Evaluation of the 12-gene molecular score and the 21-gene recurrence score as predictors of response to neo-adjuvant chemotherapy in estrogen receptor-positive, HER2-negative breast cancer Journal Article


Authors: Soliman, H.; Wagner, S.; Flake, D. D. 2nd; Robson, M.; Schwartzberg, L.; Sharma, P.; Magliocco, A.; Kronenwett, R.; Lancaster, J. M.; Lanchbury, J. S.; Gutin, A.; Gradishar, W.
Article Title: Evaluation of the 12-gene molecular score and the 21-gene recurrence score as predictors of response to neo-adjuvant chemotherapy in estrogen receptor-positive, HER2-negative breast cancer
Abstract: Background: Neo-adjuvant chemotherapy (NaCT) facilitates complete surgical resection in locally advanced breast cancer. Due to its association with improved outcome, complete pathologic response (pCR) to neo-adjuvant treatment has been accepted as a surrogate for long-term outcome in clinical trials of human epidermal growth factor receptor 2 (HER2)-positive, triple-negative, or luminal B breast cancer patients. In contrast, NaCT is effective in only ~ 7–10% of estrogen receptor (ER)-positive, HER2-negative disease. Response biomarkers would enable such patients to be selected for NaCT. Methods: Two commercially available breast cancer prognostic signatures [12-gene molecular score (MS) and the 21-gene Recurrence Score (RS)] were compared in their ability to predict pCR to NaCT in ER-positive, HER2-negative breast cancer in six public RNA expression microarray data sets. Scores were approximated according to published algorithms and analyzed by logistic regression. Results: Expression data were available for 764 ER-positive, HER2-negative breast cancer samples, including 59 patients with pCR. The two scores were well correlated. Either score was a significant predictor of pCR (12-gene MS p = 9.4 × 10−5; 21-gene RS p = 0.0041). However, in a model containing both scores, the 12-gene MS remained significant (p = 0.0079), while the 21-gene RS did not (p = 0.79). Conclusions: In this microarray study, two commercial breast cancer prognostic scores were significant predictors of response to NaCT. In direct comparison, the 12-gene MS outperformed the 21-gene RS as a predictive marker for NaCT. Considering pCR as surrogate for improved survival, these results support the ability of both scores to predict chemotherapy sensitivity. © 2020, The Author(s).
Keywords: cancer chemotherapy; treatment response; unclassified drug; major clinical study; doxorubicin; fluorouracil; cancer combination chemotherapy; paclitaxel; protein bcl 2; gene expression; epidermal growth factor receptor 2; protein; cyclophosphamide; docetaxel; microarray analysis; celecoxib; intermethod comparison; epirubicin; neoadjuvant chemotherapy; taxane derivative; anthracycline; ixabepilone; aurora a kinase; cd68 antigen; glutathione transferase m1; estrogen receptor alpha; cancer prognosis; estrogen receptor positive breast cancer; bag1 protein; human; article; evaluation study; stromelysin 3; prognostic assessment; growth factor receptor bound protein 7; 21 gene recurrence score; human epidermal growth factor receptor 2 negative breast cancer; azgp1 protein; birc5 protein; ccnb1 protein; ctsl2 protein; dhcr7 protein; il6st protein; mgp protein; rbbp8 protein; stc2 protein; ube2c protein; 12 gene molecular score
Journal Title: Annals of Surgical Oncology
Volume: 27
Issue: 3
ISSN: 1068-9265
Publisher: Springer  
Date Published: 2020-03-01
Start Page: 765
End Page: 771
Language: English
DOI: 10.1245/s10434-019-08039-7
PUBMED: 31907749
PROVIDER: scopus
PMCID: PMC7000508
DOI/URL:
Notes: Article -- Export Date: 2 March 2020 -- Source: Scopus
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MSK Authors
  1. Mark E Robson
    444 Robson