Comparison of dose-dense versus standard neoadjuvant chemotherapy for HER2 negative breast cancer: Retrospective, multicenter, real-world, Japanese study (JONIE5).

e12601 Background: Based on the Norton-Simon model, dose-dense (dd) chemotherapy with shortened intervals between administrations has been adopted in perioperative chemotherapy for breast cancer. However, the safety and efficacy of dd chemotherapy in neoadjuvant settings have not been thoroughly investigated. Methods: The aim of this study is to evaluate the efficacy and safety of dd versus standard regimen in neoadjuvant chemotherapy. The patients with HER2-negative breast cancer who underwent neoadjuvant chemotherapy (NAC) with anthracycline-taxane were continuously identified between 2014 and 2023. These patients were divided into a triple negative breast cancer (TNBC) cohort with HR < 10% and a luminal cohort with hormone receptor (HR) ≥ 10%, and pathologic complete response (pCR) and relapse-free survival (RFS) were evaluated in each group. Results: A total of 525 patients with HER2-negative breast cancer were identified from 11 institutions in Japan. In the overall cohort, 229 patients were in the dd group and 296 patients were in the standard group, with no significant differences between the two groups in terms of age, nuclear grade (NG), T and N categories. In the dd group, 100% of the cases received dd AC/EC, and 75% of the cases received dd PTX. The pCR rate in the TNBC cohort was 42% in the dd group and 32% in the standard group (p=0.101), and in the subgroup with HR < 1%, it was 39% and 30%, respectively (p=0.167). In the Luminal cohort, the pCR rate for NG3 vs. NG1 or 2 was 27% and 5%, respectively (p=0.005), but in NG3 was 12% in the dd group and 16% in the standard group each(p=0.445). Regarding RFS in the dd group and the standard group, no significant differences were observed in either the TNBC cohort or the Luminal cohort (Logrank P =0.516, 0.946, with median follow up periods of 33 months and 56 months, respectively). The average relative dose intensity of chemotherapy was 96.5% in the dd group, and 95.3% in the standard group. The mean period from the first NAC administration to surgery was 140 days in the dd group and 191 days in the standard group. The incidence of adverse events (AEs) was significantly higher in the standard group compared to the dd group, with a particularly higher incidence of Grade 3 or higher neutropenia and peripheral neuropathy. When analyzed by age, the incidence of neutropenia was significantly higher in the standard group in patients under 65 years of age. Conclusions: This study is the first to demonstrate the safety and efficacy of the dd regimen in NAC for Japanese breast cancer patients. The dd regimen, compared to the standard, showed comparable results in terms of AEs, pCR rate, and prognosis. With a shorter treatment duration, the dd regimen should be considered a preferred NAC regimen for breast cancer. Further evaluation is needed to assess the long-term survival.