Mutations of the PIK3CA gene in patients with breast cancer in the Krasnoyarsk region

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Abstract

Aim. To identify population characteristics of the PIK3CA gene mutation among breast cancer patients in the Krasnoyarsk region.

Materials and methods. The study included 140 patients with breast cancer with a certain mutation status of the PIK3CA gene, observed at the Krasnoyarsk Regional Clinical Oncology Center named after A.I. Kryzhanovsky. Determination of PIK3CA gene mutations (exons 2, 5, 8, 10 and 21) was carried out using commercial kits on equipment from Roche (Germany). Statistical processing of the obtained data was carried out using Microsoft Excel and Statistica 12 software products. The assessment of the factor of influence on the relapse-free and overall survival was carried out by constructing and comparing Kaplan–Meier curves. The result was considered statistically significant at a significance level of p <0.05.

Results and conclusion. The overall frequency of occurrence of PIK3CA gene mutations is 38.6 %. The most common mutations are H1047X (55.4 %) in exon 21 and E545K (27.8 %) in exon 10. The median age of breast cancer patients with mutation status in the PIK3CA gene was 58.9 [49.0; 67.0] years, median time to relapse or progression was 62.2 [27.0; 84.0] months. There were no statistically significant differences in relapse-free survival between the presence and absence of mutations (p = 0.8). The effect of changes in PIK3CA on a decrease in overall survival rates (p = 0.047) in breast cancer patients was shown.

About the authors

A. V. Zyuzyukina

Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Ministry of Health of Russia; Krasnoyarsk Regional Clinical Cancer Center named after A.I. Kryzhanovsky

Author for correspondence.
Email: alena-vz@mail.ru
ORCID iD: 0000-0002-6758-4800

Alena Vladimirovna Zyuzyukina

1 Partizana Zheleznyaka St., Krasnoyarsk 660022; 161-ya Smolenskaya St., Krasnoyarsk 660133

Russian Federation

E. Yu. Yakunina

Krasnoyarsk Regional Clinical Cancer Center named after A.I. Kryzhanovsky

ORCID iD: 0009-0004-1544-8606

161-ya Smolenskaya St., Krasnoyarsk 660133

Russian Federation

V. I. Borodulina

Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Ministry of Health of Russia

1 Partizana Zheleznyaka St., Krasnoyarsk 660022

Russian Federation

L. A. Vasilovskaya

Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Ministry of Health of Russia

1 Partizana Zheleznyaka St., Krasnoyarsk 660022

Russian Federation

E. V. Slepov

Krasnoyarsk Regional Clinical Cancer Center named after A.I. Kryzhanovsky

ORCID iD: 0000-0002-3787-3126

161-ya Smolenskaya St., Krasnoyarsk 660133

Russian Federation

V. A. Komissarova

Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Ministry of Health of Russia; Krasnoyarsk Regional Clinical Cancer Center named after A.I. Kryzhanovsky

ORCID iD: 0000-0002-5862-1761

1 Partizana Zheleznyaka St., Krasnoyarsk 660022; 161-ya Smolenskaya St., Krasnoyarsk 660133

Russian Federation

R. A. Zukov

Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Ministry of Health of Russia; Krasnoyarsk Regional Clinical Cancer Center named after A.I. Kryzhanovsky

ORCID iD: 0000-0002-7210-3020

1 Partizana Zheleznyaka St., Krasnoyarsk 660022; 161-ya Smolenskaya St., Krasnoyarsk 660133

Russian Federation

References

  1. Mikhalenko E.P., Shchayuk A.N., Kilchevsky A.V. Signaling pathways: mechanism for regulating proliferation and survival of tumor cells. Molekulyarnaya i prikladnaya genetika = Molecular and Applied Genetics 2019;(26):145–57. (In Russ.).
  2. Dronova T.A., Babyshkina N.N., Matvienko N.V. et al. PI3K/AKT/MTOR: contribution to the formation of a tumor phenotype sensitive to tamoxifen. Rossiyskiy bioterapevticheskiy zhurnal = Russian Biotherapeutic Journal 2021;20(1):16–23. (In Russ.). doi: 10.17650/1726-9784-2021-20-1-16-23
  3. Sobhani N., Roviello G., Corona S.P. et al. The prognostic value of PI3K mutational status in breast cancer: A meta-analysis. J Cellular Biochem 2018;119(6):4287–92. doi: 10.1002/jcb.26687.
  4. Neven P., Petrakova K., Val Bianchi G. et al. Biomarker analysis by baseline circulating tumor DNA alterations in the MONALEESA-3 study. Cancer Res 2019;79(4 Suppl):PD2-05. doi: 10.1158/1538-7445.SABCS18-PD2-05
  5. Tolaney S., Toi M., Neven P. et al. Clinical outcomes of patients with PIK3CA mutations in circulating tumor DNA: Update from the MONARCH 2 study of abemaciclib plus fulvestrant. Cancer Res 2020;80(16 Suppl):766. doi: 10.1158/1538-7445.AM2020-766
  6. Cristofanilli M., Turner N.C., Bondarenko I. et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): Final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 2016;17(4):425–39. doi: 10.1016/S1470-2045(15)00613-0
  7. Hortobagyi G., Chen D., Piccart M. et al. Correlative analysis of genetic alterations and everolimus benefit in hormone receptorpositive, human epidermal growth factor receptor 2-negative advanced breast cancer: Results from BOLERO-2. J Clin Oncol 2016;34(5):419–26. doi: 10.1200/JCO.2014.60.1971
  8. André F., Ciruelos E., Rubovszky G. et al. SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. New Engl J Med 2019;380(20):1929–40. doi: 10.1056/NEJMoa1813904
  9. Campbell R.A., Bhat-Nakshatri P., Patel N.M. et al. Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: A new model for anti-estrogen resistance. J Biol Chem 2001;276:9817–24.
  10. Ellis M.J., Lin L., Crowder R. et al. Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer. Breast Cancer Res Treat 2010;119:379–90.
  11. Wang L., Zhang Q., Zhang J. et al. PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib. BMC Cancer 2011;11:248.
  12. Wu G., Xing M., Mambo E. et al. Somatic mutation and gain of copy number of PIK3CA in human breast cancer. Breast Cancer Res 2005;7:R609-16.
  13. Gonzalez-Angulo A.M., Chen H., Karuturi M.S. et al. Frequency of mesenchymal-epithelial transition factor gene (MET) and the catalytic subunit of phosphoinositide-3-kinase (PIK3CA) copy number elevation and correlation with outcome in patients with early stage breast cancer. Cancer 2013;119:7–15.
  14. Samuels Y., Wang Z., Bardelli A. et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004;304:554.
  15. Saal L.H., Holm K., Maurer M. et al. PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res 2005;65:2554–9.
  16. Sokolova T.N., Aleksakhina S.N., Janus G.A. et al. Frequency and spectrum of PIK3CA mutations in hormone-dependent HER2- negative advanced breast cancer in Russian patients. Sovremennaya onkologiya = Modern Oncology 2021;23(1):61–7. (In Russ.). doi: 10.26442/18151434.2021.1.200744
  17. Sokolova T.N., Solovyova T.I., Aleksakhina S.N. et al. Clinical and morphological features of breast tumors with PIK3CA mutations in Russian patients: аn observational study. Sovremennaya onkologiya = Modern Oncology 2022;24(1):12–23. (In Russ.). doi: 10.26442/18151434.2022.1.201435

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