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.

Background: 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).
Methods: 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).
Results: 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).
Conclusions: 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.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Diogo Martins-Branco: Honoraria and advisory board fees from Daiichi Sankyo, Janssen, Pfizer, Merck Sharp & Dohme, Angelini, AstraZeneca, and Novartis, meeting/travel grants from LEO Farmacêuticos, Merck Sharp & Dohme, Ipsen, Janssen, Roche, Laboratórios Vitória, and Novartis, and institutional research grants from F. Hoffmann-La Roche Ltd and Novartis (all outside the submitted work); Guilherme Nader-Marta: Support to attend medical conferences: Roche, AstraZeneca, and Bayer (all outside the submitted work); Chiara Molinelli: Honoraria and advisory board fees from Lilly and Novartis; travel grant by Gilead (all outside the submitted work); Michail Ignatiadis: Honoraria from Novartis, Seattle Genetics; travel grants from Amgen, Roche, Gilead; research grant to my institution Roche/GNE, Pfizer, Natera Inc, Inivata Inc (all outside the submitted work); Philippe Aftimos: Honoraria and advisory board fees from Eli Lilly, Gilead, Menarini, Novartis, and Roche; travel grant from Daiichi Sankyo; and research funding from Roche (all outside the submitted work); Roberto Salgado: Honoraria from BMS, Exact Sciences, and Roche; intellectual property rights/patent from Merk; and research funding from Roche, Merk, and Puma Biotechnology (all outside the submitted work); Evandro de Azambuja: Honoraria and/or advisory board from Roche/GNE, Novartis, SeaGen, Zodiac, Libbs; Pierre Fabre, Lilly, Astra-Zeneca, MSD, and Gilead. Travel grants from Roche/GNE and Astra-Zeneca. Research grant to my institution from Roche/GNE, Astra-Zeneca, GSK/Novartis, and Servier (all outside the submitted work). Lieveke Ameye and Marianne Paesmans have no conflicts of interest to declare.
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