Rb expression in metastatic ER-positive breast cancer: implications for precision oncology

Area of Science:

• Oncology
• Cell Biology
• Genetics

Background:

• Retinoblastoma protein (Rb) is a key cell-cycle regulator.
• Loss of Rb function confers resistance to CDK4/6 inhibitors (CDK4/6i).
• CDK4/6i are standard treatment for ER-positive metastatic breast carcinoma (mBC).

Purpose of the Study:

• Determine the prevalence of Rb loss in ER+ mBC using immunohistochemistry (IHC).
• Correlate Rb loss with RB1 genetic inactivation.
• Assess the utility of Rb IHC for personalized breast cancer management.

Main Methods:

• Analyzed Rb IHC in 50 ER+ mBC cases.
• Performed p16 IHC in Rb-deficient cases.
• Retrospectively analyzed targeted next-generation sequencing (NGS) data (MSK-IMPACT) in 38 mBCs.

Main Results:

• Rb loss detected in 20% (10/50) of mBC (partial 8%, complete 12%).
• Rb loss associated with p16 positivity (100%) and neuroendocrine (NE) features (40%).
• Pathogenic RB1 alterations found in 33% (2/6) of Rb-deficient cases via NGS; one case showed acquired Rb loss upon disease progression.

Conclusions:

• Rb IHC reliably detects Rb loss in mBC, especially with p16 co-expression.
• Rb IHC is a rapid, cost-effective method for assessing Rb status.
• This approach identifies Rb-deficient tumors potentially missed by NGS, guiding personalized mBC therapy.