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) 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.

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 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.

CONCLUSIONS

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.