Bustreo Sara, Osella-Abate Simona, Cassoni Paola, Donadio Michela, Airoldi Mario, Pedani Fulvia, Papotti Mauro, Sapino Anna, Castellano Isabella
Department of Medical Oncology 1, Città della Salute e della Scienza Hospital, Turin, Italy.
Division of Pathology, Department of Medical Sciences, University of Torino, Via Santena 7, 10126, Turin, Italy.
Breast Cancer Res Treat. 2016 Jun;157(2):363-371. doi: 10.1007/s10549-016-3817-9. Epub 2016 May 7.
Although Ki67 index suffers from poor reproducibility, it is one of the most important prognostic markers used by oncologists to select the treatment of estrogen receptor (ER) positive breast cancer patients. In this study, we aim to establish the optimal Ki67 cut-offs for stratifying patient prognosis and to create a comprehensive prognostic index for clinical applications. A mono-institutional cohort of 1.577 human epidermal growth factor receptor 2 negative/ER+ breast cancer patients having complete clinical, histological, and follow-up data was collected. The 14 and 20 % Ki67 cut-offs were correlated to disease-free interval (DFI) and disease-specific survival (DSS). To create a comprehensive prognostic index, we used independent variables selected by uni/multivariate analyses. In terms of DFI and DSS, patients bearing tumors with Ki67 < 14 % proliferation index did not differ from those with Ki67 values between 14 and 20 %. Patients with tumor with Ki67 > 20 % showed the poorest prognosis. Moreover, to tumor size, the number of metastatic lymph nodes and Ki67 > 20 % was given a score value, varying depending on definite cut-offs and used to create a prognostic index, which was applied to the population. Patients with a prognostic index ≥3 were characterized by significant risk of relapse [DFI: Hazard Ratio (HR) = 4.74, p < 0.001] and death (DSS: HR = 5.03, p < 0.001). We confirm that the 20 % Ki67 cut-off is the best to stratify high-risk patients in luminal breast cancers, and we suggest to integrate it with other prognostic factors, to better stratify patients at risk of adverse outcome.
尽管Ki67指数的重复性较差，但它是肿瘤学家用于选择雌激素受体（ER）阳性乳腺癌患者治疗方案的最重要的预后标志物之一。在本研究中，我们旨在确定用于分层患者预后的最佳Ki67临界值，并创建一个用于临床应用的综合预后指数。收集了一个单机构队列中1577例人表皮生长因子受体2阴性/ER+乳腺癌患者的完整临床、组织学和随访数据。将14%和20%的Ki67临界值与无病生存期（DFI）和疾病特异性生存期（DSS）相关联。为了创建一个综合预后指数，我们使用了单变量/多变量分析选择的自变量。就DFI和DSS而言，Ki67增殖指数<14%的肿瘤患者与Ki67值在14%至20%之间的患者没有差异。Ki67>20%的肿瘤患者预后最差。此外，根据肿瘤大小、转移淋巴结数量和Ki67>20%给予一个评分值，该值根据确定的临界值而变化，并用于创建一个应用于该人群的预后指数。预后指数≥3的患者具有显著的复发风险[DFI：风险比（HR）=4.74，p<0.001]和死亡风险（DSS：HR=5.03，p<0.001）。我们证实，20%的Ki67临界值最适合对管腔型乳腺癌的高危患者进行分层，并且我们建议将其与其他预后因素相结合，以更好地对有不良结局风险的患者进行分层。
