Translational breast cancer research in luminal breast cancer

Luminal breast cancer constitutes almost all ER-positive tumours and as such constitutes around 75 to 80% of the disease. The luminal group is highly heterogeneous in terms of genetic aberrations such as mutations, amplifications/deletions and translocations, and also phenotypic characteristics such as proliferation and the expression of oestrogen-dependent proteins such as PgR, TFF1 and GREB1. While assessment of some of these molecular characteristics at presentation can act as a guide to outcome, there remains substantial uncertainty in prognostic and predictive algorithms. Our approach has been to study the biological relationships by applying specific suppressants of the synthesis of oestrogen - that is, aromatase inhibitors (AIs) - in the presurgical setting. The changes in proliferation (Ki67) that occur are related to treatment benefit and the residual Ki67 to residual risk of recurrence. In addition, the molecular changes can be characterized as intermediate endpoints of response.

The POETIC trial of 2 weeks' AI or not in the window of time between diagnosis and surgery has now recruited over 2,000 patients (August 2011). Biopsies taken before and after the AI are providing a uniquely powerful set of data to understand the mechanisms of response and resistance to oestrogen deprivation. Pilot work has indicated that although luminal B tumours have higher initial Ki67 levels, their antiproliferative response to an AI is proportionally similar to luminal A tumours, indicating a similar initial responsiveness but higher residual risk of recurrence.