Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Division of Surgical Oncology, Department of Surgery, Houston Methodist Hospital, Houston, TX, USA.
Breast Cancer Res Treat. 2022 Feb;192(1):19-32. doi: 10.1007/s10549-021-06482-3. Epub 2022 Jan 12.
Sentinel lymph node biopsy 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 heterogeneous 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.
Clinical and transcriptomic data of breast cancer patients were obtained from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 1903) and The Cancer Genome Atlas (TCGA, n = 1046) Pan-cancer study cohorts.
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 among older women.
Older women with breast cancers who had low expression level of RUFY3 were more frequently diagnosed with LN-positive tumors, which translated into worse prognosis.
对于临床淋巴结（LN）阴性、激素受体阳性的老年乳腺癌患者（≥70 岁），省略前哨淋巴结活检，因为这不会影响辅助治疗决策。然而，老年女性在虚弱方面存在异质性，而随着寿命的延长，复发的可能性会增加。因此，一种可以识别 LN 转移的生物标志物可能有助于治疗决策。RUFY3 与癌症进展有关。我们评估了 RUFY3 表达水平作为老年女性 LN 阳性乳腺癌的生物标志物。
从乳腺癌国际分子分类联盟（METABRIC，n=1903）和癌症基因组图谱（TCGA，n=1046）泛癌研究队列中获得了乳腺癌患者的临床和转录组数据。
共确定了 510 名（METABRIC）和 211 名（TCGA）老年女性。LN 阳性乳腺癌占 51.4%（METABRIC）和 48.4%（TCGA），表现出更差的无病生存、疾病特异性生存和总生存。无论年龄大小，LN 阳性肿瘤的 RUFY3 水平均显著降低。受试者工作特征曲线下的面积（AUC-ROC）曲线显示 RUFY3 预测 LN 转移。低 RUFY3 富集氧化磷酸化、DNA 修复、MYC 靶标、未折叠蛋白反应和 mTORC1 信号基因集，与辅助性 T 细胞 1 细胞浸润、肿瘤内异质性和改变分数有关。低 RUFY3 表达与老年女性的 LN 阳性乳腺癌和疾病特异性生存较差相关。
RUFY3 表达水平较低的老年女性乳腺癌患者更常被诊断为 LN 阳性肿瘤，这转化为预后较差。
