Clinico-pathologic relationships with Ki67 and its change with short-term aromatase inhibitor treatment in primary ER + breast cancer: further results from the POETIC trial (CRUK/07/015).
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Authors
Vidya, Raghavan
Issue Date
2023-04-12
Journal
Type
Peer-Reviewed Publication
Article
Article
Keywords
Aromatase inhibitor
Breast cancer
Breast neoplasms
ErbB-2 receptor
Ki-67 antigen
Letrozole
MK167 protein
Multicentre study
Oestrogen receptor-positive
Peer-reviewed article
POETIC study
Primary breast cancer
Progesterone receptors
Randomised controlled trial
Breast cancer
Breast neoplasms
ErbB-2 receptor
Ki-67 antigen
Letrozole
MK167 protein
Multicentre study
Oestrogen receptor-positive
Peer-reviewed article
POETIC study
Primary breast cancer
Progesterone receptors
Randomised controlled trial
Journal Title
Breast Cancer Research
Volume
25
Issue
1
Begin page
39
End page
DOI
Abstract
Purpose: Ki67 assessed at diagnosis (Ki67baseline) is an important prognostic factor in primary oestrogen receptor-positive (ER +) breast cancer. Proportional change in Ki67 after 2 weeks (∆Ki672week) is associated with clinical benefit from endocrine therapies and residual Ki67 (Ki672week) with recurrence-free survival. The aim was to define the association between Ki67baseline and after aromatase inhibitor (AI) exposure ∆Ki672week and Ki672week with key prognostic and biologic factors utilising data from the POETIC study.
Patients and methods: 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.
Results: Established associations of Ki67baseline 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 Ki67baseline. In control group Ki672week was 18% lower than Ki67baseline (p < 0.001) when Ki672week was measured in excision biopsies but not when measured in core-cuts. Median suppression by AIs (∆Ki672week) 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.
Conclusions: The magnitude of this study allowed characterisation of relationships between Ki67baseline, ∆Ki672week and Ki672week 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 ∆Ki672week or Ki672week is used in routine clinical practice to aid treatment decisions or in clinical trials assessing new drug therapies.
Citation
Bliss JM, Tovey H, Evans A, Holcombe C, Horgan K, Mallon E, Vidya R, Skene A, Dodson A, Hills M, Detre S, Zabaglo L, Banerji J, Kilburn L, Morden JP, Robertson JFR, Smith I, Dowsett M; POETIC Trialists. Clinico-pathologic relationships with Ki67 and its change with short-term aromatase inhibitor treatment in primary ER + breast cancer: further results from the POETIC trial (CRUK/07/015). Breast Cancer Res. 2023 Apr 12;25(1):39. doi: 10.1186/s13058-023-01626-3. PMID: 37046348; PMCID: PMC10099675.