Multivariable regression analysis of febrile neutropenia occurrence in early breast cancer patients receiving chemotherapy assessing patient-related, chemotherapy-related and genetic risk factors

Alena M Pfeil,Christof Vulsteke,Patrick Neven,Robert Paridaens,Diether Lambrechts,Hans Wildiers,Thomas D Szucs,Anne-Sophie Dieudonné,Matthias Schwenkglenks,Ruth Pettengell,Sigrid Hatse

doi:10.1186/1471-2407-14-201

Alena M Pfeil, Christof Vulsteke + Show 9 more

Open Access

https://doi.org/10.1186/1471-2407-14-201

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Abstract

BackgroundFebrile neutropenia (FN) is common in breast cancer patients undergoing chemotherapy. Risk factors for FN have been reported, but risk models that include genetic variability have yet to be described. This study aimed to evaluate the predictive value of patient-related, chemotherapy-related, and genetic risk factors.MethodsData from consecutive breast cancer patients receiving chemotherapy with 4–6 cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) or three cycles of FEC and docetaxel were retrospectively recorded. Multivariable logistic regression was carried out to assess risk of FN during FEC chemotherapy cycles.ResultsOverall, 166 (16.7%) out of 994 patients developed FN. Significant risk factors for FN in any cycle and the first cycle were lower platelet count (OR = 0.78 [0.65; 0.93]) and haemoglobin (OR = 0.81 [0.67; 0.98]) and homozygous carriers of the rs4148350 variant T-allele (OR = 6.7 [1.04; 43.17]) in MRP1. Other significant factors for FN in any cycle were higher alanine aminotransferase (OR = 1.02 [1.01; 1.03]), carriers of the rs246221 variant C-allele (OR = 2.0 [1.03; 3.86]) in MRP1 and the rs351855 variant C-allele (OR = 2.48 [1.13; 5.44]) in FGFR4. Lower height (OR = 0.62 [0.41; 0.92]) increased risk of FN in the first cycle.ConclusionsBoth established clinical risk factors and genetic factors predicted FN in breast cancer patients. Prediction was improved by adding genetic information but overall remained limited. Internal validity was satisfactory. Further independent validation is required to confirm these findings.

Highlights

Febrile neutropenia (FN) is common in breast cancer patients undergoing chemotherapy
Chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) are serious and frequent complications in breast cancer patients receiving adjuvant chemotherapy, and they result in hospitalisations [1,2,3] and chemotherapy dose reductions or delays that impact on treatment outcome and short-term mortality [4]
Haematological toxicities included were: FN (defined as an absolute neutrophil count (ANC) < 0.5 × 109/L and a body temperature ≥ 38°C according to the Infectious Diseases Society of America), prolonged grade 4 neutropenia (≥ 5 days), deep neutropenia (< 100/μl), grade 3/4 thrombocytopenia, and grade 3/4 anaemia during FEC chemotherapy cycles

Summary

Introduction

Febrile neutropenia (FN) is common in breast cancer patients undergoing chemotherapy. Antibacterial or antifungal prophylaxis has recently been recommended for neutropenic patients expected to have a prolonged low neutrophil count or with other risk factors that favour complications [6]. Prophylaxis with granulocyte colony-stimulating factor (GCSF) in patients at high risk of FN (>20%) is recommended in international guidelines [5,7,8]. For chemotherapy regimens with an intermediate FN risk (10-20%), the European Organisation for Research and Treatment of Cancer (EORTC) GCSF guideline recommends that patient risk factors should be considered to determine individual risk of FN [5] and the likely benefit of prophylactic GCSF. It is important to identify patients at high risk of FN before the initiation of chemotherapy to provide them with appropriate prophylactic measures

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