高21基因复发风险评分（RS）和高Ki-67水平是雌激素受体（ER）阳性ERBB2阴性（ER+/ERBB-）乳腺癌患者的不良预后因素，然而两者之间存在差异。对于这两个生物标志物的生存差异还不十分了解。本研究旨在评估ER+/ERBB-乳腺癌低RS患者中RS和Ki-67表达以及Ki-67表达与无复发生存之间的关联。该队列研究包括韩国两家医院2010年3月至2020年12月接受21基因RS检测的ER+/ERBB2-乳腺癌患者。研究指标为复发风险评分和Ki-67水平。采用Cox比例风险回归模型考察Ki-67与无复发生存（RFS）的关联，并采用二元逻辑回归模型考察Ki-67与继发内分泌耐药的关联。高Ki-67表达定义为大于等于20%，低基因组风险定义为RS不超过25。继发内分泌耐药定义为至少2年内分泌治疗之后且在5年辅助内分泌治疗结束后的第一年期间发生的乳腺癌复发。共纳入2295例女性患者（平均[标准差]年龄，49.8[9.3]岁），其中有1948例（84.9%）属于低基因组风险组，1425例（62.1%）Ki-67水平较低。中位随访期为40个月（范围：0-140个月）。RS和Ki-67水平呈中等相关（R=0.455，P<0.001）。Ki-67水平较低的患者中，有1341例（94.1%）RS较低，而Ki-67水平较高的870例患者中有607例（69.8%）RS较低。在RS较低的患者中，根据Ki-67水平，RFS存在显著差异（低Ki-67，98.5% vs 高Ki-67，96.5%；P=0.002）。在1807例未接受化疗的低基因组风险患者中，高Ki-67水平与复发独立相关（风险比，2.51；95%置信区间，1.27-4.96；P=0.008）。根据Ki-67水平，3年后的复发存在显著差异（低Ki-67，98.7% vs 高Ki-67，95.7%；P=0.003），而在3年内的复发没有差异（低Ki-67，99.3% vs 高Ki-67，99.3%；P=0.90）。此外，在未接受化疗的低RS患者中，Ki-67与继发内分泌耐药相关（比值比，2.49；95%置信区间，1.13-5.50；P=0.02）。在这项针对ER+/ERBB2-乳腺癌患者的队列研究中，Ki-67与RS之间存在中等相关，低基因组风险患者中高Ki-67水平与继发内分泌耐药风险增加相关。

Both high 21-gene recurrence score (RS) and high Ki-67 level are poor prognostic factors in patients with estrogen receptor (ER)-positive ERBB2-negative (ER+/ERBB-) breast cancer; however, a discrepancy between the 2 has been noted. Survival differences according to these 2 biomarkers are not well known.To assess the associations between RS and Ki-67 expression and between Ki-67 expression and recurrence-free survival in patients with ER+/ERBB- breast cancer with low RS.This cohort study included women treated for ER+/ERBB2- breast cancer who underwent the 21-gene RS test from March 2010 to December 2020 in 2 hospitals in Korea.Recurrence score and Ki-67 level.A Cox proportional hazards regression model was used to examine the association of Ki-67 with recurrence-free survival (RFS), while a binary logistic regression model was used to examine the association between Ki-67 and secondary endocrine resistance. High Ki-67 expression was defined as 20% or greater, and low genomic risk as an RS of 25 or less. Secondary endocrine resistance was defined as breast cancer recurrence that occurred after at least 2 years of endocrine therapy and during or within the first year after completing 5 years of adjuvant endocrine therapy.A total of 2295 female patients were included (mean [SD] age, 49.8 [9.3] years), of whom 1948 (84.9%) were in the low genomic risk group and 1425 (62.1%) had low Ki-67 level. The median follow-up period was 40 months (range, 0-140 months). The RS and Ki-67 level had a moderate correlation (R = 0.455; P < .001). Of the patients with low Ki-67 level, 1341 (94.1%) had low RS, whereas 607 of 870 patients with high Ki-67 level (69.8%) had low RS. In patients with low RS, the RFS differed significantly according to Ki-67 level (low Ki-67, 98.5% vs high Ki-67, 96.5%; P = .002). Among the 1807 patients with low genomic risk who did not receive chemotherapy, high Ki-67 level was independently associated with recurrence (hazard ratio, 2.51; 95% CI, 1.27-4.96; P = .008). Recurrence after 3 years differed significantly according to Ki-67 level (low Ki-67, 98.7% vs high Ki-67, 95.7%; P = .003), whereas recurrence within 3 years did not differ (low Ki-67, 99.3% vs high Ki-67, 99.3%; P = .90). In addition, Ki-67 was associated with secondary endocrine resistance in patients with low RS who did not receive chemotherapy (odds ratio, 2.49; 95% CI, 1.13-5.50; P = .02).In this cohort study of patients with ER+/ERBB2- breast cancer, a moderate correlation was observed between Ki-67 and RS, and high Ki-67 level in patients with low genomic risk was associated with increased risk of secondary endocrine resistance.