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Topics:
Breast Cancer • Medical Oncology • ASCO Journal Club • Cancer Predisposition • Breast Cancer, Metastatic
Would you consider use of PARP inhibitors in patients with metastatic breast cancer with moderate penetrance germline mutations such as CHEK2, ATM, RAD51?
What about a higher penetrance PV such as PALB2?
See JCO OGR 8/2021 by @Mark E. Robson discussing management of non-BRCA pathogenic variants, and companion study (Kraft et al, 8/2021) evaluating the role of further characterization of polygenic risk score.
Answer from: Medical Oncologist at Academic Institution
In the Olaparib Expanded (TBCRC 048) study published by @Nadine M. Tung in JCO, there were no responses to olaparib in metastatic breast cancer with germline or somatic CHEK2 or ATM pathogenic variants (mutations). In contrast, responses were seen in metastatic breast cancer with PALB2 pathogenic va...
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Answer from: Medical Oncologist at Academic Institution
There are limited data about the use of PARP inhibitors in women with moderate penetrance alterations. Those data suggest that cancers associated with PALB2 alterations are highly sensitive to PARP inhibitors. However, alterations in the other genes such as ATM and CHEK2 do not appear to be sensitiv...
Answer from: Medical Oncologist at Community Practice
There's no evidence to treating patients with CHEK2 mutation with PARP inhibitors.