Journal Article
. 2021 Jun; 10(13):4658-4674.
doi: 10.1002/cam4.4022.

A pharmacophore-based classification better predicts the outcomes of HER2-negative breast cancer patients receiving the anthracycline- and/or taxane-based neoadjuvant chemotherapy

Xuan Li 1 Hefen Sun 1 Qiqi Liu 1 Yang Liu 1 Yifeng Hou 1 Wei Jin 1 
Affiliations
  • PMID: 34076352
  •     44 References
  •     1 citations

Abstract

Aims: Prognosis of patients for human epidermal growth factor receptor 2 (HER2)-negative breast cancer post neoadjuvant chemotherapy is not well understood. The aim of this study was to develop a novel pharmacophore-based signature to better classify and predict the risk of HER2-negative patients after anthracycline-and/or taxane-based neoadjuvant chemotherapy (NACT).

Main Methods: Anthracycline and taxane pharmacophore-based genes were obtained from PharmMapper. Drug-targeted genes (DTG) related clinical and bioinformatic analyses were undertaken in four GEO datasets.

Key Findings: We used 12 genes from the pharmacophore to develop a DTG score (DTG-S). The DTG-S classification exhibited significant prognostic ability with respect to disease free survival (DFS) for HER2-negative patients who receive at least one type of neoadjuvant chemotherapy that included anthracycline and/or taxane. DTG-S associated with a high predictive ability for pathological complete response (pCR) as well as for prognosis of breast cancer. Using the DTG-S classification in other prediction models may improve the reclassification accuracy for DFS. Combining the DTG-S with other clinicopathological factors may further improve its predictive ability of patients' outcomes. Gene ontology and KEGG pathway analysis showed that the biological processes of DTG-S high group were associated with the cell cycle, cell migration, and cell signal transduction pathways. Targeted drug analysis shows that some CDK inhibitors and PI3K-AKT pathway inhibitors may be useful for high DTG-S patients.

Significance: The DTG-S classification adds prognostic and predictive information to classical parameters for HER2-negative patients who receive anthracycline-and/or taxane-based NACT, which could improve the patients' risk stratification and may help guide adjuvant treatment.

Keywords: HER2-negative breast cancer; gene expression; neoadjuvant chemotherapy; pharmacophore; prognosis.

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