دورية أكاديمية
PI3K mutations detected in liquid biopsy are associated to reduced sensitivity to CDK4/6 inhibitors in metastatic breast cancer patients
| العنوان: | PI3K mutations detected in liquid biopsy are associated to reduced sensitivity to CDK4/6 inhibitors in metastatic breast cancer patients |
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| المؤلفون: | Del Re M., Crucitta S., Lorenzini G., De Angelis C., Diodati L., Cavallero D., Bargagna I., Cinacchi P., Fratini B., Salvadori B., Ghilli M., Roncella M., Fontana A., Danesi R., Cucchiara F. |
| المساهمون: | Del Re, M., Crucitta, S., Lorenzini, G., De Angelis, C., Diodati, L., Cavallero, D., Bargagna, I., Cinacchi, P., Fratini, B., Salvadori, B., Ghilli, M., Roncella, M., Fontana, A., Danesi, R., Cucchiara, F. |
| سنة النشر: | 2021 |
| المجموعة: | ARPI - Archivio della Ricerca dell'Università di Pisa |
| مصطلحات موضوعية: | Advanced breast cancer, CDK4/6 inhibitor, Liquid biopsy, Personalized medicine, PI3K |
| الوصف: | Background: PI3K pathway hyperactivation due to PIK3CA mutations contributes to endocrine resistance, and PIK3CA is one of the most frequently mutated genes in breast cancer (BC), occurring approximately 40 % of HR+, HER2- advanced BC (ABC). Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have changed the treatment landscape of HR+, HER2- ABC. Putative mechanisms of resistance to CDK4/6i have been identified, but limited data are available on PI3K deregulation. The present study evaluates the impact of PIK3CA mutations on CDK4/6i plus hormone therapy and evaluates potential characteristics that may suggest for a PI3K screening in patients with ABC. Methods: ABC patients were enrolled, and 12 mL of blood were collected in EDTA tubes at baseline prior to CDK4/6i plus hormone therapy. Plasma was separated and circulating free DNA (cfDNA) was extracted. PIK3CA mutation analysis was performed on a ddPCR. Selected and analyzed mutations included: p.C420R, p.E542 K, p.E545A, p.E545D, p.E545G, p.E545K, p.Q546E, p.Q546R, p.H1047L, p.H1047R, p.H1047Y. Statistical analysis were performed to investigate the predictive power of such mutations and any association with clinical factors. Results: Thirty patients were enrolled. PIK3CA mutation status at baseline was independently associated with shorter median PFS (7.44 vs 12.9 months, p = 0.01) in subject receiving CDK4/6i plus hormone therapy. PIK3CA mutations were found to be associated to Ki67 expression in primary lesions (p = 0.006). Moreover, the probability to find a PI3K mutation improved considering also the therapeutic management in previous lines of treatment (McFadden's R2 = 0.415, p = 0.004; AUC of the ROC curve = 0.914). Conclusion: The findings of this pilot study suggest that the presence of a PI3K mutation in liquid biopsy correlates with a worse PFS in patients with ABC receiving CDK4/6i, and that liquid biopsy is a useful tool to suggests a better tailored pharmacological intervention. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/33049397; info:eu-repo/semantics/altIdentifier/wos/WOS:000609226800023; volume:163; firstpage:1; lastpage:7; numberofpages:7; journal:PHARMACOLOGICAL RESEARCH; http://hdl.handle.net/11568/1069158Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85096494060 |
| DOI: | 10.1016/j.phrs.2020.105241 |
| الإتاحة: | https://doi.org/10.1016/j.phrs.2020.105241Test http://hdl.handle.net/11568/1069158Test |
| رقم الانضمام: | edsbas.BF709AE2 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.phrs.2020.105241 |
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