Durable clinical and metabolic response to Trastuzumab Deruxtecan in heavily Pretreated male HER2-low metastatic breast cancer: a case report

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Background: Male breast cancer (MBC), accounting for < 1% of all breast malignancies, remains underrepresented in clinical trials evaluating human epidermal growth factor receptor 2 (HER2)-targeted therapies. Most MBCs are hormone receptor-positive (HR+), with a high rate of HER2-low expression. However, men were excluded from clinical trials evaluating HER2-directed agents, which is an absolute evidence gap. Case Report: We present the case of a 76-year-old man with heavily pretreated, HR+/HER2-low (immunohistochemistry [IHC] 1+) metastatic breast cancer (mBC) who achieved a complete metabolic response (CMR) following four cycles of trastuzumab deruxtecan (T-DXd) without any grade ≥ 2 (G ≥ 2) toxicity. Conclusion: This case highlights the potential efficacy and tolerability of T-DXd in men and challenges the systematic exclusion of male patients from clinical trials involving HER2-low mBC. We advocate routine HER2-low testing and gender-inclusive trial design.

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