This is particularly important on adjuvant setting. Patients who are HRD positive should received adjuvant PARP not CK4/6

Thanks, All, for your wonderful input! Does anyone else see clinical value in the findings of this study? Will more data points on genomic biomarkers change your approach?

I think the continued difficulty is how to balance ordering comprehensive panel testing which could come back with a number of prognostic findings (like FGFR1 amplification, PTEN loss, etc) but that will not change management. Testing for abnormalities that will change management is a no-brainer as per the NCCN guidelines, and clinical trial eligibility is an important consideration, but findings associated with poor prognosis are not particularly impactful in the clinic.

Key Points
• Source: Cancers
• Conclusion/Relevance: “In this retrospective analysis, genomic biomarkers including FGFR1 amplification, PTEN loss, and DNA repair pathway gene mutations showed significant associations with shorter PFS for patients receiving CDK4/6 inhibitor therapy.”
• The mechanisms underlying intrinsic and acquired resistance to CDK4/6 inhibitors require elucidation.
• In the current retrospective study, researchers grouped 109 HR+ MBC patients treated with CDK4/6i and antiestrogen therapy into the following groups: early (<6 months); intermediate (6–24 months for 0–1 lines; 6–9 months for ≥2 lines); or late progressors (>24 months for 0–1 lines; >9 months PFS for ≥2 lines).
• They identified 17 genes related to PFS. The researchers examined whole transcriptome RNAseq for 22% of patients with 0–1 prior lines of therapy and 56 genes associated with PFS.
• In the current study, only 16% of patients received tumor genomic testing, with only 7% of community dwellers receiving testing.
• “The patients included in this study were treated prior to 2020, when broad-panel NGS was commonly adopted as routine clinical practice,” the authors wrote. “NCCN Guidelines for Breast Cancer include NGS and comprehensive genomic profiling (CGP) as a method of detecting actionable mutations and fusions such as BRCA1/2 mutations, PIK3CA mutations, ESR1 mutation, HER2 mutation, MSI-H status, and deficient mismatch repair (dMMR). Integrating community oncologists into the academic paradigm of personalized medicine, including continued development of interpersonal relationships between community oncologists and academic site physicians through molecular tumor board teams, will play a major role in personalized therapy advancements in oncology.”
• Limitations of the current study include its small sample size and a minority participants receiving CDK4/6i genomic sequencing.

PTEN loss is common on NGS testing