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Risk Assessment after Neoadjuvant Chemotherapy in Luminal Breast Cancer Using a Clinicomolecular Predictor

Sibylle Loibl, Karsten Weber, Jens Huober, Kristin Krappmann, Frederik Marme, Christian Schem, Knut Engels, Berit Maria Pfitzner, Sherko Kümmel, Jenny Furlanetto, Arndt Hartmann, Silvia Darb-Esfahani, Volkmar Müller, Annette Staebler, Gunter Von Minckwitz, Ralf Kronenwett & Carsten Denkert

abstract This study aimed to evaluate a modified EPclin test (mEPclin), a combination of EndoPredict (EP) score, post-neoadjuvant pathologic tumor size and nodal status, for predicting the risk of distance recurrence after neoadjuvant chemotherapy (NACT) in patients with residual estrogen receptor (ER)-positive/HER2-negative breast cancer. We also compared the prognostic power of the mEPclin with that of the CPS-EG score. A total of 428 formalin-fixed, paraffin-embedded tumor samples from GeparTrio and GeparQuattro studies were evaluated for mRNA expression of eight cancer-related and three reference genes. The mEPclin score was computed using a modified algorithm and predefined cut-off values were used to classify each patient at low or high risk. Primary endpoint was disease-free survival (DFS). A higher continuous mEPclin score was significantly associated with increased risk of relapse [HR, 2.16; 95% confidence interval (CI), 1.86-2.51; < 0.001] and death (HR, 2.28; 95% CI, 1.90-2.75; < 0.001). Similarly, patients classified at high risk by dichotomous mEPclin showed significantly poorer DFS and overall survival compared with those at low risk. In contrast with CPS-EG, the mEPclin remained significantly prognostic for DFS in multivariate analysis (HR, 2.13; 95% CI, 1.73-2.63; < 0.001). Combining CPS-EG and other clinicopathological variables with mEPclin yielded a significant improvement of the prognostic power for DFS versus without mEPclin (c-indices: 0.748 vs. 0.660; < 0.001). The mEPclin score independently predicted the risk of distance recurrence and provided additional prognostic information to the CPS-EG score to assess more accurately the prognosis after NACT in the luminal non-pCR patient population. Therefore, this approach can be used to select patients for additional post-neoadjuvant therapies. .
   
citation Loibl S, Weber K, Huober J, Krappmann K, Marme F, Schem C, Engels K, Pfitzner B M, Kümmel S, Furlanetto J, Hartmann A, Darb-Esfahani S, Müller V, Staebler A, von Minckwitz G, Kronenwett R, Denkert C. Risk Assessment after Neoadjuvant Chemotherapy in Luminal Breast Cancer Using a Clinicomolecular Predictor. Clin Cancer Res 2018; 24:3358-3365.
   
type journal paper/review (English)
date of publishing 04-04-2018
journal title Clin Cancer Res (24/14)
ISSN electronic 1557-3265
pages 3358-3365
PubMed 29618617
DOI 10.1158/1078-0432.CCR-17-2947