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

Abstract

Purpose: 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.Experimental Design: 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).Results: A higher continuous mEPclin score was significantly associated with increased risk of relapse [HR, 2.16; 95% confidence interval (CI), 1.86-2.51; P < 0.001] and death (HR, 2.28; 95% CI, 1.90-2.75; P < 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; P < 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; P < 0.001).Conclusions: 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. Clin Cancer Res; 24(14); 3358-65. ©2018 AACR.

• Authors: Sibylle Loibl, Karsten Weber, Jens Huober, Kristin Krappmann, Frederik Marmé, 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
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 24 Issue 14 Pg. 3358-3365 (07 15 2018) ISSN: 1557-3265 [Electronic] United States
• PMID: 29618617 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2018 American Association for Cancer Research.

Chemical References

• Biomarkers, Tumor

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor
• Breast Neoplasms (drug therapy, etiology, metabolism, pathology)
• Chemotherapy, Adjuvant
• Clinical Trials, Phase III as Topic
• Combined Modality Therapy
• Female
• Gene Expression Profiling
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Grading
• Neoplasm Staging
• Prognosis
• Risk Assessment
• Treatment Outcome