Kantonsspital St.Gallen

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

Serena Di Cosimo, Tiziana Triulzi, Sara Pizzamiglio, Loris De Cecco, Evandro De Azambuja, Debora Fumagalli, Lajos Putzai, Nadia Harbeck, Miguel Izquierdo, Lorena De La Peña, Maria Grazia Daidone, Jens Huober, Stefania Gori, Saverio Cinieri, Valter Torri, José Baselga, Martine Piccart, Filippo G De Braud, Giovanni Apolone, Paolo Verderio & Elda Tagliabue


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.

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.

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.

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.
citation 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, Verderio P, Tagliabue E. The 41-gene classifier TRAR predicts response of HER2 positive breast cancer patients in the NeoALTTO study. Eur J Cancer 2019; 118:1-9.
type journal paper/review (English)
date of publishing 05-07-2019
journal title Eur J Cancer (118)
ISSN electronic 1879-0852
pages 1-9
PubMed 31284184
DOI 10.1016/j.ejca.2019.06.001