Breast cancer in men is rare. It is the formation of malignant cells in the tissues of the breast. Though most of the growths of the breast tissue in men are benign, e.g. gynecomastia, certain growths can be cancerous as well. According to American Cancer society, every year nearly 2000 men are diagnosed with breast cancer. Often the disease comes to light at an advanced stage as men are ignorant about the condition. However, keeping in mind the aggressive nature of the disease, it is essential for men to know about breast cancer, and they should consult their doctor immediately if they notice any abnormal growth of the breast tissue.
Breast cancer in men accounts for approximately 1% of all breast cancer cases in the US and 0.1% mortality in men. Breast cancer of men is more common in North America and Europe and is less common in Asia. The prominent features that set it apart from female breast cancer include a high prevalence in certain parts of Africa, a higher incidence of estrogen receptor positivity and more aggressive clinical behavior.
The incidence of breast cancer in men has increased with time. According to the National Cancer Institute in the US, the incidence of male breast cancer has increased from 0.86 to 1.08 per 100,000 men. The breast cancer in men is usually diagnosed at a later age and at a more advanced stage, and is more likely to have lymph node involvement.
Men are more likely to be diagnosed with breast cancer in the late sixth and early seventh decade of their life. The average age at which breast cancer is diagnosed in men is around 60 years, which is ten years more than in females.
Causes and Risk factors
Some of the common risk factors for breast cancer in men include:
Advancing age: It is usually diagnosed in men over the age of 60 years.
Positive family history: A population based study of 54 patients of male breast cancer, found that almost 17% of these patients have at least one first degree relative with breast cancer.
Alteration in estrogen-testosterone ratio: Conditions that can cause an alteration in the normal estrogen testosterone ratio in men predispose them to develop breast cancer. Klinefelter’s syndrome, a condition where there is an extra X chromosome, carries a fifty times increased risk of breast cancer and accounts for 3% of all breast cancer cases. Conditions which lead to extra estrogen in the body, like liver cirrhosis, and conditions where estrogen is given exogenously, e.g. in the treatment of prostate cancer, can all lead to male breast cancer. Treatment with estrogen in gender changing operations can also cause breast cancer. Similarly, conditions where there is testosterone deficiency like mumps, un-descended testis or testicular injury, have also been implicated in the development of male breast cancer.
BRCA2 gene mutation: Although both BRCA1 and BRCA2 gene mutations can lead to development of breast cancer, in case of hereditary breast cancer in males, mutations of BRCA2 gene account for the majority of cancers.
Jewish ancestry: It has been seen that men of Jewish descent are at an increased risk of developing breast cancer. Sephardic Jews suffer from advanced forms of breast cancer at a young age while Ashkenazi Jews carry an increased risk of breast cancer throughout their life.
Gynecomastia: Gynecomastia has been seen in 6 to 38% of patients of breast cancer and has been implicated as a risk factor.
Obesity: Studies have found that obesity is also a significant risk factor for male breast cancer. It may be due to the fact that fat serves as a storehouse of estrogen.
Exposure to radiation: Occupational exposure to radiation may cause testicular damage resulting in decreased levels of testosterone. Similarly, exposure to radiation as part of cancer therapy, like in Hodgkin’s lymphoma, may also predispose a man to breast cancer.
Different Types of Breast Cancer
The following types of breast cancer are found in men:
Ductal carcinoma in situ
Infiltrating ductal carcinoma- It is the commonest type of breast cancer affecting men with an incidence rate of 64 to 93%.
Inflammatory breast cancer
Papillary type of breast cancer- It is the second most common variant of breast cancer affecting 2.6 to 5% of men.
Medullary, tubular, small cell and mucinous carcinoma- They constitute less than 15% of breast cancers in men.
Lobular carcinoma- A variant common in females, it is rarely found in men because of under-developed lobular system of breast tissue in them.
64 to 85 % of breast cancers in men are estrogen receptor positive while more than 70% of them are progesterone receptor positive. The breast cancers in men have been known to metastasize to distant organs like bones, prostate and lungs.
Breast cancer in men usually presents as an abnormal growth or lump in the breast tissue, nipple or chest musculature. A hard eccentric non- tender mass can be palpated in 75 to 95% of cases. The diameter of the lump can extend from 0.5 cm to 12.5 cm though it is usually about 3 cm to 3.5 cm in size. The skin above the lump may appear scaly or may even ulcerate. The nipple may be retracted, fixed or show an eczematous appearance in 40 to 50% patients. There may be some abnormal blood stained or colorless discharge from the nipples. Around 5% cases present with an associated Paget’s disease of the breast. There may be itching or swelling of the concerned breast. Lymph nodes in the axilla are commonly involved and clinically suspicious lymphadenopathy may be seen in 40 to 55% of patients. Around 1.9% patients present with features of bilateral breast cancer. The patients may show a reduced appetite and appear lethargic. In case of distant metastasis to bones or lungs, the patients may complain of bone pain or fractures and breathlessness, respectively.
As the breast tissue in men is less, a suspicious growth or lump can be easily palpated on clinical examination. However, men tend to ignore the symptoms till late, either due to ignorance or because they are shy to discuss about the disease with a gynecologist. This, coupled with the fact that the disease can rapidly spread to the adjoining tissues because of less breast tissue, leads to a late diagnosis of breast cancer in men.
Mammography is an important tool in establishing the diagnosis of breast cancer in men. A malignant mass appears as an irregular subareolar mass with spiculated or indistinct margins on mammography and can be associated with calcifications and gynecomastia, unlike a benign mass, which usually presents as micro calcifications. Fine needle aspiration cytology (FNAC) is helpful in diagnosing the nature of the malignancy. Ultrasound imaging is useful in regional staging of lymph nodes. The discharge from the nipple can also be sent for a pathological examination. Sometimes, biopsy from the tumor is taken to establish the presence of hormone receptors on the surface of the cancer cells.
As in females, staging of male breast cancer is essential to determine the type of treatment required and the prognosis of the cancer. The staging in done on the basis of:
The size of the tumor
The extent of involvement of the lymph nodes
The extent of metastasis to distant organs
Taking into consideration these three factors, the breast cancer in men can be staged from stage 0 (carcinoma in situ) to stage IV (advanced breast cancer). The chances of survival following treatment are inversely proportional to the stage of breast cancer at the time of diagnosis.
The modality of treatment for breast cancer is usually decided on the basis of the pathological nature of the cancer and the stage of the cancer at the time of presentation. The patient’s age and health and the presence or absence of cancer cells in the other breast is also taken into consideration. The different types of treatment modalities for breast cancer in men are:
The most preferred mode of surgery in breast cancer in men is “modified radical mastectomy". The entire breast tissue along with the skin, the underlying chest muscles and the lining over them is removed. This is because the cancer in men usually infiltrates these adjacent structures as the breast tissue is less. The axillary lymph nodes are also excised depending upon there involvement.
For ductal carcinoma in situ and stage I cancer, lumpectomy may be considered. However, the high rates of local recurrence associated with this operation can be reduced with the use of adjuvant local radiotherapy.
Sentinel lymph node biopsy (SLNB) is being adopted as a standard surgical procedure in male patients because it compares favorably with SLNB in females, where it has been proved to be a highly effective and recommended procedure.
Chemotherapy, hormonal and radiation therapy are often used as an adjuvant to surgery to improve the efficacy of the treatment. In a retrospective study of patients who underwent treatment for male breast cancer, the median survival rate of those patients who received additional radiation, hormonal or chemotherapy, either alone or in combination, shot up to 86 months as compared to just 33 months in patients who underwent surgery alone. Adjuvant therapy is especially beneficial in tumors which are of large size, node positive or poorly differentiated.
As most of the breast cancers in men are estrogen receptor (ER) positive, they respond very well to Tamoxifen. Hormonal therapy is used to block the receptors which, in turn, decrease the rate of growth of tumor or prevent its recurrence after surgery.
Surgical procedures like orchidectomy, hypophysectomy and adrenalectomy, to manipulate the levels of estrogen, have also been found to be effective.
Chemotherapy isfound to be a useful adjuvant therapy in case of men with nodes testing positive for cancer cells. In a large study, where 24 node positive men were treated with cyclophosphamide, 5-flourouracil and methotrexate, there was a five-year actuarial survival of 80% with a median follow up of 46 months.
Systemic chemotherapy is the second choice of treatment when the hormonal therapy has failed or when the patients are ER negative.
High energy radiations are used to kill the cancer cells or damage them so that they can no longer replicate. It is an important form of treatment and is used as an adjuvant therapy along with surgery.
Apart from these standard forms of treatment, targeted monoclonal antibody therapy is also being increasingly used these days in the treatment of male breast cancer.
Treatment of metastatic cancer
Hormonal therapy is especially useful in the treatment of metastatic disease. Tamoxifen has been found to be effective in treating visceral dominant, bone dominant and soft tissue dominant metastasis, in cases where ER positivity is good.
38% cases of metastatic male breast cancer have been found to respond favorably to treatment with Diethylstilbestrol. It is especially useful in metastatic soft tissue disease, as when the cancer has metastasized to the chest wall or into the lymph nodes.
Staging of the cancer, depending upon the tumor size and the involvement of the lymph nodes, is the most important factor in deciding the prognosis of the disease. A study by Giordano et al has shown that the five year overall survival rate for patients is 78% for stage I cancer, 67% for stage II cancer, 40% for stage III, and 19% for stage IV cancer. Another study has shown that the five year survival rate for node negative patients is 70% and for node positive patients, it is in between 37% to 54%.
Male breast cancer has a poor prognosis as compared to female breast cancer because the patients usually present at an advanced stage of disease. As the breast tissue in men is less, therefore the disease tends to advance and involve adjacent tissues rapidly. The dermal lymphatic spread and regional and distant metastasis also occurs earlier.
As the men usually approach their doctors after a considerable delay, sometimes the lag time between the first symptoms and surgery is twice as long as in women. This accounts for the poor prognosis of breast cancer in men. However, if the stage of diagnosis of cancer is same as in women, then the survival rate of men with breast cancer is also similar to that of women.
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