Male Breast Cancer Biology, Screening, Treatment, and Follow-Up: A Narrative Review
Abstract
Male breast cancer (MBC) is a rare type of cancer that affects men, accounting for only 1% of all cancers in men and all breast cancer cases worldwide. Its rarity is due to the differences in male endocrine function and the smaller amount of mammary tissue in males. Due to its infrequency, there is limited knowledge about the disease, and treatment recommendations are often based on extrapolation from clinical trial data involving female breast cancer patients. Men with MBC typically present in their 50s or older and may mistake a suspicious breast mass for a benign condition called gynecomastia. Various known risk factors contribute to breast cancer in men. Currently, there are no international randomized control trials (RCTs) specifically focused on MBC, and management guidelines are primarily derived from studies conducted among female patients. Localized and resectable cases of breast cancer typically require surgical intervention, followed by radiotherapy, chemotherapy, hormonal therapy, or potentially utilizing recent advancements in immune-oncology agents. A comprehensive approach that involves a multidisciplinary team ensures appropriate treatment and can lead to favorable outcomes. However, screening for MBC is limited due to the lack of large-scale international RCTs demonstrating its effectiveness in reducing MBC-related mortality.
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3. Cardoso F, Bartlett J, Slaets L, et al (2018). Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Ann Oncol, 29 (2):405-417.
4. Sidiropoulou Z, Vasconcelos AP, Couceiro C, et al (2023). Prevalence of Imaging Detected Silent Male Breast Cancer in Autopsy Specimens: Study of the Disease Held by Image-Guided Biopsies. Acad Forensic Pathol, 13(1):16-33.
5. Roshandel G, Ferlay J, Ghanbari‐Motlagh A, et al (2021). Cancer in Iran 2008 to 2025: Recent incidence trends and short‐term predictions of the future burden. Int J Cancer, 149 (3):594-605.
6. Aryannejad A, Saeedi Moghaddam S, Mashinchi B, et al (2023). National and subnational burden of female and male breast cancer and risk factors in Iran from 1990 to 2019: results from the Global Burden of Disease study 2019. Breast Cancer Res, 25 (1):47.
7. Xu S, Liu Y, Zhang T, et al (2021). The global, regional, and national burden and trends of breast cancer from 1990 to 2019: Results from the global burden of disease study 2019. Front Oncol, 11:689562.
8. Konduri S, Singh M, Bobustuc G, et al (2020). Epidemiology of male breast cancer. Breast, 54:8-14.
9. Kwong A, Ho CYS, Shin VY, et al (2023). Molecular characteristics of Asian male BRCA-related cancers. Breast Cancer Res Treat, 198(2):391-400.
10. Network NCC (2020). Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. Practice Guidelines in, 3.
11. Li S, Silvestri V, Leslie G, et al (2022). Cancer risks associated with BRCA1 and BRCA2 pathogenic variants. J Clin Oncol, 40 (14):1529-1541.
12. Bootsma TI, Duijveman P, Pijpe A, et al (2020). Unmet information needs of men with breast cancer and health professionals. Psychooncology, 29(5):851-860.
13. Scagliotti MF, Boietti BR, Knoblovits P (2023). Prevalence of men's health history in male breast cancer patients. Endocrinol Diabetes Nutr (Engl Ed), 70(6):415-420.
14. Hejrati A, Rahmanian V, Hasannejad H, et al (2023). Association between Non-alcoholic Fatty Liver Disease and Breast Cancer: A Systematic Review and Meta-analysis Study. Middle East J Cancer, 14 (4):471-480.
15. Zehr KR (2019). Diagnosis and treatment of breast cancer in men. Radiol Technol, 91 (1):51M-61M.
16. Niewoehner CB, Schorer AE (2008). Gynaecomastia and breast cancer in men. BMJ, 336 (7646):709-713.
17. Nofal M, Yousef A (2019). The diagnosis of male breast cancer. Neth J Med, 77 (10):356-359.
18. Sanguinetti A, Polistena A, Lucchini R, et al (2016). Male breast cancer, clinical presentation, diagnosis and treatment: Twenty years of experience in our Breast Unit. Int J Surg Case Rep, 20S(Suppl):8-11.
19. Gao Y, Heller SL (2023). Breast cancer screening in men. J Breast Imaging, 5 (2):104-111.
20. Gaddam S, Heller SL, Babb JS, Gao Y (2021). Male breast cancer risk assessment and screening recommendations in high-risk men who undergo genetic counseling and multigene panel testing. Clin Breast Cancer, 21 (1):e74-e79.
21. Woods RW, Salkowski LR, Elezaby M, et al (2020). Image-based screening for men at high risk for breast cancer: Benefits and drawbacks. Clin Imaging, 60 (1):84-89.
22. Gao Y, Goldberg JE, Young TK, et al (2019). Breast cancer screening in high-risk men: a 12-year longitudinal observational study of male breast imaging utilization and outcomes. Radiology, 293 (2):282-291.
23. Hoda RS, Arpin III RN, Gottumukkala RV, et al (2019). Diagnostic value of fine-needle aspiration in male breast lesions. Acta Cytol, 63 (4):319-327.
24. Yang Y, Li S, Liu G, Shao Z (2019). Is core needle biopsy effective at diagnosing male breast lesions? Breast Cancer Res Treat, 177:507-511.
25. Forbes C, Fayter D, de Kock S, Quek RG (2019). A systematic review of international guidelines and recommendations for the genetic screening, diagnosis, genetic counseling, and treatment of BRCA-mutated breast cancer. Cancer Manag Res, 11:2321-2337.
26. Reichl F, Muhr D, Rebhan K, et al (2021). Cancer spectrum, family history of cancer and overall survival in men with germline BRCA1 or BRCA2 mutations. J Pers Med, 11 (9):917.
27. Fanale D, Incorvaia L, Filorizzo C, et al (2020). Detection of germline mutations in a cohort of 139 patients with bilateral breast cancer by multi-gene panel testing: impact of pathogenic variants in other genes beyond BRCA1/2. Cancers (Basel), 12 (9):2415.
28. Fentiman IS (2018). Surgical options for male breast cancer. Breast Cancer Res Treat, 172:539-544.
29. Madden NA, Macdonald OK, Call JA, et al (2016). Radiotherapy and male breast cancer. Am J Clin Oncol, 39 (5):458-462.
30. Forster T, Köhler C, El Shafie R,et al (2020). Adjuvant Radiation Therapy for Male Breast Cancer—A Rare Indication? Cancers (Basel), 12 (12):3645.
31. Separham A, Ghaffari S, Najafi H, et al (2016). The impact of allopurinol on patients with acute ST elevation myocardial infarction undergoing thrombolytic therapy. J Cardiovasc Pharmacol, 68 (4):265-268.
32. Gucalp A, Traina TA, Eisner JR, et al (2019). Male breast cancer: a disease distinct from female breast cancer. Breast Cancer Res Treat, 173:37-48.
33. Khan NAJ, Tirona M (2021). An updated review of epidemiology, risk factors, and management of male breast cancer. Med Oncol, 38:39.
34. Hassett MJ, Somerfield MR, Baker ER, et al (2020). Management of male breast cancer: ASCO guideline. J Clin Oncol, 38 (16):1849-1863.
35. A Baudino T (2015). Targeted cancer therapy: the next generation of cancer treatment. Curr Drug Discov Technol, 12 (1):3-20.
36. Bachelot T, Ciruelos E, Schneeweiss A, et al (2019). Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE). Ann Oncol, 30 (5):766-773.
37. Lima ZS, Ghadamzadeh M, Arashloo FT, et al (2019). Recent advances of therapeutic targets based on the molecular signature in breast cancer: genetic mutations and implications for current treatment paradigms. J Hematol Oncol, 12:38.
38. Liu N, Johnson KJ, Ma CX (2018). Male breast cancer: an updated surveillance, epidemiology, and end results data analysis. Clin Breast Cancer, 18 (5):e997-e1002.
39. Mutebi M, Anderson BO, Duggan C, et al (2020). Breast cancer treatment: A phased approach to implementation. Cancer, 126 Suppl 10:2365-2378.
40. O'Malley CD, Prehn AW, Shema SJ, Glaser SL (2002). Racial/ethnic differences in survival rates in a population‐based series of men with breast carcinoma. Cancer, 94 (11):2836-2843.
41. Zheng G, Leone JP (2022). Male breast cancer: An updated review of epidemiology, clinicopathology, and treatment. J Oncol, 2022: 1734049.
42. Shahjahani M, Abroun A, Saki N, et al (2020). STAT5: from pathogenesis mechanism to therapeutic approach in acute leukemia. Lab Med, 51 (4):345-351.
43. Jesser EA, Brady NJ, Huggins DN, et al (2021). STAT5 is activated in macrophages by breast cancer cell-derived factors and regulates macrophage function in the tumor microenvironment. Breast Cancer Res, 23:104.
44. Masci G, Caruso M, Caruso F, et al (2015). Clinicopathological and immunohistochemical characteristics in male breast cancer: a retrospective case series. Oncologist, 20 (6):586-592.
45. Coates AS, Winer EP, Goldhirsch A, et al (2015). Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer Ann Oncol, 26 (8):1533-1546.
46. Wood ME, McKinnon W, Garber J (2020). Risk for breast cancer and management of unaffected individuals with non‐BRCA hereditary breast cancer. Breast J, 26 (8):1528-1534.
2. Chen Z, Xu L, Shi W, et al (2020). Trends of female and male breast cancer incidence at the global, regional, and national levels, 1990–2017. Breast Cancer Res Treat, 180:481-490.
3. Cardoso F, Bartlett J, Slaets L, et al (2018). Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Ann Oncol, 29 (2):405-417.
4. Sidiropoulou Z, Vasconcelos AP, Couceiro C, et al (2023). Prevalence of Imaging Detected Silent Male Breast Cancer in Autopsy Specimens: Study of the Disease Held by Image-Guided Biopsies. Acad Forensic Pathol, 13(1):16-33.
5. Roshandel G, Ferlay J, Ghanbari‐Motlagh A, et al (2021). Cancer in Iran 2008 to 2025: Recent incidence trends and short‐term predictions of the future burden. Int J Cancer, 149 (3):594-605.
6. Aryannejad A, Saeedi Moghaddam S, Mashinchi B, et al (2023). National and subnational burden of female and male breast cancer and risk factors in Iran from 1990 to 2019: results from the Global Burden of Disease study 2019. Breast Cancer Res, 25 (1):47.
7. Xu S, Liu Y, Zhang T, et al (2021). The global, regional, and national burden and trends of breast cancer from 1990 to 2019: Results from the global burden of disease study 2019. Front Oncol, 11:689562.
8. Konduri S, Singh M, Bobustuc G, et al (2020). Epidemiology of male breast cancer. Breast, 54:8-14.
9. Kwong A, Ho CYS, Shin VY, et al (2023). Molecular characteristics of Asian male BRCA-related cancers. Breast Cancer Res Treat, 198(2):391-400.
10. Network NCC (2020). Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. Practice Guidelines in, 3.
11. Li S, Silvestri V, Leslie G, et al (2022). Cancer risks associated with BRCA1 and BRCA2 pathogenic variants. J Clin Oncol, 40 (14):1529-1541.
12. Bootsma TI, Duijveman P, Pijpe A, et al (2020). Unmet information needs of men with breast cancer and health professionals. Psychooncology, 29(5):851-860.
13. Scagliotti MF, Boietti BR, Knoblovits P (2023). Prevalence of men's health history in male breast cancer patients. Endocrinol Diabetes Nutr (Engl Ed), 70(6):415-420.
14. Hejrati A, Rahmanian V, Hasannejad H, et al (2023). Association between Non-alcoholic Fatty Liver Disease and Breast Cancer: A Systematic Review and Meta-analysis Study. Middle East J Cancer, 14 (4):471-480.
15. Zehr KR (2019). Diagnosis and treatment of breast cancer in men. Radiol Technol, 91 (1):51M-61M.
16. Niewoehner CB, Schorer AE (2008). Gynaecomastia and breast cancer in men. BMJ, 336 (7646):709-713.
17. Nofal M, Yousef A (2019). The diagnosis of male breast cancer. Neth J Med, 77 (10):356-359.
18. Sanguinetti A, Polistena A, Lucchini R, et al (2016). Male breast cancer, clinical presentation, diagnosis and treatment: Twenty years of experience in our Breast Unit. Int J Surg Case Rep, 20S(Suppl):8-11.
19. Gao Y, Heller SL (2023). Breast cancer screening in men. J Breast Imaging, 5 (2):104-111.
20. Gaddam S, Heller SL, Babb JS, Gao Y (2021). Male breast cancer risk assessment and screening recommendations in high-risk men who undergo genetic counseling and multigene panel testing. Clin Breast Cancer, 21 (1):e74-e79.
21. Woods RW, Salkowski LR, Elezaby M, et al (2020). Image-based screening for men at high risk for breast cancer: Benefits and drawbacks. Clin Imaging, 60 (1):84-89.
22. Gao Y, Goldberg JE, Young TK, et al (2019). Breast cancer screening in high-risk men: a 12-year longitudinal observational study of male breast imaging utilization and outcomes. Radiology, 293 (2):282-291.
23. Hoda RS, Arpin III RN, Gottumukkala RV, et al (2019). Diagnostic value of fine-needle aspiration in male breast lesions. Acta Cytol, 63 (4):319-327.
24. Yang Y, Li S, Liu G, Shao Z (2019). Is core needle biopsy effective at diagnosing male breast lesions? Breast Cancer Res Treat, 177:507-511.
25. Forbes C, Fayter D, de Kock S, Quek RG (2019). A systematic review of international guidelines and recommendations for the genetic screening, diagnosis, genetic counseling, and treatment of BRCA-mutated breast cancer. Cancer Manag Res, 11:2321-2337.
26. Reichl F, Muhr D, Rebhan K, et al (2021). Cancer spectrum, family history of cancer and overall survival in men with germline BRCA1 or BRCA2 mutations. J Pers Med, 11 (9):917.
27. Fanale D, Incorvaia L, Filorizzo C, et al (2020). Detection of germline mutations in a cohort of 139 patients with bilateral breast cancer by multi-gene panel testing: impact of pathogenic variants in other genes beyond BRCA1/2. Cancers (Basel), 12 (9):2415.
28. Fentiman IS (2018). Surgical options for male breast cancer. Breast Cancer Res Treat, 172:539-544.
29. Madden NA, Macdonald OK, Call JA, et al (2016). Radiotherapy and male breast cancer. Am J Clin Oncol, 39 (5):458-462.
30. Forster T, Köhler C, El Shafie R,et al (2020). Adjuvant Radiation Therapy for Male Breast Cancer—A Rare Indication? Cancers (Basel), 12 (12):3645.
31. Separham A, Ghaffari S, Najafi H, et al (2016). The impact of allopurinol on patients with acute ST elevation myocardial infarction undergoing thrombolytic therapy. J Cardiovasc Pharmacol, 68 (4):265-268.
32. Gucalp A, Traina TA, Eisner JR, et al (2019). Male breast cancer: a disease distinct from female breast cancer. Breast Cancer Res Treat, 173:37-48.
33. Khan NAJ, Tirona M (2021). An updated review of epidemiology, risk factors, and management of male breast cancer. Med Oncol, 38:39.
34. Hassett MJ, Somerfield MR, Baker ER, et al (2020). Management of male breast cancer: ASCO guideline. J Clin Oncol, 38 (16):1849-1863.
35. A Baudino T (2015). Targeted cancer therapy: the next generation of cancer treatment. Curr Drug Discov Technol, 12 (1):3-20.
36. Bachelot T, Ciruelos E, Schneeweiss A, et al (2019). Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE). Ann Oncol, 30 (5):766-773.
37. Lima ZS, Ghadamzadeh M, Arashloo FT, et al (2019). Recent advances of therapeutic targets based on the molecular signature in breast cancer: genetic mutations and implications for current treatment paradigms. J Hematol Oncol, 12:38.
38. Liu N, Johnson KJ, Ma CX (2018). Male breast cancer: an updated surveillance, epidemiology, and end results data analysis. Clin Breast Cancer, 18 (5):e997-e1002.
39. Mutebi M, Anderson BO, Duggan C, et al (2020). Breast cancer treatment: A phased approach to implementation. Cancer, 126 Suppl 10:2365-2378.
40. O'Malley CD, Prehn AW, Shema SJ, Glaser SL (2002). Racial/ethnic differences in survival rates in a population‐based series of men with breast carcinoma. Cancer, 94 (11):2836-2843.
41. Zheng G, Leone JP (2022). Male breast cancer: An updated review of epidemiology, clinicopathology, and treatment. J Oncol, 2022: 1734049.
42. Shahjahani M, Abroun A, Saki N, et al (2020). STAT5: from pathogenesis mechanism to therapeutic approach in acute leukemia. Lab Med, 51 (4):345-351.
43. Jesser EA, Brady NJ, Huggins DN, et al (2021). STAT5 is activated in macrophages by breast cancer cell-derived factors and regulates macrophage function in the tumor microenvironment. Breast Cancer Res, 23:104.
44. Masci G, Caruso M, Caruso F, et al (2015). Clinicopathological and immunohistochemical characteristics in male breast cancer: a retrospective case series. Oncologist, 20 (6):586-592.
45. Coates AS, Winer EP, Goldhirsch A, et al (2015). Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer Ann Oncol, 26 (8):1533-1546.
46. Wood ME, McKinnon W, Garber J (2020). Risk for breast cancer and management of unaffected individuals with non‐BRCA hereditary breast cancer. Breast J, 26 (8):1528-1534.
| Files | ||
| Issue | Vol 53 No 12 (2024) | |
| Section | Review Article(s) | |
| Keywords | ||
| Gynecomastia Breast neoplasm Male breast Risk of malignancy Treatment | ||
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How to Cite
1.
Akbari M, Nasiri H, Ziaee M. Male Breast Cancer Biology, Screening, Treatment, and Follow-Up: A Narrative Review. Iran J Public Health. 2024;53(12):2694-2704.
