Department of Breast Medical Oncology, National Institute of Cancer (INCan), Mexico City, Mexico.
Department of Breast Pathology, National Institute of Cancer (INCan), Mexico City, Mexico.
Oncologist. 2018 Jun;23(6):670-678. doi: 10.1634/theoncologist.2017-0396. Epub 2018 Feb 28.
Several breast cancer (BC) trials have adopted pathological complete response (pCR) as a surrogate marker of long-term treatment efficacy. In patients with luminal subtype, pCR seems less important for outcome prediction. BC is a heterogeneous disease, which is evident in residual tumors after neoadjuvant-chemotherapy (NAC). This study evaluates changes in Ki67 in relation to disease-free survival (DFS) and overall survival (OS) in patients without pCR.
SUBJECTS, MATERIALS, AND METHODS: Four hundred thirty-five patients with stage IIA-IIIC BC without pCR after standard NAC with anthracycline and paclitaxel were analyzed. We analyzed the decrease or lack of decrease in the percentage of Ki67-positive cells between core biopsy samples and surgical specimens and correlated this value with outcome.
Twenty-five percent of patients presented with luminal A-like tumors, 45% had luminal B-like tumors, 14% had triple-negative BC, 5% had HER2-positive BC, and 11% had triple-positive BC. Patients were predominantly diagnosed with stage III disease (52%) and high-grade tumors (46%). Median Ki67 level was 20% before NAC, which decreased to a median of 10% after NAC. Fifty-seven percent of patients had a decrease in Ki67 percentage. Ki67 decrease significantly correlated with better DFS and OS compared with no decrease, particularly in the luminal B subgroup. Multivariate analysis showed that nonreduction of Ki67 significantly increased the hazard ratio of recurrence and death by 3.39 (95% confidence interval [CI] 1.8-6.37) and 7.03 (95% CI 2.6-18.7), respectively.
Patients without a decrease in Ki67 in residual tumors after NAC have poor prognosis. This warrants the introduction of new therapeutic strategies in this setting.
This study evaluates the change in Ki67 percentage before and after neoadjuvant chemotherapy (NAC) and its relationship with survival outcomes in patients with breast cancer who did not achieve complete pathological response (pCR). These patients, a heterogeneous group with diverse prognoses that cannot be treated using a single algorithm, pose a challenge to clinicians. This study identified a subgroup of these patients with a poor prognosis, those with luminal B-like tumors without a Ki67 decrease after NAC, thus justifying the introduction of new therapeutic strategies for patients who already present a favorable prognosis (luminal B-like with Ki67 decrease).
多项乳腺癌（BC）临床试验已将病理完全缓解（pCR）作为长期治疗效果的替代标志物。在管腔亚型患者中，pCR 似乎对预后预测的重要性较低。BC 是一种异质性疾病，在新辅助化疗（NAC）后的残留肿瘤中表现明显。本研究评估了 Ki67 变化与无 pCR 患者的无病生存（DFS）和总生存（OS）的关系。
对 435 例接受标准蒽环类和紫杉醇新辅助化疗后无 pCR 的 IIA-IIIC 期 BC 患者进行分析。我们分析了核心活检样本和手术标本之间 Ki67 阳性细胞百分比的降低或缺乏，并将该值与结果相关联。
25%的患者为管腔 A 样肿瘤，45%为管腔 B 样肿瘤，14%为三阴性 BC，5%为 HER2 阳性 BC，11%为三阳性 BC。患者主要诊断为 III 期疾病（52%）和高级别肿瘤（46%）。NAC 前 Ki67 中位水平为 20%，NAC 后降至 10%。57%的患者 Ki67 百分比下降。与无下降相比，Ki67 下降与更好的 DFS 和 OS 显著相关，特别是在管腔 B 亚组中。多变量分析显示，Ki67 无减少显著增加了复发和死亡的风险比分别为 3.39（95%置信区间[CI] 1.8-6.37）和 7.03（95%CI 2.6-18.7）。
NAC 后残留肿瘤中 Ki67 无减少的患者预后不良。这需要在这种情况下引入新的治疗策略。
本研究评估了新辅助化疗（NAC）前后 Ki67 百分比的变化及其与未达到完全病理缓解（pCR）的乳腺癌患者生存结局的关系。这些患者是一组异质性患者，预后各不相同，不能用单一算法治疗，这对临床医生构成了挑战。本研究确定了这些患者的一个预后不良亚组，即 NAC 后管腔 B 样肿瘤 Ki67 无减少的患者，这证明了为已经具有良好预后（管腔 B 样，Ki67 减少）的患者引入新的治疗策略是合理的。
