Abstract 495P
Background
PIK3CA mutations are described in about 30-40% of BC. They confer resistance to endocrine therapy and overall worse prognosis. Concordance between testing methods (tissue & plasma) are not widely studied. We aim to correlate tissue & plasma assays and to analyze the prognostic value of PIK3CA mutations in HR+/HER2- BC.
Methods
Retrospective and unicentric analysis of PIK3CA mutational status in tissue & plasma samples in patients (p) with HR+/HER2- BC from Feb/21 to Mar/23. PIK3CA test: Cobas®PIK3CA Mutation Kit. We correlated both diagnostic methods and analysed progression-free survival (PFS) in PIK3CA mutated (PIK3CAm) vs wild-type (wt).
Results
We analyzed 225 samples in 161p with HR+/HER2- BC (149 in tissue & 76 in plasma). PIK3CA mutations were detected in 62p (38.5%), of which 39.6% (59p) in tissue and 11.8% (9p) in plasma. Hotspot mutations: H1047X (45.7%), E545X (20%) and E542K (12.8%). Tissue & plasma correlation was conducted in 64p (M1 stage), with overall correlation rate of 70.3%. 19 cases (29.7%) were positive in tissue but not in plasma. 80p received treatment with CDK4/6 inhibitors + endocrine therapy. PFS was shorter in PIK3CAm vs wt (24m vs 30m; HR=1.39 [95%CI,0.7-2.4], p=0.25). A sub-analysis was performed based on exons 9 & 20, showing a significantly lower PFS in PIK3CAm exon 9 vs 20 population (9.7m vs 30.3m; HR=2.84 [95%CI,1.1-7.4], p=0.02). Although we observed a poorer PFS in p with visceral involvement in PIK3CAm (21.9m vs 30.1m; HR=2.82 [95%CI,0.6-12.3], p=0.14), in a multivariate analysis, mutations in exon 9 were an independent poor prognostic factor regardless visceral involvement; p=0.027. Table: 495P
Tissue | ||||
Mutated | Wild-type | Total | ||
Plasma | Mutated | 9 (32.1%) | 0 (0%) | 9 (14.1%) |
Wild-type | 19 (67.8%) | 36 (100%) | 55 (85.9%) | |
Total | 28 (100%) | 36 (100%) | 64 (100%) | |
Positive agreement: 9/28 (32.1%) | ||||
Negative agreement: 36/36 (100%) | ||||
Overall agreement: 45/64 (70.3%) |
Conclusions
Our results support the determination of PIK3CA in tissue as the diagnostic method of choice, although further studies are needed to assess the role of liquid biopsy in the detection of PIK3CAm. In our population, the presence of PIK3CAm confers worse prognosis in luminal BC, being significantly worse in mutation carriers in exon 9 regardless visceral involvement.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
R. Lozano Mejorada: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, Roche, Bayer, IPSEN, AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen, Merck/Pfizer, Orion Pharma, Advanced Accelerator Applications (Novartis); Financial Interests, Personal, Other, Travel / accommodation: MSD, Sanofi; Financial Interests, Personal, Other, Travel / accommodation: BMS; Non-Financial Interests, Member: Sociedad Española de Oncología Médica. All other authors have declared no conflicts of interest.
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