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BRCA1/2 reversion mutations that restore protein function and lead to clinically significant rates of acquired resistance can be detected in an unbiased analysis of cell-free DNA, an analysis of plasma and tumor samples from 30 patients with high-grade serous ovarian cancer (HGSC) and BRCA1 or BRCA2 germline mutation shows.
The findings suggest that detection of these mutations could be useful for predicting chemotherapy response in recurrent HGSC, reported Elizabeth L. Christie, PhD, of Peter MacCallum Cancer Centre, Melbourne, and her colleagues.
The findings of this study suggest that detection of BRCA1/2 reversion mutations in cfDNA by targeted amplicon sequencing is feasible and predictive of poor response to platin-based therapy or PARP inhibition, which is important given the current lack of predictive markers of response to guide drug selection in patients with recurrent HGSC, the investigators said.
Further evaluation is needed, but the findings suggest that analysis of cell-free DNA has the potential to be used to direct treatment in recurrent HGSC, they concluded.
Dr. Christie reported having no conflicts of interest.
BRCA1/2 reversion mutations that restore protein function and lead to clinically significant rates of acquired resistance can be detected in an unbiased analysis of cell-free DNA, an analysis of plasma and tumor samples from 30 patients with high-grade serous ovarian cancer (HGSC) and BRCA1 or BRCA2 germline mutation shows.
The findings suggest that detection of these mutations could be useful for predicting chemotherapy response in recurrent HGSC, reported Elizabeth L. Christie, PhD, of Peter MacCallum Cancer Centre, Melbourne, and her colleagues.
The findings of this study suggest that detection of BRCA1/2 reversion mutations in cfDNA by targeted amplicon sequencing is feasible and predictive of poor response to platin-based therapy or PARP inhibition, which is important given the current lack of predictive markers of response to guide drug selection in patients with recurrent HGSC, the investigators said.
Further evaluation is needed, but the findings suggest that analysis of cell-free DNA has the potential to be used to direct treatment in recurrent HGSC, they concluded.
Dr. Christie reported having no conflicts of interest.
BRCA1/2 reversion mutations that restore protein function and lead to clinically significant rates of acquired resistance can be detected in an unbiased analysis of cell-free DNA, an analysis of plasma and tumor samples from 30 patients with high-grade serous ovarian cancer (HGSC) and BRCA1 or BRCA2 germline mutation shows.
The findings suggest that detection of these mutations could be useful for predicting chemotherapy response in recurrent HGSC, reported Elizabeth L. Christie, PhD, of Peter MacCallum Cancer Centre, Melbourne, and her colleagues.
The findings of this study suggest that detection of BRCA1/2 reversion mutations in cfDNA by targeted amplicon sequencing is feasible and predictive of poor response to platin-based therapy or PARP inhibition, which is important given the current lack of predictive markers of response to guide drug selection in patients with recurrent HGSC, the investigators said.
Further evaluation is needed, but the findings suggest that analysis of cell-free DNA has the potential to be used to direct treatment in recurrent HGSC, they concluded.
Dr. Christie reported having no conflicts of interest.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point:
Major finding: Five of 30 patients – all in the recurrent disease group – had reversion mutations. Reversion mutations were detected in the cell-free DNA only from those with tumor-detected reversion.
Data source: Plasma and tumor samples from 30 women in the Australian Ovarian Cancer Study.
Disclosures: Dr. Christie reported having no conflicts of interest.