Abstract 47P
Background
Activating mutations of PIK3CA gene are described in around 30-40% of breast cancer (BC) patients. They confer worse prognosis and resistance to endocrine and chemotherapeutic therapy. Concordance between testing methods (tissue & plasma) are not well studied. We aim to compare tissue & plasma assays and to analyze the clinicopathological features and the prognostic value of PIK3CA mutations in HR+/HER2-.
Methods
We performed a retrospective and unicentric analysis of PIK3CA mutational status in tissue & plasma samples in patients (p) with HR+/HER2- BC from Feb/21 to Dec/22. PIK3CA test: Cobas®PIK3CA Mutation Kit. We carried out a correlation between both test assays. We used X2 test to compare patients’ features and Kaplan Meier to analyze progression-free survival (PFS) in PIK3CA mutated (PIK3CAm) vs wild-type (wt).
Results
189 samples were analyzed in 155p with HR+/HER2- BC (128 in tissue & 61 in plasma). PIK3CA mutations were detected in 56p (36.1%), of which 39.1% (50p) in tissue and 13.1% (8p) in plasma. Hotspot mutations: H1047X (46%), E545X (20.6%) and E542K (12.7%). Tissue-plasma correlation was available in 34p (M1 stage), with overall correlation rate of 70.6%. 10 cases (29.4%) were positive in tissue but not in plasma. Patient characteristics are described in the table: significant differences were observed in histological type (p=0.005) and grade (p=0.03). 57p received 1L treatment with CDK4/6 inhibitors + endocrine therapy. PFS was significantly shorter in PIK3CAm vs wt (24m [95%CI;3.4-44.6] vs 35.6m [95%CI;19.6-51.6]; p=0.03). A trend towards lower objective response rate (64.7% vs 71.8%, p=0.59) was observed in PIK3CAm patients.
Table: 47P
| Age (median) | 56 [24-91] | PIK3CA m | PIK3CA wt | p-value |
| Histological type | Ductal | 45(76.3%) | 85(81.7%) | P=0.005 |
| Lobular | 12(20.3%) | 6(5.8%) | ||
| Other | 2(3.4%) | 13(12.5%) | ||
| Histological grade | 1 | 19(34.5%) | 17(17%) | P=0.03 |
| 2 | 30(54.6%) | 65(66%) | ||
| 3 | 6(10.9%) | 18(18%) | ||
| Ki67(%) | <14% | 28(50%) | 52(50.9%) | P=0.91 |
| ≥14% | 28(50%) | 50(49.1%) | ||
| Tumour size | <50mm | 41(74.5%) | 88(85.4%) | P=0.09 |
| ≥50mm | 14(25.5%) | 15(14.6%) | ||
| Nodes(N) | N0 | 19(41.3%) | 29(32,6%) | P=0.31 |
| N+ | 27(58.7%) | 60(67.4%) | ||
| Debut M1 | Yes | 10(34.5%) | 21(38.2%) | P=0.73 |
| No | 19(65.5%) | 34(61.8%) | ||
| Visceral metastases | Yes | 24(82.8%) | 40 (72.7%) | P=0.31 |
| No | 5(17.2%) | 15(27.3%) |
Conclusions
Mutational spectrum and clinical features in PIK3CAm luminal BC in our environment are consistent with those described previously. We observed worse prognosis and resistance to endocrine therapy in PIK3CAm luminal BC. We need larger studies to evaluate the role of liquid biopsy in the detection of PIK3CAm.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C.A. Rodríguez Sanchez: Non-Financial Interests, Institutional, Advisory Role: Novartis, Lilly, Pfizer, Roche, Daiichi Sankyo, AstraZeneca, MSD, Veracyte, Gilead. All other authors have declared no conflicts of interest.