Cancer Res Treat.  2020 Jul;52(3):689-696. 10.4143/crt.2019.497.

PIK3CA H1047R Mutation Associated with a Lower Pathological Complete Response Rate in Triple-Negative Breast Cancer Patients Treated with Anthracycline-Taxane–Based Neoadjuvant Chemotherapy

Affiliations
  • 1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
  • 2German Breast Group, Neu-Isenburg, Charité Universitätsmedizin Berlin, Berlin, Germany
  • 3Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany

Abstract

Purpose
PIK3CA, encoding for subunit p110a of phosphatidylinositol 3 kinase, is frequently mutated in breast cancer. PIK3CAmutation was predictive for pathological complete response (pCR) in human epidermal growth factor 2 positive breast cancer. This study explores the association of PIK3CA mutation and pCR in triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy.
Materials and Methods
A total of 92 patients with TNBC derived from a prospectively randomized phase II trial GeparSixto study (NCT01426880). Exon 9 and exon 20 of PIK3CA mutations were evaluated by using classical Sanger method with formalin-fixed paraffin-embedded tumor tissues.
Results
Seven of 90 tumors (7.8%) were detectable with a PIK3CA H1047R mutation. Overall, PIK3CA H1047R mutation was significantly associated with a lower pCR rate (14.3% vs. 56.6%; odds ratio, 0.128; 95% confidence interval [CI], 0.015 to 1.108; p=0.047). In carboplatin- containing treatment patients, H1047R mutation trended to predict a lower pCR rate (20% vs. 62.5%; p=0.146). In a multivariable analysis, H1047R mutation trended to predict a lower pCR rate (hazard ratio, 0.1; 95% CI, 0.01 to 1; p=0.056).
Conclusion
TNBC with a PIK3CA H1047R mutation was less likely to achieve pCR after anthracyclinebased neoadjuvant chemotherapy. Development of H1047R mutant selective inhibitors might be helpful to conquer this subtype of breast cancer.

Keyword

H1047R mutation; Triple-negative breast cancer; Pathological complete response

Figure

  • Fig. 1. PIK3CA mutation genotyping. Nucleotide sequence of PIK3CA mutations are shown. (A) 1624G>A (p. E542K) in one tumor. (B) 1633G>A (p.E545K) in one tumor. (C) c.1639G>A (p.E547K) in one tumor. (D) c.3110A>G (protein E1037G) in one tumor. (E) c.3140A>G (p.H1047R) in seven tumors. (F) c.3075 T>C (p. T1025T) in 1 tumor. (G) 3236T>C in one tumor. No tumor was detected with two mutations.


Reference

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