Advanced Stage Is a Risk for Severe Neutropenia in Breast Cancer Patients Undergoing Neoadjuvant Adriamycin/Cyclophosphamide/Docetaxel Chemotherapy

Kazuki Moro, Masayuki Nagahashi, Haruka Uchida, Maiko Oji, Junko Tsuchida, Kumiko Yamaura, Chie Toshikawa, Mae Nakano, Mayuko Ikarashi, Yusuke Muneoka, Yosuke Tajima, Hiroshi Ichikawa, Yoshifumi Shimada, Jun Sakata, Yu Koyama, Kazuaki Takabe, Toshifumi Wakai


Background: Severe neutropenia, including febrile neutropenia, is a major toxicity of systemic chemotherapy that leads to delays in treatment, higher costs, and mortality. Severe neutropenia may occur during neoadjuvant chemotherapy even when the patients are free from known risk factors. Pegfilgrastim, a covalent conjugant of filgrastim that stimulate the production of neutrophils, is used for prevention. The current study aimed to reveal the characteristics of patients who need pegfilgrastim for primary prophylaxis to prevent severe neutropenia, including febrile neutropenia and grade 3 neutropenia, during neoadjuvant chemotherapy.

Methods: A retrospective analysis of 83 patients treated with neoadjuvant adriamycin/cyclophosphamide followed by docetaxel chemotherapy was performed. The factors which associated with severe neutropenia were examined by univariate and multivariate analyses.

Results: Severe neutropenia developed in one of 22 patients (5%) with pegfilgrastim for primary prophylaxis and in 17 of 61 patients (28%) without it. In 83 patients, the incidence of severe neutropenia was significantly decreased in the patients with pegfilgrastim for primary prophylaxis shown by the univariate analysis (P = 0.023) and multivariate analysis (P = 0.030). In 61 patients without pegfilgrastim for primary prophylaxis, the univariate analysis showed that severe neutropenia was associated with tumor size (P = 0.004), clinical stage (P = 0.009), and cancer antigen 15-3 (CA15-3) (P = 0.026). The multivariate analysis showed that clinical stage was associated with severe neutropenia (P = 0.021).

Conclusions: The current study demonstrated that advanced stage is a risk for severe neutropenia in patients treated with neoadjuvant adriamycin/cyclophosphamide followed by docetaxel chemotherapy. Given that prophylaxis with pegfilgrastim was associated with significantly lower incidence of severe neutropenia, patient with advance stage breast cancer may benefit from pegfilgrastim during neoadjuvant chemotherapy.

World J Oncol. 2022;13(6):379-386


Advanced stage; Breast cancer; Neoadjuvant chemotherapy; Neutropenia

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