Abstract PS5-07-07: Toward optimization of treatment strategies for early breast cancer: a multicenter observational study integrating whole genome and transcriptome sequencing within the National Whole Genome Project in Japan (WJOG16822B)

Abstract Background: Despite curative-intent treatment, approximately 30% of patients with operable breast cancer experience recurrence. In patients with early-stage triple-negative breast cancer (TNBC), the phase 3 KEYNOTE-522 trial showed significant improvement in overall survival (OS) with the addition of pembrolizumab to neoadjuvant chemotherapy. However, the prognosis of patients who do not achieve a pathologic complete response (pCR) remains poor, highlighting the need for novel therapeutic strategies. While most patients with hormone receptor-positive (HR+), HER2-negative (HER2-) early breast cancer do not experience recurrence under current standard therapies, a substantial proportion−particularly those with high-risk clinical or pathological features−are at risk of developing distant metastases, often within the first few years after treatment. Optimized treatment strategies are needed to reduce early relapse and prevent metastatic progression in this high-risk population. Study Design: This is a multicenter, prospective observational cohort study embedded within the National Whole Genome Project in Japan, conducted at 17 sites of the West Japan Oncology Group (WJOG). Tumor samples are collected prior to neoadjuvant chemotherapy and at the time of surgery. Blood samples are collected at baseline and prior to surgery. Tumor specimens and matched blood samples undergo whole genome sequencing (WGS) and RNA sequencing. Multiplex immunohistochemistry is performed to evaluate immune cell infiltration such as CD4+/CD8+ T cells, regulatory T cells, B cells and M2 macrophages, as well as the expression of immune markers including PD-L1, PD-L2, granzyme B. Peripheral blood mononuclear cells are analyzed for immune cell subset profiling and functional status. Circulating tumor DNA is analyzed for genomic profiling and detection of minimal residual disease. The results of WGS are reviewed by an institutional Molecular Tumor Board and returned to participants in a clinical report format. Eligibility Criteria: Key eligibility criteria includes age ≥18, ECOG PS 0-2, stage II-III TNBC or HR+, HER2- breast cancer, and a planned treatment with anthracycline- and taxane-based neoadjuvant chemotherapy, with or without pembrolizumab. Objectives: The primary objective is to identify genomic and immunologic biomarkers associated with pCR following neoadjuvant chemotherapy. Secondary objectives include identification of biomarkers associated with survival outcomes including invasive disease-free survival, breast cancer-specific survival, OS and treatment-related adverse events. Additionally, the study aims to identify novel treatment targets for patients who do not achieve pCR. Present and Target Accrual: Target accrual is 240 patients (TNBC cohort: 100; HR+/HER2- cohort: 140) over 2 years. Enrollment began in December 2023, and 150 patients have been enrolled at the time of submission. Clinical trial information: jRCT1030250152 Citation Format: J. Masuda, Y. Ozaki, M. Kubo, Y. Takano, N. Tomioka, K. Matsumoto, H. Bando, N. Hayashi, T. Iwasa, M. Takahashi, N. Kawaguchi-Sakita, A. Fushimi, T. Mukohara, M. Futamura, M. Doi, M. Miyashita, M. Baba, M. Tsukabe, N. Yamashita, K. Nonogaki, S. Amino, M. Yamashita, E. Habano, M. Akiya, M. Takamatsu, T. Osako, A. Ueki, K. Takeuchi, N. Tanaka, S. Mori, I. Fukada, S. Takahashi, S. Morita, S. Imoto, T. Ueno, T. Takano, S. Kitano. Toward optimization of treatment strategies for early breast cancer: a multicenter observational study integrating whole genome and transcriptome sequencing within the National Whole Genome Project in Japan (WJOG16822B) [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 PS5-07-07.