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. 2025 May 30;17(11):1833.
doi: 10.3390/cancers17111833.

Clinical and Morphological Features of ER-Positive HER2-Negative Breast Tumors with PIK3CA Mutations in Russian Patients

Tatyana N Sokolova  1 , Grigory A Yanus  1   2 , Svetlana N Aleksakhina  1 , Yana V Belysheva  1 , Aleksandra P Chernyakova  1 , Yulia S Zharnakova  1 , Alisa S Nikitina  1 , Tatyana M Stebneva  1 , Aleksandr S Martianov  1 , Alla Yu Goryainova  3 , Mark I Gluzman  4   5 , Rashida V Orlova  4   5 , Anastasiya I Stukan'  3 , Alena V Zyuzyukina  6 , Ruslan A Zukov  7 , Polina R Korzun  2 , Jeyla O Binnatova  2 , Anastasia S Abuzova  2 , Yulia N Murunova  8 , Aleksandr V Sultanbaev  9 , Elena N Vorobeva  10 , Leonid M Mikhaevich  5 , Victoria N Pyliv  11 , Anna N Lysenko  12 , Zarema K Khachmamuk  3 , Andrey E Kozlov  13 , Sergey Yu Bakharev  14 , Shagen G Parsyan  5 , Elena I Rossokha  14 , Leri D Osidze  5 , Irina S Shumskaya  15 , Anna V Agaeva  16 , Tatyana A Kasmynina  17 , Veronika V Klimenko  1 , Kamila T Akhmetgareeva  18 , Almira A Vakhitova  5 , Madina D Chakhkieva  19 , Vadim N Dmitriev  20 , Yana I Bakshun  21 , Alexey E Vasiliev  22 , Dunya D Gasimly  7 , Nadezhda A Kravchenko  23 , Dmitriy A Maksimov  24 , Alfia I Nesterova  25 , Ineza O Sharvashidze  5 , Christina Kh Gadzaova  26 , Galina G Rakhmankulova  16 , Zaur M Khamgokov  27 , Irina K Amirkhanova  28 , Ludmila V Bembeeva  5 , Vladimir I Vladimirov  29 , Oleg L Petrenko  30 , Natalia G Ruskova  21 , Ekaterina L Serikova  5 , Ksenia S Subbotina  31 , Svetlana A Tkachenko  32 , Victor L Chang  33 , Sanal P Erdniev  5 , Victoria S Barbara  30 , Anna V Vasilevskaya  34 , Yulia V Mikheeva  35 , Natalia O Popova  36 , Anastasia V Fateeva  37 , Denis Yu Yukalchuk  23 , Anna A Grechkina  37 , Khedi S Musayeva  38 , Svetlana V Odintsova  39 , Petimat I Khabibulaeva  38 , Alina G Khlobystina  5 , Kseniya A Shvaiko  40 , Elena A Basova  17 , Irina A Bogomolova  41 , Marina B Bolieva  26 , Viktor E Goldberg  36 , Marianna V Kibisheva  27 , Konstantin V Menshikov  9 , Dmitriy V Ryazanov  42 , Yana A Udalova  43 , Aleksandr V Shkradyuk  44 , Idris M Khabriev  19 , Dmitriy V Kirtbaya  45 , Alexey M Degtyarev  45 , Aleksandr A Epkhiev  26 , Yana A Tyugina  46 , Mirza A Murachuev  47 , Alena S Stelmakh  48 , Aglaya G Iyevleva  1   2 , Evgeny N Imyanitov  1   2
Affiliations

Clinical and Morphological Features of ER-Positive HER2-Negative Breast Tumors with PIK3CA Mutations in Russian Patients

Tatyana N Sokolova et al. Cancers (Basel). .

Abstract

Background: Several targeted drugs have been recently approved for the treatment of PIK3CA-mutated hormone receptor-positive (HR+)/HER2-negative (HER2-) breast cancer (BC). This study aimed at a comprehensive evaluation of the spectrum of PIK3CA alterations in Russian BC patients.

Methods: The tumor material from 1872 patients with ER+/HER2- BC was tested by a combination of PCR-based methods.

Results: Mutations were detected in 693/1872 (37%) cases, including 46 BC with two PIK3CA lesions. The three most common substitutions (E542K, E545K, and H1047R) were identified in 542/693 (78%) PIK3CA-mutated cases, while as many as 5.5-12% of identified mutations were not potentially detectable by common commercial kits. The study included patients of Slavic and non-Slavic ethnicities residing in regions with different climate conditions, however, these factors did not influence the distribution of PIK3CA mutations. The presence of PIK3CA variants was associated with older patient age at diagnosis (p = 0.0002), smaller tumor size (p = 0.005), lower grade (p = 0.005), Ki67 <20% (p = 0.0001) and progesterone receptor-positive status (p = 0.002) at the initial disease diagnosis, and fewer distant metastases at the time of the detection of BC spread (p = 0.0001). In a subgroup of 413 BC patients who received adjuvant tamoxifen or aromatase inhibitors, PIK3CA mutations were not associated with resistance to either type of treatment.

Conclusions: The results of this study highlight the need to extend the PIK3CA testing beyond the hotspot regions of this gene. Although PIK3CA alterations contribute to the pathogenesis of HR+/HER2- BC and represent a target for several novel drugs, they are not intrinsically associated with unfavorable clinical characteristics of this subtype of cancer disease.

Keywords: PIK3CA; hormone receptor-positive (HR+)/HER2-negative (HER2−) breast cancer; mutation.

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Conflict of interest statement

Author Svetlana V. Odintsova was employed by the company EuroCityClinic LLC, The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the spectrum of PIK3CA mutations.
Figure 2
Figure 2
Associations between PIK3CA mutations and clinicopathological characteristics. Asterisks note the comparisons with p < 0.01. Clinicopathological characteristics include age at diagnosis (a), tumor size (b), tumor grade (c), Ki67 proliferation index (d), PR status (e), Federal district (f), number of metastatic zones (g), types of metastatic sites (h). In (f), only Federal districts with >100 analyzed cases are shown. In (h): ST—soft tissues, LN—lymph nodes.
Figure 3
Figure 3
Associations between clinical parameters, PIK3CA mutations, and event-free survival. The evaluated parameters include age at diagnosis (a), tumor size (b), regional lymph node status (c), PIK3CA mutations (d).
See this image and copyright information in PMC

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