For a study, researchers sought to present the breast cancer cohort. In a previous study, they reported on safety. They recommended a phase 2 dose (RP2D) of olaparib combined with the PI3Kα-specific inhibitor alpelisib in patients with high-grade serous ovarian cancer as studied in a phase 1b trial (NCT01623349). Investigators presented here the breast cancer cohort from that study. Patients were enrolled in a dose-escalation or -expansion cohort if they had recurrent triple-negative breast cancer (TNBC) or recurrent breast cancer of any subtype with a germline BRCA mutation. After the RP2D was defined, secondary endpoints included safety and objective response rate (ORR). Using circulating-free DNA, exploratory analyses were carried out (cfDNA). About 17 TNBC patients with a median of 3 prior lines of chemotherapy were enrolled. The most familiar diagnosis grade 3–4 adverse events were hyperglycemia (18%) and rash (12%). The ORR was 18% (23% for patients treated at the RP2D), and 59% had disease control. The median response time was 7.4 months. Patients with TFx of less than 15% after the first cycle had longer progression-free survival than those with TFx of more than equal to 15% (6.0 vs. 0.9 months; P=0.0001). In patients with previously treated TNBC, alpelisib combined with olaparib was tolerable, with evidence of activity in non-BRCA carriers. The cDNA provided critical prognostic information. The findings highlighted the potential synergistic use of a PI3K inhibitor to sensitize HR-proficient (BRCA wild-type) TNBC to PARP inhibition and suggest that PARP inhibition may be used in tumors other than BRCA-mutant tumors.