Naslov
Preliminary Results of PIK3CA Mutation Analysis in Advanced Breast Cancer

Autori
Ramić, Snježana ; Perić Balja, Melita ; Tečić Vuger, Ana ; Šeparović, Robert

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
14 hrvatski onkološki kongres 14th Croatian Oncology Congress / Eduard Vrdoljak, Marijana Jazvić - Zagreb : Klinika za tumore, Klinički bolnički centar Sestre milosrdnice Ilica 197, 10 000 Zagreb, 2021, 040-041

Skup
14 hrvatski onkološki kongres 14th Croatian Oncology Congress ; Virtual Congress

Mjesto i datum
Hrvatska, 22.04.2021. - 25.04.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
breast cancer, PIK3CA mutations

Sažetak
Based on the SOLAR-1 trial in 2019 FDA approved therapy with PIK3CA inhibitors for patients with HR-positive and HER2-negative advanced breast cancer previously treated with aromatase inhibitors. Patients with mutation treated with PIK3CA-targeted inhibitors had improved progression-free survival of an average of 11 months compared with 5.7 months of an average in patients without PIK3CA inhibitor therapy. PIK3- kinase (phosphoinositide-3-kinase) activates diverse cellular processes (cell growth, differ- entiation, proliferation, survival). Activating somatic mutations in its catalytic subunit p110α (PIK3CA) are present in about 40% of BC, and via the AKT/mTOR signaling pathway are involved in oncogenesis and cancer growth. Material and method: Qualitative detection of somatic PIK3CA mutations was performed on DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue of 159 patients with advanced BC who met the criteria for treatment with PIK3CA inhibitors. The tissue available for analysis was a primary tumor or metastasis. PIK3CA mutations were detected by real-time PCR using Roche Cobas® PIK3CA mutation assay that can detect 17 hotspot single amino acid substitutions in five exons (ex1, ex4, ex7, ex9, and ex20), provided by Roche Company. Results: Median age of patients with advanced BC included in our study was 63 years (range from 34-89 years). Patients without mutation in the PIK3CA gene (wild type) were somewhat older than patients with detected mutation (64 vs. 62 years). PIK3CA mutation was detected in 56 patients (36.1%). In only four cases, the result was invalid due to poor material. As expected, most mutations were in exons 9 and 20 (87.5%) while less frequent mutations in ex1, ex4 and ex7 were detected in 12.5% of cases. Hotspot mutations were detected as follows: in ex4 N345K (six cases) ; ex7 C420R (one case) ; ex9 codons E542K (six cases) and E545A/ D/G/K (19 cases), and ex20 codon H1047L/R/Y (24 cases). It remains to be seen whether cancers show differ- ent effects of therapy depending on hotspot mutations. 57.4% of the analysis was performed on metastatic lesions with 31.4% of mutations detected compared to 40.3% of mutations in primary breast cancer (χ2=2.38, P=0.123). In 31% of cases, the tissue used for analysis (FFPE) was older than three years, but this did not affect the detection itself, and PIK3CA mutations were detected in 39.3% of such cases. Conclusion: Frequencies of PIK3CA mutations were as expected, and both primary and metastatic lesions were acceptable for analysis. We will continue to monitor our patients to obtain more information about their course of the disease, treatment response, and outcomes.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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