Approximately 90 percent of MBCs are invasive ductal carcinomas, while lobular histology is rare. Although most of the histologic subtypes that are seen in women are also present in men, the distribution is different. Lobular cancers accounted for 1.5 percent of cases in a series of 2000 MBCs reported from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute, while in women, it accounts for up to 15 percent. The male breast can be induced to develop true acini and lobules with estrogenic stimulation, but the normal unstimulated male breast lacks these structures.

There are also differences in the incidence and clinical characteristics of ductal carcinoma in situ (DCIS). DCIS accounts for a significantly higher proportion of breast cancers in women compared to men (approximately 20 versus 7 to 11 percent, respectively). DCIS in men tends to occur at a later age, presents more frequently in an intraductal papillary form, and is more often low-grade. Paget's disease and inflammatory breast cancer have been rarely described in men.

Hormone receptors - In females, 60 to 70 percent of breast cancers are estrogen receptor (ER) or progesterone receptor (PR) positive. In contrast, approximately 90 percent of MBCs express ER, and over 80 percent express PR. As with female breast cancer, rates of hormone receptor positivity increase with age. ER/PR expression may provide a growth advantage; some data suggest that in men, ER+/PR+ breast cancers have higher proliferative activity than do ER-/PR- tumors.

Androgen receptor - (AR) expression is detected in 34 to 95 percent of MBCs. However, no association between AR expression and other clinicopathologic features or measures of outcome has been reported. AR gene mutations, which are predominantly in the DNA-binding domain in an area responsible for transcriptional control, have been implicated in the development of MBC. However, their contribution to tumorigenesis is not completely clear, and at least two separate series have failed to find any AR mutations in tumor material from 128 MBCs.

HER2 expression - Early data suggested similarities in the rate of expression of HER2 in MBC as compared to female breast cancer. However, more recent studies using standardized methodology have shown a lower rate of HER-2.neu overexpression in men (2 to 15 percent in three different series). Approximately 30 percent of female breast cancers overexpress HER2.

In women with breast cancer, HER2 overexpression is a marker of poor prognosis.

Whether HER2 overexpression is a marker of poor prognosis in MBC is uncertain. HER2 amplification and/or overexpression has been associated with adverse outcome in many but not all studies.

Plasminogen activators - Urokinase plasminogen activator (uPA) converts plasminogen to plasmin, which is involved in the degradation of extracellular matrix during tumor cell invasion. Tumor expression of plasminogen activators and their inhibitors, plasminogen activator inhibitor (PAI) types 1 and 2, have been associated with shorter survival in women with breast cancer. Perhaps more importantly, early data suggested that the absence of these factors may permit the selection of patients who do well without adjuvant chemotherapy, even in the presence of nodal metastases. However, assay methodology is problematic and routine assessment of these markers continues to be considered investigational.

Few data exist regarding the prognostic value of plasminogen activators in men. In one report of 40 MBCs, expression of PAI-1, but not uPA or PAI-2, was associated with a significantly worse prognosis. There are no studies exploring the relationship between expression of uPA or PAIs and response to adjuvant therapy in men.

Cytogenetics - Multiple nonrandom non-germline cytogenetic abnormalities have been described in MBC, including loss of the Y chromosome. The pathogenetic role of these changes is uncertain.

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 Updated by Medical Writers Group, LLC, New York, for John W. Nick Foundation, Inc. - January, 2008. (Made possible through a grant provided by Cancer Research and Prevention Foundation.)