Introduction

When risk estimation in older patients with hormone receptor positive breast cancer (HR + BC) is based on the same factors as in younger patients, age-related factors regarding recurrence risk and other-cause mortality are not considered. Genomic risk assessment could help identify patients with ultralow risk BC who can forgo adjuvant treatment. However, assessment tools should be validated specifically for older patients. This study aims to determine whether the 70-gene signature test (MammaPrint) can identify patients with HR + BC aged ≥70 years with ultralow risk for distant recurrence.

Materials and Methods

Inclusion criteria: ≥70 years; invasive HR + BC; T1-2N0-3M0. Exclusion criteria: HER2 + BC; neoadjuvant therapy. MammaPrint assays were performed following standardized protocols. Clinical risk was determined with St. Gallen risk classification.

Primary endpoint was 10-year cumulative incidence rate of distant recurrence in relation to genomic risk. Subdistribution hazard ratios (sHR) were estimated from Fine and Gray analyses. Multivariate analyses were adjusted for adjuvant endocrine therapy and clinical risk.

Results

This study included 418 patients, median age 78 years (interquartile range [IQR] 73–83). Sixty percent of patients were treated with endocrine therapy. MammaPrint classified 50 patients as MammaPrint-ultralow, 224 patients as MammaPrint-low, and 144 patients as MammaPrint-high risk. Regarding clinical risk, 50 patients were classified low, 237 intermediate, and 131 high. Discordance was observed between clinical and genomic risk in 14 MammaPrint-ultralow risk patients who were high clinical risk, and 84 patients who were MammaPrint-high risk, but low or intermediate clinical risk. Median follow-up was 9.2 years (IQR 7.9–10.5).

The 10-year distant recurrence rate was 17% (95% confidence interval [CI] 11–23) in MammaPrint-high risk patients, 8% (4–12) in MammaPrint-low (HR 0.46; 95%CI 0.25–0.84), and 2% (0–6) in MammaPrint-ultralow risk patients (HR 0.11; 95%CI 0.02–0.81). After adjustment for clinical risk and endocrine therapy, MammaPrint-high risk patients still had significantly higher 10-year distant recurrence rate than MammaPrint-low (sHR 0.49; 95%CI 0.26–0.90) and MammaPrint-ultralow patients (sHR 0.12; 95%CI 0.02–0.85). Of the 14 MammaPrint-ultralow, high clinical risk patients none developed a distant recurrence.

Discussion

These data add to the evidence validating MammaPrint's ultralow risk threshold. Even in high clinical risk patients, MammaPrint-ultralow risk patients remained recurrence-free ten years after diagnosis. These findings justify future studies into using MammaPrint to individualize adjuvant treatment in older patients.

中文翻译：

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验证 70 基因特征测试 (MammaPrint) 以确定年龄≥ 70 岁且远处复发风险极低的乳腺癌患者：一项基于人群的队列研究

介绍

当激素受体阳性乳腺癌老年患者 (HR + BC) 的风险评估基于与年轻患者相同的因素时，不考虑与复发风险和其他原因死亡率相关的年龄相关因素。基因组风险评估可以帮助识别可以放弃辅助治疗的超低风险 BC 患者。然而，评估工具应该专门针对老年患者进行验证。本研究旨在确定 70 基因特征测试 (MammaPrint) 是否可以识别年龄≥70 岁且远处复发风险极低的 HR + BC 患者。

材料和方法

纳入标准：≥70岁；侵入性 HR + BC；T1-2N0-3M0。排除标准：HER2+BC；新辅助治疗。MammaPrint 检测按照标准化方案进行。临床风险由圣加仑风险分类确定。

主要终点是与基因组风险相关的 10 年远处复发累积发生率。细分分布风险比 (sHR) 是根据精细分析和灰色分析估算的。针对辅助内分泌治疗和临床风险调整了多变量分析。

结果

这项研究包括 418 名患者，中位年龄 78 岁（四分位间距 [IQR] 73–83）。百分之六十的患者接受了内分泌治疗。MammaPrint 将 50 名患者分类为 MammaPrint-ultralow，将 224 名患者分类为 MammaPrint-low，将 144 名患者分类为 MammaPrint-high 风险。关于临床风险，50 名患者被归类为低风险、237 名中等风险和 131 名高风险。在 14 名具有高临床风险的 MammaPrint-超低风险患者和 84 名具有 MammaPrint-高风险但低或中等临床风险的患者中，观察到临床和基因组风险之间存在不一致。中位随访时间为 9.2 年（IQR 7.9–10.5）。

MammaPrint 高风险患者的 10 年远处复发率为 17%（95% 置信区间 [CI] 11-23），MammaPrint 低风险患者为 8%（4-12）（HR 0.46；95%CI 0.25-0.84） ), 和 2% (0-6) 在 MammaPrint-超低风险患者 (HR 0.11; 95%CI 0.02-0.81)。调整临床风险和内分泌治疗后，MammaPrint 高风险患者的 10 年远处复发率仍显着高于 MammaPrint 低 (sHR 0.49；95%CI 0.26–0.90) 和 MammaPrint 超低患者 (sHR 0.12；95%)置信区间 0.02–0.85）。在 14 名 MammaPrint-ultralow、高临床风险患者中，没有人出现远处复发。

讨论

这些数据增加了验证 MammaPrint 超低风险阈值的证据。即使在高临床风险患者中，MammaPrint-超低风险患者在诊断后十年仍保持无复发。这些发现证明了未来使用 MammaPrint 对老年患者进行个体化辅助治疗的研究是合理的。