Abstract Background: Chemotherapy-induced alopecia (CIA) remains one of the most distressing side effects of breast cancer treatment, especially for younger patients. Scalp cooling systems such as the PAXMAN Orbis have shown promising results in reducing the incidence and severity of CIA, particularly in regimens involving taxanes and anthracyclines. However, most existing studies focus on single regimens, and comparative evaluations across chemotherapy backbones remain limited. This study aimed to compare the efficacy of PAXMAN in two commonly used neoadjuvant/adjuvant regimens with differing first-line agents: a dose-dense anthracycline-first regimen (ddAC→ddPTX) and a taxane-based HER2-targeted regimen (trastuzumab + pertuzumab + docetaxel: HP+DTX). Methods: We retrospectively analyzed 62 patients with early-stage breast cancer who underwent scalp cooling using the PAXMAN system during chemotherapy at our institution between January 2021 and December 2024. Of these, 37 patients received the ddAC→ddPTX regimen, and 25 received the HP+DTX regimen. Scalp cooling was administered during each chemotherapy session. Hair loss was assessed at the end of each regimen using the CTCAE v5.0 grading system. Grade 1 or lower alopecia was defined as successful hair preservation. Results: The overall cohort had a mean age of 49 years. In the ddAC→ddPTX group, 59.5% of patients maintained Grade 1 or lower alopecia at the end of chemotherapy. In the HP+DTX group, 64% achieved Grade 1 or lower alopecia. No serious adverse events related to scalp cooling were reported. The treatment adherence and tolerance of the PAXMAN system were high in both groups. Discussion: Our study is one of the first to directly compare the effectiveness of scalp cooling between anthracycline-first and taxane-first chemotherapy regimens. The comparable success rates of hair preservation between the ddAC→ddPTX and HP+DTX groups suggest that PAXMAN is effective across different chemotherapy backbones, including those with known high alopecic potential. These findings provide reassurance that scalp cooling can be equally beneficial regardless of the sequencing of anthracyclines or taxanes. This is especially relevant in clinical settings where regimen choice is dictated by tumor subtype, as in HER2-positive disease. To our knowledge, this is the first comparative report from Japan on this topic. The results offer valuable evidence supporting the routine use of scalp cooling in Asian populations, who may differ in hair structure and density from Western cohorts studied previously. Further prospective, larger-scale studies are warranted to validate these findings and optimize personalized scalp cooling protocols. Citation Format: S. Nagasawa, K. Matsui, M. Furukawa, E. Kanaya, M. Araki, S. Sekine, T. Fujii. Comparative Analysis of the Effectiveness of Scalp Cooling with PAXMAN Between Dose-Dense AC→PTX and Trastuzumab+Pertuzumab+Docetaxel Regimens in Japanese Breast Cancer Patients abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-02-08.
Nagasawa et al. (Tue,) studied this question.