Background Majority of published findings on chemotherapy–induced febrile neutropenia (FN) are restricted to three ethnic groups: Asians, Caucasians, and African Americans. In this two–part study, we examined FN incidence and risk factors in Chinese, Malay and Indian chemotherapy–treated breast cancer (BC) patients in Southeast Asia. Methods Hospital records or ICD codes (fever:ICD9/10:2880/D70 and neutropenia:ICD9/10:7806/R509) were used to identify patients with FN, during or within 30 days from the last chemotherapy session. In both Singapore Breast Cancer Cohort (SGBCC) and Joint Breast Cancer Registry (JBCR), time to first FN from start of chemotherapy was estimated using Cox regression. Multinomial regression was used to evaluate differences in patient, tumour, and treatment characteristics across ethnicities. Results FN was observed in 170 of 1,014 patients (16.7%) in SGBCC. Cox model showed that non–Chinese were at higher risk of developing FN (HRMalay[95% CI]:2.04[1.44–2.88], p < 0.001; HRIndian:1.88[1.11–3.18], p = 0.018). In JBCR, FN was observed in 965 of 7449 patients (13.0%). Indian patients, lower baseline absolute neutrophil count, non– luminal A proxy subtypes, and anthracycline–containing regimens were identified as risk factors for FN in the univariable Cox models. Disparities across ethnicities risk (HRMalay: 1.29 [1.07–1.54], p = 0.006; HRIndian: 1.50 [1.19–1.88], p < 0.001) remained significant even after further adjustments. Finally, age–adjusted multinomial model showed that as compared to Chinese patients, non–Chinese (ORMalay vs Chinese(ref):3.65[1.45–9.16],p = 0.006;ORIndian vs Chinese(ref):4.43[1.45–13.60],p = 0.009) were significantly more likely to develop multiple episodes of FN during treatment. Conclusion Ethnic differences in chemotherapy–induced FN among BC patients exist. Further studies can focus on investigating pharmacogenetic differences across ethnicities.

The majority of published findings on chemotherapy-induced febrile neutropenia (FN) are restricted to three ethnic groups: Asians, Caucasians, and African Americans. In this two-part study, we examined FN incidence and risk factors in Chinese, Malay, and Indian chemotherapy-treated breast cancer (BC) patients. Hospital records or ICD codes were used to identify patients with FN. In both the Singapore Breast Cancer Cohort (SGBCC) and the Joint Breast Cancer Registry (JBCR), the time of the first FN from the start of chemotherapy was estimated using Cox regression. Multinomial regression was used to evaluate differences in various characteristics across ethnicities. FN was observed in 170 of 1014 patients in SGBCC. The Cox model showed that non-Chinese were at higher risk of developing FN (HRMalay [95% CI]:2.04 [1.44–2.88], p < 0.001; HRIndian:1.88 [1.11–3.18], p = 0.018). In JBCR, FN was observed in 965 of 7449 patients. Univariable Cox models identified ethnicity, a lower baseline absolute neutrophil count, non-luminal A proxy subtypes, and anthracycline-containing regimens as risk factors. Disparities across ethnicities’ risk (HRMalay:1.29 [1.07–1.54], p = 0.006; HRIndian:1.50 [1.19–1.88], p < 0.001) remained significant even after further adjustments. Finally, an age-adjusted multinomial model showed that Malays (p = 0.006) and Indians (p = 0.009) were significantly more likely to develop multiple episodes of FN during treatment. Ethnic differences in chemotherapy-induced FN among BC patients exist. Further studies can focus on investigating pharmacogenetic differences across ethnicities.

e12540 Background: An inflammatory state in various cancer populations may correlate with mortality. Neutrophil-lymphocyte ratio is a surrogate marker of an inflammatory state. A recent meta-analysis showed the predictive value of neutrophil to lymphocyte ratio in breast cancers, but series are generally small. We aim to study the associations of Neutrophil-Lymphocyte Ratio (NLR) with outcomes in stage I–III breast cancer in patients who received neo-adjuvant chemotherapy (NAC) or upfront surgery. The endpoints are overall survival (OS) and breast cancer-specific survival (BCSS). In the NAC group, association with pathological complete response (PCR) rate was also studied. Methods: Data of patients with stage I–III breast cancer treated from 2011–2017 were extracted from a prospectively maintained registry and merged with full blood count (FBC) results from a clinical management software. FBC were performed within one-month pre-chemo for NAC patients and one-month pre-surgery for upfront surgery patients. PCR is defined as stage ypT0/isN0M0. OS is defined as death from any cancer from diagnosis date, censored at last follow-up. BCSS is defined as death from breast cancer from diagnosis date, censored at last follow up or death from any cause. The NLR values with the maximal Youden’s indexes calculated for each outcome were used as cut-off, logistic regression was used to determine PCR association and cox regression and log rank for OS and BCSS. Results: A total of 2,479 eligible patients were analysed. Overall, treatment compliance was high (87.6% of ER+ patients received endocrine treatment, and 94.1% of HER2+ NAC patients had targeted therapy). In the NAC group (n = 357), 23% achieved PCR. NLR did not show any statistically significant association with PCR. In unadjusted analysis, high NLR was associated with worse BCSS (log-rank p = 0.003 figure 1). In multivariable analysis (MVA), only triple negative and HER-enriched cancers were significantly associated with PCR. In NAC patients, NLR was associated with OS (cut-off 2.63; OR 1.6, p = 0.077) and BCSS (cut-off 3.58; OR 2.2, p = 0.003) in MVA. In patients treated with up-front surgery (n = 2122), unadjusted analysis showed high NLR was associated with worse BCSS (OR 1.55, p = 0.05; figure 2). In MVA, NLR (cut-off 2.13, OR 1.57, p = 0.005), triple negative histology, stage and age were significant predictors of OS. BCSS was not significantly associated with NLR (OR 1.38 95%CI 0.90-2.12 p = 0.145). Conclusions: Using a large cohort of patients, a high NLR was found to be associated with worse outcomes in NAC and upfront surgery breast cancer patients.

e12548 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. [Table: see text]