Ki-67 index after neoadjuvant endocrine therapy as a prognostic biomarker in patients with ER-positive/HER2-negative early breast cancer: a systematic review and meta-analysis.

Neoadjuvant treatment discriminates responders, but pathologic complete response is uncommon in oestrogen receptor (ER)-positive/HER2-negative early breast cancer. We aimed to assess the prognostic value of Ki-67 index after neoadjuvant endocrine therapy (NET). We conducted a systematic literature search of PubMed, Embase, CENTRAL, and conference proceedings up to 22nd August 2023 to identify studies reporting the association of Ki-67 index after NET with recurrence-free survival (RFS) and/or overall survival (OS) in women with ER-positive/HER2-negative early breast cancer. We combined RFS and OS hazard ratios (HRs) with 95% confidence intervals (CIs). Twelve studies including 7897 patients were analysed. Most studies were clinical trials (n = 7547) including only postmenopausal women (n = 3953) treated with aromatase inhibitor (n = 3359). Three studies evaluated Ki-67 in a preplanned core biopsy at 2–4 weeks of NET (n = 3348), while nine evaluated Ki-67 in the surgical specimen (n = 4549) after 2–24 weeks of NET. Median follow-up ranged between 37 and 95 months for RFS and 62–84 months for OS. High Ki-67 index after NET was significantly associated with worse RFS (HR 2.48, 95% CI 1.86–3.30) and OS (HR 2.66, 95% CI 1.65–4.28). A sensitivity analysis including three studies that measured Ki-67 in a preplanned core biopsy showed similar association with RFS (HR 2.41, 95% CI 1.77–3.30). High Ki-67 after NET is associated with worse survival outcomes, even after a short course of NET, emphasising the prognostic value of this biomarker in women with ER-positive/HER2-negative early breast cancer. • Meta-analysis of Ki-67 prognostic value after neoadjuvant endocrine therapy. • Twelve studies reporting data from 7897 women with ER+/HER2− early breast cancer. • High Ki-67 was associated with worse recurrence-free survival and overall survival. • Ki-67 index after neoadjuvant endocrine therapy is a strong prognostic biomarker. • These findings will better inform clinical trials design and future clinical practice. [ABSTRACT FROM AUTHOR]