AUTHOR INFORMATION	Section 1 of 8
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Author: Marilyn A Roubidoux, MD, Professor of Radiology, Department of Breast Imaging, University of Michigan Medical Center Coauthor(s): Stephanie K Patterson, MD, Clinical Assistant Professor, Department of Breast Imaging, University of Michigan Medical Center

Marilyn A Roubidoux, MD, is a member of the following medical societies: Radiological Society of North America

Editor(s): John M Lewin, MD, Consulting Radiologist, Radiology, Diversified Radiology of Colorado; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Edward Azavedo, MD, PhD, Director of Clinical Breast Imaging Services, Associate Professor, Department of Radiology, Karolinska University Hospital, Sweden; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; and Eugene C Lin, MD, Consulting Staff, Department of Radiology, Virginia Mason Medical Center

Disclosure

	INTRODUCTION	Section 2 of 8
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Background: Breast cancer in males is similar to breast cancer in females when considering etiology, family history, prognosis, and treatment. In approximately 30% of males with breast cancer, family history is positive for the disease. A familial form of breast cancer is seen in which both genders are at increased risk for breast cancer. Male breast cancer is relatively rare, in contrast to gynecomastia, which is relatively common.

For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education articles Breast Cancer, Breast Lumps and Pain, and Breast Self-Exam.

Pathophysiology: Males with Klinefelter syndrome have a risk of breast cancer that approaches that of females. Exogenous hormone therapy, such as treatment for prostate cancer, is not associated with increased risk, and breast masses in these patients more commonly are found to be metastatic disease than primary breast cancer. A few transsexual patients have been reported with the disease 5-10 years after initiation of estrogen therapy. However, it is not known whether these patients are at increased risk compared to males.

Increased risk was found in men exposed to estrogen-containing creams in the soap and perfume industry and in men with gonadal injury. These epidemiologic factors, plus studies that suggest that men with breast cancer have elevated estriol production, indicate a relationship between male breast cancer and hormones. Case reports indicate that radiation is carcinogenic in men as well as in women.

The overwhelming histologic subtype of breast carcinoma in men is ductal or unclassified (93.7%), followed by papillary (2.6%). Infiltrating lobular carcinoma is rare in males, likely due to the rarity of terminal lobules in the male breast. Ductal carcinoma in situ is also less common among male patients with breast cancer, most likely because a higher prevalence of screening detects ductal carcinoma in situ in women. All other types of breast cancer, including medullary, colloid, cystosarcoma phyllodes, and Paget disease, are reported in males. Estrogen receptors are present more commonly in males with breast cancer than in women, occurring in 75-94% of males with cancer.

Frequency:

• In the US: Male breast cancer is not common, accounting for approximately 1% of all breast cancers (ie, 1/100th the incidence of breast cancer in females). However, the incidence of male breast cancer increased from 1973-1998, and the reasons for this are unclear. Approximately 2000 patients per year are diagnosed.

• Internationally: Male breast cancer is distributed similarly to that of female breast cancer, with the exception of Egypt and Africa. Male breast cancer is more common in Egypt, representing 6 percent of all breast cancers, and in Zambia where it represents 15% of all breast cancers. This may be due to the higher prevalence of liver diseases (from schistosomiasis or malnutrition) with resulting increases in endogenous estrogens. Incidence is low in Japan and higher in North America and Great Britain.

Mortality/Morbidity: Male breast cancer is staged similarly to that of female breast cancer. As in women, the strongest prognostic factor is axillary nodal status and tumor size, with survival rates dependent upon these factors. Five-year survival rates range from 30-85%. A more advanced disease state is found in men more commonly than in women, which likely results from delayed detection. Relative survival rates are very similar between men and women with stage I-IV breast carcinoma. Overall survival rates for men with breast carcinoma, stratified by stage of disease, are lower than for women with breast carcinoma. At presentation, 28-60% of males have node positive disease. As in women, tumor metastases occur in the lungs, liver, and bone.

Race: The National Cancer Institute Surveillance, Epidemiology and End Results (NCI SEER) registry reports that breast cancer is found in 14 black men per million, as compared to 8 white men per million.

Sex: Male-to-female ratio is approximately 1:100.

Age: As in females, risk increases with age, with median age of approximately 67 years; it rarely occurs in those younger than 30 years. Two male children were reported to have the disease.

Anatomy: The male breast is primarily composed of fat tissue, with a few branching ducts and connective tissue. Lobules are typically absent from the male breast, which may be the reason that lobular carcinoma is more rare in males. The breast tissue in males responds to hormonal stimulation, with growth of ducts and connective tissue resulting in gynecomastia.

Clinical Details: Male breast cancer typically presents as a painless retroareolar mass. It is often eccentric to the nipple. Nipple discharge is rare, but when present, most likely results from the malignancy. The upper outer quadrant is the second most common site.

Gynecomastia, the chief entity in the differential, typically presents as a smooth disk centered immediately behind the nipple.

Preferred Examination: The clinical examination is key in the evaluation of a palpable mass in a male. If the clinical features strongly suggest gynecomastia, further evaluation may not be necessary. If the clinical features are equivocal, fine-needle aspiration guided by palpation and/or excisional biopsy are necessary to make the diagnosis. Accurate diagnosis with mammography alone has been reported, with a sensitivity and specificity of at least 90%. If clinical examination and mammography both reveal benign findings, biopsy may be unnecessary. Given the rarity of male breast cancer, mammography screening guidelines are not available for men.

Ultrasound can demonstrate a cyst in a male, but cysts are rare. A mammogram showing only fat can be helpful in cases of unilateral breast enlargement without mass, but in general, this finding is not concerning for breast cancer and does not require further evaluation in the breast.

MRI has not been studied regarding sensitivity in diagnosis, but since the lesions are always palpable and can be biopsied easily under palpation, there is no clear role for MRI.

Limitations of Techniques: Although some mammographic findings do suggest male breast cancer (eg, an eccentric spiculated mass), mammography or ultrasonography has not been compared with the predictive value of a clinical breast examination and fine-needle aspiration. Considerable overlap also exists in the ultrasound (US) appearance of these entities.

	DIFFERENTIALS	Section 3 of 8
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Other Problems to be Considered:

Inflammation
Gynecomastia
Fat necrosis
Abscess

	RADIOGRAPH	Section 4 of 8
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Findings: On mammography, male breast cancer is subareolar or somewhat eccentric to the nipple, with well-defined, ill-defined, or spiculated margins. Calcifications are observed less commonly than in female breast cancer, and when found, are coarser in appearance. Calcifications also can be seen in fat necrosis. Axillary adenopathy may be observed.

Degree of Confidence: Mammography is highly sensitive and specific for breast cancer in men, but it should be used to complement the clinical examination. At present, not enough clinical data are available to determine whether the combination of imaging and clinical findings can replace biopsy for the diagnosis of palpable breast abnormalities in men. Ultimately, biopsy should be considered to diagnose male breast cancer because findings of inflammation, gynecomastia, or fat necrosis may be similar.

False Positives/Negatives: Inflammation, gynecomastia, and fat necrosis may appear similar on mammograms; thus, these are false-positive findings. Cases of carcinoma have been found by ultrasound after they were obscured by gynecomastia on previous mammograms.