Abstract
Male breast cancer (MaBC) is a rare disease, and treatment approaches are often extrapolated from female breast cancer protocols. We present the case of a 55-year-old male diagnosed with estrogen receptor-positive metastatic breast cancer who exhibited primary resistance to first-line treatment with a combination of Palbociclib (CDK4/6 inhibitor) and Letrozole (aromatase inhibitor), despite the proven efficacy of this combination in female breast cancer. Surprisingly, upon switching to Tamoxifen, the patient showed rapid and significant clinical improvement documented as a good partial response on radiologic assessment. This case highlights the potential limitations of CDK4/6 inhibitors plus aromatase inhibitors in MaBC and suggests that Tamoxifen could remain a more reliable first-line endocrine therapy in males. It underscores the need for cautious extrapolation of female breast cancer treatment strategies to MaBC and emphasizes the adherence to classical approaches, such as tamoxifen.