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Breast Cancer in Men

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Breast Cancer in men is very rare. It accounts for only 0.2% of cancer in men and 0.8% of cases of breast cancer. Because it seen so infrequently, there is relatively little research on breast cancer in men compared to the amount of research on breast cancer in women. Many of the men who get breast cancer have no identifiable risks, but there are some conditions which are linked to male breast cancer (MBC), several of which are related to hormone imbalance. These conditions include: family history of breast cancer (especially related to the BRCA-2 gene), Klinefelter’s syndrome, testicular disease and benign breast disease. Some conditions have been found to contribute to a lesser degree, these include: obesity, low level of physical activity and a history of bone fracture after the age of 45. The treatment for MBC is mostly the same as for breast cancer in women, but a few differences in treatment, especially related to hormonal therapy, are found for MBC.

Statistics

Male breast cancer accounts for less than 1 % of cancer in males as well as less than 1% of cases of breast cancer. Almost 2000 new cases of MBC were diagnosed in 2009 and about 450 deaths due to male breast cancer occurred in that year. The average age of diagnosis for MBC is 67, which is 5-10 years older than the average age of diagnosis in women. MBC rates are highest in North America and Europe, similar to the distribution of breast cancer in women. Also similarly, the incidence of breast cancer in men has risen more that 25% in the past 25 years.

 

As with female breast cancer, the most important factors relating to prognosis are the tumor size and whether lymph node invasion has occurred. Overall, survival rates are lower for MBC than female breast cancer, but this is due to the older age of patients with MBC and the tendency for diagnosis to occur when the tumor is already at a more advanced stage. When accounting for age and stage, the prognosis for men and women with breast cancer is almost equal. Factors that do confer a worse prognosis are African American race, hormone receptor negative tumors and BRCA-2 mutations.

 

Signs and Symptoms

Male breast cancer is most commonly found as a painless lump, usually just beneath the areola, the darkly pigmented skin around the nipple. Because there is less breast tissue in men, it is easier for the mass to reach up to the skin, causing nipple retraction in about 1 in 10 men with MBC. Nipple discharge as well as skin sores over the mass are seen in about 6% of cases. The left breast is more often affected than the right and about 1% of cases occur on both sides at the same time. The presence of a breast lump, just as in women, does not automatically mean cancer. There are several other conditions which may cause these symptoms: gynecomastia (increased growth of the small amount of breast tissue in men, usually due to hormonal factors), abscess (a pocket of pus beneath the skin) and lipoma (a benign tumor of fatty tissue).


Risk Factors

One major risk factor for MBC is an imbalance in the relative amounts of the hormones estrogen, the primary female hormone, and testosterone, the primary male hormone. Various conditions in men that cause the amount of estrogen to increase or the amount of testosterone to decrease are associated with MBC. Some testicular problems that lead to this imbalance include: undescended testicles, congenital hernias of the inguinal (groin) area, infertility, orchiectomy (removal of the testicles) and orchitis (swelling of the testicles). A tumor of pituitary gland in the brain, called a prolactinoma, causes decreased amounts of testosterone and therefore higher MBC risk. Also, liver disease causes increased amounts of estrogen and therefore higher risk as well. Obesity and bone fractures are lesser risk factors, but can also indicate increased estrogen levels. Gynecomastia is a condition often associated with such hormone imbalances, but is not a separate risk factor for MBC. Men who take estrogen supplements or medications have also been shown to have higher rates of MBC. Additionally, a drug called finasteride (Proscar) which is used to treat benign prostate hyperplasia (BPH), also known as enlarged prostate, has been associated with higher rates of MBC in the past. Finasteride also affects hormone levels, and works by decreasing the amount of the male hormone testosterone. Formal studies showed that the increase in MBC rates with finasteride is not significant. However, because gynecomastia is a known side effect of finasteride and over 50 cases of MBC have occurred in men taking the drug, it is recommended that men taking the drug monitor for changes in their breasts.

 

Genetics also contribute to risk for MBC. A common genetic condition associated with MBC is Klinefelter syndrome. The syndrome occurs when a male is born with an extra female (X) chromosome, in addition to the one male (Y) and one female chromosome that normal males are born with. Klinefelter’s syndrome causes tall stature, shrunken testicles, gynecomastia and infertility. It occurs in 1 of 1000 male births and increases the risk of MBC by 20-50 times. The other major genetic risk factor for MBC is the BRCA-2 gene.  Studies estimate that over 20% of males with breast cancer have a family history of breast cancer. The BRCA genes are not as highly associated with breast cancer in men as they are in women. However, depending on the study, it is estimated that as high as 40% of cases of MBC are related to the BRCA-2 gene. Men who have the BRCA-2 gene have a 6% chance of having MBC in their lifetime. The cancer also tends to occur earlier and be found at a more advanced stage than in men with MBC who do not have the gene. BRCA-2 mutations also cause increased risk of other cancers in the future; therefore, men with breast cancer are usually offered BRCA-2 testing.

 

There a few additional risk factors for MBC. Radiation exposure can cause increased risk of MBC. It will not occur due to a few simple chest x-rays, but is more common in people who have to undergo many frequent or long lasting radiological tests. Also, radiation treatment to the chest area increases the risk of future MBC. Less well defined risk factors that have been suggested by some studies include: alcohol use, obesity, electromagnetic radiation and diet.


Diagnosis and Treatment

As with female breast cancer, MBC is usually diagnosed using mammogram or ultrasound. The mass is also biopsied in the same way to look for cancerous cells. Also similarly, the tumor is evaluated for hormone receptors. Staging is the same as for breast cancer in women, however, over 50% of men are found to be at a more advanced stage (III or IV) at the time of diagnosis. A difference between men and women is that over 90% of MBC is the ductal carcinoma type. Less than 2% is the lobular type compared to 10-15% lobular type in women. This difference is due to the lack of development of functioning breast tissue in males and therefore the lack of lobules.

 

The standard treatment for MBC is modified radical mastectomy with either lymph node dissection or sentinel node biopsy. Breast conservation (lumpectomy) is usually not considered in men due to the small amount of breast tissue to begin with. Mastectomy is usually followed with radiation therapy as with female breast cancer. One difference in treatment relates to hormonal therapy; because about 90% of MBC is estrogen receptor positive, hormonal treatment is also standard treatment for MBC. A drug called Tamoxifen, which affects the estrogen receptors, is almost always used. However, men tend to have more side effects from tamoxifen, which include hot flashes, mood swings, depression and blood clots. Due to these side effects, over 20% of men stop tamoxifen therapy sooner than the recommended time, usually 5 years. A large percent of remaining MBC has other hormone sensitivities and can be treated with drugs for those specific hormones. Treatment with chemotherapy is based on studies of female breast cancer and is usually recommended for men with intermediate or high risk disease or with hormone receptor negative tumors.


Conclusion

Male breast cancer is a very rare condition that is similar to female breast cancer in many respects, but has certain differences in risk factors and treatment. Genetic factors, such as the BRCA-2 gene, cause increased risk. The other major risk factors are conditions which cause an imbalance of male and female hormones. The standard treatment for MBC is modified radical mastectomy and treatment with Tamoxifen. Other aspects of treatment are very similar to those for female breast cancer.

 

Megan Walker


References:

[1] Goldman: Cecil Medicine, 23rd ed. - 2007 - Saunders, An Imprint of Elsevier

[2] Abeloff: Abeloff's Clinical Oncology, 4th ed. - 2008 - Churchill Livingstone, An Imprint of Elsevier

[3] Cancer Treat Rev. 2010 Oct;36(6):451-7. Epub 2010 Mar 2.Male breast cancer. Gómez-Raposo C, Zambrana Tévar F, Sereno Moyano M, López Gómez M, Casado E. Medical Oncolgy Department, Hospital Infanta Sofía, San Sebastián de los Reyes, Madrid, Spain.

[4] Finasteride in benign prostatic hyperplasia. Wysowski DK, Farinas E. N Engl J Med. 2004 Mar 25;350(13):1359-61;