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RB1 Loss CDK4/6 Resistance — SCE Medical Oncology MCQ

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HardBreast CancerRB1 Loss CDK4/6 ResistanceSCE Medical Oncology

A 65-year-old woman with ER+/HER2- breast cancer develops bone metastases after 7 years of endocrine therapy. Genomic analysis of the metastatic biopsy shows an acquired RB1 loss. What is the clinical significance?

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Correct answer: A — RB1 loss may confer resistance to CDK4/6 inhibitors

CDK4/6 inhibitors exert their anti-tumour effect by preventing RB phosphorylation, maintaining RB in its active (hypophosphorylated) tumour-suppressive state. Loss of RB protein (through RB1 mutation/deletion) eliminates the drug target, conferring resistance. RB1 loss is found in approximately 5% of ER+ breast cancers at CDK4/6 inhibitor progression. This is an example of predictive biomarker-driven resistance informing subsequent treatment selection.

Reference: https://www.nice.org.uk/guidance/conditions-and-diseases/cancer