PIK3CA alterations in metastatic breast cancer (mBC)

Abstract

Background: The anticipated approval of the first specific PIK3CA inhibitor, apelisib, has increased interest in the frequency and range of PIK3CA genomic alterations (GA) in the major subtypes of mBC. Method(s): DNA was extracted from 3,871 mBC: 1,259 ER+/HER2-, 1,969 HER2 amplified (amp) and 643 TNBC. GA, tumor mutational burden (TMB) and microsatellite instability (MSI) were identified by hybrid-capture. PD-L1 was determined by IHC. Result(s): PIK3CA GA were significantly higher in ER+(39%) and HER2amp (37%) and lower in TNBC (21%) groups and dominated by point mutations and indels (mut) (Table). The H1047R was the most frequent PIK3CA GA in all groups. ESR1 GA were highest in ER+ and BRCA1 GA were most frequent in PIK3CAmut-TNBC and BRCA2 GA were most frequent in PIK3CAmut-ER+. FGFR1 GA were significantly more frequent in PIK3CAmut-ER+ and EGFR and BRAF GA were most frequent in PIK3CAmut+ TNBC. Biomarkers of potential immunotherapy benefit including CD274amp and PD-L1 expression in immunocytes were most frequent in the TNBC patients, while TMB was highest in the PIK3CAmut+ cohort, regardless of subtype. Conclusion(s): A wide variety of PIK3CA GA are identified in mBC and appear to influence other important biomarkers such as BRCA1/2 GA and TMB status. The PIK3CA GA distribute differently among the ER+, HER2+ and TNBC cohorts and may impact the initial and future use of PIK3CA inhibitors in the treatment of the disease.