National Cancer Centre Singapore, Singapore, Singapore
Min Li Tey , Siqin Zhou , Phyu Nitar , Hanis Mariyah Mohd Ishak , Christina Shi-Hui Yang , Grace Kusumawidjaja , Wen Yee Chay , Fuh-Yong Wong , Ru Xin Wong
Background: The ratios of blood-based inflammatory biomarkers, such as NLR and AGR, have been found to correlate with outcomes in various malignancies. Higher NLR values reflect a pro-inflammatory state and are generally associated with worse outcomes. Conversely, higher AGR values reflect a fitter nutritional status and/or less chronic inflammation, and may hence be associated with better outcomes. We aim to investigate the association between NLR and AGR with survival among stage I-III breast cancer patients treated curatively, and with pathological complete response (pCR) rates among patients who have undergone neoadjuvant chemotherapy (NACT). Methods: A retrospective study of stage I-III breast cancer patients treated in a healthcare cluster in Singapore from 2011-2017 was performed. Clinical data was extracted from a prospectively maintained registry alongside full blood count (FBC) and liver function test (LFT) results. FBC and LFT were performed either 1-month pre-chemotherapy or pre-operatively. pCR is defined as stage ypT0/isN0M0 among patients who have undergone NACT. Optimal cut-offs for the NLR and AGR values are determined by maximal Youden’s Index for pCR, DFS and OS. Multivariate logistic regression, with NLR, AGR, age, stage, grade, and subtype, was used, with survival data between groups compared using the Cox regression analysis and log-rank tests. Results: A total of 1,188 patients were included in our study, with 323 patients receiving NACT, and 865 patients undergoing upfront surgery. On multivariable analysis of patients treated with NACT, higher AGR was associated with higher pCR (cutoff >1.3, HR 2.0, p=0.02) and better DFS (>1.6, HR 0.4, p=0.02) while a higher NLR with worse DFS (>4.1, HR 1.8, p=0.03). In upfront surgery patients, higher AGR was associated with better OS (cutoff >1.2, HR 0.5, p=0.00) while a higher NLR predicted for worse OS (>2.4, HR 1.6, p=0.02). Conclusions: Inflammatory markers may be useful in predicting response to NACT and prognosticating survival. Larger studies should be undertaken to explore their value in clinical decision making.
Co-variates | NACT DFS | HR (95%CI) | P value | Upfront surgery OS | HR (95%CI) | P value |
---|---|---|---|---|---|---|
Age | 1.02 (1.00-1.04) | 0.06 | 1.07 (1.05-1.09) | p<0.001 | ||
NLR | Low (≤4.09) | 1 | Low (≤2.38) | 1 | ||
High (>4.09) | 1.77 (1.07-2.91) | 0.026 | High (>2.38) | 1.63 (1.09-2.44) | 0.018 | |
AGR | Low (≤1.55) | 1 | Low (≤1.17) | 1 | ||
High (>1.55) | 0.37 (0.16-0.85) | 0.019 | High (>1.17) | 0.54 (0.36-0.82) | 0.004 | |
Stage | Stage 3 | 1 | Stage 3 | 1 | ||
Stage 2 | 0.45 (0.26-0.78) | 0.005 | Stage 2 | 0.47 (0.31-0.73) | 0.001 | |
Stage 1 | NE | Stage 1 | 0.28 (0.15-0.53) | p<0.001 | ||
Grade and histological subtype | n.s | n.s |
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