Causes Control. 1994;5(1):9–14.

    CAS  PubMed  Google Scholar 

  10. Little MP, McElvenny DM. Male breast cancer incidence and mortality risk in the Japanese atomic bomb survivors–differences in excess relative and absolute risk from female breast cancer. Environ Health Perspect. 2016;125(2):223–9.

    PubMed  PubMed Central  Google Scholar 

  11. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W, Bell R. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;7:66–71.

    Google Scholar 

  12. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G, Barfoot R. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995;378(6559):789.

    CAS  PubMed  Google Scholar 

  13. Easton DF, Ford D, Bishop DT. Breast and ovarian cancer incidence in BRCA1-mutation carriers breast cancer linkage consortium. Am J Human Genet. 1995;56(1):265.

    CAS  Google Scholar 

  14. Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. Am J Human Genet. 1998;62(3):676–89.

    CAS  Google Scholar 

  15. Thorlacius S, Tryggvadottir L, Olafsdottir GH, Jonasson JG, Ogmundsdottir HM, Tulinius H, Eyfjord JE. Linkage to BRCA2 region in hereditary male breast cancer. Lancet. 1995;346(8974):544–5.

    CAS  PubMed  Google Scholar 

  16. Easton DF, Steele L, Fields P, Ormiston W, Averill D, Daly PA, McManus R, Neuhausen SL, Ford D, Wooster R, Cannon-Albright LA. Cancer risks in two large breast cancer families linked to BRCA2 on chromosome 13q12-13. Am J Hum Genet. 1997;61(1):120.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Deb S, Lakhani SR, Ottini L, Fox SB. The cancer genetics and pathology of male breast cancer. Histopathology. 2016;68(1):110–8.

    PubMed  Google Scholar 

  18. Haraldsson K, Loman N, Zhang QX, Johannsson O, Olsson H, Borg Å. BRCA2 germ-line mutations are frequent in male breast cancer patients without a family history of the disease. Cancer Res. 1998;58(7):1367–71.

    CAS  PubMed  Google Scholar 

  19. Tai YC, Domchek S, Parmigiani G, Chen S. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007;99(23):1811–4.

    CAS  PubMed  Google Scholar 

  20. Lynch HT, Watson P, Narod SA. The genetic epidemiology of male breast carcinoma. Cancer. 1999;86(5):744–6.

    CAS  PubMed  Google Scholar 

  21. Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Fan I, Tang J, Li S, Zhang S, Shaw PA, Narod SA. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin–cohort study in Ontario, Canada. J Natl Cancer Inst. 2006;98(23):1694–706.

    CAS  PubMed  Google Scholar 

  22. Stratton MR, Ford D, Neuhasen S, Seal S, Wooster R, Friedman LS, King MC, Egilsson V, Devilee P, McManus R, Daly PA. Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q. Nat Genet. 1994;7(1):103.

    CAS  PubMed  Google Scholar 

  23. NCCN Clinical Practice Guidelines in Oncology. Genetic/Familial High-risk Assessment: Breast and Ovarian, 2019 https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf.

  24. Meijers-Heijboer H, van den Ouweland A, Klijn J, Wasielewski M, de Snoo A, Oldenburg R, Hollestelle A, Houben M, Crepin E, van Veghel-Plandsoen M, Elstrodt F, CHEK2-Breast Cancer Consortium MR. Low-penetrance susceptibility to breast cancer due to CHEK2 (*) 1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet. 2002;31:55–9.

    CAS  PubMed  Google Scholar 

  25. Seal S, Thompson D, Renwick A, Elliott A, Kelly P, Barfoot R, Chagtai T, Jayatilake H, Ahmed M, Spanova K, North B. Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nat Genet. 2006;38(11):1239.

    CAS  PubMed  Google Scholar 

  26. Renwick A, Thompson D, Seal S, Kelly P, Chagtai T, Ahmed M, North B, Jayatilake H, Barfoot R, Spanova K, McGuffog L. ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet. 2006;38(8):873.

    CAS  PubMed  Google Scholar 

  27. Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, Reid S, Spanova K, Barfoot R, Chagtai T, Jayatilake H. PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet. 2007;39(2):165.

    CAS  PubMed  Google Scholar 

  28. Shaag A, Walsh T, Renbaum P, Kirchhoff T, Nafa K, Shiovitz S, Mandell JB, Welcsh P, Lee MK, Ellis N, Offit K. Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population. Hum Mol Genet. 2005;14(4):555–63.

    CAS  PubMed  Google Scholar 

  29. Fackenthal JD, Marsh DJ, Richardson AL, Cummings SA, Eng C, Robinson BG, Olopade OI. Male breast cancer in Cowden syndrome patients with germline PTEN mutations. J Med Genet. 2001;38(3):159–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Goss PE, Reid C, Pintilie M, Lim R, Miller N. Male breast carcinoma: a review of 229 patients who presented to the princess Margaret hospital during 40 years: 1955–1996. Cancer. 1999;85(3):629–39.

    CAS  PubMed  Google Scholar 

  31. Ribeiro GG, Swindell R, Harris M, Banerjee SS, Cramer A. A review of the management of the male breast carcinoma based on an analysis of 420 treated cases. Breast. 1996;5(3):141–6.

    Google Scholar 

  32. Williams MJ. Gynecomastia: its incidence, recognition and host characterization in 447 autopsy cases. Am J Med. 1963;34(1):103–12.

    CAS  PubMed  Google Scholar 

  33. Niell BL, Lourenco AP, Moy L, Baron P, Didwania AD, Heller SL, Holbrook AI, Le-Petross HT, Lewin AA, Mehta TS, Slanetz PJ. ACR Appropriateness Criteria® evaluation of the symptomatic male breast. J Am Coll Radiol. 2018;15(11):S313–20.

    PubMed  Google Scholar 

  34. Vetto J, Schmidt W, Pommier R, DiTomasso J, Eppich H, Wood W, Moseson D. Accurate and cost-effective evaluation of breast masses in males. Am J Surg. 1998;175(5):383–7.

    CAS  PubMed  Google Scholar 

  35. Westenend PJ, Jobse C. Evaluation of fine-needle aspiration cytology of breast masses in males. Cancer Cytopathol. 2002;96(2):1–5.

    Google Scholar 

  36. NCCN Clinical Practice Guidelines in Oncology. NCCN guidelines for genetic/ familial high-risk assessment: breast and ovarian. 2017 https://www.nccn.org/professionals/physiciangls/default.aspx.

  37. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population based to a more personalized approach to cancer staging. CA A Cancer J Clin. 2017;67(2):93–9.

    Google Scholar 

  38. Pappo I, Wasserman I, Halevy A. Ductal carcinoma in situ of the breast in men: a review. Clin Breast Cancer. 2005;6(4):310–4.

    CAS  PubMed  Google Scholar 

  39. Leon-Ferre RA, Giridhar KV, Hieken TJ, Mutter RW, Couch FJ, Jimenez RE, Hawse JR, Boughey JC, Ruddy KJ. A contemporary review of male breast cancer: current evidence and unanswered questions. Cancer Metastasis Rev. 2018;37(4):599–614.

    PubMed  Google Scholar 

  40. Javidiparsijani S, Rosen LE, Gattuso P. Male breast carcinoma: a clinical and pathological review. Int J Surg Pathol. 2017;25(3):200–5.

    PubMed  Google Scholar 

  41. Cardoso F, Bartlett JMS, Slaets L, et al. Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG international male breast cancer program. Ann Oncol. 2018;29(2):405–17. https://doi.org/10.1093/annonc/mdx651.

    Article  CAS  PubMed  Google Scholar 

  42. Chavez-MacGregor M, Clarke CA, Lichtensztajn D, Hortobagyi GN, Giordano SH. Male breast cancer according to tumor subtype and race: a population-based study. Cancer. 2013;119(9):1611–7.

    PubMed  Google Scholar 

  43. Anderson WF, Jatoi I, Tse J, Rosenberg PS. Male breast cancer: a population-based comparison with female breast cancer. J Clin Oncol. 2010;28(2):232.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  45. Leone JP, Leone J, Zwenger AO, Iturbe J, Leone BA, Vallejo CT. Locoregional treatment and overall survival of men with T1a, b, cN0M0 breast cancer: a population-based study. Eur J Cancer. 2017;1(71):7–14.

    Google Scholar 

  46. Fogh S, Kachnic LA, Goldberg SI, Taghian AG, Powell SN, Hirsch AE. Localized therapy for male breast cancer: functional advantages with comparable outcomes using breast conservation. Clin Breast Cancer. 2013;13(5):344–9.

    PubMed  Google Scholar 

  47. Flynn LW, Park J, Patil SM, Cody HS III, Port ER. Sentinel lymph node biopsy is successful and accurate in male breast carcinoma. J Am Coll Surg. 2008;206(4):616–21.

    PubMed  Google Scholar 

  48. Abrams MJ, Koffer PP, Wazer DE, Hepel JT. Postmastectomy radiation therapy is associated with improved survival in node-positive male breast cancer: a population analysis. Int J Radiat Oncol Biol Phys. 2017;98(2):384–91.

    PubMed  Google Scholar 

  49. Weir J, Zhao YD, Herman T, Algan Ö. Clinicopathologic features and radiation therapy utilization in patients with male breast cancer: a national cancer database study. Breast Cancer. 2018;19(12):1178223418770687.

    Google Scholar 

  50. Hassett MJ, Somerfield MR, Baker ER, Cardoso F, Kansal KJ, Kwait DC, Plichta JK, Ricker C, Roshal A, Ruddy KJ, Safer JD. Management of male breast cancer: ASCO guideline. J Clin Oncol. 2020;38(16):1849–63.

    PubMed  Google Scholar 

  51. Eggemann H, Ignatov A, Smith BJ, Altmann U, von Minckwitz G, Röhl FW, Jahn M, Costa SD. Adjuvant therapy with tamoxifen compared to aromatase inhibitors for 257 male breast cancer patients. Breast Cancer Res Treat. 2013;137(2):465–70.

    CAS  PubMed  Google Scholar 

  52. Hayes FJ, Seminara SB, DeCruz S, Boepple PA, Crowley WF Jr. Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback. J Clin Endocrinol Metab. 2000;85(9):3027–35.

    CAS  PubMed  Google Scholar 

  53. Patel HZ, Buzdar AU, Hortobagyi GN. Role of adjuvant chemotherapy in male breast cancer. Cancer. 1989;64(8):1583–5.

    PubMed  Google Scholar 

  54. Izquierdo MA, Alonso C, de Andres L, Ojeda B. Male breast cancer report of a series of 50 cases. Acta Oncol. 1994;33(7):767–71.

    CAS  PubMed  Google Scholar 

  55. Walshe JM, Berman AW, Vatas U, Steinberg SM, Anderson WF, Lippman ME, Swain SM. A prospective study of adjuvant CMF in males with node positive breast cancer: 20-year follow-up. Breast Cancer Res Treat. 2007;103(2):177–83.

    PubMed  Google Scholar 

  56. Bagley CS, Wesley MN, Young RC, Lippman ME. Adjuvant chemotherapy in males with cancer of the breast. Am J Clin Oncol. 1987;10(1):55–60.

    CAS  PubMed  Google Scholar 

  57. Massarweh SA, Sledge GW, Miller DP, McCullough D, Petkov VI, Shak S. Molecular characterization and mortality from breast cancer in men. J Clin Oncol. 2018;36(14):1396.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Di Lauro L, Vici P, Barba M, Pizzuti L, Sergi D, Rinaldi M, Di Benedetto A, Sperduti I, Shaaban AM, Speirs V, Mottolese M. Antiandrogen therapy in metastatic male breast cancer: results from an updated analysis in an expanded case series. Breast Cancer Res Treat. 2014;148(1):73–80.

    PubMed  Google Scholar 

  59. Doyen J, Italiano A, Largillier R, Ferrero JM, Fontana X, Thyss A. Aromatase inhibition in male breast cancer patients: biological and clinical implications. Ann Oncol. 2010;21(6):1243–5.

    CAS  PubMed  Google Scholar 

  60. Zagouri F, Sergentanis TN, Chrysikos D, Dimopoulos MA, Psaltopoulou T. Fulvestrant and male breast cancer: a pooled analysis. Breast Cancer Res Treat. 2015;149(1):269–75.

    CAS  PubMed  Google Scholar 

  61. Wedam S, Fashoyin-Aje L, Bloomquist E, Tang S, Sridhara R, Goldberg KB, Theoret MR, Amiri-Kordestani L, Pazdur R, Beaver JA. FDA approval summary: palbociclib for male patients with metastatic breast cancer. Clin Cancer Res. 2020;26(6):1208–12.

    CAS  PubMed  Google Scholar 

  62. NCCN Clinical Practice Guidelines in Oncology. NCCN guidelines for breast cancer. 2020 (NCCN Clinical Practice Guidelines in Oncology)

  63. Di Lauro L, Pizzuti L, Barba M, Sergi D, Sperduti I, Mottolese M, Del Medico P, Belli F, Vici P, De Maria R, Maugeri-Saccà M. Efficacy of chemotherapy in metastatic male breast cancer patients: a retrospective study. J Exp Clin Cancer Res. 2015;34(1):1–5.

    Google Scholar 

  64. Chen L, Weng YM, Hu MX, Peng M, Song QB. Effects of HER2 status on the prognosis of male breast cancer: a population-based study. OncoTargets Therapy. 2019;12:7251.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Ottini L, Capalbo C, Rizzolo P, Silvestri V, Bronte G, Rizzo S, Russo A. HER2-positive male breast cancer: an update. Breast Cancer. 2010;2:45.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Cutuli B, Le-Nir CC, Serin D, Kirova Y, Gaci Z, Lemanski C, De Lafontan B, Zoubir M, Maingon P, Mignotte H, de Lara CT. Male breast cancer. Evolution of treatment and prognostic factors. Analysis of 489 cases. Crit Rev Oncol/Hematol. 2010;73(3):246–54.

    CAS  Google Scholar 

  67. Yadav S, Karam D, Bin Riaz I, **e H, Durani U, Duma N, Giridhar KV, Hieken TJ, Boughey JC, Mutter RW, Hawse JR. Male breast cancer in the United States: treatment patterns and prognostic factors in the 21st century. Cancer. 2020;126(1):26–36.

    CAS  PubMed  Google Scholar 

  68. Leone JP, Leone J, Zwenger AO, Iturbe J, Vallejo CT, Leone BA. Prognostic significance of tumor subtypes in male breast cancer: a population-based study. Breast Cancer Res Treat. 2015;152(3):601–9.

    CAS  PubMed  Google Scholar 

  69. Auvinen A, Curtis RE, Ron E. Risk of subsequent cancer following breast cancer in men. J Natl Cancer Inst. 2002;94(17):1330–2.

    PubMed  Google Scholar 

  70. Dong C, Hemminki K. Second primary breast cancer in men. Breast Cancer Res Treat. 2001;66(2):171.

    CAS  PubMed  Google Scholar 

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  1. Department of Hematology and Oncology, Joan C. Edwards School of Medicine at Marshall University, 1400 Hal Greer Blvd, Huntington, WV, 25701, USA

    Noman Ahmed Jang Khan MD & Maria Tirona MD, FACP

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  1. Noman Ahmed Jang Khan MD
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Khan, N.A.J., Tirona, M. An updated review of epidemiology, risk factors, and management of male breast cancer. Med Oncol 38, 39 (2021). https://doi.org/10.1007/s12032-021-01486-x

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