Males at High Risk for Breast Cancer: Who Are They and How Should We Screen Them?


Background: It is estimated that 2240 males in the United States will develop invasive breast cancer (BC) in 2013, resulting in 410 deaths. Overall, male breast cancers (MBCs) are diagnosed with larger tumor size, more frequent lymphatic invasion, and advanced tumor stage compared to their female counterparts. Several risk factors have been elucidated for the development of MBC, and this paper aims to critically review the existing literature on at-risk populations and provide screening recommendations. Methods: A comprehensive search for all published studies on populations at risk for MBC using PubMed, EBSCOhost, and Google Scholar was performed (1982- 2013). The search focused specifically on genetic and epidemiologic risk factors, and screening for MBC. Keywords searched included “male breast cancer risk factors”, “male breast cancer epidemiology”, and “male breast cancer genetics”. A total of 34 studies involving 4,865,819 patients were identified. Results: Five studies (N = 327,667) focused primarily on family history of breast cancer as a risk factor for MBC. 15% - 20% of men with BC have a family history of breast or ovarian cancer, and a family history of BC among first-degree relatives confers a 2-to 3-fold increase in MBC risk (odds ratio = 3.3). Seventeen studies (N = 5451) analyzed associations between several heritable genes and MBC. Lifetime MBC risk among BRCA1 mutation carriers is 1% - 5%, while MBC risk in BRCA2 mutation carriers is higher and varies between 4% - 40%. Less clear associations between MBC and PALB2, Androgen Receptor gene, CYP17, and CHEK2 mutations have also been documented. Five studies (N = 16,667) have addressed occupational risk factors for MBC. An 8-fold increase in MBC is reported in males working in the cosmetic cream manufacturing, and the motor vehicle industries. A meta-analysis of 18 trials also identified electromagnetic field exposure as a potential MBC risk, though causation remains undocumented. Eleven studies (N = 4,843,598) analyzed the role of abnormalities in the androgen-to-estrogen ratio as a risk factor for MBC. Conditions associated with increased MBC risk include Klinefelter’s syndrome (relative risk, RR = 29.64), obesity (RR = 1.98), orchitis/epididymitis (RR = 1.84), and gynecomastia (RR = 5.86). Conclusion: Routine screening for MBC should be considered in all high risk male populations, including those with a prior history of breast carcinoma, a strong family history of BC (defined as an affected mother or sister), a positive BRCA2 mutation status (regardless of family history), and men diagnosed with Klinefelter’s syndrome, or those in the chemical or motor vehicle industries. Genetic testing for BRCA2 should be recommended for all MBC patients. Increased public and physician education on MBC is necessary to raise awareness about this rare disease and the need for screening of at-risk populations.

Share and Cite:

Swergold, N. , Murthy, V. and Chamberlain, R. (2014) Males at High Risk for Breast Cancer: Who Are They and How Should We Screen Them?. Surgical Science, 5, 320-331. doi: 10.4236/ss.2014.57054.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] American Cancer Society (2013) Breast Cancer in Men. American Cancer Society, Inc., Atlanta.
[2] Korde, L.A., Zujewski, J.A., Karmin, L., et al. (2012) Multidisciplinary Meeting on Male Breast Cancer: Summary and Research Recommendations. Journal of Clinical Oncology, 28, 2114-2122.
[3] Ottini, L., Palli, D., Rizzo, S., et al. (2010) Male Breast Cancer. Critical Reviews in Oncology/Hematology, 73, 141-155.
[4] Friedman, L.S., Gayther, S.A., Kurosaki, T., et al. (1997) Mutation Analysis of BRCA1 and BRCA2 in a Male Breast Cancer Population. The American Journal of Human Genetics, 60, 313-319.
[5] Rosenblatt, K.A., Thomas, D.B., McTiernan, A., et al. (1991) Breast Cancer in Men: Aspects of Familial Aggregation. Journal of the National Cancer Institute, 83, 849-854.
[6] Haraldsson, K., Loman, N., Zhang, Q.X., et al. (1996) BRCA2 Germ-Line Mutations Are Frequent in Male Breast Cancer Patients without a Family History of the Disease. Cancer Research, 58, 1367-1371.
[7] Brinton, L.A., Richesson, D.A., Gierach, G.L., et al. (2008) Prospective Evaluation of Risk Factors for Male Breast Cancer. Journal of the National Cancer Institute, 100, 1477-1481.
[8] Johnson, K.C., Pan, S. and Mao, Y. (2002) Risk Factors for Male Breast Cancer in Canada, 1994-1998. European Journal of Cancer Prevention, 11, 253-263.
[9] D’Avanzo, B. and La Vecchia, C. (1995) Risk Factors for Male Breast Cancer. British Journal of Cancer, 71, 1359-1362.
[10] Ewertz, M., Holmberg, L., Tretli, S., et al. (2001) Risk Factors for Male Breast Cancer—A Case-Control Study from Scandinavia. Acta Oncologica, 40, 467-471.
[11] Thorlacius, S., Olafsdottir, G., Tryggvadottir, L., Neuhausen, S., Jonasson, J.G., Tavtigian, S.V., Tulinius, H., Ogmundsdottir, H.M. and Eyfjord, J.E. (1996) A Single BRCA2 Mutation in Male and Female Breast Cancer Families from Iceland with Varied Cancer Phenotypes. Nature Genetics, 13, 117-119.
[12] Couch, F.J., Farid, L.M., DeShano, M.L., Tavtigian, S.V., Calzone, K., Campeau, L., et al. (1996) BRCA2 Germline Mutations in Male Breast Cancer Cases and Breast Cancer Families. Nature Genetics, 13, 123-125.
[13] Young, I.E., Kurian, K.M., Mackenzie, M.A.F., Kunkler, I.H., Cohen, B.B., Hooper, M.L., Wyllie, A.H. and Steel, C.M. (2000) The CAG Repeat within the Androgen Receptor Gene in Male Breast Cancer Patients. Journal of Medical Genetics, 37, 139-140.
[14] Gudmundsdottir, K., Thorlacius, S., Jonasson, J.G., Sigfusson, B.F., Tryggvadottir, L. and Eyfjord, J.E. (2003) CYP17 Promoted Polymorphisms and Breast Cancer Risk in Males and Females in Relation to BRCA2 Status. British Journal of Cancer, 88, 933-936.
[15] Ding, Y.C., Steele, L., Kuan, C.J., Greilac, S. and Neuhausen, S.L. (2011) Mutations in BRCA2 and PALB2 in Male Breast Cancer Cases from the United States. Breast Cancer Research and Treatment, 126, 771-778.
[16] Csokay, B., Udvarhelyi, N., Sulyok, Z., Besznyak, I., Ramus, S., Ponder, B. and Olah, E. (1999) High Frequency of Germ-Line Brca2 Mutations among Hungarian Male Breast Cancer Patients without Family History. Cancer Research, 59, 995-998.
[17] Mavraki, E., Gray, I.C., Bishop, D.T. and Spurr, N.K. (1997) Germline RBCA2 Mutations in Men with Breast Cancer. British Journal of Cancer, 76, 1428-1431.
[18] Syrjakoski, K., Kuukasjarvi, T., Waltering, K., Haraldsson, K., Auvinen, A., Borg, A., Kainu, T., Kallioniemi, O.P. and Koivisto, P.A. (2004) BRCA2 Mutations in 154 Finnish Male Breast Cancer Patients. Neoplasia, 6, 541-545.
[19] Basham, V.M., Lipscombe, J.M., Ward, J.M., Gayther, S.A., Ponder, B.A.J., Easton, D.F. and Pharoah, P.D.P. (2002) BRCA1 and BRCA2 Mutations in a Population-Based Study of Male Breast Cancer. Breast Cancer Research, 4, R2.
[20] Meijers-Heijboer, H., van den Ouweland, A., Kiln, J., Wasielewski, M., de Snoo, A., Oldenburg, R., et al. (2002) Low-Penetrance Susceptibility to Breast Cancer Due to CHEK2*1100delC in Noncarriers of BRCA1 or BRCA2 Mutations. Nature Genetics, 31, 55-59.
[21] Chodick, G., Struewing, J.P., Ron, E., Rutter, J.L. and Iscovich, J. (2008) Similar Prevalence of Founder BRCA1 and BRCA2 Mutations among Ashkenazi and Non-Ashkenazi Men with Breast Cancer: Evidence from 261 Cases in Israel, 1976-1999. The European Journal of Medical Genetics, 51, 141-147.
[22] Tai, Y.C., Domchek, S., Parmigiani, G. and Chen, S.N. (2007) Breast Cancer Risk among Male BRCA1 and BRCA2 Mutation Carriers. Journal of the National Cancer Institute, 99, 1811-1814.
[23] Risch, H.A., McLaughlin, J.R., Cole, D.E.C., Rosen, B., Bradley, L., Fan, I., et al. (2006) Population BRCA1 and BRCA2 Mutation Frequencies and Cancer Penetrances: A Kin-Cohort Study in Ontario, Canada. Journal of the National Cancer Institute, 98, 1694-1706.
[24] Frank, T.S., Deffenbaugh, A.M., Reid, J.E., Hulick, M., Ward, B.E., Lingenfelter, B., et al. (2002) Clinical Characteristics of Individuals with Germline Mutations in BRCA1 and BRCA2: Analysis of 10,000 Individuals. Journal of Clinical Oncology, 20, 1480-1490.
[25] National Cancer Institute (2013) Genetics of Breast and Ovarian Cancer (PDQ).
[26] Ottini, L., Rizzolo, P., Zanna, I., Falchetti, M., Masala, G., Ceccarelli, K., et al. (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 Research and Treatment, 116, 577-586.
[27] Malone, K.E., Daling, J.R., Doody, D.R., Hsu, L., Bernstein, L., Coates, R.J., et al. (2006) Prevalence and Predictors of BRCA1 and BRCA2 Mutations in a Population-Based Study of Breast Cancer in White and Black American Women Ages 35 to 64 Years. Cancer Research, 66, 8297.
[28] McLaughlin, J.K., Malker, H.S.R., Blot, W.J., Weiner, J.A., Ericsson, J.L. and Fraumeni, J.F. (1988) Occupational Risks for Male Breast Cancer in Sweden. British Journal of Industrial Medicine, 45, 275-276.
[29] Sun, J.W., Li, X.R., Gao, H.Y., Yin, J.Y., Qin, Q., Nie, S.F. and Wei, S. (2013) Electromagnetic Field Exposure and Male Breast Cancer Risk: A Meta-Analysis of 18 Studies. Asian Pacific Journal of Cancer Prevention, 14, 523-528.
[30] Cocco, P., Figgs, L., Dosemeci, M., Hayes, R., Linet, M.S. and Hsing, A.W. (1998) Case-Control Study of Occupational Exposures and Male Breast Cancer. Occupational and Environmental Medicine, 55, 599-604.
[31] Villeneuve, S., Cyr, D., Lynge, E., Orsi, L., Sabroe, S., Merletti, F., et al. (2010) Occupation and Occupational Exposure to Endocrine Disrupting Chemicals in Male Breast Cancer: A Case-Control Study in Europe. Occupational and Environmental Medicine, 67, 837-844.
[32] Hansen, J. (2000) Elevated Risk for Male Breast Cancer after Occupational Exposure to Gasoline and Vehicular Combustion Products. American Journal of Industrial Medicine, 37, 349-352.<349::AID-AJIM4>3.0.CO;2-L
[33] Nirmul, D., Pegoraro, R.J., Jialal, I., Naidoo, C. and Joubert, S.M. (1982) The Sex Hormone Profile of Male Patients with Breast Cancer. British Journal of Cancer, 48, 423-427.
[34] Brinton, L.A., Carreon, J.D., Gierach, G.L., McGlynn, K.A. and Gridley, G. (2010) Etiologic Factors for Male Breast Cancer in the U.S. Veterans Affairs Medical Care System Database. Breast Cancer Research and Treatment, 119, 185-192.
[35] Casagrande, J.T., Hanisch, R., Pike, M.C., et al. (1988) A Case-Control Study of Male Breast Cancer. Cancer Research, 48, 1326-1330.
[36] Hsing, A.W., McLaughlin, J.K., Cocco, P., Co Chien, H.T. and Fraumeni Jr., J.F. (1998) Risk Factors for Male Breast Cancer (United States). Cancer Causes and Control, 9, 269-275.
[37] Olsson, H., Bloodstream, A. and Alm, P. (2002) Male Gynecomastia and Risk for Malignant Tumors—A Cohort Study. BMC Cancer, 2, 26.
[38] Altinli, E., Gorgun, E., Karabicak, I., Uras, C., Unal, H. and Akcal, T. (2002) Anthropometric Measurements in Male Breast Cancer. Obesity Surgery, 12, 869-870.
[39] Guenel, P., Cyr, D., Sabroe, S., Lynge, E., Merletti, F., Ahrens, W., et al. (2004) Alcohol Drinking May Increase Risk of Breast Cancer in Men: A European Population-Based Case-Control Study. Cancer Causes and Control, 15, 571-580.
[40] Sorensen, H.T., Friis, S., Olsen, J.H., Thulstrup, A.M., Mellemkjaer, L., Linet, M., Trichopoulos, D., Vilstrup, H. and Olsen, J. (1998) Risk of Breast Cancer in Men with Liver Cirrhosis. American Journal of Gastroenterology, 93, 231-233.
[41] Al-Naggar, R.A. and Al-Naggar, D.H. (2012) Perceptions and Opinions about Male Breast Cancer and Male Breast Self-Examination: A Qualitative Study. Asian Pacific Journal of Cancer Prevention, 13, 243-246.
[42] Bunkley, D.T., Robinson, J.D., Bennett Jr., N.E. and Gordon, S. (2000) Breast Cancer in Men: Emasculation by Association? Journal of Clinical Psychology in Medical Settings, 7, 91-97.
[43] France, L., Michie, S., Barrett-Lee, P., Brain, K., Harper, P. and Gray, J. (2000) Male Cancer: A Qualitative Study of Male Breast Cancer. The Breast, 9, 343-348.
[44] Nicholas, D.R. (2000) Men, Masculinity, and Cancer: Risk-Factor Behaviors, Early Detection, and Psychosocial Adaptation. Journal of American College Health, 49, 27-33.
[45] Kiluk, J.V., Lee, M.C., Park, C.K., Meade, T., Minton, S., Harris, E., Kim, J. and Laronga, C. (2011) Male Breast Cancer: Management and Follow-Up Recommendations. The Breast Journal, 17, 503-509.
[46] Haché, K.D., Gray, S., Barnes, P.J., Dewar, R., Younis, T. and Rayson, D. (2007) Clinical and Pathological Correlations in Male Breast Cancer: Intratumoral Aromatase Expression via Tissue Microarray. Breast Cancer Research and Treatment, 105, 169-175.
[47] Dershaw, D.D., Borgen, P.I., Deutch, B.M. and Liberman, L. (1993) Mammographic Findings in Men with Breast Cancer. American Journal of Roentgenology, 160, 267-270.
[48] Evans, G.F.F., Anthony, T., Appelbaum, A.H., Schumpert, T.D., Levy, K.R., Amirkhan, R.H., Cambell, T.J., Lopez, J. and Turnage, R.H. (2001) The Diagnostic Accuracy of Mammography in the Evaluation of Male Breast Disease. American Journal of Surgery, 181, 96-100.
[49] Brenner, R.J., Weitzel, J.N., Hansen, N. and Boasberg, P. (2004) Screening-Detected Breast Cancer in a Man with BRCA2 Mutation: Case Report. Radiology, 230, 553-555.
[50] Estala, S.M. (2006) Proposed Screening Recommendations for Male Breast Cancer. The Nurse Practitioner, 31, 62-63.
[51] Freedman, B.C., Keto, J. and Rosenbaum Smith, S.M. (2012) Screening Mammography in Men with BRCA Mutations: Is There a Role? The Breast Journal, 18, 73-75.
[52] Patterson, S.K., Helvie, M.A., Aziz, K. and Nees, A.V. (2006) Outcome of Men Presenting with Clinical Breast Problems: The Role of Mammography and Ultrasound. The Breast Journal, 12, 418-423.
[53] Dershaw, D.D. (1986) Male Mammography. American Journal of Roentgenology, 146, 127-131.
[54] Ruddy, K.J. and Winer, E.P. (2013) Male Breast Cancer: Risk Factors, Biology, Diagnosis, Treatment, and Survivorship. Annals of Oncology, 24, 1434-1443.

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.