Supplementary Figures 1 - 12, Tables 1 - 5 from Favorable Prognostic Impact in Loss of TP53 and PIK3CA Mutations after Neoadjuvant Chemotherapy in Breast Cancer

Jiang, Yi-Zhou; Yu, Ke-Da; Bao, Jing; Peng, Wen-Ting; Shao, Zhi-Ming

doi:10.1158/0008-5472.22403741.v1

00085472can140092-sup-tab1-12fig1-5.pdf (1.91 MB)

Supplementary Figures 1 - 12, Tables 1 - 5 from Favorable Prognostic Impact in Loss of TP53 and PIK3CA Mutations after Neoadjuvant Chemotherapy in Breast Cancer

journal contribution

posted on 2023-03-30, 22:47 authored by Yi-Zhou Jiang, Ke-Da Yu, Jing Bao, Wen-Ting Peng, Zhi-Ming Shao

PDF file - 909K, Supplementary Table S1. Validated somatic mutations comparing pre- with post-treatment tumor tissues of P1 and P2 Supplementary Table S2. Distribution of TP53 and PIK3CA mutations Supplementary Table S3. List of TP53 and PIK3CA somatic mutations in breast cancer tissues before and after neoadjuvant chemotherapy Supplementary Table S4. TP53 mutation shift in tumor tissues before and after neoadjuvant chemotherapy in the first cohort (n=206) and second cohort (n=158) Supplementary Table S5. PIK3CA mutation shift in tumor tissues before and after neoadjuvant chemotherapy in the first cohort (n=206) and second cohort (n=158) Supplementary Table S6. Distribution of TP53 and PIK3CA mutation shift in different molecular subtypes of breast cancer in the first cohort (n=206) and second cohort (n=158) Supplementary Table S7. Distribution of TP53 mutation shift in different molecular subtypes of breast cancer in the first cohort (n=206) and second cohort (n=158) Supplementary Table S8. Distribution of PIK3CA mutation shift in different molecular subtypes of breast cancer in the first cohort (n=206) and second cohort (n=158) Supplementary Table S9. Association of TP53 mutation shift with tumor response to neoadjuvant chemotherapy in the first cohort (n=206) and second cohort (n=158) Supplementary Table S10. Association of PIK3CA mutation shift with tumor response to neoadjuvant chemotherapy in the first cohort (n=206) and second cohort (n=158) Supplementary Table S11. Multivariate analysis of disease-free survival including TP53 and PIK3CA mutation status separately Supplementary Table S12. Multivariate analysis of disease-free survival including the combination of TP53 and PIK3CA mutation status Supplementary Fig. S1. Distribution of TP53 (A) and PIK3CA (B) mutations according to different molecular subtypes in pre-treatment breast cancer in the two cohorts. Supplementary Fig. S2. Representative images of hematoxylin and eosin stainings from the post-treatment tumors where mutation loss occurred. Scale bar, 20 �m. Supplementary Fig. S3. Quantification of the frequency of mutant alleles in pre- and post-treatment tumors from which mutation loss occurred (A: loss of TP53 mutations; B; loss of PIK3CA mutations) by pyrosequencing in the two cohorts. Supplementary Fig. S4. Kaplan-Meier estimates of disease-free survival (DFS) and overall survival (OS) according to TP53 mutation shift in the first (A, n=206) and second cohorts (B, n=158). Supplementary Fig. S5. Kaplan-Meier estimates of disease-free survival (DFS) and overall survival (OS) according to PIK3CA mutation shift in the first (A, n=206) and second cohorts (B, n=158).

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ARTICLE ABSTRACT

We investigated the loss of somatic mutations in TP53 and PIK3CA in breast cancer tissue after neoadjuvant chemotherapy (NCT) and the clinical relevance of the observed mutation profiles. Samples were derived from three cohorts: Cohort 1 consisting of 206 patients undergoing NCT with matched pre- and postchemotherapy tumor tissues; Cohort 2 consisting of 158 additional patients undergoing NCT; and Cohort 3, consisting of 81 patients undergoing chemotherapy with prechemotherapy tumor tissues. In the first cohort, somatic mutations in TP53 or PIK3CA were identified in 24.8% of the pre-NCT tumor samples but in only 12.1% of the post-NCT tumor samples (P < 0.001). Patients with initial TP53 and PIK3CA mutations who became negative for the mutations after NCT had a higher Miller–Payne score (P = 0.008), improved disease-free survival, and improved overall survival than those with no change or the opposite change. The association of loss of mutations in TP53 and PIK3CA and improved survival was successfully validated in the second cohort. In addition, 28.4% of the tumors showed intratumoral heterogeneity of somatic mutations in TP53 or PIK3CA, whereas 71.6% were homogeneous, either with or without the mutations. Our data reveal the novel concept that chemotherapy may reduce mutation frequency in patients with breast cancer. Furthermore, the loss of somatic mutations in TP53 and PIK3CA may be translated to biomarkers for prognosis via further verification, which may optimize the choice of sequential therapy and improve patient survival. Cancer Res; 74(13); 3399–407. ©2014 AACR.