Male Breast Cancer

Breast cancer occurs in both women and men. Both women and men have breast tissue, and those cells can turn into cancer. Breast cancer starts in the breast and occurs when cells change and start to grow out of control.

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ABOUT THIS CONDITION

Understanding Male Breast Cancer

What is male breast cancer?

Breast cancer in men is a very rare event, as only 0.5–1% of all breast cancers diagnosed occur in men. Although only approximately 2,200 cases of male breast cancer will be diagnosed annually, the incidence of male breast cancer has increased by approximately 25% over the last 25 years.

Cancer is a disease caused by uncontrolled growth of abnormal cells. Just like in other organs, cancer can grow in breast tissue. The breast is composed of two types of tissue: epithelium and stroma.

  • Epithelium. This is a type of tissue that is composed of glands that make milk and transport it to the nipple. Epithelial tissue is made of small units called duct-lobular units, which connect to form 20–30 large channels called lactiferous ducts. These ducts open into the nipple.

  • Stroma. This is breast tissue that is made of fat, blood vessels and fibrous tissue and acts as the connective, supportive framework for the epithelial tissue.

Cancer can grow in both of these types of breast tissues. The most common types of breast cancers grow from epithelial tissue.

Risk factors for male breast cancer

A risk factor is anything that can increase the chance or likelihood of developing a disease such as cancer. The risk factors for male breast cancer are similar to those for post-menopausal women with breast cancer. Although there are some weak associations between female and male breast cancer in families, the majority of men with breast cancer have no identified increased risks including family history. Some risk factors for male breast cancer are as follows:

Age

Aging is an important breast cancer risk factor in both men and women. In general, men with breast cancer are over the age of 65 when they are diagnosed. The incidence of breast cancer in women increases with their decade of life; however, men tend to be approximately 5–10 years older than women at the time of their initial diagnosis.

Genetics

Klinefelter’s syndrome is a rare condition that affects 1 in 1,000 men. This is a congenital condition in which the male sex has two X chromosomes (similar to a female) plus one Y chromosome. This is atypical, as the male sex usually has one X and one Y chromosome. Men with Klinefelter’s syndrome have smaller than usual testicles and are usually infertile as they are unable to produce functioning sperm. They may have lower levels of the male hormone androgen as well as female hormones and they may develop a benign male breast growth called gynecomastia. Studies suggest men with Klinefelter’s syndrome are more likely to get breast cancer than other men. 

This chance for developing breast cancer is 1 in 100 or 1%.  

A family history of breast cancer in males or females can be associated with an increased risk of male breast cancer. Approximately 15–20% of men with breast cancer have a family history of breast cancer, whereas only 7% of the general male population will have a history of breast cancer. The female breast and ovarian cancer genes, BRCA1 and BRCA2, account for approximately 80% of genetic breast cancer. Particular changes, specifically deleterious or harmful mutations, in these genes can also increase the risk of breast cancer in men. Mutations in the BRCA2 gene are more likely to be associated with male breast cancer. Men who inherit the BRCA2 mutation have approximately a 6% lifetime risk of developing breast cancer, which is almost 100 fold higher than the risk in the general male population. Because of the increased association with breast cancer, all men diagnosed with breast cancer should be referred for genetic counseling and possible BRCA testing.

Mutations in other genes can also increase a man’s risk for breast cancer. Although mutations in PTEN, a tumor suppressor gene linked to Cowden’s syndrome, TP53 (Li–Fraumeni syndrome), PALB B2 and genes associated with Lynch hereditary nonpolyposis colorectal cancer can increase a man’s chance of developing breast cancer, the absolute risk of cancer with these mutations is quite low. There are no guidelines regarding screening mammography or prophylactic mastectomy in men who have a deleterious mutation.

High levels of blood estrogen

Men who have high blood levels of estrogen may be at increased risk for male breast cancer. These high levels can occur by the body making too much estrogen (endogenous production) or consuming extra estrogens (exogeneous release). Both men and women have the hormone estrogen in the bloodstream. Women before menopause (premenopausal women) have high levels of estrogen, and these levels decrease after menopause. In general, men have lower levels of estrogen than women throughout their lives; however, there are conditions where the estrogen levels in men are higher than normal.

Liver disease

Men with liver disease may have higher levels of blood estrogen. The liver provides binding proteins that carry hormones to the bloodstream. These binding proteins can affect hormone activity such as estrogen or testosterone. Men with cirrhosis or severe liver disease will have lower levels of androgen (male hormone) and higher levels of estrogen. Studies show that these levels can be associated with the development of gynecomastia (increased breast tissue) as well as an increased risk of developing breast cancer.

Alcohol

Heavy drinking of alcohol may increase the chances of developing breast cancer. This is in part because of the effect the alcohol may have on the liver.

Obesity

Obesity or being overweight may be a risk factor for both male and female breast cancer. This is in part because fat cells in the body can convert male hormones into female hormones. This can mean obese males can have higher levels of circulating estrogen. It is unknown whether exercise and maintaining a healthy weight can reduce the risk of men developing breast cancer. However, some studies suggest exercise and maintaining normal weight can reduce a woman’s chances of developing breast cancer. We do recommend a healthy lifestyle of exercise and healthy eating to maintain normal weight.

Estrogen therapy

Estrogen drugs can increase a man’s risk for the development of breast cancer. These hormones were previously used in some men for the treatment of prostate cancer. It is possible women who take high doses of estrogen as part of sex reassignment or gender transition will have higher risks of breast cancer.

Occupation

Certain workplaces may be associated with an increased risk of male breast cancer. Although studies are limited, men who work in hot environments such as steel mills or those who work around gasoline fumes may be at higher risk for developing breast cancer. Because this risk is poorly understood, more research is needed.

Radiation exposure

Exposure to radiation can increase the likelihood of breast cancer. Radiation treatments that include the chest wall can increase the chances of developing breast cancer in both men and women. In general, this radiation treatment was recommended for people with Hodgkin’s and non-Hodgkin’s lymphomas. The development of breast cancer secondary to other forms of radiation exposure is poorly understood.

Diagnosis of male breast cancer

Because mammograms are not routinely recommended for men, most male breast cancer is detected by the patient, family member or healthcare professional. Usually, men present with a lump or change in the breast tissue. After the lump is identified, it is recommended men undergo diagnostic testing similar to women with breast cancer. Usually this consists of a diagnostic mammogram and/or ultrasound, and if the lump is felt to be suspicious, a biopsy of the tissue will be recommended. The tissue obtained from the biopsy is evaluated in the same way for both men and women. This analysis includes testing to determine if the tissue is cancer. If the pathologist determines the tissue is cancer, additional stains may be performed on the tissue to determine if the cancer is fed by hormones, estrogen and progesterone receptor-positive, or driven by a growth factor, HER2-neu. For breast cancers that stain positive for estrogen and progesterone receptors, hormone therapy can often be used to stop the cancer from growing or spreading. Patients whose cancers are HER2-neu positive often require targeted therapies, such as the monoclonal antibody trastuzumab which can prevent the cancer from dividing and growing.

Prognosis with male breast cancer

The prognosis for male breast cancer and chance of recovery for male breast cancer depends on the following: the stage of the cancer (how far the cancer has spread at the time of diagnosis), the type of cancer, the presence of the biomarkers estrogen receptor and progesterone receptor, the patient’s age and general health. In general, the survival for men with breast cancer is similar to the survival of breast cancer in women. However, because we do not offer screening to men, most breast cancers in men will be more advanced at the time of their diagnosis. A more advanced stage at diagnosis can be associated with a less favorable outcome.

Male breast cancer survival rates

Rate of survival in breast cancer depends upon the previous outcomes of large numbers of people with the disease. These factors must also take into account an individual person’s overall health, the treatment received and how well the cancer responds to treatment. In general, patients diagnosed with early stage breast cancer will have a much better outcome than those with more advanced breast cancer. For male breast cancer, most of the available data reports five-year relative survival rate, the percentage of patients who live at least five years after their cancer is diagnosed. Remember that most men with early stage breast cancer will live much longer than five years and many patients will be cured.

The five-year survival rate based on initial male breast cancer stages is as follows:

  • Stage 0: 100%

  • Stage I: 100%

  • Stage II: 91%

  • Stage III: 72%

  • Stage IV: 20%

Treatment of male breast cancer

The treatment of male breast cancer today is very similar to that recommended for female breast cancer. Male breast cancer is staged using the same system that is used for women, TNM (tumor-node-metastasis). See the section Breast Cancer Staging for more information. Following staging, both local control and systemic treatment for breast cancer will be recommended. Local control is designed to eliminate the cancer cells in the breast and surrounding region, whereas systemic control is designed to prevent the cancer from spreading from the breast to other organs such as the bones, lungs, liver or brain.

Local control options

Mastectomy vs. breast conservation

Local control options for male breast cancer include mastectomy or breast cancer conservation with lumpectomy and radiation. Because most breast cancers in men present as a lump and men generally have less breast tissue than women, many men elect to have a mastectomy, which removes all the identified breast tissue. Men can be offered reconstruction after mastectomy. However, breast conservation with lumpectomy and radiation can be an option for some male breast cancer patients.

Lymph node surgery

Breast cancer can leave the breast region and spread to another organ using lymphatic channels or directly into the bloodstream.

To determine if the cancer has spread under the arm (axilla), one or more lymph nodes will be analyzed. This is usually done by a technique called sentinel lymph node examination. In this procedure, the surgeon identifies and removes the sentinel or guard nodes. Usually these are the first nodes into which the tumor drains and will be more likely to contain cancer cells if the tumor has spread. If there are no cancer cells in the sentinel lymph node(s), it is unlikely that the cancer has used the lymphatic system to spread and no additional lymph node surgery is suggested. If there are positive lymph nodes identified in the armpit, your surgeon will discuss with you possible additional surgery.

Radiation therapy for male breast cancer

Radiation therapy uses high-energy rays to destroy cancer cells. This technique is often recommended to kill possible cancer cells in the breast or remaining on the chest wall or lymph node area. Most of the time radiation will be recommended for patients who have breast conserving surgery such as a lumpectomy. Radiation may also be recommended after a mastectomy if the tumor is larger than 5 centimeters (about 2 inches) in size or if the cancer has spread to lymph nodes. Radiation is also an effective way to treat breast cancer that has spread to other organs such as the bones or brain.

External beam radiation is the typical radiation administered to men with breast cancer. The treatment is painless and each treatment lasts only a few minutes. However, the time to set up the radiation may take much longer. Usually breast radiation is given five days a week, Monday through Friday, for 4–7 weeks. Brachytherapy, or internal radiation, is occasionally prescribed for the treatment of male breast cancer. However, it is less studied in men than in women.

Side effects of local therapy

Side effects of radiation include fatigue and skin changes like a sunburn. You will be given information on how to prevent this sunburn reaction by your radiation oncology treating team. Patients may also experience numbness and tingling in the chest and armpit or down the arm. This neuropathy may require treatment to reduce numbness, pain or weakness in the shoulder, arm and hand.

Lymphedema, or swelling in the arm and armpit, can also occur after radiation and surgery. It is more likely to occur if a patient has received both radiation and surgery. Unfortunately this swelling can occur any time after breast cancer treatment, although it becomes less likely with the passage of time. One of the first symptoms of lymphedema can be tightness in the arm or hand along with swelling. In general, we recommend that you avoid blood draws and blood pressures taken from the side where the lymph nodes were removed at the time of your surgery. Any injury to the arm or hand or sign of infection should be reported to your breast cancer team. Additional handouts and information regarding management and diagnosis can be obtained from your breast cancer team.

Systemic control options

Chemotherapy for male breast cancer

Chemotherapy, a chemical treatment, is used to kill cancer cells that can spread using the blood or lymphatic system. The medication(s) can be given by vein (intravenously) or by mouth. Systemic treatment, either adjuvant or neoadjuvant, is often recommended to patients with early stage invasive cancers. Adjuvant chemotherapy is

administered after surgery has removed all the identified cancer but the breast cancer team believes that it is likely that straggling cancer cells have been left behind. These cancer cells cannot be identified on imaging tests or in the blood. Because this treatment is administered through the blood, it is designed to kill remaining undetectable cancer cells before they have a chance to form a metastatic lesion in distant organs such as the bone, lung or liver. In adjuvant treatment, multiple chemotherapy drugs are usually administered for a 3–6 month time period. Some HER- 2/neu targeted therapies may be given for one year.

Neoadjuvant chemotherapy often uses the same chemotherapy drugs; however, the medicines are administered after the cancer is diagnosed and before surgery. The UC Cancer Center breast cancer team will discuss with you whether adjuvant or neoadjuvant treatment is preferred. Chemotherapy can also be used for advanced breast cancers where the tumor has already spread under the arms or to other distant sites. Because many different types of chemotherapy are available, the type, course of treatment and side effects will depend on the biology of the cancer and the patient’s overall health and personal wishes.

Hormone therapy for male breast cancer

Hormone therapy is another form of systemic treatment carried by the blood stream. It is usually given in the adjuvant setting after surgery has been completed or radiation treatment has concluded, although it can also be offered before surgery as a neoadjuvant treatment. Many breast cancers grow in response to estrogen. While

estrogen is typically considered a female hormone, men also have levels of estrogen. However, these blood levels are usually much lower in men compared to women. Approximately 80% of male breast cancers are hormone receptor-positive, which makes them more likely to respond to hormone treatments. These hormone drugs are only effective in estrogen and/or progesterone receptor-positive tumors. First-line hormone treatment for men with breast cancer is tamoxifen, a selective estrogen receptor modulator.  

Tamoxifen is a pill taken daily, and it reduces the chances of hormone sensitive cancer returning by approximately 50%. In early stage breast cancer, we recommend receiving the drug for five years. Although newer studies in women suggest  years of treatment may be more beneficial than five years, we do not have data on extended use of the drug in men. Tamoxifen is also used to treat advanced breast cancers. The most common side effects of tamoxifen include fatigue, hot flashes and sexual problems. Although less common, blood clots in the leg or lung can also occur.

Although other classes of hormone drugs, including aromatase inhibitors and estrogen receptor down regulators, are often used in the treatment of hormone-dependent breast cancers in women, these drugs have been less studied in male breast cancer. Luteinizing hormone-releasing hormone analogs (LHRH analogs) such as leuprolide and goserelin can affect the pituitary gland, which lowers the male hormone, testosterone. These drugs are administered as monthly shots, and they are sometimes prescribed alone or in combination with an aromatase inhibitor to treat advanced breast cancer in men.

HER-2/neu targeted therapy for male breast cancer

Some male breast cancers will be stimulated by too much HER-2/neu protein on the outside of cancer cells. These cancers are called HER-2/neu positive, and special tests (immunostaining and fluorescent in situ hybridization) can be performed on the breast cancer to determine if the cancer is driven by HER-2/neu. Several HER-2/neu targeted treatments are currently approved for breast cancer in women. Unfortunately, studies have not been performed in men yet.

However, general treatment guidelines for men are the same as for women. Targeted treatment against these cancers can include the use of trastuzumab (Herceptin) which has been well studied in HER-2/neu positive breast cancer in women. In early stage female breast cancer, this monoclonal antibody improves survival by approximately 50%. Trastuzumab (Herceptin), a monoclonal antibody that attaches to HER-2/neu, can slow the growth of HER-2/neu positive cancers. The drug is given by vein (intravenously) every three weeks, and for women it has been approved in neoadjuvant, adjuvan, and advanced settings.  

Side effects are uncommon but can include alteration in heart pumping, nausea, weakness, fatigue and headache. Assessment of heart function is routinely performed throughout the course of treatment. Pertuzumab (Perjeta) is also a monoclonal antibody that attaches to the HER2-neu protein in a different location than trastuzumab. This drug is often prescribed with trastuzumab and chemotherapy drug, docetaxel, in the neoadjuvant, adjuvant and advanced female breast cancer setting. Another HER2 targeted treatment includes Ado-trastuzumab emtansine (TDM-1, Kadcyla). This drug is a fusion product: monoclonal antibody, trastuzumab, combined with a chemotherapy drug (DM-1). It is currently approved for the treatment of advanced female breast cancer. Lapatinib (Tykerb) is an oral pill that can target the HER2-neu protein, and it is prescribed primarily for the treatment of advanced HER2-neu positive cancer in which trastuzumab is no longer effective.

Bone-directed therapy for male breast cancer

The bone is one of the most common sites where breast cancer spreads. Metastatic breast cancer in the bone can cause pain, create fractures or breaks, and elevate blood calcium levels. Medicines including, bisphosphonates (zoledronic acid [Zometa]) and denosumab (Xgeva) can strengthen the bones and reduce the chance of fracture and bone pain. These drugs may also reduce the chance that cancer will spread to the bone. Bisphosphonates, which are given intravenously once a month, can have side effects including flu-like symptoms, bone pain and kidney problems. A very rare side effect can be the development of osteonecrosis of the jaw (ONJ). Denosumab (Xgeva, Prolia) can also decrease the chance of bone fractures and bone pain. This medicine is given subcutaneously (under the skin) once a month, and side effects can include low blood calcium levels, fever and jaw pain (osteonecrosis of the jaw) but it is unlikely to affect kidney function. Some studies suggest denosumab may be more effective than zoledronic acid. Because the medication works differently than the bisphosphonates,  denosumab may be effective if the bisphosphonates are no longer working.

Survivorship for male breast cancer

Completion of treatment for breast cancer can be exciting as well as overwhelming. As with women, it is always a joyous day to be told that your treatment has been completed; however, it is common to worry that the cancer may return. Most male breast cancer survivors lead normal, productive, full lives. It is important for you to have follow-up care after your surgery, radiation and chemotherapy/hormone therapy have been completed. You will be watched closely by your UC Cancer Center Breast Cancer Center team. During your routine follow-up visits, your physician will try to identify problems that may indicate whether the cancer has returned. Usually, these appointments are scheduled every 3–6 months, and after five years these visits will be less often. For patients who have received breast conserving surgery, mammography will be recommended and mammograms on the opposite breast may also be recommended. For men receiving an aromatase inhibitor or luteinizing hormone releasing hormone analog, a bone density test will be recommended to evaluate you for osteoporosis (thinning of the bones). Blood testing for prostate cancer (PSA [prostate specific antigen]) and colonoscopy to evaluate for colon cancer may be periodically recommended. In general, we do not recommend blood tumor tests and routine bone scans, chest x-rays, CAT scans or PET scans. These tests may be ordered if you have developed symptoms or physical findings suggesting a recurrence.

Living a healthy lifestyle is very important. This involves eating a diet high in plant-based foods and exercising regularly to maintain a normal healthy weight. Minimizing alcohol to 7–10 drinks per week and discontinuing cigarette smoking are encouraged. Stress reduction is also important. Your UC Cancer Center Breast Cancer Center team can provide referrals to Integrative Medicine, nutritional counseling and more.

UC Health Breast Cancer High Risk Program

The Breast and Ovarian Cancer High Risk Program exists to promote awareness about breast and ovarian cancer risk to patients, families and healthcare providers. The

program provides an expert evaluation for patients who are identified as high risk for either breast or ovarian cancer.  

After a patient is evaluated, he or she is offered appropriate counseling, testing and primary prevention measures to reduce the likelihood of cancer development. This multidisciplinary approach to cancer risk assessment and management (RAMP) will utilize the services of breast imaging and genetics along with surgical oncology, medical oncology and gynecologic oncology.

Who would be considered at high risk?

  • A person who has one or more first-generation relatives with breast or ovarian cancer before the age of 50.

  • An individual who has one first-generation relative with bilateral breast cancer.

  • Individuals with a known personal or family genetic abnormality in a breast cancer-causing gene, such BRCA or CHEK-2.

  • A person with prior breast biopsy showing atypical ductal hyperplasia or lobular neoplasia.

  • Individuals with a Gail Model breast cancer risk of greater than or equal to 1.67% over the next five years or greater than 20% lifetime risk.

  • An individual with a history of chemoradiotherapy to treat Hodgkin’s disease.

 

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