Review
An update on male breast cancer and future directions for research and treatment

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Abstract

Male breast cancer is a rare disease for which treatment has been based on the evidence available from female breast cancer. The new genomic tools can better characterize the biology of breast cancer. It is hoping that these will help to clarify possible differences of breast cancer behaviour in male patients, which will have a major impact on treatment strategies and on the conduct of clinical trials in this setting. In this review we will summarize available information on epidemiology, risk factors for breast cancer in men, the new insights of the biology of this disease, current recommendations for treatment and insights for future research.

Introduction

Male breast cancer is a rare disease that accounts for less than 1% of all cases of cancer in men (Sasco et al., 1993). Limited research has been conducted in this setting and most available data comes from observational retrospective studies. Therefore treatment of male breast cancer has been extrapolated from results of trials conducted in female patients, which renders knowledge uncertain about the optimal therapy in this setting. Furthermore the incidence of male breast cancer seems to be rising (Giordano et al., 2004), bringing increasing interest to this disease and a need for advances in research.

Section snippets

Epidemiology

Male breast cancer accounts for less than 1% of all breast cancers diagnoses worldwide. Similarly to women the incidence of breast cancer in men has increased about 26% over the past 25 years (Giordano et al., 2004). Like female breast cancer its incidence rates are higher in North America and Europe and lower in Asia (Weiss et al., 2005). In Africa high incidence rates have been reported in Uganda (5%) and Zambia (15%) and it has been speculated that endemic infectious diseases leading to

Genetics

Affected men with Klinefelter's syndrome (addition of at least one X chromosome to the normal karyotype XY) have a risk of male breast cancer that is 20–50 times higher than men with normal karyotype (Harnden et al., 1971, Hultborn et al., 1997). It has been estimated that 3–7.5% of men with breast cancer have this syndrome (Evans and Crichlow, 1987, Hultborn et al., 1997), characterized by testicular dysgenesis, gynaecomastia, low testosterone concentrations, and increased gonadotrophins. This

Clinical features and diagnosis

Male breast tumours are usually found by palpation. The most common presentation is a painless sub-areolar mass (50–97%) (Günhan-Bilgen et al., 2002). As in women, there is a slight predilection for the left breast (1.07:1) (Giordano et al., 2002). Nipple retraction is present in 10–51%, local pain in 4–20%, nipple ulceration in 4–17%, nipple discharge in 1–12% and nipple bleeding in 2–9% (Giordano et al., 2002). Bilateral breast cancer is a rare form of presentation (less than 2%) (Buzdar, 2003

Prognosis and survival

Mortality from male breast cancer has improved from 1975 to 2005 (Korde et al., 2010). Estimates for overall 5-year survival are around 36–66%, with a broad range related to heterogeneity of disease stage and different treatments strategies across time. (Cutuli et al., 1964, 1995; Donegan et al., 1998; Ribeiro et al., 1996; Goss et al., 1999, Joshi et al., 1996, Scott-Conner et al., 1999, Giordano et al., 2004). The most important prognostic indicators are stage at diagnosis and lymph node

Surgery

Standard treatment for localized disease includes surgery. Literature reveals rates of modified radical mastectomy in male breast cancer approximately 70%, radical mastectomy 8–30%, total mastectomy 5–14%, and lumpectomy with or without radiation 1–13% (Cutuli, 2007). The use of radical mastectomy has declined and only cases of extensive chest wall muscle involvement may benefit from this procedure, although in these cases a systemic neoadjuvant treatment strategy might be the best choice. The

Conclusion

Male breast cancer is a rare entity for which biology is still unclear. Only retrospective data from small and single institution series are available and therefore treatment strategies have been guided from extrapolation from data obtained in female breast cancer.

Surgery when feasible is considered standard of care, consisting of modified radical mastectomy and sentinel lymph node biopsy (small tumours and clinically negative axilla) or axillary dissection. Tamoxifen in the adjuvant or

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