Male Breast Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI]

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General Information About Male Breast Cancer

Incidence and Mortality

Estimated new cases and deaths from breast cancer (men only) in the United States in 2017:[1]

  • New cases: 2,470.
  • Deaths: 460.

Male breast cancer is rare.[2] Less than 1% of all breast carcinomas occur in men.[3,4] The mean age at diagnosis is between 60 and 70 years, though men of all ages can be affected with the disease.

Risk Factors

Predisposing risk factors [5] appear to include radiation exposure, estrogen administration, and diseases associated with hyperestrogenism, such as cirrhosis or Klinefelter syndrome.[6] Definite familial tendencies are evident with an increased incidence seen in men who have a number of female relatives with breast cancer. An increased risk of male breast cancer has been reported in families with BRCA mutations, although the risks appear to be higher with inherited BRCA2 than with BRCA1 mutations.[7,8] Genes other than BRCA may also be involved in predisposition to male breast cancer, including mutations in the PTEN tumor suppressor gene, TP53 (Li-Fraumeni syndrome), PALB2 mutations, and mismatch repair mutations associated with hereditary nonpolyposis colorectal cancer (Lynch syndrome).[9,10,11]

Histopathology

The pathology is similar to that of female breast cancer, and infiltrating ductal cancer is the most common tumor type.[12] Intraductal cancer has been described as well. Inflammatory carcinoma and Paget disease of the nipple have also been seen in men, but lobular carcinoma in situ has not.[12] Lymph node involvement and the hematogenous pattern of spread are similar to those found in female breast cancer. The TNM staging system for male breast cancer is identical to the staging system for female breast cancer. (Refer to Histopathologic Classification of Breast Cancer in the General Information About Breast Cancer section and Definitions of TNM and AJCC Stage Groupings in the Stage Information for Breast Cancer section in the PDQ summary on Breast Cancer Treatment for more information.)

Prognostic Factors

Prognostic factors that have been evaluated include the size of the lesion and the presence or absence of lymph node involvement, both of which correlate well with prognosis.[5,13] Estrogen-receptor and progesterone-receptor status and HER2/neu gene amplification should be reported.[14]

Survival

Overall survival is similar to that of women with breast cancer. The impression that male breast cancer has a worse prognosis may stem from the tendency toward diagnosis at a later stage.[2,5,15]

References:

  1. American Cancer Society: Cancer Facts and Figures 2017. Atlanta, Ga: American Cancer Society, 2017. Available online. Last accessed May 25, 2017.
  2. Giordano SH, Cohen DS, Buzdar AU, et al.: Breast carcinoma in men: a population-based study. Cancer 101 (1): 51-7, 2004.
  3. Borgen PI, Wong GY, Vlamis V, et al.: Current management of male breast cancer. A review of 104 cases. Ann Surg 215 (5): 451-7; discussion 457-9, 1992.
  4. Fentiman IS, Fourquet A, Hortobagyi GN: Male breast cancer. Lancet 367 (9510): 595-604, 2006.
  5. Giordano SH, Buzdar AU, Hortobagyi GN: Breast cancer in men. Ann Intern Med 137 (8): 678-87, 2002.
  6. Hultborn R, Hanson C, Köpf I, et al.: Prevalence of Klinefelter's syndrome in male breast cancer patients. Anticancer Res 17 (6D): 4293-7, 1997 Nov-Dec.
  7. Wooster R, Bignell G, Lancaster J, et al.: Identification of the breast cancer susceptibility gene BRCA2. Nature 378 (6559): 789-92, 1995 Dec 21-28.
  8. Thorlacius S, Tryggvadottir L, Olafsdottir GH, et al.: Linkage to BRCA2 region in hereditary male breast cancer. Lancet 346 (8974): 544-5, 1995.
  9. Ding YC, Steele L, Kuan CJ, et al.: Mutations in BRCA2 and PALB2 in male breast cancer cases from the United States. Breast Cancer Res Treat 126 (3): 771-8, 2011.
  10. Silvestri V, Rizzolo P, Zanna I, et al.: PALB2 mutations in male breast cancer: a population-based study in Central Italy. Breast Cancer Res Treat 122 (1): 299-301, 2010.
  11. Boyd J, Rhei E, Federici MG, et al.: Male breast cancer in the hereditary nonpolyposis colorectal cancer syndrome. Breast Cancer Res Treat 53 (1): 87-91, 1999.
  12. Burstein HJ, Harris JR, Morrow M: Malignant tumors of the breast. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1401-46.
  13. Cutuli B, Lacroze M, Dilhuydy JM, et al.: Male breast cancer: results of the treatments and prognostic factors in 397 cases. Eur J Cancer 31A (12): 1960-4, 1995.
  14. Giordano SH: A review of the diagnosis and management of male breast cancer. Oncologist 10 (7): 471-9, 2005.
  15. Ravandi-Kashani F, Hayes TG: Male breast cancer: a review of the literature. Eur J Cancer 34 (9): 1341-7, 1998.

Treatment Options for Male Breast Cancer

The approach to the treatment of breast cancer in men is similar to that in women. Because male breast cancer is rare, there is a lack of randomized data to support specific treatment modalities. As in women, men with early-stage breast cancer are treated with locoregional therapy with surgery plus or minus radiation and systemic therapy with endocrine therapy, chemotherapy, and HER2-directed therapies.

Initial Surgical Management

Primary standard treatment is a modified radical mastectomy with axillary dissection.[1,2,3] Responses are generally similar to those seen in women with breast cancer.[2] Breast conservation surgery with lumpectomy and radiation therapy has also been used and results have been similar to those seen in women with breast cancer.[4] (Refer to Surgery in the Early/Localized/Operable Breast Cancer section in the PDQ summary on Breast Cancer Treatment for more information.)

Adjuvant Therapy

In men with node-negative tumors, adjuvant therapy should be considered on the same basis as for a woman with breast cancer since there is no evidence that response to therapy is different for men or women.[5]

In men with node-positive tumors, both chemotherapy plus tamoxifen and other hormonal therapy have been used and can increase survival to the same extent as in women with breast cancer. Currently, no controlled studies have compared adjuvant treatment options. Approximately 85% of all male breast cancers are estrogen receptor-positive, and 70% of them are progesterone receptor-positive.[2,6] Response to hormone therapy correlates with presence of receptors. Hormonal therapy has been recommended in all receptor-positive patients.[1,2] Tamoxifen use, however, is associated with a high rate of treatment-limiting symptoms, such as hot flashes and impotence in male breast cancer patients.[7] (Refer to the PDQ summary on Hot Flashes and Night Sweats for more information on these symptoms.) Responses are generally similar to those seen in women with breast cancer.[2] (Refer to Postoperative Systemic Therapy and Preoperative Systemic Therapy in the Early/Localized/Operable Breast Cancer section in the PDQ summary on Breast Cancer Treatment for more information.)

Adjuvant chemotherapy regimens include:

  • CMF: cyclophosphamide plus methotrexate plus fluorouracil.[8]
  • CAF: cyclophosphamide plus doxorubicin plus fluorouracil.
  • Trastuzumab.[9]
  • Tamoxifen.[9]

In regard to endocrine therapy, tamoxifen is generally used instead of an aromatase inhibitor (AI) as the data supporting the use of an AI in men with breast cancer are limited. A retrospective analysis of 257 men with stage I to III breast cancer included 50 men treated with an AI and 207 men treated with tamoxifen. With a median follow-up of 42 months, treatment with an AI was associated with a higher risk of death compared with tamoxifen (32% with AI vs. 18% with tamoxifen; hazard ratio,1.55; 95% confidence interval, 1.13-2.13).[10] These findings suggest that tamoxifen should be used rather than an AI as adjuvant endocrine therapy for men with breast cancer.

The use of AI therapy with a luteinizing hormone-releasing hormone (LH-RH) agonist has been reported in several cases in the literature.[11] The German Breast Group is conducting a randomized phase II clinical trial (NCT01638247) of tamoxifen with or without gonadotropin-releasing hormone (GnRH) analogue versus AI plus GnRH analogue in men with early-stage hormone receptor-positive breast cancer, and results are pending.

Hormonal modalities include:

  • Tamoxifen.[1]
  • Aromatase inhibitors with LH-RH agonist.[9,11,12,13,14]

Locally Recurrent Disease

Surgical excision or radiation therapy combined with chemotherapy is recommended.[2] Responses are generally similar to those seen in women with breast cancer.[2,5] (Refer to the Metastatic Breast Cancer section in the PDQ summary on Breast Cancer Treatment for more information.)

Distant Metastases

Hormonal therapy, chemotherapy, or a combination of both have been used with some success. Initially, hormonal therapy is recommended.[2,5] (Refer to the Metastatic Breast Cancer section of the Breast Cancer Treatment summary for more information.)

Responses are generally similar to those seen in women with breast cancer.[2] (Refer to Initial hormone therapy in the Metastatic Breast Cancer section in the PDQ summary on Breast Cancer Treatment for more information.)

References:

  1. Borgen PI, Wong GY, Vlamis V, et al.: Current management of male breast cancer. A review of 104 cases. Ann Surg 215 (5): 451-7; discussion 457-9, 1992.
  2. Giordano SH, Buzdar AU, Hortobagyi GN: Breast cancer in men. Ann Intern Med 137 (8): 678-87, 2002.
  3. Kinne DW: Management of male breast cancer. Oncology (Huntingt) 5 (3): 45-7; discussion 47-8, 1991.
  4. Golshan M, Rusby J, Dominguez F, et al.: Breast conservation for male breast carcinoma. Breast 16 (6): 653-6, 2007.
  5. Kamila C, Jenny B, Per H, et al.: How to treat male breast cancer. Breast 16 (Suppl 2): S147-54, 2007.
  6. Joshi MG, Lee AK, Loda M, et al.: Male breast carcinoma: an evaluation of prognostic factors contributing to a poorer outcome. Cancer 77 (3): 490-8, 1996.
  7. Anelli TF, Anelli A, Tran KN, et al.: Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients. Cancer 74 (1): 74-7, 1994.
  8. Walshe JM, Berman AW, Vatas U, et al.: A prospective study of adjuvant CMF in males with node positive breast cancer: 20-year follow-up. Breast Cancer Res Treat 103 (2): 177-83, 2007.
  9. Giordano SH: A review of the diagnosis and management of male breast cancer. Oncologist 10 (7): 471-9, 2005.
  10. Eggemann H, Ignatov A, Smith BJ, et al.: Adjuvant therapy with tamoxifen compared to aromatase inhibitors for 257 male breast cancer patients. Breast Cancer Res Treat 137 (2): 465-70, 2013.
  11. Giordano SH, Hortobagyi GN: Leuprolide acetate plus aromatase inhibition for male breast cancer. J Clin Oncol 24 (21): e42-3, 2006.
  12. Cocconi G, Bisagni G, Ceci G, et al.: Low-dose aminoglutethimide with and without hydrocortisone replacement as a first-line endocrine treatment in advanced breast cancer: a prospective randomized trial of the Italian Oncology Group for Clinical Research. J Clin Oncol 10 (6): 984-9, 1992.
  13. Gale KE, Andersen JW, Tormey DC, et al.: Hormonal treatment for metastatic breast cancer. An Eastern Cooperative Oncology Group Phase III trial comparing aminoglutethimide to tamoxifen. Cancer 73 (2): 354-61, 1994.
  14. Zagouri F, Sergentanis TN, Koutoulidis V, et al.: Aromatase inhibitors with or without gonadotropin-releasing hormone analogue in metastatic male breast cancer: a case series. Br J Cancer 108 (11): 2259-63, 2013.

Changes to This Summary (05 / 25 / 2017)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information About Male Breast Cancer

Revised text to state that an increased risk of male breast cancer has been reported in families with BRCA mutations, although the risks appear to be higher with inherited BRCA2 than with BRCA1 mutations. Added text to state that genes other than BRCA may also be involved in predisposition to male breast cancer, including mutations in the PTEN tumor suppressor gene, TP53, PALB2 mutations, and mismatch repair mutations associated with hereditary nonpolyposis colorectal cancer (Lynch syndrome) (cited Ding et al. as reference 9, Silvestri et al. as reference 10, and Boyd et al. as reference 11).

Treatment Options for Male Breast Cancer

Added text to state that the approach to treatment of breast cancer in men is similar to that in women, but because male breast cancer is rare, there is a lack of randomized data to support specific treatment modalities. Also added that as in women, men with early stage breast cancer are treated with locoregional therapy with surgery plus or minus radiation and systemic therapy with endocrine therapy, chemotherapy, and HER2-directed therapies.

Added text to state that in regard to endocrine therapy, tamoxifen is generally used instead of an aromatase inhibitor (AI) as the data supporting the use of an AI in men with breast cancer are limited. Also added a retrospective analysis of 257 men with stage I to III breast cancer, which included 50 men treated with an AI and 207 men treated with tamoxifen. At a median follow-up of 42 months, treatment with an AI was associated with a higher risk of death compared with tamoxifen (cited Eggemann et al. as reference 10). These findings suggest that tamoxifen should be used rather than an AI as adjuvant endocrine therapy for men with breast cancer.

Added text to state that the use of AI therapy with a luteinizing hormone-releasing hormone (LH-RH) agonist has been reported in several cases in the literature (cited Giordano et al. as reference 11). Also added that the German Breast Group is conducting a randomized phase II clinical trial of tamoxifen with or without gonadotropin-releasing hormone (GnRH) analogue versus AI plus GnRH analogue in men with early-stage hormone receptor-positive breast cancer, and results are pending.

Revised list of hormonal modalities to include tamoxifen and AI with LH-RH agonist (cited Zagouri et al. as reference 14).

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of male breast cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Male Breast Cancer Treatment are:

  • Roisin Connolly, MB, BCh (Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins)
  • Beverly Moy, MD, MPH (Massachusetts General Hospital)
  • Joseph L. Pater, MD (NCIC-Clinical Trials Group)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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The preferred citation for this PDQ summary is:

PDQ® Adult Treatment Editorial Board. PDQ Male Breast Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/breast/hp/male-breast-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389234]

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Last Revised: 2017-05-25