The three chemotherapy regimens most frequently used in breast cancer patients with axillary lymph node metastasis are AC-T (doxorubicin, cyclophosphamide, docetaxel), AT (doxorubicin, paclitaxel), and TAC. According to the National Comprehensive Cancer Network (NCCN) guidelines, all three regimens pose a high risk of neutropenia and its complications (> 20%).[3]
Our study focused on the TAC regimen, which was the most likely to show the prophylactic effect of IPC due to the high incidence of FN. Six-cycle TAC has the advantage of similar efficacy, but with a shorter treatment period, than eight-cycle AC followed by docetaxel.[13] However, the TAC regimen has a very high rate of FN, with CIN occurring in 100% of patients receiving TAC chemotherapy and FN in 42.5–63.4%.[8, 14] In our study, 97.6% patients developed CIN and 18.8% developed FN.
Chemotherapy-induced FN is a severe adverse effect that can delay the chemotherapy schedule, reduce the relative dose intensity, and increase the hospitalization period, which increases costs.[15, 16] In addition, FN can cause life-threatening infections, with fatality rates of 5–11%.[16] The mortality rate of FN in our study was 12.5% (2/14), and there was no death in the IPC group. Risk factors for FN include age, performance status, gender, comorbidities, laboratory abnormalities, BMI, chemotherapy regimen, neutropenia prophylaxis, tumor type, disease progression, and genetic risk factors.[17] In this study, these factors were controlled or analyzed, and only IPC and comorbidity were independently related to the development of FN.
The use of prophylactic G-CSF improves the prognosis of patients on the TAC regimen by lowering the incidence and duration of FN.[15] The NCCN, American Society of Clinical Oncology, and European Organization for the Research and Treatment of Cancer guidelines recommend routine use of primary G-CSF prophylaxis for high-risk cases (risk of FN > 20%) based on several randomized controlled trials.[18–20] The use of prophylactic ciprofloxacin can also lower the incidence of FN.[5] Despite these efforts, however, the rates of FN and its complications are still high.[5–8] In addition, the side effects of these prophylactic drugs cannot be ignored. Ciprofloxacin can cause pancytopenia and G-CSF is associated with the development of acute myeloid leukemia.[21, 22] In comparison, mask wearing and physical distancing are free from the potential risks of various pharmaceutical preventive methods.
All patients in this study had an ECOG score of 0, and received primary prophylactic pegfilgrastim to prevent FN and its complications, as well as prophylactic antibiotics when grade 4 NIC developed. The patients received all of these prophylactic drugs, and additional IPC significantly reduced the FN incidence rate, hospitalization duration, and hospital costs.
One of the main causes of fever in CIN patients is respiratory infection, which has a high mortality rate. Most respiratory infections in FN are bacterial or fungal, which can be controlled to some extent with drugs. However, viruses are also a cause, and one study detected a virus in 41% of patients.[9, 23] After the COVID-19 outbreak, the World Health Organization and Centers for Disease Control promoted mask wearing and physical distancing. This prevention guidance has proven effective against the transmission of respiratory diseases.[12, 24, 25] Our study showed that these guidelines were also effective in reducing the likelihood of FN in patients receiving TAC.
There were limitations to this study. First, it was retrospective. However, it was conducted under conditions controlled by the state due to the pandemic, it should have higher reliability than other retrospective studies. Second, the number of patients was insufficient for a single-center study. However, the TAC regimen has a high incidence of FN and the preventive effect of IPC was better than expected; significant results were obtained despite the small study population.