Department of Surgery, Dongtan Sacred Heart Hospital, Hallym University, Dongtan, Republic of Korea.
Department of Medicine, Yonsei University Graduate School, Seoul, Republic of Korea.
JAMA Netw Open. 2023 Aug 1;6(8):e2330961. doi: 10.1001/jamanetworkopen.2023.30961.
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.
DESIGN, SETTING, AND PARTICIPANTS: 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.
在雌激素受体（ER）阳性 ERBB2 阴性（ER+/ERBB-）乳腺癌患者中，高 21 基因复发评分（RS）和高 Ki-67 水平都是不良预后因素；然而，两者之间存在差异。根据这两个生物标志物的生存差异尚不清楚。
评估 ER+/ERBB-乳腺癌中 RS 和 Ki-67 表达之间以及 Ki-67 表达与低 RS 患者无复发生存率（RFS）之间的相关性。
设计、地点和参与者：本队列研究纳入了 2010 年 3 月至 2020 年 12 月在韩国的 2 家医院接受 ER+/ERBB2-乳腺癌治疗的女性患者，这些患者接受了 21 基因 RS 检测。
复发评分和 Ki-67 水平。
使用 Cox 比例风险回归模型检查 Ki-67 与 RFS 的相关性，同时使用二项逻辑回归模型检查 Ki-67 与继发内分泌抵抗之间的相关性。高 Ki-67 表达定义为 20%或更高，低基因组风险定义为 RS 为 25 或更低。继发内分泌抵抗定义为内分泌治疗至少 2 年后且在完成 5 年辅助内分泌治疗期间或之后 1 年内发生的乳腺癌复发。
共纳入 2295 名女性患者（平均[SD]年龄，49.8[9.3]岁），其中 1948 名（84.9%）处于低基因组风险组，1425 名（62.1%）Ki-67 水平较低。中位随访时间为 40 个月（范围，0-140 个月）。RS 和 Ki-67 水平有中度相关性（R=0.455；P<0.001）。在 Ki-67 水平较低的患者中，1341 名（94.1%）RS 较低，而在 870 名 Ki-67 水平较高的患者中，607 名（69.8%）RS 较低。在 RS 较低的患者中，根据 Ki-67 水平，RFS 差异有统计学意义（Ki-67 低，98.5%比 Ki-67 高，96.5%；P=0.002）。在未接受化疗的 1807 名低基因组风险患者中，高 Ki-67 水平与复发独立相关（危险比，2.51；95%CI，1.27-4.96；P=0.008）。Ki-67 水平与 3 年后的复发显著相关（Ki-67 低，98.7%比 Ki-67 高，95.7%；P=0.003），而 3 年内的复发则没有差异（Ki-67 低，99.3%比 Ki-67 高，99.3%；P=0.90）。此外，Ki-67 与未接受化疗的低 RS 患者继发内分泌抵抗相关（比值比，2.49；95%CI，1.13-5.50；P=0.02）。
在这项 ER+/ERBB2-乳腺癌患者的队列研究中，Ki-67 与 RS 之间存在中度相关性，低基因组风险患者中高 Ki-67 水平与继发内分泌抵抗风险增加相关。
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