Clinical Trials and Statistics Unit (ICR-CTSU), The Institute of Cancer Research, London, UK.
Poole Hospital, Poole, UK.
Breast Cancer Res. 2023 Apr 12;25(1):39. doi: 10.1186/s13058-023-01626-3.
Ki67 assessed at diagnosis (Ki67) is an important prognostic factor in primary oestrogen receptor-positive (ER +) breast cancer. Proportional change in Ki67 after 2 weeks (∆Ki67) is associated with clinical benefit from endocrine therapies and residual Ki67 (Ki67) with recurrence-free survival. The aim was to define the association between Ki67 and after aromatase inhibitor (AI) exposure ∆Ki67 and Ki67 with key prognostic and biologic factors utilising data from the POETIC study.
In POETIC 4480 postmenopausal patients with primary ER and/or PgR + breast cancer were randomised 2:1 to 2 weeks' presurgical AI (anastrozole or letrozole) or no presurgical treatment (control). Ki67 was measured centrally in core-cut biopsies taken prior to AI and in core-cuts or the excision biopsy at surgery. Relationships between the Ki67 and biologic factors were explored using linear regression.
Established associations of Ki67 with biologic factors including PgR status, tumour grade, tumour size, histological subtype, nodal status, and vascular invasion were confirmed in the HER2- subpopulation. In the HER2 + subpopulation only grade and tumour size were significantly associated with Ki67. In control group Ki67 was 18% lower than Ki67 (p < 0.001) when Ki67 was measured in excision biopsies but not when measured in core-cuts. Median suppression by AIs (∆Ki67) was 79.3% (IQR: -89.9 to -54.6) and 53.7% (IQR: -78.9 to -21.1) for HER2-negative and HER2-positive cases, respectively. Significantly less suppression occurred in PgR- vs PgR + and HER2 + vs HER2- tumours which remained apparent after adjustment for 2-week sample type.
The magnitude of this study allowed characterisation of relationships between Ki67, ∆Ki67 and Ki67 with high degrees of confidence providing a reference source for other studies. Lower values of Ki67 occur when measured on excision biopsies and could lead to apparent but artefactual decreases in Ki67: this should be considered when either ∆Ki67 or Ki67 is used in routine clinical practice to aid treatment decisions or in clinical trials assessing new drug therapies.
诊断时 Ki67 （Ki67）是原发性雌激素受体阳性（ER+）乳腺癌的重要预后因素。治疗 2 周后 Ki67 的比例变化（∆Ki67）与内分泌治疗的临床获益相关，而残留 Ki67（Ki67）与无复发生存率相关。本研究旨在利用 POETIC 研究的数据，定义 Ki67 与芳香化酶抑制剂（AI）暴露后 ∆Ki67 和 Ki67 与关键预后和生物学因素之间的关系。
POETIC 研究中，4480 例绝经后原发性 ER 和/或 PgR+乳腺癌患者按 2:1 随机分为 2 周术前 AI（阿那曲唑或来曲唑）或无术前治疗（对照组）。在 AI 前进行核心活检，在手术时进行核心切取或切除活检，对 Ki67 进行中心测量。使用线性回归探索 Ki67 与生物学因素之间的关系。
在 HER2-亚组中，Ki67 与生物学因素（包括 PgR 状态、肿瘤分级、肿瘤大小、组织学亚型、淋巴结状态和血管侵犯）的既定关联得到了证实。在 HER2+亚组中，仅分级和肿瘤大小与 Ki67 显著相关。在对照组中，Ki67 在切除活检中比 Ki67（p<0.001）低 18%，但在核心切取中则不然。阿那曲唑的中位抑制率（∆Ki67）分别为 HER2 阴性和 HER2 阳性病例的 79.3%（IQR：-89.9 至-54.6）和 53.7%（IQR：-78.9 至-21.1）。PgR-与 PgR+和 HER2+与 HER2-肿瘤相比，抑制作用明显降低，调整 2 周样本类型后仍然明显。
本研究的规模允许在 Ki67、∆Ki67 和 Ki67 与高可信度之间建立关系，为其他研究提供参考来源。当 Ki67 在切除活检中测量时，Ki67 的值会更低，这可能导致 Ki67 出现明显但人为的降低：在常规临床实践中使用∆Ki67 或 Ki67 来辅助治疗决策或评估新药物治疗的临床试验时，应考虑这一点。
