Breast cancer is women’s most common malignant tumor globally [1]. Endocrine therapy is a reasonably necessary treatment for HR+ breast cancer. In recent years, with the emergence and widespread application of endocrine-targeted drugs, treatment strategies have resulted in revolutionary changes, further improving patients’ overall survival time and quality of life. CDK4/6 inhibitors are one of the most representative stars. Combination with aromatase inhibitors (AIs) or Fulvestrant has become the preferred first-line treatment for HR+HER2- advanced breast cancer patients [2, 3]. Currently, three CDK4/6 inhibitors worldwide used in the world: Ribociclib, Palbociclib, and Abemaciclib [4, 5]. The most common adverse events (AEs) consist of neutropenia, leukopenia, anemia, fatigue, liver dysfunction, and diarrhea. What’s more, treatment with CDK 4/6 inhibitors also be associated with several potential dermatologic toxicities, including alopecia, which is the most frequent [6]. Vitiligo-like lesions induced by CDK4/6 inhibitors are rare, although some case reports have described vitiligo-like lesions caused by Ribociclib [7, 8].

Here we describe a rare case of vitiligo-like lesions developing after treatment with Palbociclib, a CDK4/6 inhibitor. This 58-year-old woman did not experience any discomfort and insisted on taking the drug for further use of the regimen. We adopted the “watch and wait” strategy, and her progression-free survival time has exceeded 24 months. Intending to share our experience to raise awareness among clinicians and contribute to the literature, we present the following information based on the CARE reporting checklist [9].

Paloma-2 [10], a randomized controlled double-blind phase III clinical study investigating the efficacy and safety of Palbociclib in combination with letrozole in patients with primary HR+HER2− advanced breast cancer. A total of 666 patients were enrolled in the study. Median progression-free survival was 24.8 months for Palbociclib -letrozole versus 14.5 months for placebo-letrozole (hazard ratio, 0.58; 95% CI, 0.46 to 0.72; p < 0.001). The most common treatment-related adverse events (AEs) of grade 3 or 4 were neutropenia, leukopenia, anemia, and fatigue. Dermatologic AEs reported in this article included alopecia (Any grade 32.9%), rash (Any grade 17.8, Grade 3 0.9%), and dry skin (Any grade 32.9%). No dermatologic AEs of vitiligo-like lesions were reported.

Vitiligo is an acquired pigmentary autoimmune disorder consisting of developing hypopigmented macules due to the selective loss of melanocytes. Possible mechanisms for the development of vitiligo include autoimmunity, oxidative stress, melanocyte self-destruction, and genetic predisposition [7, 11]. It’s not life-threatening. Nevertheless, it affects patients’ psychosocial health, interpersonal communication, and health-related quality of life [12]. In patients treated with immune checkpoint inhibitors, vitiligo-like lesions caused by antineoplastic drugs are occasionally reported. We were also surprised to find occasional reports of vitiligo-like lesions associated with B-cell leukemia/lymphoma-2 (Bcl-2) inhibitor Venetoclax [13].

Vitiligo-like lesions induced by cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are rare, and the pathogenesis of vitiligo-like lesions induced by CDK4/6 inhibitors is also poorly understood. Zhou [14] hypothesized that CDK inhibitors can block the cell cycle and deregulate the expression of small ubiquitin-like modulators expression in keratinocytes, eventually resulting in the occurrence of vitiligo.

To our knowledge, only three cases of Pabociclib-induced vitiligo-like lesions have been reported in the literature. The data on the previous reports were summarized data are enumerated in Table 1. Sollena [15], on behalf of the European Network for Cutaneous ADverse event to Oncologic drugs (ENCADO) group, first reported two cases of vitiligo-like lesions after using Palbociclib in the treatment of 16 patients with metastatic breast cancer in six European university-based centers. Both two patients experienced cutaneous pruritus. Patient No. 1 was affected with vitiligo-like lesions in 60% of BSA after taking 8 months of Palbociclib and Fulvestrant was treated with oral corticosteroids and calcineurin inhibitors, the outcome of dermatologic treatment is PR, the lesions reached an improvement and the area reduced. Patient No. 2 found vitiligo-like lesions in 12 months of using Palbociclib and Letrozole was treated with topical oral corticosteroids. No. 3 is a patient who appeared hypopigmented lesions after 1 month of changing from Ribociclib to Pabociclib. At the same time, she decided to refuse to take any treatment, and the cutaneous lesions were stable within a 4-month follow-up [16].

Our patient was diagnosed with vitiligo after 10 months of Palbociclib and letrozole treatment. Her occurrence time of vitiligo-like lesions is approximately consistent with the patients’ described in Sollena’s study. As she did not experience any discomfort, such as inflammation or pruritus, she does not agree to any additional medication. Tumors and vitiligo were observed to remain stable for up to now, more than 14 months. We have reason to suspect that these vitiligo-like skin lesions are related to Palbociclib in the absence of prior evidence that letrozole may cause specific hypopigmented macules. We need to be vigilant about this rarely-seen adverse; counselling patients regarding the possibility of vitiligo¬like lesions prior to initiation of Palbociclib may help lessen the impact of this adverse event on the patient’s mental health and quality of life.

Our case adds to the knowledge gained from the existing case reports in the literature. Firstly, vitiligo-like skin lesions can be encountered late in Palbociclib therapy. Second, the range of vitiligo-like skin lesions does not show remission during an intermission in treatment, which provides evidence that these lesions induced by Palbociclib are irreversible. Future large-scale clinical studies are needed to provide more evidence for this hypothesis.