Association of PIK3CA Mutation Status before and after Neoadjuvant Chemotherapy with Response to Chemotherapy in Women with Breast Cancer

Abstract

Purpose: The association between PIK3CA mutations and response to neoadjuvant chemotherapy in women with primary breast cancer is not fully elucidated.

Experimental design: PIK3CA mutations in breast cancer tissues that were taken prior to the initiation of neoadjuvant chemotherapy were identified in 729 operable primary breast cancer patients who received neoadjuvant chemotherapy. Among these, the PIK3CA mutations were also reassessed in tumor tissues procured following operation in 102 patients after completion of neoadjuvant chemotherapy.

Results: A total of 206 out of 729 (28.3%) patients had PIK3CA mutations, and 19.5% of patients (142/729) in this cohort achieved a pathologic complete response (pCR) after neoadjuvant chemotherapy. Patients with PIK3CA mutations exhibited a lower pCR rate than did those with wild-type (14.6% vs. 21.4%, P = 0.035). No significant differences in disease-free survival (DFS) or distant disease-free survival (DDFS) were observed between PIK3CA mutant and wild-type in the entire study population. Among the 102 patients with PIK3CA mutation statuses available before and after neoadjuvant chemotherapy, 24 patients (23.5%) had PIK3CA mutations before neoadjuvant chemotherapy. Of these 24 patients, 15 patients retained their initial PIK3CA mutations and 9 patients lost their initial mutations after neoadjuvant chemotherapy. Patients who retained the initial mutations after neoadjuvant chemotherapy (n = 15) had a worse DDFS than the remaining patients (n = 87) in this subgroup [unadjusted HR, 2.34; 95% confidence interval (CI), 0.98-5.62; P = 0.050].

Conclusions: Patients with PIK3CA mutations are less likely to respond to neoadjuvant chemotherapy. Patients who retain their initial PIK3CA mutations after neoadjuvant chemotherapy have an unfavorable survival.