PIK3CA alterations in metastatic breast cancer (mBC)

Albanell, Joan; Casadevall, David; Sokol, E.S.; Albacker, Lee A.; Elvin, J.A.; Vergilio, J.-A.; Killian, J. Keith; Ngo, Nhu; Lin, Doris; Ramkissoon, S.; Severson, Eric Allan; Ali, SM; Schrock, Alexa B.; Chung, Jing-Gung; Reddy, Prasanth; Miller, Vincent A.; Alexander, Brian M.; McGregor, K.; Ross, Jeffrey S.; Leyland‐Jones, Brian

doi:10.1093/annonc/mdz242.001

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“…According to the Cancer Genome Atlas Network, PIK3CA mutations are more frequent in luminal A (45%) compared to luminal B (29%) subtypes, also occurring in basal-like (9%) and HER2-enriched (39%) subtypes (Cancer Genome Atlas Network, 2012). A recent study including a large number of metastatic breast carcinomas (n = 3871) confirmed these data, reporting the presence of PIK3CA mutations in 39% of HR+/ HER2-and 37% of HER2-amplified tumors, besides 21% of triplenegative carcinomas (Albanell et al, 2019). The presence of PIK3CA mutations represents an independent adverse prognostic factor in breast carcinoma (Sobhani et al, 2018) and has been associated with more aggressive disease and poor outcomes in metastatic disease (Fitzgerald et al, 2019).…”

Section: Introductionmentioning

confidence: 86%

Evaluation of PIK3CA mutations in advanced ER+/HER2-breast cancer in Portugal – U-PIK Project

Peixoto

Cirnes

Carvalho

et al. 2023

Front. Mol. Biosci.

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Background: Around 40% of ER+/HER2-breast carcinomas (BC) present mutations in the PIK3CA gene. Assessment of PIK3CA mutational status is required to identify patients eligible for treatment with PI3Kα inhibitors, with alpelisib currently the only approved tyrosine kinase inhibitor in this setting. U-PIK project aimed to conduct a ring trial to validate and implement the PIK3CA mutation testing in several Portuguese centers, decentralizing it and optimizing its quality at national level.Methods: Eight Tester centers selected two samples of patients with advanced ER+/HER2- BC and generated eight replicates of each (n = 16). PIK3CA mutational status was assessed in two rounds. Six centers used the cobas®PIK3CA mutation test, and two used PCR and Sanger sequencing. In parallel, two reference centers (IPATIMUP and the Portuguese Institute of Oncology [IPO]-Porto) performed PIK3CA mutation testing by NGS in the two rounds. The quality of molecular reports describing the results was also assessed. Testing results and molecular reports were received and analyzed by U-PIK coordinators: IPATIMUP, IPO-Porto, and IPO-Lisboa.Results: Overall, five centers achieved a concordance rate with NGS results (allele frequency [AF] ≥5%) of 100%, one of 94%, one of 93%, and one of 87.5%, considering the overall performance in the two testing rounds. NGS reassessment of discrepancies in the results of the methods used by the Tester centers and the reference centers identified one probable false positive and two mutations with low AF (1–3%, at the analytical sensitivity threshold), interpreted as subclonal variants with heterogeneous representation in the tissue sections processed by the respective centers. The analysis of molecular reports revealed the need to implement the use of appropriate sequence variant nomenclature with the identification of reference sequences (HGVS-nomenclature) and to state the tumor cell content in each sample.Conclusion: The concordance rates between the method used by each tester center and NGS validate the use of the PIK3CA mutational status test performed at these centers in clinical practice in patients with advanced ER+/HER2- BC.

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Section: Introductionmentioning

confidence: 86%