Characterizing the 70-gene MammaPrint risk stratification in Chinese luminal type breast cancer and its correlation with clinicopathological characteristics, immune and metabolic functions.

Abstract

e12559 Background: The 70-gene MammaPrint is endorsed by the NCCN guidelines for predicting 5-year distant metastasis risk in HR+, HER2-, with 0-3 lymph nodes, early invasive breast cancer. Similarly, it is recommended by the CSCO breast cancer guidelines for prognostic assessment post breast cancer surgery. However, no prior studies have investigated its application in Chinese luminal-type breast patients or its correlation with immune and metabolic functions. Methods: This analysis encompasses 76 early-stage invasive Luminal breast cancer patients, registered at the First People's Hospital of Foshan between 2020 and 2023, with recorded clinical characteristics under informed consent. Patient-reported data include clinical features, pathology, and the 70-gene MammaPrint risk of recurrence. Additionally, RNA-seq analysis was conducted in 24 patients. Results: Among 76 enrolled patients,55.3% were categorized as MammaPrint low risk (MP-Low), and 44.7% as MammaPrint high risk (MP-High). Patients over 50 were more likely MP-Low (p=0.028, OR=2.860), while those with >20% Ki67-stained cells were prone to MP-High (p<0.001, OR=0.160). Comparing with MINDACT, there was 52.3% consistency, with 55.6% of MP-Low patients being C-Low (MINDACT risk Low) and 47.1% of MP-High patients being C-High (MINDACT risk High). Notably,21% of C-Low patients showed MP-High risk, and 27% of C-High patients exhibited MP-Low risk, of which 83.3% were ≥50 years old. Based on MINDACT and ISPY2 trial outcomes, patients were further categorized into four groups: MP-Ultralow, MP-Low but not ultralow (LNUL), MP-High but not ultrahigh (HNUH) and MP-Ultrahigh. The study identified an 18% MP-Ultralow population, suggesting that excessive adjuvant therapy might be avoided in these patients. Additionally, 41% of patients were identified as LNUL group, indicating potential benefit from adjuvant treatment or endocrine prolongation therapy. 4% were identified as MP-Ultrahigh group, suggesting potential benefits from neoadjuvant targeted therapy, albeit a poorer long-term benefit in the non-pCR portion. Further transcriptome analysis in 24 patients revealed significantly higher levels of Th2 cells in the MP-High group, with no significant difference observed in CD8 T cells between the two groups. Meanwhile, metabolic-related signatures also differed, with significantly higher levels of Dopamine, Norepinephrine, Heme, and Epinephrine biosynthesis in the MP-Low group. Conclusions: This study elucidates the intricate relationships between MammaPrint prediction results of 70 genes and clinical characteristics, immune and metabolic signatures in Chinese Luminal type breast cancer patients. The refined risk classification provides valuable insights for precision treatment, advancing personalized therapeutic strategies.