Incidence and Mortality

Estimated new cases and deaths from breast cancer (men only) in the United States in 2024:

• New cases: 2,790.
• Deaths: 530.

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

Anatomy

Risk Factors

Predisposing risk factors for male breast cancer appear to include the following:

• 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 mutations than with BRCA1 mutations. At age 70 years, men have an estimated cumulative risk of breast cancer of 1.2% if they are BRCA1 mutation carriers and 6.8% if they are BRCA2 mutation carriers. Genes other than BRCA may also be involved in predisposition to male breast cancer, including mutations in the PTEN tumor suppressor gene, TP53 mutations (Li-Fraumeni syndrome), PALB2 mutations, and mismatch repair mutations associated with hereditary nonpolyposis colorectal cancer (Lynch syndrome). For more information, see the sections on High-Penetrance Breast and/or Gynecologic Cancer Susceptibility Genes in Genetics of Breast and Gynecologic Cancers, and Male Breast Cancer Screening and Surveillance for BRCA1/2 Carriers in BRCA1 and BRCA2: Cancer Risks and Management.

Clinical Features

Most breast cancers in men present with a retroareolar mass. Other signs include the following:

• Nipple retraction.
• Bleeding from the nipple.
• Skin ulceration.
• Peau d’orange.
• Palpable axillary adenopathy.

Because of delays in diagnosis, breast cancer in men is more likely to present at an advanced stage.

Diagnostic Evaluation

Breast imaging should be performed when breast cancer is suspected. The American College of Radiology recommends ultrasonography as the first imaging modality in men younger than 25 years because breast cancer is highly unlikely. Mammography is performed if ultrasonography findings are suspicious.

For men aged 25 years or older, or those who have a highly concerning physical examination, mammography is recommended as the initial test and ultrasonography is useful if mammography is inconclusive or suspicious. Suspicious findings should be confirmed with a core biopsy. If the presence of tumor is confirmed, estrogen receptor, progesterone receptor, and human epidermal growth factor type 2 (HER2) expression/amplification should be evaluated.

Histopathologic Classification

Infiltrating ductal cancer is the most common tumor type of breast cancer in men, while invasive lobular carcinoma is very rare. Breast cancer in men is almost always hormone receptor positive. In a male breast cancer series, 99% of the tumors were estrogen receptor positive, 82% were progesterone receptor positive, 9% were HER2 positive, and 0.3% were triple negative.

Prognosis and Predictive Factors

Tumor size, lymph node involvement, and grade are anatomical prognostic factors, while estrogen receptor, progesterone receptor, and HER2 status are predictive of response to therapy.

A more advanced stage at diagnosis confers a worse prognosis for men with breast cancer. A study found that mortality after breast cancer diagnosis was higher in male patients than in female patients. This disparity appeared to persist after accounting for clinical characteristics, treatment factors, and access to care, suggesting that biological factors and treatment efficacy may play a role.

Staging for male breast cancer is identical to staging for female breast cancer.

The American Joint Committee on Cancer (AJCC) staging system provides a strategy for grouping patients with respect to prognosis. Therapeutic decisions are formulated in part according to staging categories but also other clinical factors such as the following, some of which are included in the determination of stage:

• 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.
• Menopausal status.
• General health of the patient.

The standards used to define biomarker status are described as follows:

• Estrogen receptor (ER) expression: ER expression is measured primarily by immunohistochemistry (IHC). Any staining of 1% of cells or more is considered positive for ER.
• Progesterone receptor (PR) expression: PR expression is measured primarily by IHC. Any staining of 1% of cells or more is considered positive for PR.
• HER2 expression: HER2 is measured primarily by either IHC to assess expression of the HER2 protein or by in situ hybridization (ISH) to assess gene copy number. The American Society of Clinical Oncology/College of American Pathologists consensus panel has published guidelines for cases when either IHC or ISH testing is equivocal.

  IHC:

  • Negative: 0 or 1+ staining
  • Equivocal: 2+ staining
  • Positive: 3+ staining

  ISH (dual probe):

  • Possible negative results:
    • HER2/chromosome enumeration probe (CEP17) ratio 2.0 ANDHER2 copy number 4
  • Possible equivocal results: (requires performing alternative ISH test to confirm equivocal or IHC if not previously performed)
    • HER2/CEP17 ratio 2.0 ANDHER2 copy number ≥4 but 6
  • Possible positive results:
    • HER2/CEP17 ratio ≥2.0 by ISH
    • HER2 copy number ≥6 regardless of ratio by ISH

  ISH (single probe):

  • Negative: 4 HER2 copies
  • Equivocal: ≥4 HER2 copies but 6 HER2 copies
  • Positive: ≥6 HER2 copies

The approach to the treatment of men with breast cancer is similar to that for women. Because male breast cancer is rare, there is a lack of randomized data to support specific treatment modalities. Treatment options for men with breast cancer are described in Table 1.

As in women, 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 treatment is a mastectomy with axillary lymph node dissection. Responses in men are generally similar to those seen in women with breast cancer. Breast conservation surgery with lumpectomy and radiation therapy has also been used and can be offered if standard criteria for breast conservation therapy are met. Results in men have been similar to those seen in women with breast cancer.

Adjuvant Therapy

The optimal systemic treatment in men with breast cancer has not been studied in randomized clinical trials. Adjuvant therapy should be administered according to the same criteria used for women. Adjuvant therapies used to treat early/localized/operable male breast cancer are outlined in Table 2.

Table 2. Adjuvant Therapy Used to Treat Early/Localized/Operable Male Breast Cancer

Tamoxifen

Evidence (tamoxifen):

In men with contraindications for tamoxifen, single-agent AI therapy is not recommended. AIs should be combined with gonadotropin-releasing hormone (GnRH) analogues.

In male breast cancer patients, tamoxifen use is associated with a high rate of treatment-limiting symptoms such as hot flashes and impotence.

The German Breast Group conducted a randomized phase II clinical trial (NCT01638247) of tamoxifen with or without a GnRH analogue versus AI plus a GnRH analogue in men with early-stage, hormone receptor–positive breast cancer. Results of this trial are pending.

Treatment options for men with locally advanced breast cancer include the following:

• Neoadjuvant chemotherapy.
• Surgical excision.
• Radiation therapy and endocrine therapy.

The decisions regarding the order and choice of treatments in men are guided by the same principles used for the treatment of breast cancer in women (in particular, evaluation of pathological response).

Treatment options for men with metastatic breast cancer include the following:

• Aromatase inhibitor (AI) therapy in conjunction with a gonadotropin-releasing hormone (GnRH) agonist.

The management of metastatic hormone receptor–positive male breast cancer relies on the same treatment options used in women. However, data regarding the activity of AIs with GnRH agonists and fulvestrant in men are limited to case series. The administration of an AI in conjunction with a GnRH agonist is recommended on the basis of the adjuvant data. There are no data comparing the activity of fulvestrant alone with fulvestrant in combination with a GnRH agonist.

Based on real world data and limited studies, it is reasonable to extrapolate the use of additional treatment options for men. These treatment options include cyclin-dependent kinase (CDK) 4/6 inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and phosphatidylinositol-3 kinase (PI3K) inhibitors, used in combination with endocrine therapy.

The use of chemotherapy, human epidermal growth factor receptor 2 (HER2)-targeted therapy, immunotherapy, and poly (ADP-ribose) polymerase (PARP) inhibitors in men with metastatic breast cancer is guided by similar treatment principles as in women.