The impact of patient-related factors on the occurrence of febrile neutropenia in breast cancer patients receiving (neo-)adjuvant chemotherapy with 5-fluorouracil, epirubicin, and cyclofosfamide (FEC) x6 or FEC x3 followed by docetaxel (D) x3.

Abstract

1078 Background: Recently we described the impact of genetic variability on severe toxicity in breast cancer patients receiving (neo-) adjuvant FEC chemotherapy (Annals of Oncology 2013, In Press). We now further assessed the impact of a wide range of patient-related factors on FEC toxicity in routine clinical setting. Methods: Patients with early breast cancer receiving (neo-)adjuvant 6 cycles FEC or sequential 3 cycles of FEC and 3 cycles D were retrospectively evaluated through electronic chart review for febrile neutropenia (primary endpoint; CTC 3.0). Age at diagnosis, body mass index, body surface area, number of cycles received, germline genetic polymorphisms, and baseline biochemical variables (white blood cell count, absolute neutrophil count, platelets, aspartate aminotransferase, alanine aminotransferase, total bilirubin and creatinine) were available for most patients (missing data <10%). All patients had follow up for progression free survival (PFS) and overall survival (OS). Multivariate logistic regression analysis was performed including univariate associates of outcome with a p-value <0.25. Results: We identified 1,031 patients treated between 2000-2010 with 6x FEC (n=488) or 3x FEC followed by 3x D (n=543). 174 (16.9%) patients developed febrile neutropenia during FEC. After logistic regression analysis febrile neutropenia was found to be significantly associated with carriers of the rs45511401 variant T-allele in the MRP1 gene found in 12% of patients (p= 0.03, OR1.99, CI 1.07-3.71) and with increasing serum creatinine values (p=0.05 OR 4.58/CI 0.99-20.98); all other investigated patient-related parameters were not retained by the model. At a mean follow up of 5.2 years, the occurrence of febrile neutropenia was not correlated with PFS and OS. Conclusions: In this study, only the baseline level of serum creatinine and germline genetic polymorphisms in the MRP-1 gene were predictive for the occurrence of febrile neutropenia in patients receiving FEC chemotherapy. The occurrence of febrile neutropenia did not seem to impact on outcome.