We found that in the BMI-high group of HR-positive advanced breast cancer patients treated with first-line CDK4/6 inhibitors, OS was significantly longer than in the BMI-low group (46.6 vs. 78.9 months, p = 0.047), and there was also a trend toward extended PFS (25 vs. 33 months), although the latter did not reach statistical significance. This evidence concerns the gene CDK4 and breast cancer.