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新辅助化疗后残留三阴性乳腺癌中Ki67变化的预后价值:一项基于瑞典全国登记处的研究

The prognostic value of changes in Ki67 following neoadjuvant chemotherapy in residual triple-negative breast cancer: a Swedish nationwide registry-based study.

作者信息

Nyqvist-Streng Jenny, Helou Mikael, Helou Khalil, Chamalidou Chaido, Kovács Anikó, Parris Toshima Z

机构信息

Department of Surgery, Region Västra Götaland, Skaraborg Hospital, Skövde, Sweden.

Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

出版信息

Breast Cancer Res Treat. 2025 Apr;210(3):719-736. doi: 10.1007/s10549-025-07610-z. Epub 2025 Jan 12.

Abstract

PURPOSE

To evaluate the prognostic significance of changes in pre- and post-neoadjuvant chemotherapy (NACT) Ki67 in patients with primary invasive triple-negative breast cancer (TNBC).

METHODS

Population-based registry data were retrieved for patients diagnosed with TNBC between 2007 and 2021 (n = 9262). Multivariable Cox regression analysis was performed for disease-specific survival (DSS) and overall survival (OS) adjusted for age and residual disease in the breast and nodes (RDBN).

RESULTS

Of the 1777 TNBC patients receiving NACT, 54 achieved pathologic complete response (pCR) and 755 had residual disease. Most patients were overweight with stage II disease (78%), grade 3 tumors (53%), and RDBN score 3 (42%). Compared to baseline, tumor size (30 vs. 15 mm; P < 0.0001) and Ki67 levels (63% vs. 48%; P < 2.2e - 16) generally decreased after NACT. Although only 5% of samples increased in size, Ki67 levels often remained unchanged (75%) or increased (0.9%) after treatment, respectively. However, 34% of patients discontinued treatment. Patients showing no changes in Ki67% had more unfavorable OS (P < 0.0001) and DSS (P = 0.00032), with significantly lower 5-year survival probabilities (OS: 66%; DSS: 78%) than those with decreased Ki67% (OS: 87%; DSS: 89%). All patients reaching pCR were alive 5 years after diagnosis. However, only the RDBN score was an independent predictor of survival in the multivariable analyses.

CONCLUSION

Ki67 often remained unchanged in TNBC patients treated with neoadjuvant chemotherapy, resulting in adverse clinical outcomes. These findings highlight the need for individualized treatment regimens and dynamic monitoring of TNBC patients with high Ki67 post-NACT.

摘要

目的

评估新辅助化疗(NACT)前后原发性浸润性三阴性乳腺癌(TNBC)患者Ki67变化的预后意义。

方法

检索2007年至2021年期间诊断为TNBC的患者的基于人群的登记数据(n = 9262)。对疾病特异性生存(DSS)和总生存(OS)进行多变量Cox回归分析,并根据年龄以及乳腺和淋巴结残留疾病(RDBN)进行调整。

结果

在1777例接受NACT的TNBC患者中,54例达到病理完全缓解(pCR),755例有残留疾病。大多数患者超重,患有II期疾病(78%)、3级肿瘤(53%)和RDBN评分为3(42%)。与基线相比,NACT后肿瘤大小(30 vs. 15 mm;P < 0.0001)和Ki67水平(63% vs. 48%;P < 2.2e - 16)总体下降。虽然只有5%的样本大小增加,但Ki67水平在治疗后常保持不变(75%)或升高(0.9%)。然而,34%的患者停止治疗。Ki67%无变化的患者的OS(P < 0.0001)和DSS(P = 0.00032)更差,5年生存概率(OS:66%;DSS:78%)显著低于Ki67%下降的患者(OS:87%;DSS:89%)。所有达到pCR的患者在诊断后5年仍存活。然而,在多变量分析中,只有RDBN评分是生存的独立预测因素。

结论

接受新辅助化疗的TNBC患者的Ki67常保持不变,导致不良临床结局。这些发现凸显了对NACT后Ki67高的TNBC患者制定个体化治疗方案并进行动态监测的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aae7/11953087/7b08642e89a6/10549_2025_7610_Fig1_HTML.jpg

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