Abstract
BACKGROUND: Existing evidence indicates that germline BRCA mutation (gBRCA-m) may increase chemotherapy sensitivity and toxicity. However, its role in chemotherapy-induced myelosuppression (CIM) remains unclear. We conducted this study to investigate the influence of gBRCA-m on CIM incidence and severity in patients with epithelial ovarian carcinoma (EOC). METHODS: Patients with EOC treated at the First Affiliated Hospital of Nanjing Medical University from January 2018 to August 2023 were classified into two groups: gBRCA-m and gBRCA wild-type. Chemotherapy regimen and myelosuppression data were retrospectively reviewed. Multivariate analysis assessed the association between gBRCA-m and CIM incidence and severity in patients with EOC receiving first-line chemotherapy. RESULTS: Sixty six (27%) of 242 included patients were gBRCA-m carriers. The median times to myelosuppression onset and the most severe occurrence were significantly shorter for patients with gBRCA-m (6.0 vs. 27.0 days, p < 0.001; 73.5 vs. 121.0 days, p < 0.001). Patients with gBRCA-m had a greater likelihood of Grade IV (GIV) myelosuppression at onset (aOR = 5.585, 95% CI = 1.621-19.241). During the most severe myelosuppression, patients with gBRCA-m experienced more pronounced decreases in white blood cells (1.83 × 10(9) vs. 2.33*10(9) cells/L, p = 0.002), neutrophils (0.73 × 10(9) vs. 1.08 × 10(9) cells/L, p = 0.001), haemoglobin levels (90.41 vs. 94.14 g/L, p = 0.017) and platelets (81.62 × 10(9) vs. 97.63 × 10(9) cells/L, p = 0.001) and were more prone to febrile GIV myelosuppression (aOR = 2.882, 95% CI = 1.071-7.754). The incidences of chemotherapy dose reduction (aOR = 4.322, 95% CI = 2.048-9.124) and delay (aOR = 6.045, 95% CI = 2.266-16.126) were significantly greater in patients with gBRCA-m. An analysis across all chemotherapy cycles indicated that patients with gBRCA-m had greater risks of GIII (aOR = 2.356, 95% CI = 1.770-3.137), GIV (aOR = 2.324, 95% CI = 1.685-3.207) myelosuppression and GIV myelosuppression with fever (aOR = 2.097, 95% CI = 1.077-4.083), as well as a greater incidence of chemotherapy dose reduction (aOR = 2.606, 95% CI = 1.785-3.805) and delay (aOR = 4.118, 95% CI = 2.213-7.663). CONCLUSIONS: EOC patients with gBRCA-m experienced earlier and more severe CIM, highlighting the need for careful monitoring and tailored management.