Febrile neutropenia in adjuvant and neoadjuvant chemotherapy
for breast cancer: a retrospective study in routine clinical practice
from a single institution
Anne Béthune Volters
Received: 20 December 2017 /Accepted: 17 May 2018
Springer-Verlag GmbH Germany, part of Springer Nature 2018
Background Febrile neutropenia (FN) is one of the most common and most critical adverse effects of chemotherapy. Despite
many existing guidelines based on the use of granulocyte-colony stimulating factor (G-CSF), FN continues to impair the quality
of life and interfere with the treatment of many patients. The purpose of this study was to assess the incidence and management of
FN associated with chemotherapy for early breast cancer in routine clinical practice.
Methods All patients with early-stage breast cancer (ESBC) treated by chemotherapy at Institut Curie, Hôpital René Huguenin,
in 2014 were retrospectively included. The incidence and management of FN were reported. Risk factors associated with FN
were studied by robust-error-variance Poisson regression.
Results A total of 524 patients received either neoadjuvant (N = 130) or adjuvant chemotherapy (N = 394). Most patients (80%)
were treated with a combination of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC100; 3 cycles) followed by docetaxel
(D; 3 cycles). The overall incidence of FN was 17%. Eighteen percent of patients received primary prophylaxis (PP)
for FN with G-CSF, using pegfilgrastim in 64% of cases and 74% of patients over the age of 70 received PP. Less than 5% of
patients who received PP experienced FN. Recurrent FN after secondary prophylaxis was observed in 9% of patients. Forty-
seven percent of cases of FN occurred after the first cycle and 30% occurred after the fourth cycle, corresponding to D ±
trastuzumab (T). The FEC100 regimen was associated with a relative risk of FN of 1.98 (p = 0.09). Autoimmune (AI) and
inflammatory diseases were associated with a higher risk of FN (RR 3.08; p < 0.01). No significant difference in the incidence of
FN was observed between adjuvant and neoadjuvant chemotherapy. FN was managed on an outpatient basis in 72% of cases.
Outpatients with FN were mainly treated by a combination of amoxicillin–clavulanic acid and ciprofloxacin. Dose reduction or
chemotherapy regimen modification were necessary in 25% of patients after FN. No toxic death was reported.
Conclusion The incidence of FN induced by adjuvant/neoadjuvant chemotherapy in ESBC is higher in routine clinical practice
than in clinical trials. AI or inflammatory diseases were significant independent risk factors for FN. Primary prophylaxis in
patients at risk (elderly, comorbid patients), especially treated with the FEC regimen, is the keystone of management of this
adverse effect. Prevention and management of FN to ensure the patient’s safety and quality of life are a major issue for both
medical oncologists and supportive care physicians.
Early-stage breast cancer
Breast cancer is the most common cancer in women in France
and worldwide, with an estimated 54,062 new cases
diagnosed in 2015.  As a result of many clinical trials,
treatment has improved the overall survival of breast cancer.
Most of the drugs used in the treatment of breast cancer can
cause blood disorders, such as neutropenia. This common
toxicity associated with fever is responsible for substantial
morbidity, mortality, and escalating healthcare costs and
also leads to chemotherapy dose reductions, which compro-
mise survival outcomes in the curative setting. 
A decreased incidence of FN has been clearly established
in patients receiving granulocyte-colony stimulating factors
* Joy Bacrie
Institut Curie, Hôpital René Huguenin, Saint Cloud, France
Supportive Care in Cancer