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)

PURPOSE: Ki67 assessed at diagnosis (Ki67(baseline)) is an important prognostic factor in primary oestrogen receptor-positive (ER +) breast cancer. Proportional change in Ki67 after 2 weeks (∆Ki67(2week)) is associated with clinical benefit from endocrine therapies and residual Ki67 (Ki67(2week)) with recurrence-free survival. The aim was to define the association between Ki67(baseline) and after aromatase inhibitor (AI) exposure ∆Ki67(2week) and Ki67(2week) 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 Ki67(baseline) 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(baseline). In control group Ki67(2week) was 18% lower than Ki67(baseline) (p < 0.001) when Ki67(2week) was measured in excision biopsies but not when measured in core-cuts. Median suppression by AIs (∆Ki67(2week)) 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 Ki67(baseline), ∆Ki67(2week) and Ki67(2week) 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(2week) or Ki67(2week) is used in routine clinical practice to aid treatment decisions or in clinical trials assessing new drug therapies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-023-01626-3.