Abstract

Cutaneous squamous cell carcinoma (SCC) is a common skin cancer with a favorable prognosis when diagnosed at an early stage and fully resected. While the risk of recurrence and metastasis is relatively low for most patients, management of unresectable or metastatic SCC can be challenging due to poor responses to chemotherapy and therapy‐related toxicities. The HER family of receptor tyrosine kinases has been associated with cutaneous malignancies including SCC. However, the pathogenic influence and targetability of HER2 in cutaneous SCC are not well defined. Here, we describe a case of a patient initially presenting with metastatic SCC who underwent primary tumor resection, radiation, and four systemic therapies due to disease progression before her disease was found to harbor an ERBB2 (HER2) mutation; she was subsequently started on HER2 targeted therapy with trastuzumab and achieved a significant sustained response to treatment. This case demonstrates the clinical challenges of treating advanced SCC and highlights HER2 as a potentially targetable driver mutation. Future research is needed to evaluate the association of the HER family and cutaneous SCC, as HER2 may represent an effective therapeutic avenue for patients harboring this mutation.

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