Abstract P3-08-12: PIK3CA mutations in breast cancer: Mutational landscape and clinical implications in ER+/HER2- subtype

Abstract

Abstract Introduction: PIK3CA mutation is one of the most frequent genomic alterations in breast cancer. We evaluated PIK3CA mutational status including spatial and temporal heterogeneity, clinical characteristics and prognostic impact focused on ER+/HER2- subtype. Methods: We performed targeted ultra-deep sequencing (CancerSCAN™) of breast cancer tissue in a prospective cohort. Burden of disease was assessed by metabolic tumor volume(MTV) in 18F-FDG-PET scan. Association with clinical characteristics or survival were tested in ER+/HER2- subtype, using Chi square test or Kaplan-Meier method. Results: PIK3CA analyses were performed in 1274 breast cancer specimens from 1091 patients. 957 patients had early breast cancer. PIK3CA alterations were found in 397 patients(36.3%), and frequency of PIK3CA mutation was significantly lower in triple negative breast cancer(19.0%), compared with 40.4% in ER+/HER2-, 40.9% in ER+/HER2+, and 45.2% in ER-/HER2+ subtype(p<0.0001). 158 patients had more than two biopsies. Among 92 patients with second biopsy within one month, 11%(10/92) had spatial heterogeneity of PIK3CA mutation. After neoadjuvant chemotherapy, 10%(3/30) of patients had change of PIK3CA mutational status. Serial biopsy at time of recurrence revealed loss or gain of PIK3CA mutation in 10 out of 59 patients (17%). In ER+/HER2- subtype, PIK3CA had a trend toward longer distant disease free survival without statistical significance. In patients with stage IV ER+/HER2- disease, PIK3CA hotspot mutations were associated with significant longer overall survival(OS) (71.0 vs. 37.8 months, p=0.048) and better progression free survival(PFS) at 1st line palliative treatment (37.7 vs. 9.4 months, p = 0.0004). Frequency of symptomatic recurrence, recurrence as oligometastases, and specific metastatic sites were not associated with PIK3CA mutational status, except that bone metastases at first distant metastases was less prevalent in patients with PIK3CA hotspot mutations(35.6% vs. 53.8% in PIK3CA wt, p=0.048). Metabolic tumor volume(MTV) at time of first distant metastases was not associated with presence of PIK3CA mutation. Conclusion: We observed variations in PIK3CA mutational status in more than 10% of patients with >1 repeated biopsy. In stage IV ER+/HER2- disease, PIK3CA hotspot mutation seemed to be associated with longer PFS and OS, however metabolic tumor burden was not associated with PIK3CA alterations. Citation Format: Ahn HK, Park S, Hyun SH, Park K, Lee E, Kim J-Y, Nam SJ, Kim SW, Lee JE, Lee SK, Yu JH, Ahn JS, Im Y-H, Park YH. PIK3CA mutations in breast cancer: Mutational landscape and clinical implications in ER+/HER2- subtype [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-08-12.