How common is it?
For every 100 women who develop breast cancer in the US, one male is diagnosed with the equivalent disease. The overall incidence is between 0.1 and 3.4 cases per 100,000 man-years. This makes male breast cancer one of the rarest malignancies, contributing to the generally low level of public awareness.

What causes it?
Just as the causes of female breast cancer are still under study, the precise cause (or causes) of male breast cancer are still under study. Men have glandular breast tissue that is subject to hormonal influences. Excess estrogen, especially around the time of puberty, has been identified as a possible factor. Men with Klinefelter's syndrome have an increased risk of developing breast cancer, as do men who take estrogens or estrogen-like compounds. Androgen (and possibly progesterone) exert a protective influence. Men who are deficient in androgen seem to also be an increased risk (for example, men who have testicular atrophy from mumps orchitis, injury, or undescended testes). Brain tumors and conditions associated with excess production of prolactin have also been implicated in some cases of male breast cancer (27). Men who work in steel mills, blast furnaces, rolling mills, or other environments of intense heat have a slightly increased incidence of breast cancer (probably due to thermal suppression of androgen production). Radiation to the chest wall increases the risk of breast cancer in men, as in women (27). Finally, genetic factors have been identified in some cases of male breast cancer.

Is there a genetic basis?
In a series from Iceland, a strong familial tendency has been identified with over 40% of cases of male breast cancer diagnosed over the past 40 years being traced to 21 families (26). A family history of breast cancer (both male and female) is common in men with breast cancer. The breast cancer genes BRCA-1 and BRCA-2 are under study in this population. To date, mutations in BRCA-2 (but not BRCA-1) have been identified in a significant subset of male breast cancer patients (4,10).

Is gynecomastia related to breast cancer?
Gynecomastia (literally "female breast") is a condition in which the male breast enlarges and becomes tender. In some cases hyperplastic changes are florid and the differential diagnosis from cancer may be difficult (25). There have not been any reported cases of gynecomastia progressing to carcinoma, but two case reports of gynecomastia with atypical changes suggest that such progression may occasionally occur (10).The major problem with gynecomastia is that the differential diagnosis between gynecomastia and breast cancer is sometimes difficult. Both cause subareolar masses, and both may be associated with pain and tenderness (although both are more common with gynecomastia) (18).

What are the signs and symptoms of male breast cancer?
The most common symptom is a breast mass. The mass is usually firm, nontender, and subareolar (although occasionally tumors occur in other areas). In several series, the average tumor size was approximately 2.5 cm (11,15). Because of the short distance to the nipple, nipple retraction, ulceration, or destruction are also common (occurring in almost half of the patients in one series) (15). Nipple discharge, either bloody or serous, is distinctly abnormal in men and must be fully investigated by cytology, galactography, or biopsy (8,13,20).A special kind of breast cancer, Paget's disease, may appear to be a rash or irritation of the nipple. Biopsy is required to make the diagnosis (7, 15).

How is male breast cancer diagnosed?
Because most cases present with a palpable mass, fine needle aspiration cytology is extremely useful. This is performed in the physician's office. A fine gauge needle is inserted into the mass and cells drawn out for examination under the microscope (6,17,25). Nipple discharge can be smeared on microscope slides and examined microscopically (13,20). Biopsy may be needed for confirmation. Because the condition is so rare, general screening by mammography, ultrasound, or other methods is not recommended. High risk individuals may require more careful periodic evaluation.

How do men's breasts differ from those of women?
Most of the breast tissue in a man is concentrated in the area immediately behind the nipple and areola. In most men, this tissue remains rudimentary. Androgen appears to suppress any tendency for ductal proliferation.As men age and the overall level of androgen decreases, some physiologic enlargement of the breasts can occur. In most men this is asymptomatic and of no concern. Because most of the breast tissue is beneath the nipple/areola complex, this is where most male breast cancer starts. There is a rich plexus of lymphatics beneath the nipple and areola in both men and women, and the subareolar location of most male breast cancers allows easy access of tumor cells to these lymph channels.

What hormonal influences have been identified?
The strongest association is with estrogen. The rate of estrogen receptor positivity (ranging from 64% to 87%) is significantly higher among men than women with breast cancer. Risk is increased in males with partial androgen insensitivity (12). Elevated prolactin has been identified as an etiologic factor (16).

Is the histology of male breast cancer different than female breast cancer?
Of 46 cases of male breast cancer in a representative series, 4 were noninvasive (or in situ) lesions, and 42 were invasive. Most of the invasive tumors were of low histologic and nuclear grades. The invasive cancers were primarily infiltrating ductal carcinoma (also the commonest histology found in women with breast cancer), and a mixed ductal and cribiform pattern (15). In other series, infiltrating ductal carcinoma has been the predominant histology (2,14).Lobular carcinoma, Paget's disease, and in situ lesions are quite rare in males (7,13).

How is male breast cancer staged?
The term "stage" is used to describe the anatomic extent of disease according to standardized rules. The same staging system is used for both male and female breast cancer patients. This standardized language allows clinicians and researchers to accurately describe the extent of disease. The AJCC (American Joint Committee on Cancer) staging system uses three numbers to determine the stage of the disease. T (stands for tumor) describes tumors of increasing size and local tissue destruction. N (stands for nodes) describes whether or not the tumor has metastasized to regional lymph nodes and if so, how extensive those nodal metastases are. M (stands for metastases) describes the presence or absence of systemic metastases. The AJCC staging system for breast cancer allows precise stratification of cases and is too complex to fully describe here (24).In most series, men present with more advanced disease (higher stages) women. It is not known whether this reflects delay in diagnosis, more rapid progression in disease, different breast anatomy resulting in most lesions being subareolar (with easy access to subareolar lymphatic trunks) or other factors (9,15).

How is it treated?
The treatment depends upon the stage of the disease. Surgery forms the first line of defense and is generally used. Stages I and II are locally operable and are generally treated by modified radical mastectomy. More advanced disease may require radical mastectomy, or may be treated with a lesser procedure coupled with radiation and/or chemotherapy. After surgery, the decision to proceed with chemotherapy or radiation depends upon the precise stage of the disease. This decision is made after the pathologist examines the breast and lymph nodes that were removed at the time of surgery.

What surgery is performed?
Modified radical mastectomy is performed in a manner quite similar to the way it is performed in women. It has largely replaced the earlier, more extensive, radical mastectomy that was generally recommended in the past (2,9). The contour of the chest wall and function of the arm are very well preserved. Depending upon the amount of fatty and glandular breast tissue that a man has, the resulting deformity may be minimal or may result in assymmetry that is noticeable under a thin shirt. This removes the nipple and areola, the entire breast tissue, and regional lymph nodes. It does not remove the pectoral muscles. Radical mastectomy is a more extensive procedure that removes the nipple, areola, all of the breast tissue, the underlying pectoral muscles, and the regional lymph nodes. The loss of the muscle tissue may result in decreased function in the arm, and there is a noticeable concavity below the collarbone.

Can men benefit from reconstructive surgery?
Just as many people are unaware that men get breast cancer, most people assume that post-mastectomy reconstruction is only appropriate for women. If surgical treatment of breast cancer causes a deformity such as assymetry, loss of nipple contour, or other problems, reconstructive surgery is an appropriate option that should be offered.

Is chemotherapy useful?
Adjuvant systemic chemotherapy appears to improve survival in lymph node positive men (9). Because men with breast cancer tend to be older and because most cancers are estrogen-receptor positive, Tamoxifen is a useful adjunctive therapy (5).

What about radiation therapy?
Radiation therapy is an essential part of the treatment of selected patients (23). Lumpectomy and radiation therapy, commonly offered to women, is rarely performed in men because the scanty amount of breast tissue renders the procedure difficult and because the conservation of the breast per se is generally considered to be less important.

What is the prognosis for male breast cancer?
When men and women who are the same age and with the same stage disease ("age and stage-matched") are compared, survival is equivalent in most series (2, 5, 15).In at least one series, male patients fared worse than their female counterparts (21) and it has been hypothesized that the anatomy of the male breast, with close proximity of the tumor to the skin and nipple allows early access of cancer cells to the dermal and subareolar lymphatics, favoring more rapid spread (15). Finally, since men generally have more advanced disease at the time of diagnosis than women, the overall prognosis of male breast cancer is generally felt to be worse.Just as with female breast cancer, tumor stage and grade are important prognostic factors (3). Other prognostic factors under study include ploidy analysis, estrogen receptor status, cathepsin D, C-erb-B2, and p53 (3,14,19).

Summary:
Male breast cancer is rare but afflicts approximately 1000 men per year in the U.S. Most men with breast cancer are in their 60's, but the disease can strike younger or older men. Delay in diagnosis and presentation with advanced disease are common. Any breast lump, nipple discharge, or change in the breast should be investigated. Surgery is generally required; modified radical mastectomy is the most common operation. Reconstructive surgery should be offered if cosmetic or functional deformity results. Prompt treatment can result in long-term survival.

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