Abstract PS1-05-03: Vitiligo-like Lesions Associated with CDK4/6 Inhibitors in Metastatic HR+/HER2− Breast Cancer: Multiple case reports from a Brazilian experience

Abstract Introduction CDK4/6 inhibitors have significantly changed altered the natural history of HR+/HER2− metastatic breast cancer, leading to substantial improvements in progression-free and overall survival. These drugs are generally well tolerated, with manageable toxicity profiles. However, rare dermatologic adverse events may be underreported and poorly understood. In this study, we describe case series of patients who developed vitiligo-like lesions during treatment with ribociclib or abemaciclib. Case Series Description A total of eight women with HR+/HER2− metastatic breast cancer receiving ribociclib (n=7) or abemaciclib (n=1), all in combination with endocrine therapy (aromatase inhibitor or fulvestrant), developed well-demarcated depigmented lesions consistent with vitiligo-like lesions. None had a prior history of autoimmune or dermatologic disease. Dermatologic evaluations and lesion photographs were obtained. In two cases, skin biopsies revealed pigmentary incontinence and chronic perivascular mononuclear infiltrate.Cutaneous changes developed within a median of 8 months (minimum 6 and maximum 24 months) after treatment initiation. The lesions were asymptomatic, hypopigmented, and primarily involved the face, neck, and upper limbs. No systemic symptoms were reported. Dermatological evaluation ruled out other differential diagnoses and suggested an immune-mediated mechanism. In one patient, treatment was permanently discontinued after two years due to cutaneous toxicity from vitiligo-like lesions, with sustained oncologic response; another patient had a temporary 3-month drug interruption due to lesion worsening, after which the skin changes stabilized. All patients were treated with topical corticosteroids, resulting in partial improvement. Complete lesion regression was observed in the patient who discontinued therapy; three patients had stable lesions while continuing medication; others showed partial regression after treatment change due to disease progression. Discussion The most common skin toxicities associated with ribociclib and abemaciclib include rashes and dermatitis (10-20%). Vitiligo-like reactions are rare. CDK4/6 inhibitors may affect the proliferation of keratinocyte precursors, compromising the secretion of melanocyte-supporting cytokines. Treatment-induced melanocyte apoptosis may contribute to depigmentation. Additionally, ultraviolet radiation-induced melanocyte damage may trigger immune responses, highlighting the importance of sun protection. However, the underlying pathophysiology remains unclear. Conclusion This case series highlights a potentially underrecognized cutaneous adverse event associated with CDK4/6 inhibitors (ribociclib and abemaciclib). Oncologists should be aware of vitiligo-like reactions as part of the toxicity spectrum of these agents. It is important to point out that this is not a life-threatening condition but it can affect appearance, specially of the face, causing burden for patients. Early recognition and collaborative management with dermatology can allow continuation of cancer therapy without compromising treatment outcomes or quality of life. Further studies are needed to better understand this phenomenon. Citation Format: R. M. Borges, M. C. Gouveia, C. Giro, M. Aisen, L. C. Oliveira, N. J. Gomes, A. C. Ferrari, T. G. Rivelli, M. S. Neto, M. L. Brito, R. B. Sousa, K. P. Sacardo, B. M. Zucchetti. Vitiligo-like Lesions Associated with CDK4/6 Inhibitors in Metastatic HR+/HER2− Breast Cancer: Multiple case reports from a Brazilian experience [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-05-03.