Background: In the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial.
Patients and methods: We analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinical trials of neoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2).
Results: A basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 >50% achieved a pCR rate of 40% (36 of 91) versus a pCR rate of 19% in patients with Ki67 ≤ 50% (33 of 171) (p = .0004). Ki67 predictive value was especially relevant in ER-HER2- and ER-HER2+ patients (pCR rates of 42% and 64%, respectively, in patients with Ki67 >50% versus 15% and 45%, respectively, in patients with Ki67 ≤ 50%; p = .0337 and .3238, respectively). Both multivariate analyses confirmed the independent predictive value of the Ki67 cutpoint of 50%.
Conclusion: Basal Ki67 proliferation index >50% should be considered an independent predictive factor for pCR reached after neoadjuvant chemotherapy, suggesting that cell proliferation is a phenomenon closely related to chemosensitivity. These findings could help to identify a group of patients with a potentially favorable long-term prognosis.
Implications for practice: The use of basal Ki67 status as a predictive factor of chemotherapy benefit could facilitate the identification of a patient subpopulation with high probability of achieving pathological complete response when treated with primary chemotherapy, and thus with a potentially favorable long-term prognosis.
摘要
背景. 在新辅助治疗中, 增殖标记物 Ki67 的改变与新辅助内分泌治疗的有效性有关, 但其作为化疗治疗反应预测因素的价值仍然存有争议。
患者与方法. 我们分析了来自 4 项 GEICAM (西班牙乳腺癌小组) 临床试验中乳腺癌新辅助化疗的 262 例患者, 对基底细胞 Ki67 集中进行免疫组化评价。研究旨在通过采用受试者操作特征曲线方法使 Ki67 对化疗获益的预测值最大化, 确定 Ki67 的最佳阈值。我们还评价了根据雌激素受体 (ER) 和人类表皮生长因子受体2 (HER2) 确定的明确 Ki67 临界值对分子亚型的预测作用。
结果. 基底细胞 Ki67 临界值为 50%时可预测病理学完全缓解 (pCR)。Ki67 > 50%的患者 pCR 率可达到 40% (36/91例), 而 Ki67 ≤ 50%的患者 pCR 率为 19% (33/171例) (P = 0.000 4)。Ki67 的预测值与 ER- HER2-和 ER- HER2+患者尤为相关 (pCR率: Ki67 > 50%的患者中分别为 42%和 64%, P = 0.033 7; Ki67 ≤ 50%的患者中分别为 15%和 45%, P = 0.323 8)。两种多因素分析均确认独立预测值为 Ki67 临界值为 50%。
结论. 基底细胞 Ki67 增殖指数> 50%应作为新辅助化疗后达到 pCR 的独立预测因素, 提示细胞增殖是与化疗敏感性密切相关的现象。这些结果可能有助于鉴别出可能有良好远期预后的患者组。The Oncologist 2016;21:150–155
对临床实践的提示: 使用基底细胞 Ki67 状态作为化疗获益的预测因素可有助于鉴别新辅助化疗中有较高可能达到病理学完全缓解的患者亚组, 这类患者长期预后可能较好。
Keywords: Breast cancer; Chemosensitivity; Ki67; Neoadjuvant chemotherapy; Predictive factor.
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