Fig. 5: High p16 levels associated with lack of response to CDK4/6i in ER⁺ BC patients.

A Percentage distribution of sensitivity to abemaciclib after 15 days of treatment in the neoadjuvant setting in the ABC-POP trial (n = 72). Tumors were classified as Luminal A if %KI67 < 15 or as Luminal B if %KI67 ≥ 15. Tumors showing ln KI67 < 1 at day 15 were considered sensitive and those with ln KI67 ≥ 1 were resistant to the studied drug. B Box and whiskers plot showing a logistic model to evaluate the effect of p16 on the response to abemaciclib (n = 39 Luminal B tumors). Box represents the median and the 25th and 75th percentiles, whiskers show the largest and smallest value. The mean value of each subgroup is indicated. C Forest plots displaying the odds ratios (OR; black squares) ±95% confidence intervals (CI; horizontal lines) of the association between the indicated biomarkers and the percentage of KI67 after treatment with abemaciclib for all tumors (n = 72; left panel) or Luminal B tumors (n = 39; right panel). Two-sided p-values from Wald tests in logistic models are provided. D Quantification of p16, pRb, cyclin E1 and cyclin D1 in a cohort of n = 10 advanced BC tumors detected by IHC semiquantitatively (pRb p16 cyclin E1 and cyclin D1) displayed according to the patient’s response to abemaciclib. Symbols indicate different CDK4/6i treatments. Mean values ± SEM and unpaired parametric t-test two-tailed p-value are indicated R: resistant; S: sensitive. E Forest plot displaying the odds ratios (OR; black squares) ± 95% confidence intervals (CI; horizontal lines) of the association between the indicated biomarkers and the patient’s response to the study treatments (n = 10 tumors). Fisher’s exact test two-tailed p-values are indicated. Source data are provided as a Source Data file.