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Updated: Jun 16, 2025
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Clinical and Morphological Features of ER-Positive HER2-Negative Breast Tumors with PIK3CA Mutations in Russian
Tatyana N Sokolova1, Grigory A Yanus1,2, Svetlana N Aleksakhina1
1National Medical Research Center of Oncology named after N.N. Petrov of MOH of Russia, Saint Petersburg 197758, Russia.
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.
Insights
PIK3CA mutations are common in hormone receptor-positive breast cancer, but testing should include regions beyond hotspots. These mutations are not linked to worse outcomes or resistance to common treatments.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Targeted therapies for PIK3CA-mutated hormone receptor-positive (HR+)/HER2-negative breast cancer (BC) are emerging.
- A comprehensive analysis of PIK3CA alterations in Russian BC patients is needed.
Purpose of the Study:
- To evaluate the spectrum of PIK3CA alterations in a Russian cohort of HR+/HER2- BC patients.
- To correlate PIK3CA mutations with clinical characteristics and treatment response.
Main Methods:
- Tumor samples from 1872 ER+/HER2- BC patients were analyzed using PCR-based methods.
- PIK3CA mutation status was assessed and correlated with clinical data.
Main Results:
- PIK3CA mutations were found in 37% of patients, with common variants E542K, E545K, and H1047R in 78% of mutated cases.
- A significant proportion of mutations (5.5-12%) were outside common commercial kit detection regions.
- PIK3CA variants were associated with older age, smaller tumor size, lower grade, low Ki67, progesterone receptor positivity, and fewer metastases.
- No association was found between PIK3CA mutations and resistance to tamoxifen or aromatase inhibitors.
Conclusions:
- PIK3CA testing should extend beyond hotspot regions to capture a wider spectrum of mutations.
- PIK3CA alterations are implicated in HR+/HER2- BC pathogenesis and targeted therapy, but do not inherently indicate a worse prognosis.
