Significance of PIK3CA Mutations in Patients with Early Breast Cancer Treated with Adjuvant Chemotherapy: A Hellenic Cooperative Oncology Group (HeCOG) Study

摘要: Background The PI3K-AKT pathway is frequently activated in breast cancer. PIK3CA mutations are most found the helical (exon 9) and kinase 20) domains of this protein. The aim present study was to examine role different types combination with molecular biomarkers related signaling patients early cancer. Methods Tumor tissue samples from 1008 cancer treated adjuvant chemotherapy two similar randomized trials HeCOG were examined. Tumors subtyped immunohistochemistry (IHC) FISH for ER, PgR, Ki67, HER2 androgen receptor (AR). analyzed by Sanger sequencing qPCR (Sanger/qPCR mutations). In 610 cases, next generation (NGS) mutation data also available. PTEN protein expression luminal tumors (ER and/or PgR positive), apocrine carcinomas (MAC; ER/PgR negative / AR positive) hormone (ER/PgR/AR) tumors. Results PIK3CA detected 235/1008 (23%) Sanger/qPCR 149/610 (24%) NGS. Concordance between methods good a Kappa coefficient 0.76 (95% CI 0.69–0.82). Lobular histology, low tumor grade A associated domain (PIK3CAhel), while B (PIK3CAkin). overall incidence higher as compared MAC (p = 0.004). Disease-free survival did not significantly differ respect presence type. However, statistically significant interaction status regard prognosis identified. Conclusions show any prognostic significance specific large group predominantly lymph-node positive women chemotherapy. Further analyses larger cohorts warranted investigate possible differential effect distinct small subgroups patients.