Do you prefer CDK 4/6 inhibitor or PARP inhibitor as first line treatment in a patient with HR+/HER2 neg relapsed/metastatic BRCA positive breast cancer who had previous adjuvant chemotherapy and developed metastatic recurrence while on AI?  

PARP inhibitors haven’t been compared head-to-head with CDK4/6 inhibitors in combination with endocrine therapy, but I would start with the CDK4/6 inhibitor + fulvestrant and save the PARP inhibitor for second line. If the patient has brain metastases, I would use the PARP inhibitor instead. I...

The NCCN guidelines list 1st line CDK4/6i with endocrine (fulvestrant in this case) as preferred in this setting. Use PARPi after exhausting endocrine combinations prior to treating with intravenous chemotherapy options.

Fulvestrant and CDK are reasonable. Please note growing body of evidence showing reduced efficacy of CDK4 in this patient population which would dictate response assessment strategy as in the timing of scans.  Bruno et al., JCO Precision Oncology 2022 

I prefer the CDK 4/6 inhibitor as first line for metastatic HR+/HER2 neg.

Prefer faslodex and CDK 4/6i.

Ribociclib and fulvestrant initially. At progression:- olaparib or talazoprib