Breast cancer in men

Breast cancer in men is a rare disease that accounts for less than 1% of all cancers in men and less than 1% of all diagnosed breast cancers.¹ It is a diagnosis for which optimal management is not clearly established and treatment guidelines are scarce. The medical literature regarding breast cancer in men consists mainly of case-control and retrospective studies, and there are no randomised prospective data for this disease. Recent emphasis therefore has been placed on extrapolating data derived from studies of breast cancer in women and using those data as a benchmark for treating men—what's good for the goose is good for the gander.

This year in the United States more than 1600 men will be diagnosed with breast cancer. By comparison, over 200 000 women will receive the same diagnosis.¹ An estimated 500 men will die from breast cancer compared with over 40 000 women.¹ These facts show the lower incidence of breast cancer in men and its comparable higher cancer specific death rate. However, unlike breast cancer in women, where rates have stabilised and seem to be decreasing, the incidence in men younger than 40 seem to be substantially increasing.² This increasing incidence is also reflected in other nations.³

Breast cancer in men and women contrasts in the age at diagnosis, the frequency of the histological types, and the frequency of expression of steroid hormone receptor and molecular markers. The median age at diagnosis in men in most series is 68 years compared with 63 years in women.⁴,⁵ Men with breast cancer have a higher occurrence of ductal histology. More than 85% of all cases are invasive ductal carcinomas; in women the frequency of ductal histology is 70-75%.⁶ Oestrogen, androgen, and progesterone steroid receptor expression is also higher in men with breast cancer.⁶,⁷ Her-2/neu, a proto-oncogene cell surface receptor, has been found to be expressed in 0-95% of men with breast cancer—the expression rate varies according to the number of patients examined. In women 20-40% of patients have Her-2/neu positive tumours and an association with adverse prognosis is established. The significance of Her-2/neu in breast cancer in men remains unclear. While germ line genetic mutations of BRCA 1 in women can confer a 60-80% lifetime risk for breast cancer, mutations in BRCA 1 do not increase the risk of breast cancer in men.⁸ BRCA 2 mutations, however, do appear to be a risk factor for breast cancer in men.⁸

Despite the biological differences, clinical outcomes for breast cancer in men are similar to those for women when they are matched for age, treatment, and stage of cancer.⁴,⁶,⁹ Older series have reported worse outcomes but were confounded by comparably later stage at presentation, long duration of symptoms before treatment, failure to account for nodal disease, and suboptimal treatment. Most men are treated with mastectomy. However, without established criteria for adjuvant treatment, men are more likely than women to receive suboptimal radiation treatment.⁴ Several randomised trials have established limited surgery plus radiation as the standard of care for women. In some series of men with breast cancer, however, they receive limited surgery without radiation. Likewise, post mastectomy radiation criteria are also established for women. Yet some men receive radiation inappropriately, which perhaps results in significant cardiac doses, contributing to decreased survival.

A recent analysis at our centre of men with breast cancer who were not treated with radiation after mastectomy showed that current guidelines for radiation treatment for women are applicable to men with breast cancer and can help optimise local regional control.¹⁰ Data derived from other studies at our centre show that men treated with adjuvant doxorubicin based chemotherapy for stage II or III disease had five year survival rates greater than 85%.¹¹ Furthermore using the guidelines established for women can help optimise systemic control. Currently we recommend chemotherapy for men with breast cancer with positive nodes, tumours larger than 1 cm, and hormone receptor negative metastases.¹² We also recommend hormonal treatment for five years. Yet many men with breast cancer do not receive chemotherapy or hormonal treatment, although they have a higher rate of hormone receptor positive tumours, and tamoxifen has been shown to improve survival in men.⁴,⁶

Men with breast cancer, in summary, are older, more likely to have hormone receptor positive disease, nodal metastases, and advanced stage disease than women with breast cancer.⁹ They are also likely to receive suboptimal treatment.⁴ The published data to date indicate a need for benchmarks that can be examined prospectively to determine the optimal treatment of breast cancer in men. We currently use and recommend for men the same guidelines used for treatment of breast cancer in women. As the incidence of breast cancer is currently rising in younger men we should generate new data that will contribute towards guidelines for determining when treatment for men and women should be the same or differ, and that will help optimise treatment.