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The impact of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) on the incidence of alopecia in patients with metastatic breast cancer (BC)

Alopecia induced by endocrine therapies (ET) such as tamoxifen (TAM), aromatase inhibitors (AI), and fulvestrant, is a widely recognized, albeit under-reported adverse event (AE) that affects up to 25% of patients with breast cancer (BC) and negatively impacts quality of life (QoL) [1,2]. This AE is attributed to a reduction of the estrogenic effect on hair follicles, leading them to enter a resting state and subsequent hair loss [2]. Moreover, upon blockade of estrogen receptor, dihydrotestosterone levels increase and may induce a pattern of alopecia similar to androgenetic alopecia [3]. In contemporary clinical trials, alopecia is classified as grade 1 (the most frequent grade), defined as a hair loss <50% that is not obvious from a distance but only upon close examination, and grade 2, defined as a hair loss 50% that is readily apparent and warrants a wig or hairpiece in order to be completely camouflaged [2,4]. Currently, international guidelines recommend the addition of a CDK4/6i, i.e., palbociclib, ribociclib, or abemaciclib, to ET for patients with hormone receptor-positive (HRþ)/ human epidermal growth factor receptor 2 negative (HER2 ) metastatic BC, due to their synergistic anti-tumor properties which ultimately have led to important improvements in survival outcomes in multiple randomized clinical trials [5]. CDK4/6i work by inducing cell-cycle arrest, which can further contribute to hair growth impairment and justify the increased incidence of alopecia reported thus far in individual trials. Patients receiving CDK4/6i have prolonged treatment durations and maintain a very good QoL – which heightens the negative impact of alopecia on self-image [5]. In this sense, we aimed to better quantify alopecia rates with CDK4/6i plus ET in HRþ/HER2 metastatic BC patients.