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The 41-gene classifier TRAR predicts response of HER2 positive breast cancer patients in the NeoALTTO study
- Source :
- European journal of cancer, 118
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
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.<br />SCOPUS: ar.j<br />info:eu-repo/semantics/published
- 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
Subjects
Details
- ISSN :
- 09598049
- Volume :
- 118
- Database :
- OpenAIRE
- Journal :
- European Journal of Cancer
- Accession number :
- edsair.doi.dedup.....82dbc2b7d08da38f75de24997f655071