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Prospective Decision Analysis Study of Clinical Genomic Testing in Metastatic Breast Cancer: Impact on Outcomes and
Daniel G Stover1,2, Raquel E Reinbolt1,2, Elizabeth J Adams3
1The Ohio State University College of Medicine, Columbus, OH.
Purpose:
To evaluate the impact of targeted DNA sequencing on selection of cancer therapy for patients with metastatic breast cancer (MBC).
Patients And Methods:
In this prospective, single-center, single-arm trial, patients with MBC were enrolled within 10 weeks of starting a new therapy. At enrollment, tumor samples underwent next-generation sequencing for any of 315 cancer-related genes to high depth (> 500×) using FoundationOne CDx. Sequencing results were released to providers at the time of disease progression, and physician treatment recommendations were assessed via questionnaire. We evaluated three prespecified questions to assess patients' perceptions of genomic testing.
Results:
In all, 100 patients underwent genomic testing, with a median of five mutations (range, 0 to 13 mutations) detected per patient. Genomic testing revealed one or more potential therapies in 98% of patients (98 of 100), and 60% of patients (60 of 100) had one or more recommended treatments with level I/II evidence for actionability. Among the 94 genomic text reports that were released, there was physician questionnaire data for 87 patients (response rate, 92.6%) and 31.0% of patients (27 of 87) had treatment change recommended by their physician. Of these, 37.0% (10 of 27) received the treatment supported by genomic testing. We did not detect a statistically significant difference in time-to-treatment failure (log-rank P = .87) or overall survival (P = .71) among patients who had treatment change supported by genomic testing versus those who had no treatment change. For patients who completed surveys before and after genomic testing, there was a significant decrease in confidence of treatment success, specifically among patients who did not have treatment change supported by genomic testing (McNemar's test of agreement P = .001).
Conclusion:
In this prospective study, genomic profiling of tumors in patients with MBC frequently identified potential treatments and resulted in treatment change in a minority of patients. Patients whose therapy was not changed on the basis of genomic testing seemed to have a decrease in confidence of treatment success.
Insights
Genomic testing in metastatic breast cancer (MBC) frequently identified potential therapies, but treatment changes occurred in a minority. Patients not receiving genomic-guided treatment showed decreased confidence in treatment success.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Metastatic breast cancer (MBC) management benefits from personalized treatment strategies.
- Targeted DNA sequencing offers insights into tumor molecular profiles to guide therapy selection.
Purpose of the Study:
- To assess the impact of targeted DNA sequencing on cancer therapy selection for patients with metastatic breast cancer.
- To evaluate physician treatment recommendations and patient perceptions following genomic testing.
Main Methods:
- Prospective, single-center, single-arm trial involving 100 patients with MBC.
- Next-generation sequencing of 315 cancer-related genes (FoundationOne CDx) performed on tumor samples.
- Physician treatment recommendations and patient perceptions assessed via questionnaires.
Main Results:
- Genomic testing identified potential therapies in 98% of patients; 60% had actionable recommendations (Level I/II evidence).
- Physician-recommended treatment changes based on genomic data occurred in 31% of patients, with 37% receiving such treatment.
- No significant difference in time-to-treatment failure or overall survival was observed between groups.
- Patients without genomic-guided treatment changes reported decreased confidence in treatment success.
Conclusions:
- Genomic profiling in MBC frequently identifies potential treatment options but leads to treatment modification in a subset of patients.
- Genomic testing may influence patient confidence in treatment efficacy, particularly when no change is implemented.
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