Background: 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.
Results: 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.
Conclusion: 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.
Implications for practice: 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).
摘要
背景.若干乳腺癌（BC）试验采用病理学完全缓解（pCR）作为长期治疗疗效的替代指标。对于Luminal亚型患者, pCR对于结果预测似乎不太重要。BC是一种异质性疾病, 在新辅助化疗（NAC）后的残余肿瘤中较为明显。此项研究评价了Ki67的变化与无pCR患者的无病生存期（DFS）和总生存期（OS）的关系。
受试者、材料和方法.对435例经过蒽环类药物和紫杉醇标准NAC后无pCR的IIA‐IIIC期BC患者进行了分析。我们分析了核心活检样本与手术标本之间Ki67阳性细胞百分比减少或未减少的情况, 并将此值与预后相关联。
结果.25%的患者为Luminal A样肿瘤, 45%为Luminal B样肿瘤, 14%为三阴性BC, 5%为HER2阳性BC, 11%为三阳性BC。患者主要被诊断出III期疾病（52%）和高度恶性肿瘤（46%）。NAC前中位Ki67水平为20%, NAC后中位水平降至10%。57%的患者Ki67百分比降低。Ki67降低与更好的DFS和OS显著相关（与Ki67未降低相比）, 尤其是在Luminal B亚组中。多因素分析显示Ki67未降低分别导致复发和死亡风险比分别增加3.39 [95%可信区间（CI）1.8‐6.37]和7.03（95% CI 2.6–18.7）。
结论.NAC后残余肿瘤中Ki67未降低的患者预后不佳。需要在此情况下采用新的治疗策略。
对临床实践的提示：本研究评价了新辅助化疗（NAC）前后Ki67百分比的变化及其在未实现完全病理学缓解（pCR）的乳腺癌患者中与生存结果之间的关系。这些患者组成了具有不同的预后的异质组, 不能使用单一方案进行治疗, 对临床医生构成了一大挑战。此项研究确定了这些预后不佳患者（这些患者存在Luminal B样肿瘤且经过NAC后Ki67未降低）亚组, 因此证明针对已经呈现有利预后的患者（存在Luminal B样肿瘤且Ki67降低）使用新治疗策略是合理的。
Keywords: Breast cancer; Cell proliferation; Ki67; Luminal B‐like; Pathological response.
© AlphaMed Press 2018.