Abstract P1-08-30: Vitiligo-like reaction in a patient with metastatic RH+/HER2-negative breast cancer treated with ribociclib: A case report and literature review

Abstract Introduction: Cyclin inhibitors have significantly altered the natural history of metastatic RH+/HER2-negative breast cancer and achieved excellent disease control with progression-free survival of more than two years. Ribociclib, the leading agent in this class, is highly effective with manageable side effects. Here we report the case of a patient who experienced an unusual dermatologic side effect, a vitiligo-like reaction. Case Report: A 65-year-old female patient, married and mother of two daughters, had a long-standing diagnosis of luminal-type breast cancer. Her first primary tumor was diagnosed in 2000 and treated with conservative surgery, adjuvant chemotherapy, radiotherapy and hormone therapy. This was followed by an ipsilateral local recurrence, which led to a mastectomy on the right side, and a new primary tumor in the contralateral breast, which was also treated with a mastectomy and local recurrence. Since 2018, she has been diagnosed with metastatic disease, which initially affected the bones, lymph nodes and lungs. First-line treatment with letrozole, ribociclib and denosumab was initiated. The patient showed significant radiologic improvement, with PET-CT showing complete radiologic and metabolic response, and remission persisted for approximately two years. After about two years of treatment, the patient developed hypochromic lesions on the face, chest and limbs that resembled vitiligo. A skin biopsy revealed atrophy and basal melanin hypopigmentation with negative fungal findings, suggesting post-inflammatory hypochromia. This vitiligo-like reaction was attributed to ribociclib, which was discontinued, and treatment was continued with letrozole alone. In addition, the patient received topical corticosteroid treatment. Approximately eight weeks later, the patient experienced repigmentation of the lesions and complete resolution of the disease. She is currently continuing to take letrozole with no evidence of neoplastic disease on imaging. Discussion: Ribociclib belongs to the class of CDK4/6 inhibitors and is highly effective and well tolerated. The main side effects reported include neutropenia and hepatobiliary changes. Skin reactions such as rashes, dermatitis and alopecia occur in about 5 to 10 of patients taking ribociclib. However, these are usually mild and easily manageable. Grade 3 skin rashes occur in only about 0.9% of patients. Only a few cases of vitiligo-like reactions associated with cyclin inhibitors are known in the literature. The largest series is a multicenter, retrospective study involving centers in the US and Europe, with a total of 16 patients reported, underscoring the rarity of this reaction. The exact mechanisms leading to this reaction are not fully understood, but there are hypotheses concerning the immune response to treatment. In addition, some studies suggest that these responses may be associated with better survival. In this case, several points should be emphasized. The first is the excellent response, with complete radiologic and metabolic response. The second is the long duration to the onset of the reported toxicity, which lasted about two years. The third point is the complete reversibility of the lesions after discontinuation of ribociclib and treatment with a topical corticosteroid. Conclusion: Vitiligo-like reactions associated with cyclin inhibitors are reactions that require further investigation due to their negative impact on patients' quality of life and their possible association with improved survival outcomes. Future studies are needed to better understand the pathophysiologic mechanisms involved. Citation Format: Anezka Ferrari, Herbert Amaral, Mariana Pina, Bruna Zucchetti, Ângelo Fêde, Renata Arakelian, Karina Sacardo, Cynthia Lemos, Mariana Gouveia, Manuel Cruz, Manoel Carlos Souza, Tiago Takahashi, Renata dos Anjos, Dalton dos Anjos, Romualdo Barroso. Vitiligo-like reaction in a patient with metastatic RH+/HER2-negative breast cancer treated with ribociclib: A case report and literature review [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-08-30.