The frequency and spectrum of PIK3CA mutations in patients with estrogen receptor-positive HER2-negative advanced breast cancer residing in various regions of Russia

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Abstract

Relevance. PIK3CA belongs to the top three most frequently mutated genes in breast cancer (BC), especially in estrogen receptor (ER) positive, HER2 negative BC subtype. With an approval of selective PI3K-alpha inhibitor, alpelisib, this alteration has become actionable in ER+HER2- tumors. The frequency and spectrum of PIK3CA alterations in various cohorts is affected by a number of factors, including the distribution of BC expression subtypes, histological types, patient age, and even ethnicity.

Aim. Aim of the current study was to characterize the frequency and spectrum of PIK3CA alterations in Russian BC patients.

Materials and methods. The analysis of PIK3CA exon 7, 9 and 20 mutations was performed in a cohort of Russian ER+HER2- BC patients by a combination of high-resolution melting analysis, allele-specific PCR, and digital droplet PCR.

Results. PIK3CA lesions were identified in 62/206 (30%) patients. Noteworthy, 59/62 (95%) of the identified variants were represented by the three most common p.E542K, p.E545K, and p.H1047R substitutions. The analysis of clinical and morphological characteristics revealed the trends towards association of PIK3CA mutations with older age and more frequent metastatic lung involvement.

Conclusion. The obtained data on the frequency and spectrum of PIK3CA somatic aberrations can be helpful when organizing molecular genetic testing of breast cancer patients and using PI3K inhibitors in Russian population.

About the authors

Tatiana N. Sokolova

Petrov Institute of Oncology

Author for correspondence.
Email: stretanya@yandex.ru
ORCID iD: 0000-0002-0537-7478

Research Assistant

Russian Federation, Saint Petersburg

Svetlana N. Aleksakhina

Petrov Institute of Oncology

Email: abyshevasv@gmail.com
ORCID iD: 0000-0002-2149-7728

Cand. Sci. (Biol.)

Russian Federation, Saint Petersburg

Grigoriy A. Yanus

Petrov Institute of Oncology; Saint Petersburg State Pediatric Medical University

Email: octavedoctor@yandex.ru
ORCID iD: 0000-0002-9844-4536

Cand. Sci. (Med.)

Russian Federation, Saint Petersburg; Saint Petersburg

Aleksandr V. Sultanbaev

Republican Clinical Oncological Dispensary

Email: rkodrb@yandex.ru
ORCID iD: 0000-0003-0996-5995

Cand. Sci. (Med.)

Russian Federation, Ufa

Konstantin V. Menshikov

Republican Clinical Oncological Dispensary

Email: kmenshikov80@bk.ru
ORCID iD: 0000-0003-3734-2779

Cand. Sci. (Med.)

Russian Federation, Ufa

Anna N. Lysenko

Regional Oncology Dispensary

Email: anyutadoctor@yandex.ru

oncologist

Russian Federation, Stavropol

Ruslan A. Zukov

Voino-Yasenetsky Krasnoyarsk State Medical University

Email: zukov_rus@mail.ru
ORCID iD: 0000-0002-7210-3020

D. Sci. (Med.), Prof.

Russian Federation, Krasnoyarsk

Alena V. Zyuzyukina

Voino-Yasenetsky Krasnoyarsk State Medical University

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

Cand. Sci. (Med.)

Russian Federation, Krasnoyarsk

Yulia N. Murunova

Surgut Regional Hospital

Email: murunovayn@surgutokb.ru
ORCID iD: 0000-0003-0299-980X

Cand. Sci. (Med.)

Russian Federation, Surgut

Elena I. Rossokha

Altai Regional Oncological Dispensary

Email: rossokha_e@mail.ru
ORCID iD: 0000-0002-5303-3012

Cand. Sci. (Med.)

Russian Federation, Barnaul

Sergey Y. Bakharev

Altai Regional Oncological Dispensary

Email: bachero@mail.ru
ORCID iD: 0000-0003-0429-8804

Head of the Department of Pathological Anatomy

Russian Federation, Barnaul

Elena A. Basova

Oncology Dispensary

Email: basova_elena68@mail.ru

chief physician

Russian Federation, Birobidzhan

Tatiana A. Kasmynina

Oncology Dispensary

Email: stretanya@yandex.ru

oncologist

Russian Federation, Birobidzhan

Irina S. Shumskaya

Nizhny Novgorod Regional Clinical Oncological Dispensary

Email: medicanns@mail.ru

Cand. Sci. (Med.)

Russian Federation, Nizhny Novgorod

Yana I. Bakshun

Cancer Hospital

Email: mikobacteria@gmail.com
ORCID iD: 0000-0001-8584-6299

oncologist

Russian Federation, Kostroma

Khedi S. Musaeva

Republican Oncology Dispensary

Email: musaeva.onco@mail.ru

oncologist

Russian Federation, Grozniy

Alfia I. Khasanova

Sigal Republic Clinical Oncology Dispensary; Kazan Federal University

Email: haalfy@mail.ru
ORCID iD: 0000-0002-4880-4353

Cand. Sci. (Med.)

Russian Federation, Kazan; Kazan

Vadim N. Dmitriev

Belgorod Oncology Dispensary

Email: vadd@mail.ru

D. Sci. (Med.)

Russian Federation, Belgorod

Marina B. Bolieva

Republican Oncology Dispensary

Email: marina-bolieva1985@mail.ru

oncologist

Russian Federation, Vladikavkaz

Christina H. Gadzaova

Republican Oncology Dispensary

Email: lady.onko@yandex.ru

oncologist

Russian Federation, Vladikavkaz

Oleg L. Petrenko

Kaliningrad Regional Clinical Hospital

Email: Petrenko-oleg78@mail.ru
ORCID iD: 0000-0002-6482-1698

Cand. Sci. (Med.)

Russian Federation, Kaliningrad

Dmitriy A. Maksimov

Tver Regional Clinical Oncology Dispensary

Email: dr.maksimovda@mail.ru

oncologist, Head of the Surgical Department

Russian Federation, Tver

Vladimir I. Vladimirov

Pyatigorsk Oncology Dispensary

Email: vladvlad@megalog.ru
ORCID iD: 0000-0002-7375-8950

D. Sci. (Med.)

Russian Federation, Pyatigorsk

Viktor E. Goldberg

Tomsk National Research Medical Center

Email: goldbergve@mail.ru
ORCID iD: 0000-0003-4753-5283

D. Sci. (Med.), Prof.

Russian Federation, Tomsk

Nataliya O. Popova

Tomsk National Research Medical Center

Email: popova75tomsk@mail.ru
ORCID iD: 0000-0001-5294-778X

Cand. Sci. (Med.)

Russian Federation, Tomsk

Marianna V. Kibisheva

Oncology Dispensary

Email: zareta.alix@yandex.ru

oncologist

Russian Federation, Nalchik

Zaur M. Khamgokov

Oncology Dispensary

Email: zaur0779@inbox.ru

oncologist

Russian Federation, Nalchik

Alexey E. Vasilyev

Orenburg Regional Clinical Oncological Dispensary

Email: vasiliev@rambler.ru
ORCID iD: 0000-0003-0385-6798

oncologist

Russian Federation, Orenburg

Aglaya G. Iyevleva

Petrov Institute of Oncology; Saint Petersburg State Pediatric Medical University

Email: aglayai@inbox.ru
ORCID iD: 0000-0001-5454-5186

Cand. Sci. (Med.)

Russian Federation, Saint Petersburg; Saint Petersburg

Evgeny N. Imyanitov

Petrov Institute of Oncology; Saint Petersburg State Pediatric Medical University

Email: evgeny@imyanitov.spb.ru
ORCID iD: 0000-0003-4529-7891

D. Sci. (Med.), Prof., Corr. Memb. RAS

Russian Federation, Saint Petersburg; Saint Petersburg

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