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. 2024 Aug 8;25(16):8639.
doi: 10.3390/ijms25168639.

Metabolomic Profiling of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy for Predicting Disease-Free and Overall Survival

Maria Cecília Ramiro Talarico  1 , Sophie Derchain  1 , Lucas Ferreira da Silva  2 , Maurício L Sforça  3 , Silvana A Rocco  3 , Marcella R Cardoso  4   5 , Luís Otávio Sarian  1
Affiliations

Metabolomic Profiling of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy for Predicting Disease-Free and Overall Survival

Maria Cecília Ramiro Talarico et al. Int J Mol Sci. .

Abstract

Breast cancer (BC) remains a significant global health concern, with neoadjuvant chemotherapy (NACT) offering preoperative benefits like tumor downstaging and treatment response assessment. However, identifying factors influencing post-NACT treatment response and survival outcomes is challenging. Metabolomic approaches offer promising insights into understanding these outcomes. This study analyzed the serum of 80 BC patients before and after NACT, followed for up to five years, correlating with disease-free survival (DFS) and overall survival (OS). Using untargeted nuclear magnetic resonance (NMR) spectroscopy and a novel statistical model that avoids collinearity issues, we identified metabolic changes associated with survival outcomes. Four metabolites (histidine, lactate, serine, and taurine) were significantly associated with DFS. We developed a metabolite-related survival score (MRSS) from these metabolites, stratifying patients into low- and high-risk relapse groups, independent of classical prognostic factors. High-risk patients had a hazard ratio (HR) for DFS of 3.42 (95% CI 1.51-7.74; p = 0.003) after adjustment for disease stage and age. A similar trend was observed for OS (HR of 3.34, 95% CI 1.64-6.80; p < 0.001). Multivariate Cox proportional hazards analysis confirmed the independent prognostic value of the MRSS. Our findings suggest the potential of metabolomic data, alongside traditional markers, in guiding personalized treatment decisions and risk stratification in BC patients undergoing NACT. This study provides a methodological framework for leveraging metabolomics in survival analyses.

Keywords: NMR spectroscopy; mammary cancer; metabolome; neoadjuvant chemotherapy; survival analysis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Kaplan-Meier representation of disease-free survival (A) and overall survival (B) according to MRSS risk strata: low-risk (yellow); high-risk (blue).
Figure 2
Figure 2
Kaplan-Meier representation of disease-free survival (A) and overall survival (B) according to MRSS risk strata (low and high) and disease stage. The survival curves for patients with disease stages I–II and low risk are depicted in cyan, whereas those for patients with disease stages I–II and high risk are depicted in green. For patients with disease stages III–IV, the low-risk stratum is depicted in orange, whereas the high-risk stratum is depicted in red.
Figure 3
Figure 3
Kaplan-Meier representation of disease-free survival according to MRSS risk strata (low-risk, cyan; high-risk, red) in patients with disease stages I–II (A) and disease stages III–IV (B).
Figure 4
Figure 4
Kaplan-Meier representation of overall survival according to MRSS risk strata (low-risk, cyan; high-risk, red) in patients with disease stages I–II (A) and disease stages III–IV (B).
Figure 5
Figure 5
Schematic representation of the study design. Metabolomic and clinical data combined to predict patient survival following neoadjuvant chemotherapy.
See this image and copyright information in PMC

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