Male breast cancer

What is male breast cancer?

Male breast cancer remains underdiagnosed and, due to delays in diagnosis, is often also undertreated. The investigation and management of male breast cancer are based on studies on female patients. At present there is a need for further research into male breast cancer. The symptoms, diagnosis and treatment for male breast cancer are all similar to female breast cancer.

It is estimated that more than 90% of male breast cancers are oestrogen receptor-positive (ER+) and an even greater percentage are progesterone receptor-positive.¹ Male breast cancer tissue may also be positive for androgen receptors.

How common is male breast cancer? (Epidemiology)²

• There are about 370 men diagnosed each year in the UK, compared with around 55,000 cases of breast cancer in women.

• Less than 1% of breast cancer cases in the UK are in males. 1 in 8 women and 1 in 870 men will be diagnosed with breast cancer during their lifetime.

• Male breast cancer is diagnosed in 1% of cases of male breast enlargement. The incidence of male breast cancer has increased over a period of 25 years.

• The peak age for presentation of male breast cancer is over 60 years.

Risk factors²

• Increasing age.

• Genetics.
  

  • Up to one fifth of men with breast cancer have a first-degree relative similarly affected.

  • Significantly more male breast cancers than female breast cancers arise with an underlying germline cancer predisposition and they display a vastly different penetrance compared with females.³

  • The genophenotypical association with BRCA1 present in female breast cancer is not observed in male breast cancer.

  • Male breast cancer is more commonly associated with BRCA2 mutations.⁴ Most population-based studies show that 10-15% of men with breast cancer carry a mutation in BRCA2.⁵

• Lifestyle.
  

  • Certain environments - eg, furnace work, exposure to radiation and electromagnetic fields.⁶

  • Polycyclic aromatic hydrocarbons (as in petrol and exhaust fumes).

• Hyperoestrogenism:
  

  • Exogenous oestrogen.

  • Klinefelter's syndrome (47XXY) - low testosterone and increased gonadotrophins. Breast cancer is up to 50 times more frequent in this group.⁷

  • Obesity.⁸

  • Chronic liver conditions.

  • Pituitary adenomas leading to hyperprolactinaemia (associated with bilateral breast cancer).

  • Gynaecomastia does not lead to an increased risk.

• Alcohol consumption.

• Chest irradiation.

Male breast cancer symptoms (presentation)⁹

Male breast cancer tends to present at a later stage and at a higher stage; it is more often ER+ and progesterone receptor-positive and it is less often HER2 receptor-positive.

Symptoms

• Painless lump.

• Pain (rarely).

• Nipple inversion or discharge,

• Skin changes - eg, ulceration.

• Gynaecomastia - very rarely (see box, below).

Signs

• Skin change.

• Palpable mass.

• Palpable lymph nodes.

Referral¹⁰

Refer people using a suspected cancer pathway referral (for an appointment within 2 weeks) for breast cancer if they are:

• Aged 30 and over and have an unexplained breast lump with or without pain.

• Aged 50 and over with any of the following symptoms in one nipple only: discharge, retraction.

• Other changes of concern.

Consider a suspected cancer pathway referral (for an appointment within 2 weeks) for breast cancer in people:

• With skin changes that suggest breast cancer.

• Aged 30 and over with an unexplained lump in the axilla.

Consider non-urgent referral in people aged under 30 with an unexplained breast lump with or without pain.

Investigations

• Imaging: mammography or ultrasonography.

• Tissue: fine-needle aspiration cytology (FNAC) or either core or open biopsy. Biopsy is preferred, as malignant cells on FNAC may be a ductal carcinoma in situ rather than more invasive disease.

Staging

Infiltrating ductal cancer is the most common tumour type. Inflammatory carcinoma and Paget's disease of the breast have also been seen in men. Lymph node involvement and the pattern of metastatic spread are similar to those found in female breast cancer.

The tumour, nodes, metastases (TNM) staging system for male breast cancer is identical to the staging system for female breast cancer:

• Stage 0: around 10% of male breast cancer is ductal carcinoma in situ.

• Stage I: tumour up to 2 cms in diameter and no lymph node involvement or metastasis.

• Stage II: tumour between 2 and 5 cms in diameter or there is spread to the axillary lymph nodes on the same side and the nodes are not adherent.

• Stage IIIA: tumour is over 5 cms in diameter or the nodes are adherent.

• Stage IIIB: invasive breast cancer in which a tumour of any size has spread to the breast skin, chest wall or internal mammary lymph nodes and includes inflammatory breast cancer with peau d'orange.

• Stage IV: spread beyond the breast, axilla and internal mammary nodes. It may have spread to supraclavicular nodes, bone, liver, lung or brain.

Male breast cancer treatment and management¹¹

NB: there are limited data regarding optimal treatment and follow-up strategies for those men with breast cancer.⁵

Early-stage male breast cancer

Treatment for early-stage male breast cancer includes: surgery, radiation therapy, chemotherapy, and endocrine therapy.

• Typically, men with breast cancer are treated with modified radical mastectomy, with axillary lymph node dissection or sentinel node biopsy. Breast conservation or nipple-sparing or skin-sparing mastectomies may also be performed in selected cases.

• Oncoplastic techniques should be used in view of the significant psychological and emotional impact of the physical consequences of locoregional therapies in male patients.

• Men are more likely than women to undergo mastectomy and to receive adjuvant radiotherapy as they are often diagnosed at a later stage and have nipple or skin involvement at diagnosis.

• While there are limited data on chemotherapy use for male breast cancer, chemotherapy typically relies on a similar assessment of clinicopathologic risk factors (including tumor size, nodal involvement, hormone receptor status, HER2 status, and the underlying biology of the cancer) in male breast cancer patients as they do in female breast cancer patients with early-stage disease.

• As a majority of male breast cancers express the oestrogen receptor, the use of endocrine therapy such as tamoxifen is routine for the management of male breast cancer.

• Aromatase inhibitors are not commonly used for the initial treatment of male breast cancer. In gonad-intact men, aromatase inhibitors may cause a partial decrease in oestrogens but also cause an increase in androgens. If an aromatase inhibitor is used, it is recommended that it be co-administered with chemical or surgical castration.

Metastatic male breast cancer

Since male breast cancer is almost always oestrogen receptor positive, the preferred treatment option for first-line therapy of metastatic disease is endocrine therapy.

• Tamoxifen is again the treatment of choice, unless relapse occurs while on treatment with this agent. In this circumstance, other therapeutic options should be considered such as an aromatase inhibitor (preferably associated with a luteinising hormone-releasing hormone agonist) or fulvestrant (an oestrogen receptor antagonist).

• Chemotherapy should be reserved for highly symptomatic or visceral crisis situations. When chemotherapy is indicated, the same agents and regimens recommended for female metastatic breast cancer should be used for male metastatic breast cancer.

• Combinations of endocrine and targeted agents, such as mTOR and CDK inhibitors, can be used in metastatic male breast cancer patients, as the same indications are used for their female counterparts.

Prognosis

• Men with breast cancer have a poorer disease-free survival and overall survival when compared with women.¹²

• Men also have a higher risk of contralateral tumours and second primaries compared to women.

• Five-year survival depends on the stage of the disease.

• The risk of carcinoma in the other breast is also increased.⁵

• Man with breast cancer have an increased risk of certain non-breast second malignancies (including prostate, lung, colorectal and oesophageal cancers).¹³