1. The 41-gene classifier TRAR predicts response of HER2 positive breast cancer patients in the NeoALTTO study
- Author
-
Filippo de Braud, Loris De Cecco, Debora Fumagalli, Elda Tagliabue, Valter Torri, Jens Huober, Saverio Cinieri, Maria Grazia Daidone, Miguel Izquierdo, Giovanni Apolone, Serena Di Cosimo, Martine Piccart, Lorena de la Peña, Sara Pizzamiglio, Stefania Gori, José Baselga, Nadia Harbeck, Lajos Putzai, Tiziana Triulzi, Evandro de Azambuja, and Paolo Verderio
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,Time Factors ,Receptor, ErbB-2 ,Logistic regression ,Breast cancer ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Risk Factors ,Trastuzumab ,HER2 Positive Breast Cancer ,Antineoplastic Combined Chemotherapy Protocols ,Multicenter Studies as Topic ,Precision Medicine ,Randomized Controlled Trials as Topic ,Neoadjuvant Therapy ,Predictive biomarker ,Treatment Outcome ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,medicine.medical_specialty ,Clinical Decision-Making ,Breast Neoplasms ,03 medical and health sciences ,pCR ,Predictive Value of Tests ,HER2 ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Protein Kinase Inhibitors ,Gene ,Retrospective Studies ,Receiver operating characteristic ,business.industry ,Gene Expression Profiling ,Patient Selection ,Lapatinib ,Odds ratio ,Gene expression profile ,medicine.disease ,Confidence interval ,Cancérologie ,030104 developmental biology ,Clinical Trials, Phase III as Topic ,Transcriptome ,business - Abstract
Background: Dual HER2-inhibition combined with neoadjuvant chemotherapy allows increased pathological complete response (pCR) rate. However, with the addition of new agents, there is a growing need to select patients to minimise overtreatment. Herein, we evaluated the 41-gene classifier TRAR to predict pCR to anti-HER2 therapies in the NeoALTTO trial. Patients and methods: Gene expression data were obtained using RNA from 226 pretreatment tumour biopsies. Logistic regression analysis and the area under the receiver operating characteristic (ROC) curve (AUC) were used to evaluate TRAR predictive and discriminatory capabilities. Results: TRAR levels were associated with pCR (odds ratio, OR: 0.25, 95% confidence interval, CI: 0.15–0.42). The ROC analysis showed AUC values of 0.73 (95% CI: 0.67–0.80) overall; 0.70 (0.59–0.81) and 0.71 (0.62–0.80) for positive and negative oestrogen receptor cases and 0.74 (0.60–0.88), 0.76 (0.65–0.87) and 0.71 (0.59–0.83) for trastuzumab, lapatinib and combined treatment arms, respectively. TRAR provided reliable predictive information beyond established clinicopathological variables (OR: 0.26, 95% CI: 0.14–0.47). Furthermore, addition of TRAR to these variables provided greater predictive capability than the addition of PAM50: AUC 0.78 (0.72–0.84) versus 0.74 (0.67–0.81), p = 0.04. Conclusion: TRAR represents a promising tool to refine the ability to identify patients sensitive to anti-HER2 (including trastuzumab-only)-based therapy and eligible for de-escalated treatment strategies., SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2019