Abstract P1-07-09: Results of treatment with inhibitors of cycline-dependent kinase CDK4/6 in patients with breast cancer in the presence of different types mutation in the PIK3CA gene
Authors: Sultanbaev Alexander , Nasretdinov Ainur , Menshikov Konstantin , Musin Shamil , Sultanbaeva Nadezda 
Published: March 2022

Abstract
The aim of this work is frequency evaluation of mutations in the PIK3CA gene in a group of hormone positive breast cancer patients, evaluation of different types of PIK3CA mutation influence on the effectiveness of hormonal therapy in treatment of CDK4/6 inhibitors. Materials and methods. We analyzed the treatment results in patients with metastatic breast cancer ER/PR positive, HER2-neu negative amplification who received treatment in 2019-2021. Patients under study were tested for PIK3CA mutations as part of the program “Improvement of molecular genetic diagnostics in the Russian Federation in order to increase the effectiveness of anticancer treatment” including testing of mutations: C420R (Exon 7), E542K (Exon 9), E545A (Exon 9), E545G (Exon 9), E545K (Exon 9), Q546E (Exon 9), Q546R (Exon 9), H1047L (Exon 20), H1047R (Exon 20), H1047Y (Exon 20) and E545D (Exon 9). The material for the study was tumor tissue. Results and discussion. 128 patients with ER/PR positive HER2-neu negative breast cancer have been tested. Of the one hundred and twenty eight patients thirty nine (30,5%) showed a pathogenic mutation in the PIK3CA gene, seventy three patients (57%) showed no mutations and the result from sixteen patients (12,5%) was not obtained due to inadequate quality of tumor tissue. Thirty five patients (27,3%) showed luminal A subtype of tumor, eighty five (66,4%) - luminal B subtype, and we failed to determine tumor subtype in eight patients (6,3%). Among 39 patients with mutations one (2,6%) mutation detected C420R (Exon 7), seven (17,9%) - E542K (Exon 9), one (2,6%) - E545A (Exon 9), ten (25,6%) - E542K (Exon 9), two (5,1%) - H1047L (Exon 20), eighteen (46,2%) - H1047R (Exon 20). The average age of onset tumor in patients with mutations is 54,8±2,2 years, in patients with no mutations - 51,2±2,5 years. 56 patients received therapy of inhibitors of cycline-dependent kinase CDK4/6 in combination with Letrosol or Fulvestrant.21 patients received therapy of inhibitors of cycline-dependent kinase CDK4/6 as a first line treatment, 19 patients as a second line treatment, 13 patients as a third line treatment and 3 patients as a forth and more line treatment. 37 patients out of 56 completed therapy due to progressive disease, 19 patients continue the treatment. Progression free survival in patients without mutations to patients with mutations who received therapy of inhibitors of cycline-dependent kinase CDK4/6 is 14 months against 9 months. The comparison of group of patients with mutations in 9 and 20 Exons showed improvement of PFS in a group of patients with mutation in 20 Exon: 11 months against 6 months. PFS was higher in patients without mutations in comparison with patients with mutation in 9 Exon: 15 months against 6 months, the PFS difference was insignificant in comparison of patients with mutation in 20 Exon and patients without mutations: 12 months against 14. Median time of remission in patients who received treatment in an adjuvant setting with standard hormonal therapy - Tamoxifen or aromatase inhibitors Anastrazol or Letrozol is 41 months against 50 months in groups of with mutations and without respectively. Comparison of remission medians also didn’t show any significant difference in a group of mutations in Exons 9 and 20 with a group of no mutations: 60 months against 50 months and 24 months against 50 months. Conclusion. The worst effect is in patients with the mutation in Exon 9 PIK3CA gene compared to patients with the mutation in Exon 20 while treated with anti CDK4/6 drugs. Age of onset didn’t influence the detection of mutations in PIK3CA gene. Patients with mutation in Exon9 had less PFS compared to patients without any mutations but the difference is not statistically significant.
Citation Format: Alexander Sultanbaev, Ainur Nasretdinov, Konstantin Menshikov, Shamil Musin, Nadezda Sultanbaeva. Results of treatment with inhibitors of cycline-dependent kinase CDK4/6 in patients with breast cancer in the presence of different types mutation in the PIK3CA gene [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-07-09.