Breast Cancer in Men: Rare, But Real

By Dr. Daniel Vorobiof

Breast cancer is one of the most common forms of cancer diagnosed among the female population, and although it may seem like a disease exclusive to women, breast cancer can affect men as well. Male breast cancer (MBC) is rare, making up less than 1% of all breast cancer cases diagnosed yearly, but it is important to remember that men do have breast tissue that has the potential to become malignant, similarly to women, albeit much less commonly.

Risk Factors

There are many possible risk factors associated with male breast cancer. Most importantly, inherited abnormal (mutated) genes increase a man’s risk for breast cancer.Mutations in one of several genes, especially the BRCA2, put males at greater risk of developing breast, prostate and pancreatic cancers, as well as malignant melanomas. It is well known that approximately 5-10% of breast cancers in women are a result of a gene mutation. In men, that percentage is 40%. This shows the great importance of genetic testing for men diagnosed with breast cancer.

Other risk factors include:

• Older age: The risk of breast cancer increases with age. Male breast cancer is most often diagnosed in men in their 60s.
• Exposure to estrogen: Some estrogen-related drugs increase the risk of MBC.
• Family history of breast cancer: Those with close relatives (1^st and 2^nd degree) who have had breast cancer have a greater chance of developing the disease.
• Genetic Syndromes (such as Klinefelter’s syndrome, Li Fraumeni, Cowden’s disease, etc.): These genetic syndromes can increase risk of MBC due to certain inherent mutations.
• Liver disease: Certain conditions, such as cirrhosis of the liver, can reduce male hormones and increase female hormones, heightening MBC risk.
• Obesity: Obesity is associated with higher levels of estrogen in the body, which increases the risk of MBC.
• Testicular disease or surgery: History of inflamed testicles (orchitis) or surgery to remove a testicle (orchiectomy) can increase the risk of MBC.

Incidence Statistics

Over the past decade, statistics from the National Cancer Institute (NCI) have confirmed that the lifetime risk of getting breast cancer in the U.S. is about 1 in 833 for men, compared to 1 in 8 for females. The most recent available statistics (2017) show that women have a yearly incidence of 131 new cases/100 000 and men of only 1.3/100 000. 

It is also estimated that during 2020, 2620 new cases of invasive male breast cancer will be diagnosed in the United States. MBC incidence in the U.S. varies by race and ethnicity. Black men have the highest MBC incidence overall (1.8/100 000), while Hispanic men have the lowest (0.6/100 000). Black men also have a higher breast cancer mortality rate (0.5/100 000) than White (0.6/100 000) and Hispanic men (0.1/100 000).

MBC Histologic Types

Similar to female breast cancers, the most common types of MBC are ductal or lobular carcinoma in situ (DCIS/LCIS), invasive ductal carcinoma, and invasive lobular carcinoma. Most MBCs (90%) are adenocarcinomas, which starts in the ducts (the milk ducts) or the lobules (milk-producing glands). Let’s take a deeper dive into these types:

• Cancer that begins in the milk ducts (ductal carcinoma): Nearly all MBCs are ductal carcinomas (more than 85%).
• Cancer that begins in the milk-producing glands (lobular carcinoma): This type of breast cancer is rare in men, as there are less lobules in their minimal breast tissue compared to women.
• Other types: Other, rarer types of breast cancer that can occur in men include Paget’s disease of the nipple, and inflammatory breast cancer.

Regarding hormone expression in male breast cancer, which refers to the receptors that promote the cancer growth, approximately 90% express the estrogen receptor (ER), and 81% express the progesterone receptor (PR). Studies have also found that the expression of these hormone receptors in breast cancer cases is more prevalent in males than in females.

Signs and Symptoms

Men tend to have far less breast tissue than women. Because of this, many of the following signs can be easier to notice in men than in female bodies:

• A painless lump – the most common sign of suspicious MBC
• A hard knot or thickening in the breast, chest, or underarm area 
• Changes in the size or shape of the breast 
• Dimpling, puckering or redness of the skin 
• An itchy, scaly sore or rash on the nipple
• Pulling in of the nipple (inverted nipple)
• Nipple discharge (rare sign)

Diagnosis

Following the initial clinical examination findings, a variety of tests which might include an ultrasound or a mammogram depending on the amount of breast tissue palpable, will be requested by the treating physician. If a suspicious lesion is found, a biopsy will follow to determine whether the cells are cancerous or not.

In the event that the cells are malignant, further tests will be performed to evaluate the grading of the tumor, the presence of hormonal receptors, as well as the HER2 receptor, and to evaluate the status of the axillary lymph nodes. At the same time, other tests and procedures may be recommended to determine the extent of the cancer and, depending on the patient’s particular clinical situation, this will help in staging the cancer. 

Other tests might include general blood tests (liver and kidney functions, blood counts and tumor markers) as well as imaging tests such a bone scan, a CT scan and/or a PET scan. Breast cancer stages can range from 0 (precancerous condition or in-situ) to stage 4 or metastatic breast cancer, which indicates that the cancer has spread to other areas of the body. Stages 1 and 2 are considered early disease, and stage 3 is considered a locally advanced disease. 

Treatment and Management

Treatment and management of male breast cancer typically follows the same rationale of breast cancer in females. The process consists of surgery (mastectomy or lumpectomy), followed by adjuvant endocrine therapy, chemotherapy (CT), or radiotherapy. Management of each specific patient’s condition is guided by the presence of the different prognostic factors, tumor characteristics, as well as the patient’s general condition. 

A mastectomy is the primary option for early stages with tumors that are smaller than 2cm. A lumpectomy (the removal of the tumour itself) is seldom performed. Radiation therapy is usually offered to men with larger tumors or tumors that have a higher stage or grading, positive surgical margins, or more than 4 axillary lymph nodes that test positive for cancer.

Antihormonal medications are recommended as adjuvant therapy for at least 5 years. For those patients with higher grading and stages, chemotherapy with conventional treatments, as with female breast cancer patients, is recommended. Patients with HER2 positive tumors will also benefit from receiving biological treatments.  Most metastatic male breast cancers are estrogen receptor-positive, and so combinations of antihormonal medications are usually used as first line treatments.

The Less Known and the Future 

As previously mentioned, male breast cancer is about 100 times less common than female breast cancer, and most men diagnosed are over the age of 60. In spite of these differences compared to female BC, most, if not all male breast cancer cases are treated according to current guidelines for female breast cancer. Also, and as a result of the rarity of the disease, men are usually excluded from clinical trials, and doctors often extrapolate treatment from studies applied to women. This unfortunately results in male breast cancer patients not being treated adequately. 

To counteract this, in 2006 the International Male Breast Cancer Programme was created, and is currently coordinated by a number of cooperative oncology groups in Europe and the U.S. in an effort to better understand the biology and evolution of MBC, and improve their treatments.

This programme is conducted simultaneously in Europe, the U.S., and South America, and has shown that male and female breast cancers are definitely different in terms of histology and grading, indicating that while over 90% of MBC has ER positive tumours, only 77% of them received endocrine therapy after surgery, which would have been the adequate treatment for them all. Researchers of the cooperative group also performed a study using RNA sequencing on 152 tumour samples of MBC patients. They subsequently identified five intrinsic subtypes of MBC with various gene expression profiles, indicating a breast cancer subtype occurring exclusively in men that needs to be better characterized.

Many questions still remain regarding the causes, consequences, and optimal care of male breast cancer.  More work is required to further clarify biological and molecular conditions, risks and benefits of specific treatments, and the quality of life for every patient. Hopefully, future research will develop interventions in improving the prognosis of men in this unique and understudied population.

References:

• Howlader N, Noone AM, Krapcho M, et al. (editors). Cancer Statistics Review, 1975-2017. Table 4.5: Cancer of the breast (invasive). Age-adjusted SEER incidence rates by year, race, and sex. National Cancer Institute, Bethesda.
• Ruddy K, Winer E. Male Breast Cancer, risks factors, biology, diagnosis, treatment and survivorship. Annals of Oncology 24(6), 1434, 2013.
• F Cardoso et al. Characterization of male breast cancer: results of the EORTC10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Annals of Oncology 29(2)405, 2018.

Dr. Daniel Vorobiof is the Medical Director of Belong.Life, a developer of social and professional networks for managing and navigating treatments, and the creator of the world’s largest social network and navigator app for cancer patients – Belong – Beating Cancer Together. He is the founder and former medical director of the Sandton Oncology Centre in Johannesburg and has published more than 120 peer-reviewed articles in international medical journals.