Male Breast Cancer Treatment (PDQ®)—Health Professional Version - National Cancer Institute

Male Breast Cancer Treatment (PDQ®)–Health Professional Version

General Information About Male Breast Cancer

Incidence and Mortality

Estimated new cases and deaths from breast cancer (men only) in the United States in 2019:[1]

New cases: 2,670.
Deaths: 500.

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

Anatomy

Risk Factors

Predisposing risk factors for male breast cancer appear to include the following:[5,6]

Radiation exposure to breast/chest.
Estrogen use.
Diseases associated with hyperestrogenism, such as cirrhosis or Klinefelter syndrome.
Family health history: Definite familial tendencies are evident, with an increased incidence seen in men who have a number of female relatives with breast cancer.
Major inheritance susceptibility: 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 PTENtumor suppressor gene, TP53 mutations (Li-Fraumeni syndrome), PALB2 mutations, and mismatch repair mutations associated with hereditary nonpolyposis colorectal cancer (Lynch syndrome).[9-11] (Refer to the High-Penetrance Breast and/or Gynecologic Cancer Susceptibility Genes and Management of Male Carriers of BRCA Pathogenic Variants sections in the PDQ summary on Genetics of Breast and Gynecologic Cancersfor more information.)

Clinical Features

Signs of breast cancer in men may include the following:

A lump or thickening in or near the breast or in the underarm area.
A change in the size or shape of the breast.
A dimple or puckering in the skin of the breast.
An inverted nipple.
Fluid from the nipple, especially if it is bloody.
Scaly, red, or swollen skin on the breast, nipple, or areola.
Peau d’orange.

Diagnostic Evaluation

When breast cancer is suspected, patient management generally includes the following:

Confirmation of the diagnosis.
Evaluation of the stage of disease.
Selection of therapy.

The following tests and procedures are used to diagnose breast cancer:

Clinical breast examination.
Mammography.
Ultrasonography.
Breast magnetic resonance imaging, if clinically indicated.
Biopsy, including estrogen-receptor and progesterone-receptor status and HER2/neugene amplification of the biopsy sample.[12]

(Refer to the Diagnosis section in the PDQ summary on Breast Cancer Treatment for information about evaluating the contralateral breast and molecular profiling [estrogen-receptor and progesterone-receptor status and human epidermal growth factor receptor 2 (HER2/neu) expression status of the tumor].)

Histopathologic Classification

The pathology of male breast cancer is similar to that of female breast cancer, and infiltrating ductal cancer is the most common tumor type (refer to Table 1).[13] Intraductal cancer, inflammatory carcinoma, and Paget disease of the nipple have also been seen in men, but lobular carcinoma in situ has not.[13]

Lymph node involvement and the hematogenous pattern of spread are similar to what is observed in female breast cancer.

Table 1. Tumor Location and Related Histologic Subtypes for Male Breast Cancer

Tumor Location	Histologic Subtype
NOS = not otherwise specified.
Carcinoma, NOS
Ductal	Intraductal (in situ)
	Invasive with predominant component
	Invasive, NOS
	Comedo
	Inflammatory
	Medullary with lymphocytic infiltrate
	Mucinous (colloid)
	Papillary
	Scirrhous
	Tubular
	Other
Lobular	Invasive [14]
Nipple	Paget disease, NOS
	Paget disease with intraductal carcinoma
	Paget disease with invasive ductal carcinoma
Other	Undifferentiated carcinoma
Other	Metaplastic

Prognosis and Predictive Factors

Factors that correlate well with prognosis include the following:[5,15]

Size of the lesion.
Presence or absence of lymph node involvement.

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.[2,5,16]

References

American Cancer Society: Cancer Facts and Figures 2019. Atlanta, Ga: American Cancer Society, 2019. Available online Exit Disclaimer. Last accessed January 23, 2019.
Giordano SH, Cohen DS, Buzdar AU, et al.: Breast carcinoma in men: a population-based study. Cancer 101 (1): 51-7, 2004. [PUBMED Abstract]
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. [PUBMED Abstract]
Fentiman IS, Fourquet A, Hortobagyi GN: Male breast cancer. Lancet 367 (9510): 595-604, 2006. [PUBMED Abstract]
Giordano SH, Buzdar AU, Hortobagyi GN: Breast cancer in men. Ann Intern Med 137 (8): 678-87, 2002. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
Thorlacius S, Tryggvadottir L, Olafsdottir GH, et al.: Linkage to BRCA2 region in hereditary male breast cancer. Lancet 346 (8974): 544-5, 1995. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
Giordano SH: A review of the diagnosis and management of male breast cancer. Oncologist 10 (7): 471-9, 2005. [PUBMED Abstract]
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.
Yeatman TJ, Cantor AB, Smith TJ, et al.: Tumor biology of infiltrating lobular carcinoma. Implications for management. Ann Surg 222 (4): 549-59; discussion 559-61, 1995. [PUBMED Abstract]
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. [PUBMED Abstract]
Ravandi-Kashani F, Hayes TG: Male breast cancer: a review of the literature. Eur J Cancer 34 (9): 1341-7, 1998. [PUBMED Abstract]

Stage Information for Male Breast Cancer

The AJCC staging system provides a strategy for grouping patients with a similar prognosis. The stage of the disease is determined by the following:

Tumor size.
Lymph node status.
Estrogen-receptor and progesterone-receptor levels in the tumor tissue.
Human epidermal growth factor receptor 2 (HER2/neu) status in the tumor.
Tumor grade.

Treatment decisions are based on the stage of disease and the general health of the patient.

The TNM (tumor, node, metastasis) staging system for male breast cancer is identical to the staging system for female breast cancer. (Refer to TNM Definitions in the Stage Information for Breast Cancer section in the PDQ summary on Breast Cancer Treatment for more information.)

Treatment Option Overview for Male Breast Cancer

Standard treatment options for men with breast cancer are described in Table 2.

Table 2. Standard Treatment Options for Male Breast Cancer

Stage (TNM Staging Criteria)	Standard Treatment Options
T = primary tumor; N = regional lymph node; M = distant metastasis; HER2 = human epidermal growth factor receptor 2.
Early/localized/operable breast cancer	Surgery with or without radiation therapy
Early/localized/operable breast cancer	Adjuvant therapy—chemotherapy, endocrine therapy, HER2-directed therapy
Locoregional recurrent breast cancer	Surgery
Locoregional recurrent breast cancer	Radiation therapy and chemotherapy
Metastatic breast cancer	Hormone therapy and/or chemotherapy

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.

Treatment of Early/Localized/Operable Male Breast Cancer

As in women, standard treatment options for men with early-stage breast cancer include the following:

Surgery with or without radiation therapy (locoregional therapy).
Adjuvant therapy (systemic therapy).
- Chemotherapy.
- Endocrine therapy.
- Human epidermal growth factor receptor 2 (HER2)–directed therapy.

Surgery with or without radiation therapy

Primary standard treatment is a modified radical mastectomy with axillary dissection.[1-3] 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, no controlled studies have compared adjuvant treatment options. Adjuvant therapies used to treat early/localized/operable male breast cancer are outlined in Table 3.

Table 3. Adjuvant Therapy Used to Treat Early/Localized/Operable Male Breast Cancer

Type of Adjuvant Therapy	Agents Used
HER2 = human epidermal growth factor receptor 2; LHRH = luteinizing hormone-releasing hormone.
Chemotherapy	Cyclophosphamide plus methotrexate and 5-fluorouracil (CMF) [5]
	Cyclophosphamide plus doxorubicin and fluorouracil (CAF)
	Doxorubicin plus cyclophosphamide with or without paclitaxel (AC, AC-T)
Endocrine therapy	Tamoxifen [6]
Endocrine therapy	Aromatase inhibitors with LHRH agonist [6-10]
HER2-directed therapy	Trastuzumab [1,6]
HER2-directed therapy	Pertuzumab

In men with node-negative tumors, adjuvant therapy should be considered on the same basis as for women with breast cancer because there is no evidence that response to therapy is different between men and women.[11]

In men with node-positive tumors, both chemotherapy plus tamoxifen and other hormonal therapy have been used and are believed to increase survival to the same extent as in women with breast cancer.

Approximately 85% of all male breast cancers are estrogen receptor–positive, and 70% of them are progesterone receptor–positive.[2,12] Response to hormone therapy correlates with the presence of these receptors. Hormonal therapy has been recommended in all patients with receptor-positive cancers.[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.[13] 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.)

Regarding endocrine therapy, tamoxifen is generally used instead of an aromatase inhibitor (AI) because 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 stage III breast cancer included 50 men treated with an AI and 207 men treated with tamoxifen. The following results were observed:

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).[14]
These findings suggest that instead of an AI, tamoxifen should be used as adjuvant endocrine therapy for men with breast cancer.

The use of AI therapy with a luteinizing hormone-releasing hormone agonist has been reported in several cases in the literature.[7] 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; results are pending.

Treatment of Locoregional Recurrent Male Breast Cancer

Standard treatment options for men with locoregional recurrent breast cancer include the following:[2]

Surgical excision.
Radiation therapy combined with chemotherapy.

Responses are generally similar to those seen in women with breast cancer.[2,11]

(Refer to the Locoregional Recurrent Breast Cancer section in the PDQ summary on Breast Cancer Treatment for more information.)

Treatment of Metastatic Male Breast Cancer

Standard treatment options for men with metastatic breast cancer include the following:

Hormone therapy and/or chemotherapy.

Hormonal therapy is used as the initial treatment. Responses are generally similar to those seen in women with breast cancer.[2,11]

(Refer to the Metastatic Breast Cancer section in the PDQ summary on Breast Cancer Treatment for more information.)

References

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. [PUBMED Abstract]
Giordano SH, Buzdar AU, Hortobagyi GN: Breast cancer in men. Ann Intern Med 137 (8): 678-87, 2002. [PUBMED Abstract]
Kinne DW: Management of male breast cancer. Oncology (Huntingt) 5 (3): 45-7; discussion 47-8, 1991. [PUBMED Abstract]
Golshan M, Rusby J, Dominguez F, et al.: Breast conservation for male breast carcinoma. Breast 16 (6): 653-6, 2007. [PUBMED Abstract]
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. [PUBMED Abstract]
Giordano SH: A review of the diagnosis and management of male breast cancer. Oncologist 10 (7): 471-9, 2005. [PUBMED Abstract]
Giordano SH, Hortobagyi GN: Leuprolide acetate plus aromatase inhibition for male breast cancer. J Clin Oncol 24 (21): e42-3, 2006. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
Kamila C, Jenny B, Per H, et al.: How to treat male breast cancer. Breast 16 (Suppl 2): S147-54, 2007. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]

Changes to This Summary (03/28/2019)

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

Updated statistics with estimated new cases and deaths for 2019 (cited American Cancer Society as reference 1).

Stage Information for Male Breast Cancer

Revised text about determining factors for the disease stage to include human epidermal growth factor receptor 2 status in the tumor and grade.

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:

Joseph L. Pater, MD (NCIC-Clinical Trials Group)
Karen L. Smith, MD, MPH (Johns Hopkins University at Sibley Memorial Hospital)

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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