<p>Supplementary tables S1-8. Supplementary Table S1. Primers Used for PCR Amplification of PIK3CA Entire Coding Regions Supplementary Table S2. Frequency of PIK3CA Mutations in Different Subgroups Supplementary Table S3. Multivariate Analyses of Pathological Complete Response in the Entire Study Population (n=729) Supplementary Table S4. Pathological Complete Response Rates in Patients with PIK3CA Hotspot and Non-hotspot Mutations Supplementary Table S5. Pathological Complete Response Rates in Patients with Different PIK3CA Hotspot Mutations Supplementary Table S6. Pathological Complete Response Rates by PIK3CA Status in Different Subgroups Supplementary Table S7. Breast cancer subgroups in the 102 Patients whose PIK3CA Mutation Status was Available before and after Neoadjuvant Chemotherapy Supplementary Table S8. Multivariate Analyses of DFS and DDFS in the 102 Patients whose PIK3CA Mutation Status was Available before and after Neoadjuvant Chemotherapy</p>
ARTICLE 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. Clin Cancer Res; 21(19); 4365–72. ©2015 AACR.
