How Asian Breast Cancer Patients Experience Unequal Incidence of Chemotherapy Side Effects: A Look at Ethnic Disparities in Febrile Neutropenia Rates

SIMPLE SUMMARY: In this two-part study, we assessed the risk factors associated with FN. On top of commonly associated risk factors such as age and body mass index, we found that there are ethnic differences in terms of FN incidence. Notably, patients of non-Chinese ethnicity had a higher FN incidence. This trend remained significant even after multiple adjustments with other patients, tumors, and treatment characteristics. Further analysis exploring differences across ethnicities revealed that Indian patients were more likely to experience greater dips in absolute neutrophil count during chemotherapy and Malay patients were more likely to be administered with anthracyclines, both of which contribute to higher FN risk. Importantly, we also found that non-Chinese patients were more likely to experience multiple FN episodes during chemotherapy. Additional research is needed to investigate the possibility of pharmacogenetic differences across these ethnicities. ABSTRACT: 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 (HR(Malay) [95% CI]:2.04 [1.44–2.88], p < 0.001; HR(Indian):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 (HR(Malay):1.29 [1.07–1.54], p = 0.006; HR(Indian):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.