Male Breast Cancer: It’s Time for Evidence Instead of Extrapolation

Abstract

Accessible online at: www.karger.com/onk Fax +49 761 4 52 07 14 Information@Karger.de www.karger.com treated with tamoxifen in the adjuvant setting for an estrogenreceptor positive tumor. This choice is a reasonable selection, since retrospective studies show that tamoxifen is active in metastatic male breast cancer and suggest that adjuvant tamoxifen may improve survival [5]. Despite appropriate adjuvant therapy, the patient described in this case developed a relapse while on tamoxifen and was treated with an aromatase inhibitor. Although aromatase inhibitors have excellent activity in post-menopausal women with breast cancer, the data regarding the effectiveness of aromatase inhibitors in male patients are scant. Several case reports have described male patients who responded to aromatase inhibitors. One male patient with locally advanced disease experienced tumor shrinkage on letrozole [6], and a male patient with metastatic breast cancer had a complete response to letrozole after previously receiving tamoxifen [7]. In our series of 5 male patients with metastatic disease treated with aromatase inhibitors, none had a clinical response but 2 had stable disease for greater than 6 months [8]. It is unclear whether aromatase inhibition results in complete estrogen suppression in men. In small studies of healthy male volunteers, anastrozole was found to lower estrogen levels, but not as effectively as in women [9]. Additionally, testosterone levels increased by 58% among men treated with anastrozole. Among men on aromatase inhibitors, it is possible that the hypothalamic-pituitary feedback loop results in an increase substrate for aromatization, and thus prevents complete estrogen suppression. By adding a gonadotropin-releasing hormone analog, such as leuprolide, the negative feedback loop would be interrupted and complete estrogen suppression may be achieved. We have reported on 2 patients who responded to such combination, including one who did not respond to an aromatase inhibitor without a GNRH analog [10]. Unfortunately, a clinical trial sponsored through the Southwest Oncology Group designed to test the combination of goserelin Approximately 1% of all breast cancers are diagnosed in men. In 2008, an estimated 1,990 new cases will be diagnosed in the United States [1]. Although the disease remains relatively rare, the incidence of breast cancer in men has been increasing [2]. Men tend to present with more advanced disease than women, probably due to both lack of awareness of male breast cancer and the fact that women are being screened with mammography. Considerable uncertainty still exists as to the optimal management of breast cancer in men. In the article by Bauerschmitz in this issue of ONKOLOGIE, a case of male breast cancer is described [3]. The presenting features of this tumor display some of the typical features of male breast cancer. It is an invasive ductal carcinoma, which is the most frequent histology seen in male patients. All other histologies (lobular, mucinous, medullary, and papillary) account for only 5% of cases [2]. The tumor is also strongly estrogen receptor positive. Although somewhat counterintuitive, male breast cancers are more likely than female breast cancers to express estrogen and progesterone receptors: over 90% of male breast cancers are estrogen receptor positive. Conversely, cancers of the male breast are less likely to be HER2 positive. One series of 99 male breast cancers reported that only about 10% of tumors had HER2 amplification [4]. Thus, the rates of HER2 amplification are substantially lower in male versus female breast cancers. Recommending a particular therapy for men with breast cancer is challenging, because no randomized trials have been done to determine optimal treatment. Due to the rarity of this disease, most treatment recommendations are based on retrospective series or are extrapolated from clinical trials in women with breast cancer. Using data generated from clinical trials conducted with women is probably reasonable when making chemotherapy decisions, but may be more problematic when choosing hormonal therapies given the different hormonal milieu. The patient described in this case report was Male Breast Cancer: It’s Time for Evidence Instead of Extrapolation