Association between Breast Cancer Polygenic Risk Score and Chemotherapy-Induced Febrile Neutropenia: Null Results

SIMPLE SUMMARY: The most common complication of chemotherapy for cancer patients is febrile neutropenia (FN). This is an abnormally low blood neutrophil count coupled with a fever that leaves patients susceptible to fatal infections. Genetic variants for breast cancer risk linked to chemotherapy-induced toxicity have been previously explored. We study the association between a validated 313 genetic marker-based breast cancer polygenic risk score (PRS) and chemotherapy-induced neutropenia without fever, and febrile neutropenia (FNc) in Asian breast cancer patients treated with chemotherapy. PRS distributions were not significantly different in any of the comparisons. Higher PRS(overall) quartiles were 9% less likely to develop neutropenia, and 13% less likely to develop FNc. However, the associations were not statistically significant. No dose-dependent trend was observed for the estrogen receptor- (ER-) positive weighted PRS (PRS(ER-pos)) and ER-negative weighted PRS (PRS(ER-neg)). Breast cancer PRS was not strongly associated with chemotherapy-induced neutropenia or FNc. ABSTRACT: Background: The hypothesis that breast cancer (BC) susceptibility variants are linked to chemotherapy-induced toxicity has been previously explored. Here, we investigated the association between a validated 313-marker-based BC polygenic risk score (PRS) and chemotherapy-induced neutropenia without fever and febrile neutropenia (FNc) in Asian BC patients. Methods: This observational case-control study of Asian BC patients treated with chemotherapy included 161 FNc patients, 219 neutropenia patients, and 936 patients who did not develop neutropenia. A continuous PRS was calculated by summing weighted risk alleles associated with overall, estrogen receptor- (ER-) positive, and ER-negative BC risk. PRS distributions neutropenia or FNc cases were compared to controls who did not develop neutropenia using two-sample t-tests. Odds ratios (OR) and corresponding 95% confidence intervals were estimated for the associations between PRS (quartiles and per standard deviation (SD) increase) and neutropenia-related outcomes compared to controls. Results: PRS distributions were not significantly different in any of the comparisons. Higher PRS(overall) quartiles were negatively correlated with neutropenia or FNc. However, the associations were not statistically significant (PRS per SD increase OR neutropenia: 0.91 [0.79–1.06]; FNc: 0.87 [0.73–1.03]). No dose-dependent trend was observed for the ER-positive weighted PRS (PRS(ER-pos)) and ER-negative weighted PRS (PRS(ER-neg)). Conclusion: BC PRS was not strongly associated with chemotherapy-induced neutropenia or FNc.