Clinicopathologic Characterization of Double PIK3CA Mutated Advanced Breast Cancer: A Retrospective Cohort Study from a Single Institution

Objectives: We aimed to characterize the clinicopathologic and molecular features of double PIK3CA mutated advanced breast cancer in a retrospective cohort study. Methods: This retrospective study included 196 advanced breast cancer patients who had the Oncomine next generation sequencing analysis. The clinicopathologic parameters were recorded for each individuals including age, tumor type, grade, ER, PR, HER2, and recurrence free survival. Results: PIK3CA mutations were detected in 77.5% (152/196) of advanced breast cancer patients, 129 (84.8%) of which contained single mutations, 20 (13.1%) of which contained double mutations, and 3 (2%) of which contained triple mutations. Double PIK3CA mutated tumors were mostly seen in postmenopausal women, had lower combined histologic grade, and were enriched in hormone receptor positive human epidermal growth factor receptor negative (HR+/HER2-) disease. Double PIK3CA mutations were more frequently associated with concurrent mutations of ESR1 (p=0.017) and ARID1A (p=0.054) compared to single PIK3CA mutations. No significant progression free survival differences were observed between PIK3CA mutated and wild-type groups and between double and single PIK3CA mutated groups when applied to all patients or HR+/ HER2- patients. Conclusion: Double PIK3CA mutated advanced breast cancer have similar clinicopathologic features as single mutated ones but demonstrate unique molecular features.