Nuffield Department of Population Health, University of Oxford, Oxford, UK.
The National Disease Registration Service, NHS England, Leeds, UK.
JNCI Cancer Spectr. 2023 Aug 31;7(5). doi: 10.1093/jncics/pkad054.
The percentage of cells staining positive for Ki67 is sometimes used for decision-making in patients with early invasive breast cancer (IBC). However, there is uncertainty regarding the most appropriate Ki67 cut points and the influence of interlaboratory measurement variability. We examined the relationship between breast cancer mortality and Ki67 both before and after accounting for interlaboratory variability and 8 patient and tumor characteristics.
A multicenter cohort study of women with early IBC diagnosed during 2009-2016 in more than 20 NHS hospitals in England and followed until December 31, 2020.
Ki67 was strongly prognostic of breast cancer mortality in 8212 women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early IBC (Ptrend < .001). This relationship remained strong after adjustment for patient and tumor characteristics (Ptrend < .001). Standardization for interlaboratory variability did little to alter these results. For women with Ki67 scores of 0%-5%, 6%-10%, 11%-19%, and 20%-29% the corresponding 8-year adjusted cumulative breast cancer mortality risks were 3.3% (95% confidence interval [CI] = 2.8% to 4.0%), 3.7% (95% CI = 3.0% to 4.4%), 3.4% (95% CI = 2.8% to 4.1%), and 3.4% (95% CI = 2.8% to 4.1%), whereas for women with Ki67 scores of 30%-39% and 40%-100%, these risks were higher, at 5.1% (95% CI = 4.3% to 6.2%) and 7.7% (95% CI = 6.6% to 9.1) (Ptrend < .001). Similar results were obtained when the adjusted analysis was repeated with omission of pathological information about tumor size and nodal involvement, which would not be available preoperatively for patients being considered for neoadjuvant therapy.
Our findings confirm the prognostic value of Ki67 scores of 30% or more in women with ER-positive, HER2-negative early IBC, irrespective of interlaboratory variability. These results also suggest that Ki67 may be useful to aid decision-making in the neoadjuvant setting.
Ki67 阳性细胞百分比有时用于指导早期浸润性乳腺癌（IBC）患者的决策。然而，对于最合适的 Ki67 截断值以及实验室间测量变异性的影响，仍存在不确定性。我们在考虑了实验室间变异性和 8 项患者及肿瘤特征后，研究了 Ki67 与乳腺癌死亡率之间的关系。
这是一项多中心队列研究，纳入了 2009 年至 2016 年间在英格兰 20 多家国民保健制度医院诊断的早期 IBC 女性患者，随访至 2020 年 12 月 31 日。
在 8212 例雌激素受体（ER）阳性、人表皮生长因子受体 2（HER2）阴性的早期 IBC 女性中，Ki67 对乳腺癌死亡率具有强烈的预后意义（趋势检验 < .001）。在调整了患者和肿瘤特征后，这种关系仍然很强（趋势检验 < .001）。为了标准化实验室间的变异性，我们进行了标准化处理，但这几乎没有改变这些结果。对于 Ki67 评分在 0%-5%、6%-10%、11%-19%和 20%-29%的女性，相应的 8 年累计乳腺癌死亡率分别为 3.3%（95%置信区间[CI] = 2.8%至 4.0%）、3.7%（95% CI = 3.0%至 4.4%）、3.4%（95% CI = 2.8%至 4.1%）和 3.4%（95% CI = 2.8%至 4.1%），而 Ki67 评分在 30%-39%和 40%-100%的女性中，这些风险更高，分别为 5.1%（95% CI = 4.3%至 6.2%）和 7.7%（95% CI = 6.6%至 9.1%）（趋势检验 < .001）。当对排除术前考虑新辅助治疗的患者的肿瘤大小和淋巴结受累的病理信息的调整分析进行重复时，也得到了类似的结果。
我们的研究结果证实了 Ki67 评分在 ER 阳性、HER2 阴性的早期 IBC 女性中 30%或以上的预后价值，无论实验室间的变异性如何。这些结果还表明，Ki67 可能有助于辅助新辅助治疗时的决策。
