U.O.C. Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy; Breast Unit, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
Biostatistics, Regina Elena National Cancer Institute, Roma, Italy.
Breast. 2017 Oct;35:21-26. doi: 10.1016/j.breast.2017.06.005. Epub 2017 Jun 17.
The intent of this analysis was to investigate and validate the prognostic potential of Ki67 in a multi-center series of patients affected by early stage 'pure' invasive lobular carcinoma (ILC).
Clinical-pathological data of patients affected by ILC were correlated with overall survival and disease-free survival (OS/DFS); data from a parallel invasive ductal carcinoma (IDC) patients' cohort were gathered as well. The maximally selected Log-Rank statistics analysis was applied to Ki67 continuous variable to estimate the appropriate cut-off. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed as well.
Data from overall 1097 (457/222 ILC: training/validation set; 418 IDC) patients were gathered. The identified optimal Ki67 cut-offs were 4% and 14% for DFS in ILC and IDC cohort, respectively. In ILC patients, the Ki67 cut-off was an independent OS predictor. Ten-years OS and DFS were 89.9% and 77.2% (p = 0.007) and 79.4% and 69.2% (p = 0.03) for patients with Ki67 ≤ 4% and >4%, respectively. In IDC patients, 10-years OS was 93.8% and 71.7%, p = 0.02, DFS was 84.0% and 52.6%, p = 0.0003, for patients with Ki67 ≤ 14% and >14%, respectively. In the validation set, the optimal Ki67 OS cut-off was 5%. The STEPP analysis showed that in the presence of low Ki67 values, IDC patients have a better DFS than ILC patients, while with the increase of values the prognosis tends to overlap.
Despite the retrospective design of the study, the prognostic relevance of Ki67 (as well as its optimal cut-off) seems to significantly differ according to breast cancer histology.
本分析旨在研究和验证 Ki67 在多中心早期“纯”浸润性小叶癌（ILC）患者系列中的预后潜力。
将患者的临床病理数据与总生存和无病生存（OS/DFS）相关联；同时收集了平行浸润性导管癌（IDC）患者队列的数据。应用最大选择对数秩统计分析来估计 Ki67 连续变量的适当截止值。还进行了亚组治疗效果模式图（STEPP）分析。
共收集了 1097 例（457/222 ILC：训练/验证集；418 IDC）患者的数据。在 ILC 和 IDC 队列中，DFS 的最佳 Ki67 截止值分别为 4%和 14%。在 ILC 患者中，Ki67 截止值是 OS 的独立预测因子。Ki67 ≤4%和 Ki67>4%的患者 10 年 OS 和 DFS 分别为 89.9%和 77.2%（p=0.007）和 79.4%和 69.2%（p=0.03）。在 IDC 患者中，Ki67 ≤14%和 Ki67>14%的患者 10 年 OS 分别为 93.8%和 71.7%，p=0.02，DFS 分别为 84.0%和 52.6%，p=0.0003。在验证集中，最佳 Ki67 OS 截止值为 5%。STEPP 分析表明，在 Ki67 值较低的情况下，IDC 患者的 DFS 优于 ILC 患者，而随着值的增加，预后趋于重叠。
尽管研究采用回顾性设计，但 Ki67 的预后相关性（以及其最佳截止值）似乎根据乳腺癌的组织学显著不同。
