Male Breast Cancer: a review of risk factors

Author(s):

Seyed Hesam Addin Bani Hashemi

Abstract

Male breast cancer (MBC) is so rare and uncommon that every year in USA and UK, only 0.5-1% of the patients diagnosed with breast cancer are men and among all men's cancer-related deaths less than 0.1% are caused by MBC. In this review article the most important and well-known risk factors of MBC including age, race, genetics and family history, ratio of estrogen to androgen, hormone receptors, Klinefelter's Syndrome, Cowden's Syndrome, life style, and environmental exposures are discussed.

Keywords

Male breast cancer, Breast cancer, Risk factor

References
  1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA: A Cancer Journal for Clinicians. 2014;64(1):9-29.

  2. Jepson AS, Fentiman IS. Male breast cancer. Int J Clin Pract. 1998 Nov-Dec;52(8):571-6. PubMed PMID: 10622057.

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

  4. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA: A Cancer Journal for Clinicians. 2017;67(1):7-30.

  5. White J, Kearins O, Dodwell D, Horgan K, Hanby AM, Speirs V. Male breast carcinoma: increased awareness needed. Breast Cancer Research : BCR. 2011 09/29;13(5):219-. PubMed PMID: PMC3262194.

  6. Ndom P, Um G, Bell EM, Eloundou A, Hossain NM, Huo D. A meta-analysis of male breast cancer in Africa. Breast. 2012 Jun;21(3):237-41. PubMed PMID: 22300703.

  7. Sasco AJ, Lowenfels AB, Pasker-de Jong P. Review article: epidemiology of male breast cancer. A meta-analysis of published case-control studies and discussion of selected aetiological factors. Int J Cancer. 1993 Feb 20;53(4):538-49. PubMed PMID: 8436428.

  8. Agrawal A, Ayantunde AA, Rampaul R, Robertson JF. Male breast cancer: a review of clinical management. Breast Cancer Res Treat. 2007 May;103(1):11-21. PubMed PMID: 17033919.

  9. Rudlowski C. Male Breast Cancer. Breast Care (Basel). 2008;3(3):183- PubMed PMID: 20824037. PMCID: PMC2931115.

  10. Horner M, Ries L, Krapcho M, Neyman N, Aminou R, Howlader N, et al. SEER Cancer Statistics Review, 1975-2006, National Cancer Institute. Bethesda, MD. 2009.

  11. Dawson PJ, Paine TM, Wolman SR. Immunocytochemical characterization of male breast cancer. Mod Pathol. 1992 Nov;5(6):621-5. PubMed PMID: 1369797.

  12. Giordano SH, Buzdar AU, Hortobagyi GN. Breast cancer in men. Ann Intern Med. 2002 Oct 15;137(8):678-87. PubMed PMID: 12379069.

  13. Stalsberg H, Thomas DB, Rosenblatt KA, Jimenez LM, McTiernan A, Stemhagen A, et al. Histologic types and hormone receptors in breast cancer in men: a population-based study in 282 United States men. Cancer Causes Control. 1993 Mar;4(2):143-51. PubMed PMID: 8386948.

  14. Wick MR, Sayadi H, Ritter JH, Hill DA, Reddy VB, Gattuso P. Low-stage carcinoma of the male breast: A histologic, immunohistochemical, and flow cytometric comparison with localized female breast carcinoma. American journal of clinical pathology. 1999;111(1):59-69.

  15. Cardoso F, Bartlett J, Slaets L, van Deurzen C, van Leewen-Stok E, Porter P, et al., editors. Characterization of male breast cancer: first results of the EORTC10085/TBCRC/BIG/NABCG International Male BC Program. CANCER RESEARCH; 2015: AMER ASSOC CANCER RESEARCH 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA.

  16. Jamy O, Rafiq A, Laghari A, Chawla T. Male breast cancer: a 24 year experience of a tertiary care hospital in Pakistan. Asian Pac J Cancer Prev. 2015;16(4):1559-63. PubMed PMID: 25743831.

  17. Albasri A, Hussainy AS, Sundkji I, Alhujaily A. Histopathological features of breast cancer in Al-Madinah region of Saudi Arabia. Saudi Medical Journal. 2014;35(12):1489-93. PubMed PMID: PMC4362177.

  18. Salehi A, Zeraati H, Mohammad K, Mahmoudi M, Talei AR, Ghaderi A, et al. Survival of Male Breast Cancer in Fars, South of Iran. Iranian Red Crescent Medical Journal. 2011;13(2):99-105. PubMed PMID: PMC3371920.

  19. Tawil AN, Boulos FI, Chakhachiro ZI, Otrock ZK, Kandaharian L, El Saghir NS, et al. Clinicopathologic and Immunohistochemical Characteristics of Male Breast Cancer: A Single Center Experience. The Breast Journal. 2012;18(1):65-8.

  20. Hodgson NC, Button JH, Franceschi D, Moffat FL, Livingstone AS. Male breast cancer: is the incidence increasing? Ann Surg Oncol. 2004 Aug;11(8):751-5. PubMed PMID: 15289238.

  21. Anderson WF, Althuis MD, Brinton LA, Devesa SS. Is male breast cancer similar or different than female breast cancer? Breast Cancer Res Treat. 2004 Jan;83(1):77-86. PubMed PMID: 14997057.

  22. Shin JY, Kachnic LA, Hirsch AE. The impact of race in male breast cancer treatment and outcome in the United States: a population-based analysis of 4,279 patients. Int J Breast Cancer. 2014;2014:685842. PubMed PMID: 25349739. PMCID: PMC4202310.

  23. Sun HF, Zhao Y, Gao SP, Li LD, Fu WY, Jiang HL, et al. Clinicopathological characteristics and survival outcomes of male breast cancer according to race: A SEER population-based study. Oncotarget. 2017 May 26. PubMed PMID: 28618394.

  24. Johnson KC, Pan S, Mao Y, Canadian Cancer Registries Epidemiology Research G. Risk factors for male breast cancer in Canada, 1994-1998. Eur J Cancer Prev. 2002 Jun;11(3):253-63. PubMed PMID: 12131659.

  25. Ewertz M, Holmberg L, Tretli S, Pedersen BV, Kristensen A. Risk factors for male breast cancer--a case-control study from Scandinavia. Acta Oncol. 2001;40(4):467-71. PubMed PMID: 11504305.

  26. Lenfant-Pejovic MH, Mlika-Cabanne N, Bouchardy C, Auquier A. Risk factors for male breast cancer: a Franco-Swiss case-control study. Int J Cancer. 1990 Apr 15;45(4):661-5. PubMed PMID: 2323842.

  27. Brinton LA, Richesson DA, Gierach GL, Lacey JV, Jr., Park Y, Hollenbeck AR, et al. Prospective evaluation of risk factors for male breast cancer. J Natl Cancer Inst. 2008 Oct 15;100(20):1477-81. PubMed PMID: 18840816. PMCID: PMC2720728.

  28. D'Avanzo B, La Vecchia C. Risk factors for male breast cancer. Br J Cancer. 1995 Jun;71(6):1359-62. PubMed PMID: 7779739. PMCID: PMC2033855.

  29. Gargiulo P, Pensabene M, Milano M, Arpino G, Giuliano M, Forestieri V, et al. Long-term survival and BRCA status in male breast cancer: a retrospective single-center analysis. BMC Cancer. 2016 Jul 04;16:375. PubMed PMID: 27377827. PMCID: PMC4932666.

  30. Spinelli C, Strambi S, Piccini L, Rossi L, Aretini P, Caligo A. BRCA1 gene variant p.P142H associated with male breast cancer: a two-generation genealogic study and literature review. Fam Cancer. 2015 Dec;14(4):515-9. PubMed PMID: 26085381.

  31. Biesma HD, Schouten PC, Lacle MM, Sanders J, Brugman W, Kerkhoven R, et al. Copy number profiling by array comparative genomic hybridization identifies frequently occurring BRCA2-like male breast cancer. Genes Chromosomes Cancer. 2015 Dec;54(12):734-44. PubMed PMID: 26355282.

  32. Ottini L, Rizzolo P, Zanna I, Falchetti M, Masala G, Ceccarelli K, et al. 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. 2009 Aug;116(3):577-86. PubMed PMID: 18819001.

  33. Couch FJ, Farid LM, DeShano ML, Tavtigian SV, Calzone K, Campeau L, et al. BRCA2 germline mutations in male breast cancer cases and breast cancer families. Nat Genet. 1996 May;13(1):123-5. PubMed PMID: 8673091.

  34. Friedman LS, Gayther SA, Kurosaki T, Gordon D, Noble B, Casey G, et al. Mutation analysis of BRCA1 and BRCA2 in a male breast cancer population. Am J Hum Genet. 1997 Feb;60(2):313-9. PubMed PMID: 9012404. PMCID: PMC1712407.

  35. Basham VM, Lipscombe JM, Ward JM, Gayther SA, Ponder BA, Easton DF, et al. BRCA1 and BRCA2 mutations in a population-based study of male breast cancer. Breast Cancer Res. 2002;4(1):R2. PubMed PMID: 11879560. PMCID: PMC83848.

  36. Kwiatkowska E, Teresiak M, Filas V, Karczewska A, Breborowicz D, Mackiewicz A. BRCA2 mutations and androgen receptor expression as independent predictors of outcome of male breast cancer patients. Clin Cancer Res. 2003 Oct 01;9(12):4452-9. PubMed PMID: 14555518.

  37. Holloman WK. Unraveling the mechanism of BRCA2 in homologous recombination. Nature structural & molecular biology. 2011;18(7):748-54.

  38. Ottini L, Masala G, D'Amico C, Mancini B, Saieva C, Aceto G, et al. BRCA1 and BRCA2 mutation status and tumor characteristics in male breast cancer: a population-based study in Italy. Cancer Res. 2003 Jan 15;63(2):342-7. PubMed PMID: 12543786.

  39. Sverdlov RS, Barshack I, Bar Sade RB, Baruch RG, Hirsh-Yehezkel G, Dagan E, et al. Genetic analyses of male breast cancer in Israel. Genet Test. 2000;4(3):313-7. PubMed PMID: 11142766.

  40. Evans DG, Susnerwala I, Dawson J, Woodward E, Maher ER, Lalloo F. Risk of breast cancer in male BRCA2 carriers. J Med Genet. 2010 Oct;47(10):710-1. PubMed PMID: 20587410.

  41. Tai YC, Domchek S, Parmigiani G, Chen S. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007 Dec 05;99(23):1811-4. PubMed PMID: 18042939. PMCID: PMC2267289.

  42. Ottini L, Silvestri V, Rizzolo P, Falchetti M, Zanna I, Saieva C, 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. 2012 Jul;134(1):411-8. PubMed PMID: 22527108.

  43. Deb S, Jene N, Kconfab I, Fox SB. Genotypic and phenotypic analysis of familial male breast cancer shows under representation of the HER2 and basal subtypes in BRCA-associated carcinomas. BMC Cancer. 2012 Nov 09;12:510. PubMed PMID: 23146383. PMCID: PMC3561656.

  44. Fackenthal JD, Marsh DJ, Richardson AL, Cummings SA, Eng C, Robinson BG, et al. Male breast cancer in Cowden syndrome patients with germline PTEN mutations. J Med Genet. 2001 Mar;38(3):159-64. PubMed PMID: 11238682. PMCID: PMC1734834.

  45. Deb S, Wong SQ, Li J, Do H, Weiss J, Byrne D, et al. Mutational profiling of familial male breast cancers reveals similarities with luminal A female breast cancer with rare TP53 mutations. Br J Cancer. 2014 Dec 09;111(12):2351-60. PubMed PMID: 25490678. PMCID: PMC4264438.

  46. Silvestri V, Zelli V, Valentini V, Rizzolo P, Navazio AS, Coppa A, et al. Whole-exome sequencing and targeted gene sequencing provide insights into the role of PALB2 as a male breast cancer susceptibility gene. Cancer. 2017 Jan 01;123(2):210-8. PubMed PMID: 27648926.

  47. Ding YC, Steele L, Kuan CJ, Greilac S, Neuhausen SL. Mutations in BRCA2 and PALB2 in male breast cancer cases from the United States. Breast Cancer Res Treat. 2011 Apr;126(3):771-8. PubMed PMID: 20927582. PMCID: PMC3059396.

  48. Silvestri V, Rizzolo P, Zanna I, Falchetti M, Masala G, Bianchi S, et al. PALB2 mutations in male breast cancer: a population-based study in Central Italy. Breast Cancer Res Treat. 2010 Jul;122(1):299-301. PubMed PMID: 20180015.

  49. Sauty de Chalon A, Teo Z, Park DJ, Odefrey FA, kConFab, Hopper JL, et al. Are PALB2 mutations associated with increased risk of male breast cancer? Breast Cancer Res Treat. 2010 May;121(1):253-5. PubMed PMID: 20091115.

  50. Silvestri V, Rizzolo P, Falchetti M, Zanna I, Masala G, Bianchi S, et al. Mutation analysis of BRIP1 in male breast cancer cases: a population-based study in Central Italy. Breast Cancer Res Treat. 2011 Apr;126(2):539-43. PubMed PMID: 21165771.

  51. Silvestri V, Rizzolo P, Falchetti M, Zanna I, Masala G, Palli D, et al. Mutation screening of RAD51C in male breast cancer patients. Breast Cancer Res. 2011 Feb 08;13(1):404. PubMed PMID: 21392410. PMCID: PMC3109583.

  52. Zhou B-BS, Elledge SJ. The DNA damage response: putting checkpoints in perspective. Nature. 2000;408(6811):433-9.

  53. Meijers-Heijboer H, Van den Ouweland A, Klijn J, Wasielewski M, de Snoo A, Oldenburg R, et al. Low-penetrance susceptibility to breast cancer due to CHEK2* 1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nature genetics. 2002;31(1):55-9.

  54. Neuhausen S, Dunning A, Steele L, Yakumo K, Hoffman M, Szabo C, et al. Role of CHEK2* 1100delC in unselected series of non‐BRCA1/2 male breast cancers. International journal of cancer. 2004;108(3):477-8.

  55. Falchetti M, Lupi R, Rizzolo P, Ceccarelli K, Zanna I, Calo V, et al. BRCA1/BRCA2 rearrangements and CHEK2 common mutations are infrequent in Italian male breast cancer cases. Breast Cancer Res Treat. 2008 Jul;110(1):161-7. PubMed PMID: 17661168.

  56. Martínez-Bouzas C, Beristain E, Guerra I, Gorostiaga J, Mendizabal J-L, De-Pablo J-L, et al. CHEK2 1100delC is present in familial breast cancer cases of the Basque Country. Breast cancer research and treatment. 2007;103(1):111-3.

  57. Caligo MA, Agata S, Aceto G, Crucianelli R, Manoukian S, Peissel B, et al. The CHEK2 c. 1100delC mutation plays an irrelevant role in breast cancer predisposition in Italy. Human mutation. 2004;24(1):100.

  58. Weischer M, Bojesen SE, Tybjærg-Hansen A, Axelsson CK, Nordestgaard BG. Increased risk of breast cancer associated with CHEK2* 1100delC. Journal of clinical oncology. 2006;25(1):57-63.

  59. Rizzolo P, Silvestri V, Tommasi S, Pinto R, Danza K, Falchetti M, et al. Male breast cancer: genetics, epigenetics, and ethical aspects. Ann Oncol. 2013 Nov;24 Suppl 8:viii75-viii82. PubMed PMID: 24131976.

  60. Ottini L, Palli D, Rizzo S, Federico M, Bazan V, Russo A. Male breast cancer. Crit Rev Oncol Hematol. 2010 Feb;73(2):141-55. PubMed PMID: 19427229.

  61. Brinton LA, Cook MB, McCormack V, Johnson KC, Olsson H, Casagrande JT, et al. Anthropometric and hormonal risk factors for male breast cancer: male breast cancer pooling project results. J Natl Cancer Inst. 2014 Mar;106(3):djt465. PubMed PMID: 24552677. PMCID: PMC3975166.

  62. Humphries MP, Jordan VC, Speirs V. Obesity and male breast cancer: provocative parallels? BMC Med. 2015 Jun 04;13:134. PubMed PMID: 26044503. PMCID: PMC4457166.

  63. Liukkonen S, Saarto T, Maenpaa H, Sjostrom-Mattson J. Male breast cancer: a survey at the Helsinki University Central Hospital during 1981-2006. Acta Oncol. 2010 Apr;49(3):322-7. PubMed PMID: 20397767.

  64. Brinton LA, Carreon JD, Gierach GL, McGlynn KA, Gridley G. Etiologic factors for male breast cancer in the U.S. Veterans Affairs medical care system database. Breast Cancer Res Treat. 2010 Jan;119(1):185-92. PubMed PMID: 19330525. PMCID: PMC2807736.

  65. Fentiman I. Male breast cancer: a review. Ecancermedicalscience. 2009;3:140. PubMed PMID: 22276005. PMCID: PMC3223984.

  66. Weiss JR, Moysich KB, Swede H. Epidemiology of male breast cancer. Cancer Epidemiol Biomarkers Prev. 2005 Jan;14(1):20-6. PubMed PMID: 15668471.

  67. Giordano SH. A review of the diagnosis and management of male breast cancer. Oncologist. 2005 Aug;10(7):471-9. PubMed PMID: 16079314.

  68. Thomas E. Original Research: Men's awareness and knowledge of male breast cancer. Am J Nurs. 2010 Oct;110(10):32-7, 9-40; quiz 1-2. PubMed PMID: 20885124.

  69. Thomas DB. Breast cancer in men. Epidemiol Rev. 1993;15(1):220-31. PubMed PMID: 8405206.

  70. Mabuchi K, Bross DS, Kessler, II. Risk factors for male breast cancer. J Natl Cancer Inst. 1985 Feb;74(2):371-5. PubMed PMID: 3856050.

  71. Thomas DB, Jimenez LM, McTiernan A, Rosenblatt K, Stalsberg H, Stemhagen A, et al. Breast cancer in men: risk factors with hormonal implications. Am J Epidemiol. 1992 Apr 01;135(7):734-48. PubMed PMID: 1350708.

  72. Sas-Korczynska B, Adamczyk A, Niemiec J, Harazin-Lechowska A, Ambicka A, Jakubowicz J. Androgen receptor in male breast cancer. Pol J Pathol. 2015 Dec;66(4):347-52. PubMed PMID: 27003765.

  73. Gnerlich JL, Deshpande AD, Jeffe DB, Seelam S, Kimbuende E, Margenthaler JA. Poorer survival outcomes for male breast cancer compared with female breast cancer may be attributable to in-stage migration. Ann Surg Oncol. 2011 Jul;18(7):1837-44. PubMed PMID: 21484520. PMCID: PMC3277785.

  74. Ruddy KJ, Winer EP. Male breast cancer: risk factors, biology, diagnosis, treatment, and survivorship. Ann Oncol. 2013 Jun;24(6):1434-43. PubMed PMID: 23425944.

  75. Onami S, Ozaki M, Mortimer JE, Pal SK. Male breast cancer: an update in diagnosis, treatment and molecular profiling. Maturitas. 2010 Apr;65(4):308-14. PubMed PMID: 20138719. PMCID: PMC3253821.

  76. Jaiyesimi IA, Buzdar AU, Sahin AA, Ross MA. Carcinoma of the male breast. Ann Intern Med. 1992 Nov 01;117(9):771-7. PubMed PMID: 1416579.

  77. Vaysse C, Sroussi J, Mallon P, Feron JG, Rivain AL, Ngo C, et al. Prediction of axillary lymph node status in male breast carcinoma. Ann Oncol. 2013 Feb;24(2):370-6. PubMed PMID: 23051951.

  78. Liu D, Xie G, Chen M. Clinicopathologic characteristics and survival of male breast cancer. Int J Clin Oncol. 2014 Apr;19(2):280-7. PubMed PMID: 23640121.

  79. Liu T, Tong Z, He L, Zhang L. Clinicopathological Characteristics and Survival Analysis of 87 Male Breast Cancer Cases. Breast Care (Basel). 2011 Dec;6(6):446-51. PubMed PMID: 22419898. PMCID: PMC3290016.

  80. Sas-Korczynska B, Niemiec J, Harazin-Lechowska A, Korzeniowski S, Martynow D, Adamczyk A, et al. The biological markers and results of treatment in male breast cancer patients. The Cracow experience. Neoplasma. 2014;61(3):331-9. PubMed PMID: 24824936.

  81. Samaan NA, Buzdar AU, Aldinger KA, Schultz PN, Yang KP, Romsdahl MM, et al. Estrogen receptor: a prognostic factor in breast cancer. Cancer. 1981 Feb 01;47(3):554-60. PubMed PMID: 7226005.

  82. Schippinger W, Regitnig P, Dandachi N, Wernecke KD, Bauernhofer T, Samonigg H, et al. Evaluation of the prognostic significance of androgen receptor expression in metastatic breast cancer. Virchows Arch. 2006 Jul;449(1):24-30. PubMed PMID: 16628414.

  83. Hu R, Dawood S, Holmes MD, Collins LC, Schnitt SJ, Cole K, et al. Androgen receptor expression and breast cancer survival in postmenopausal women. Clin Cancer Res. 2011 Apr 01;17(7):1867-74. PubMed PMID: 21325075. PMCID: PMC30766

  84. Peters AA, Buchanan G, Ricciardelli C, Bianco-Miotto T, Centenera MM, Harris JM, et al. Androgen receptor inhibits estrogen receptor-alpha activity and is prognostic in breast cancer. Cancer Res. 2009 Aug 01;69(15):6131-40. PubMed PMID: 19638585.

  85. Panet-Raymond V, Gottlieb B, Beitel LK, Pinsky L, Trifiro MA. Interactions between androgen and estrogen receptors and the effects on their transactivational properties. Mol Cell Endocrinol. 2000 Sep 25;167(1-2):139-50. PubMed PMID: 11000528.

  86. Park S, Koo J, Kim M, Park H, Lee J, Lee J, et al. Androgen receptor expression is significantly associated with better outcomes in estrogen receptor-positive breast cancers. Annals of Oncology. 2011;22(8):1755-62.

  87. Collins LC, Cole KS, Marotti JD, Hu R, Schnitt SJ, Tamimi RM. Androgen receptor expression in breast cancer in relation to molecular phenotype: results from the Nurses' Health Study. Modern Pathology. 2011;24(7):924-31.

  88. Cochrane DR, Bernales S, Jacobsen BM, Cittelly DM, Howe EN, D’Amato NC, et al. Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide. Breast Cancer Research. 2014;16(1):R7.

  89. Harnden D, Maclean N, Langlands A. Carcinoma of the breast and Klinefelter's syndrome. Journal of medical genetics. 1971;8(4):460.

  90. Scheike O, Visfeldt J, Petersen B. Male breast cancer. 3. Breast carcinoma in association with the Klinefelter syndrome. Acta Pathol Microbiol Scand A. 1973 May;81(3):352-8. PubMed PMID: 4767227.

  91. Hultborn R, Hanson C, Kopf I, Verbiene I, Warnhammar E, Weimarck A. Prevalence of Klinefelter's syndrome in male breast cancer patients. Anticancer Res. 1997 Nov-Dec;17(6D):4293-7. PubMed PMID: 9494523.

  92. Newman J. Breast cancer in men and mammography of the male breast. Radiol Technol. 1997 Sep-Oct;69(1):17-28; quiz 9-36. PubMed PMID: 9323763.

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

  94. Evans DB, Crichlow RW. Carcinoma of the male breast and Klinefelter's syndrome: is there an association? CA: a cancer journal for clinicians. 1987;37(4):246-51.

  95. Bardenstein DS, McLean IW, Nerney J, Boatwright R. Cowden's disease. Ophthalmology. 1988;95(8):1038-41.

  96. Gilbert HD, Plezia RA, Pietruk T. Cowden's disease (multiple hamartoma syndrome). Journal of Oral and Maxillofacial Surgery. 1985;43(6):457-60.

  97. Thyresson H, Doyle J, editors. Cowden's disease (multiple hamartoma syndrome). Mayo Clinic Proceedings; 1981.

  98. Wade TR, Kopf AW. Cowden's disease: A case report and review of the literature. The Journal of dermatologic surgery and oncology. 1978;4(6):459-64.

  99. Liaw D, Marsh DJ, Li J, Dahia PL, Wang SI, Zheng Z, et al. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nature genetics. 1997;16(1):64-7.

  100. Marsh DJ, Dahia PL, Coulon V, Zheng Z, Dorion‐Bonnet F, Call KM, et al. Allelic imbalance, including deletion of PTEN/MMAC1, at the Cowden disease locus on 10q22‐23, in hamartomas from patients with cowden syndrome and germline PTEN mutation. Genes, Chromosomes and Cancer. 1998;21(1):61-9.

  101. Marsh DJ, Coulon V, Lunetta KL, Rocca-Serra P, Dahia PL, Zheng Z, et al. Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Human molecular genetics. 1998;7(3):507-15.

  102. Nelen MR, Van Staveren WC, Peeters EA, Ben Hassel M, Gorlin RJ, Hamm H, et al. Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. Human molecular genetics. 1997;6(8):1383-7.

  103. Teng DH, Hu R, Lin H, Davis T, Iliev D, Frye C, et al. MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines. Cancer research. 1997;57(23):5221-5.

  104. Marsh DJ, Kum JB, Lunetta KL, Bennett MJ, Gorlin RJ, Ahmed SF, et al. PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome. Human molecular genetics. 1999;8(8):1461-72.

  105. Tsou HC, Teng DH-F, Ping XL, Brancolini V, Davis T, Hu R, et al. The role of MMAC1 mutations in early-onset breast cancer: causative in association with Cowden syndrome and excluded in BRCA1-negative cases. The American Journal of Human Genetics. 1997;61(5):1036-43.

  106. Hagelstrom RT, Ford J, Reiser GM, Nelson M, Pickering DL, Althof PA, et al. Breast Cancer and Non-Hodgkin Lymphoma in a Young Male with Cowden Syndrome. Pediatr Blood Cancer. 2016 Mar;63(3):544-6. PubMed PMID: 26468640.

  107. Koc M, Polat P. Epidemiology and aetiological factors of male breast cancer: a ten years retrospective study in eastern Turkey. Eur J Cancer Prev. 2001 Dec;10(6):531-4. PubMed PMID: 11916352.

  108. Johansen Taber KA, Morisy LR, Osbahr AJ, 3rd, Dickinson BD. Male breast cancer: risk factors, diagnosis, and management (Review). Oncol Rep. 2010 Nov;24(5):1115-20. PubMed PMID: 20878100.

  109. Bove FJ, Ruckart PZ, Maslia M, Larson TC. Mortality study of civilian employees exposed to contaminated drinking water at USMC Base Camp Lejeune: a retrospective cohort study. Environmental Health. 2014;13(1):68.

  110. Pollan M, Gustavsson P, Floderus B. Breast cancer, occupation, and exposure to electromagnetic fields among Swedish men. Am J Ind Med. 2001 Mar;39(3):276-85. PubMed PMID: 11241560.

  111. Cocco P, Figgs L, Dosemeci M, Hayes R, Linet MS, Hsing AW. Case-control study of occupational exposures and male breast cancer. Occup Environ Med. 1998 Sep;55(9):599-604. PubMed PMID: 9861181. PMCID: PMC1757632.

  112. Feychting M, Forssén U, Rutqvist LE, Ahlbom A. Magnetic fields and breast cancer in Swedish adults residing near high-voltage power lines. Epidemiology. 1998:392-7.

  113. Stenlund C, Floderus B. Occupational exposure to magnetic fields in relation to male breast cancer and testicular cancer: a Swedish case-control study. Cancer Causes Control. 1997 Mar;8(2):184-91. PubMed PMID: 9134242.

  114. Matanoski GM, Breysse PN, Elliott EA. Electromagnetic field exposure and male breast cancer. Lancet. 1991 Mar 23;337(8743):737. PubMed PMID: 1672204.

  115. Theriault G, Goldberg M, Miller A, Armstrong B, Guenel P, Deadman J, et al. Cancer risks associated with occupational exposure to magnetic fields among electric utility workers in Ontario and Quebec, Canada, and France: 1970–1989. American journal of epidemiology. 1994;139(6):550-72.

  116. Guénel P, Raskmark P, Andersen JB, Lynge E. Incidence of cancer in persons with occupational exposure to electromagnetic fields in Denmark. Occupational and Environmental Medicine. 1993;50(8):758-64.

  117. Rosenbaum PF, Vena JE, Zielezny MA, Michalek AM. Occupational exposures associated with male breast cancer. Am J Epidemiol. 1994 Jan 01;139(1):30-6. PubMed PMID: 8296772.