Clinical and morphological features of breast tumors with PIK3CA mutations in Russian patients: Observational study
Authors: Sokolova Tatyana N. , Solov'eva Tatyana I. , Aleksakhina Svetlana N. , Bolieva Marina   B. , Goldberg Viktor E. , Kibisheva Marianna V. , Menshikov Konstantin V. , Ryazanov Dmitrii  V. , Shkradyuk Aleksandr  V. , Chapko Yana S. , Shchukina Anna A. , Khabriev Idris   M. , Kirtbaya Dmitrii V. , Degtyarev Alexey M. , Epkhiev Aleksandr A. , Tyugina Yana A. , Togo Aleksandr  V. , Murachuev Mirza  A. , Ievleva Aglaya G. , Imyanitov Evgenii  N. , Grechkina Anna   A. , Stel'makh Alena S. , Odintsova Svetlana V. , Janus Grigorii A. , Musaeva Khedi S. , Chang Victor L. , Fateeva Anastasia V. , Startseva Ekaterina  P. , Popova Nataliya O. , Mikheeva Yulia V. , Vasilevskaya Anna V. , Barbara Victoria S. , Khabibulaeva Petimat I. , Khlobystina Alina G. , Bembeeva Ludmila V. , Vladimirov Vladimir  I. , Petrenko Oleg  L. , Ruskova Natalia  G. , Serikova Ekaterina L. , Subbotina Ksenia S. , Tkachenko Svetlana A. , Yukalchuk Denis Y. , Basova Elena A. , Stepanova Mariya L. , Erdniev Sanal P. , Goryainova Alla , Gluzman Mark I. , Orlova Rashida V. , Stukan Anastasiya I. , Zukov Ruslan A. , Zyuzyukina Alena V. , Murunova Yulia N. , Sultanbaev Aleksandr V. , Vorobeva Elena N. , Mikhaevich Leonid M. , Lysenko Anna N. , Khachmamuk Zarema K. , Kozlov Andrey E. , Bakharev Sergey Y. , Pyliv Victoria N. , Amirkhanova Irina   K. , Parsyan Shahen G. , Rossokha Elena I. , Osidze Leri D. , Shumskaya Irina S. , Agaeva Anna V. , Kasmynina Tatiana A. , Klimenko Veronika V. , Akhmetgareeva Kamila T. , Vakhitova Almira A. , Chakhkieva Madina D. , Udalova Yana  A. , Dmitriev Vadim N. , Bakshun Yana I. , Vasilyev Alexey E. , Gasimly Dunya D, , Kravchenko Nadezhda A. , Maksimov Dmitriy A. , Nesterova Alfia I. , Khamgokov Zaur M. , Sharvashidze Ineza O. , Gadzaova Christina H. , Rakhmankulova Galina G. , Shvaiko Kseniya A. 
Published: April 2022

Background. By 2020, breast cancer (BC) has become the most frequent malignancy in the world. The most common type of BC is HR+/HER2-negative cancer,2540% of which harbors PIK3CA mutations that affect the catalytic subunit of the PI3K protein. PIK3CA alterations are actionable, as such neoplasms can be treated with a combination of fulvestrant and the PI3K inhibitor alpelisib. As PIK3CA mutations have an extremely versatile effect on the characteristics of a tumor cell, numerous associations of PIK3CA mutations and various clinico-pathological characteristics of BC can be traced.
Aim. Our aim was to clarify the information on the frequency and spectrum of PIK3CA mutations in Russian patients with HR+/HER2- advanced BC, and to study the association of PIK3CA mutations with clinical and pathological parameters of BC.
Materials and methods. Tissue samples from 694 patients with HR+/HER2- advanced BC (mixed population of primary metastatic and relapsed tumors) who received any line of anti-cancer treatment in Dec 2020 to June 2021 in Russian Federation were analyzed by high-resolution melting, allele-specific PCR, digital droplet PCR and Sanger sequencing (exons 7,9, and 20 of the PIK3CA gene). Mutation rates in different BC subgroups were compared using the Fishers exact test. The age at diagnosis in patients with different PIK3CA status was compared using the MannWhitney U-test. The relationship between the PIK3CA status and the degree of tumor differentiation was compared using the CochraneArmitage test for trends. Luminal A and B BC expression subtypes were distinguished with surrogate IHC markers according to St.-Gallen recommendations (2013).
Results. Mutations were identified in 220/694 (32%) BC patients. The three most frequent missense substitutions in the PIK3CA gene (p.E542K, p.E545K, and p.H1047R) accounted for 190/220 (86%) mutations. Associations of PIK3CA mutations with luminal A subtype of BC, low proliferation index, small size of the primary tumor, and absence of signs of hereditary cancer were revealed. Associations of mutations in the kinase domain of PIK3CA (p.H1047R) with late recurrence of locally advanced BC and with non-Slavic ethnic origin of patients were found.
Conclusion. PIK3CA mutation rate of 32% confirms high prevalence of mutation in Russian population, with some differences reflecting the ethnic origin of patients.