10-15% of breast cancers are triple negative breast cancer (TNBC), an aggressive subtype that has the lowest 5-year survival rate and has shown to be recurrent in 30% of cases. TNBC has not benefitted from personalised therapies that have driven significant increases in survival in other cancer types, and the standard of care for TNBC patients is chemotherapy, which has severe adverse effects. We have shown that TNBC patients who have a combination of RB1+/p16 low markers could benefit from CDK4/6 inhibitor therapy.
We established RB1+/p16- and RB1-/p16+ cell lines to investigate this hypothesis. Firstly, we have shown how RB1+/p16- cells are more susceptible to the CDK4/6 inhibitor treatment compared to RB1-/p16+ cells. As the p16/RB1 checkpoint plays a crucial role in the cell cycle, we treated our cell lines with the CDK4/6 inhibitor palbociclib and found that RB1+/p16- cells undergo cell cycle arrest at G1 when treated with palbociclib, whereas RB1-/p16+ cells do not. Additionally, we have also examined relative tumour inhibition by palbociclib in RB1+/p16-low, RB1+/p16-moderate and RB1+/p16-high models in vivo. With treatment, the RB1+/p16-low model showed the greatest reduction in tumour volume, followed by the RB1+/p16-moderate, and the RB1+/p16-high model had the least response, demonstrating that in vivo expression of p16 negatively correlates to CDK4/6 inhibition of tumour development.
Excitingly, RB1 and p16 IHC are existing clinical pathology tests for other malignancies and CDK4/6 inhibitors are approved drugs, allowing for the potential of rapid clinical translation of these findings, and ultimately improving outcome for TNBC patients.