Homologous recombination deficiency and glycolysis‐related pathway in adjuvant chemotherapy for triple‐negative breast cancer: A genomic landscape and biomarker assessment of the PATTERN trial

• Published in: Clinical and translational medicine 2021-09, Vol.11 (9), p.e513-n/a
• Main Authors: Zhu, Si‐Yuan, Ma, Ding, Ye, Fu‐Gui, Shao, Zhi‐Ming, Yu, Ke‐Da
• Format: Article
• Language: English
• Subjects: Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Breast cancer; Cancer therapies; Chemotherapy; Chemotherapy, Adjuvant; Female; Genomics; Glycolysis - genetics; Grants; Homologous Recombination - genetics; Humans; Hypoxia; Letter to Editor; Medical prognosis; Metabolism; Middle Aged; Randomized Controlled Trials as Topic; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - mortality
• ISSN: 2001-1326; 2001-1326
• DOI: 10.1002/ctm2.513

Abbreviations BCS breast conservative surgery BLIS basal-like and immune-suppressed CEF-T fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel FUSCC Fudan University Shanghai Cancer Center HRD homologous recombination deficiency IM immunomodulatory IQR interquartile range LAR luminal androgen receptor MES mesenchymal-like PCb paclitaxel and carboplatin Dear Editor, Triple-negative breast cancer (TNBC) is associated with genome-wide instability caused by mutations in homologous recombination repair mechanism,1 and the application of DNA-damaging compounds has been explored for TNBC.2 Recently, we performed the PATTERN trial (NCT01216111) to compare six cycles of paclitaxel plus carboplatin (PCb) with a standard-dose regimen of three cycles of cyclophosphamide/epirubicin/fluorouracil followed by three cycles of docetaxel (CEF-T) in the adjuvant setting of early-stage TNBC, and the result indicated a superior efficacy of the carboplatin-containing regimen and good tolerance to both treatments.3 In this study, we conducted multi-omic profiling on 132 patients in the PATTERN cohort to investigate potential biomarkers for a more precise choice of adjuvant chemotherapy regimen for TNBC. [...]upregulation of the gene set variation analysis score of Reactome glycolysis, a representative pathway regarding hypoxia and glycolysis, predicted inferior RFS in patients receiving CEF-T (Figure 3C, left, HR = 3.43, 95% CI 1.37–8.60, p = 0.01), but not in those receiving PCb (Figure 3C, middle, HR = 0.47, 95% CI 0.10–2.23, p = 0.33). Metabolic reprogramming is a major hallmark of tumor cells, and chemotherapy-resistant TNBC cells usually display an enhanced glycolytic phenotype.9 Our findings suggest that tumor cells are possible to develop resistance to anthracycline/taxane regimen through transforming their expression of metabolic pathways. [...]application of glycolytic inhibitors could become a potential treatment strategy to adopt. [...]the HRD score may serve as a biomarker to predict the efficacy of an adjuvant carboplatin-containing regimen for TNBC.