Abstract P1-01-04: RUFY3 as a predictive intratumor biomarker for lymph node metastasis in older women with invasive breast cancer

Abstract Background: Sentinel lymph node biopsy (SLNB) is omitted in older women (≥ 70 years old) with clinical lymph node (LN)-negative hormone receptor-positive breast cancer as it does not influence adjuvant treatment decision-making. However, older women are heterogenous in frailty while the chance of recurrence increase with improving longevity. Therefore, a biomarker that identifies LN metastasis may facilitate treatment decision-making. RUFY3 is associated with cancer progression. We evaluated RUFY3 expression level as a biomarker for LN-positive breast cancer in older women. Methods: Clinical and transcriptomic data of breast cancer patients were obtained from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n=1,903) and The Cancer Genome Atlas (TCGA, n=1,046) Pan-Cancer study cohorts. Results: A total of 510 (METABRIC) and 211 (TCGA) older women were identified. LN-positive breast cancer, which represented 51.4% (METABRIC) and 48.4% (TCGA), demonstrated worse disease-free, disease-specific, and overall survival. RUFY3 levels were significantly lower in LN-positive tumors regardless of age. The area under the curve for the receiver operator characteristic (AUC-ROC) curves showed RUFY3 predicted LN metastasis. Low RUFY3 enriched oxidative phosphorylation, DNA repair, MYC targets, unfolded protein response, and mtorc1 signaling gene sets, was associated with T helper type 1 cell infiltration, and with intratumor heterogeneity and fraction altered. Low RUFY3 expression was associated with LN-positive breast cancer and with worse disease specific survival amongst older women. Conclusion: Low RUFY3 expression is associated LN-positive in breast cancer. Intratumor RUFY levels can be used for selection of older breast cancer patients for LN staging. Citation Format: Fernando A. Angarita, Masanori Oshi, Akimitsu Yamada, Li Yan, Ryusei Matsuyama, Stephen B. Edge, Itaru Endo, Kazuaki Takabe. RUFY3 as a predictive intratumor biomarker for lymph node metastasis in older women with invasive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-04.