Would you recommend olaparib for a patient with germline BRCA1 mutation and HER2+ metastatic breast cancer who has progressed through multiple lines of HER2-directed therapy including trastuzumab deruxtecan?

Although OlympiAD (Robson et al., PMID 28578601) and EMBRACA (Litton et al., PMID 30110579) studied olaparib and talazoparib in HER2negative gBRCA mutant metastatic breast cancer, the activity is based on the mechanism of synthetic lethality in BRCA deficient tumors. Thus, it is reasonable to think ...

True HER 2 amplified breast tumors are rare with germline BRCA 1 pathogenic variants (Evans et al., PMID 26888723). I would suggest confirming HER 2 expression/amplification with pathology.

There is preclinical evidence of anti tumor activity of PARPi in trastuzumab resistant HER 2 expressing cell li...

The data for olaparib from OlympiAD was for HER2- metastatic disease (including HER2 low patients). Given the size of DESTINY-Breast04, there were probably very few BRCA mutated patients actually treated to make any conclusions on efficacy, but I don't think there would be a lot of cross resistance ...

Metastatic HER2+ breast cancer is treated with HER2-targeted therapy combined with a cytotoxic therapy. The FDA approvals for olaparib and talazoparib were based on clinical trials that excluded patients with HER2+ breast cancer, so insurance might not pay for a PARP inhibitor in the HER2+ setting, ...