Abstract Introduction: Hand-foot syndrome, also known as palmar-plantar erythrodysesthesia, is a common side effect observed in patients undergoing various chemotherapeutic treatments, including capecitabine. It is characterized by symmetrical palmoplantar numbness, pain, erythema with or without edema, and desquamation. Case Presentation: A 38-year-old woman was diagnosed with multifocal mucinous invasive carcinoma of the left breast, which was ER+, PR+, and HER-2-. She underwent neoadjuvant therapy with docetaxel and trastuzumab, followed by bilateral mastectomy. Postoperatively, radiation therapy was administered to the chest wall, and Tamoxifen and trastuzumab were prescribed. Disease progression occurred after 15 months, involving the sternum, retroperitoneal lymph nodes, and supraclavicular areas. Gemcitabine plus trastuzumab was initiated, along with Zometa for supportive care, resulting in a favorable response for five months. Chemotherapy was discontinued, and the patient received goserelin with anastrozole. One month after discontinuing gemcitabine, she developed recurrent lung disease. Lapatinib plus Capecitabine were administered for 12 months, resulting in further progression to the brain. Brain lesions were managed through whole brain radiation, stereotactic radiosurgery, and a palliative craniectomy. The patient developed a chronic left-sided hemiparesis and a contracture in her left hand. Ado-trastuzumab was initiated but resulted in disease progression. Subsequently, Capecitabine and Neratinib were administered, with a positive response. However, within six months, she developed grade 2 hand-foot syndrome, characterized by erythema and desquamation of the right palm and soles. Supportive care and dose reduction of Capecitabine improved symptoms. Discussion: The pathogenesis of Hand-Foot Syndrome (HFS) remains incompletely understood and may vary depending on the chemotherapeutic agents used. Possible causes include direct toxicity to eccrine coils, activation of enzymes leading to increased metabolite concentration, micro-trauma causing persistent drug extravasation and tissue damage, and activation of inflammatory pathways. Further research is needed to better understand the neurovascular mechanisms involved in HFS. Conclusion: This case report provides insights into the pathophysiological mechanisms of Hand-Foot Syndrome associated with capecitabine use. Preexisting hemiparesis may play a role in protecting against HFS development, suggesting the involvement of mechanical stress. Patients should be advised to avoid activities that subject the palms and soles to excessive friction. Clinicians should be aware of atypical presentations of HFS in patients with neurological disorders and medications that can trigger HFS. Future studies should focus on elucidating the neurovascular mechanisms to enhance patient management. Citation Format: Daniela Urueta Portillo, Kate Lathrop. A rare unilateral expression of hand-foot syndrome: a case report [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-20-09.
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