The 41-gene classifier TRAR predicts response of HER2 positive breast cancer patients in the NeoALTTO study

Serena Di Cosimo, Tiziana Triulzi, Sara Pizzamiglio, L. De Cecco, Evandro de Azambuja, Debora Fumagalli, L. Putzai, N. Harbeck, Miguel Izquierdo, Lorena de la Peña, Maria Grazia Daidone, Jens Huober, Stefania Gori, Saverio Cinieri, Valter Torri, Jose Baselga, Martine Piccart, Filippo G. de Braud, Giovanni Apolone, P. VerderioElda Tagliabue

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalEuropean Journal of Cancer
Volume118
DOIs
Publication statusPublished - Sep 2019

Keywords

  • Breast cancer
  • Gene expression profile
  • HER2
  • pCR
  • Predictive biomarker
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Di Cosimo, S., Triulzi, T., Pizzamiglio, S., De Cecco, L., de Azambuja, E., Fumagalli, D., Putzai, L., Harbeck, N., Izquierdo, M., Peña, L. D. L., Daidone, M. G., Huober, J., Gori, S., Cinieri, S., Torri, V., Baselga, J., Piccart, M., de Braud, F. G., Apolone, G., ... Tagliabue, E. (2019). The 41-gene classifier TRAR predicts response of HER2 positive breast cancer patients in the NeoALTTO study. European Journal of Cancer, 118, 1-9. https://doi.org/10.1016/j.ejca.2019.06.001