An RB-1 loss of function gene signature as a tool to predict response to neoadjuvant chemotherapy plus anti-HER2 agents: a substudy of the NeoALTTO trial (BIG 1-06)
| العنوان: | An RB-1 loss of function gene signature as a tool to predict response to neoadjuvant chemotherapy plus anti-HER2 agents: a substudy of the NeoALTTO trial (BIG 1-06) |
|---|---|
| المؤلفون: | Stefania Vitale, Amelia McCartney, Luca Malorni, Serena Di Cosimo, Ilenia Migliaccio, Chiara Biagioni, Jens Huober, Angelo Di Leo, Dario Romagnoli, Cristina Guarducci, Giulia Boccalini, Matteo Benelli, Emanuela Risi, Florentine Hilbers, Christos Sotiriou, Martina Bonechi, Laura Biganzoli |
| المصدر: | Therapeutic Advances in Medical Oncology Therapeutic Advances in Medical Oncology, Vol 11 (2019) Therapeutic advances in medical oncology, 11 |
| بيانات النشر: | Universität Ulm, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Oncology, medicine.medical_specialty, medicine.medical_treatment, Induktionstherapie, Lapatinib, lcsh:RC254-282, Trastuzumab, Internal medicine, medicine, gene expression profiling, Brustkrebs, In patient, ddc:610, predictive biomarker, RB pathway, Loss function, Original Research, Chemotherapy, business.industry, Médecine pathologie humaine, HER2+ breast cancer, Biomarker, Gene signature, Sciences bio-médicales et agricoles, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Gene expression profiling, Cancérologie, Genexpression, Neoadjuvant therapy, Gene expression, Anti her2, Breast neoplasms, business, DDC 610 / Medicine & health, Biomarkers, medicine.drug, neoadjuvant chemotherapy |
| الوصف: | Background: Chemotherapy added to anti-HER2 agents (H) is the treatment of choice in patients with HER2+ early breast cancer. However, HER2+ tumours are clinically and biologically heterogeneous, and treatment response varies significantly by hormone receptor (HR) status and molecular subtype. Predictive biomarkers are needed in this context. This study assessed whether an RB-1 loss of function gene signature (RBsig) is predictive of response to neoadjuvant chemotherapy in combination with trastuzumab, lapatinib or both, within the NeoALTTO trial. Methods: We collected RNA-sequencing data from pretreatment biopsies derived from the NeoALTTO trial. RBsig expression was computed retrospectively and correlated with pathological complete response (pCR) using receiver-operating characteristic (ROC) curves. The RBsig was dichotomised as High/Low in correspondence to the 25th percentile. Reported p values resulted from Fisher’s exact test. Results: Of 455 NeoALTTO patients, 244 were eligible for this substudy (HR+ n = 129; HR− n = 115). Overall, pCR rate was significantly higher in patients with RBsig High tumours than those with RBsig Low (35% versus 18% respectively; p = 0.01). The area under the ROC curve (AUC) was 0.60 (95% CI 0.52–0.67). A remarkably low pCR rate of 11% was seen in HR+/RBsig Low patients versus 28% in HR+/RBsig High. Conclusions: These results indicate RBsig may add valuable information to HER2 and HR expression, which may in turn inform treatment choices. HR+/HER2+/RBsig Low breast cancers exhibited the poorest pathological response following chemotherapy plus H. Accordingly, in such patients, endocrine therapy in combination with H and, possibly, a CDK4/6 inhibitor, may potentially prove to be a more effective treatment. SCOPUS: ar.j info:eu-repo/semantics/published |
| وصف الملف: | application/pdf; 4 full-text file(s): application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6c5a2f2a3160ba6079581c700d4cf26eTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6c5a2f2a3160ba6079581c700d4cf26e |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |