Molecular signatures of endocrine resistance in ER+ breast cancer, V1
Research type
Research Study
Full title
Molecular signatures of endocrine resistance in postmenopausal ER+ breast cancer patients receiving an aromatase inhibitor in the neoadjuvant setting
IRAS ID
216762
Contact name
Mitch Dowsett
Contact email
Sponsor organisation
Royal Marsden Hospital NHS Foundation Trust
Duration of Study in the UK
0 years, 6 months, 0 days
Research summary
Almost all postmenopausal patients with ER+ breast cancer will receive at least 5 years of a hormonal agent such as tamoxifen or an aromatase inhibitor (AI; an oestrogen suppressant) after surgery to minimise the chances of recurrence. However large numbers of patients recur as a result of poorly defined resistant mechanisms. Over recent years, drugs targeted at many putative resistance mechanisms resistance have been developed and applied in metastatic disease. This has the major drawback that by the time metastases develop, genetic instability and heterogeneity has markedly increased to provide multiple routes of escape from therapy. Success has consequently been limited. While a small number of these targeted agents have begun to be assessed in early disease alongside endocrine therapy these trials do not attempt to target the populations most likely to benefit.
We recently proposed POETIC-2 (PeriOperative Endocrine Therapy for Individualised Therapy-2) in which the dominant mechanism(s) of endocrine resistance in individual patients at above average risk of recurrence would be identified in a “window-of-opportunity” study between the time of diagnosis and surgery. This will allow the immediate addition of targeted treatment to the endocrine therapy and permit evaluation of the most relevant agent for the respective mechanism(s). The full POETIC-2 trial platform is in planning and expected to be launched in 2018. In order to identify the dominant mechanism(s) of endocrine resistance in POETIC-2 we have derived molecular signatures of endocrine therapy resistance based on ligand-independent ER action (Patani 2014), E2F activation (Miller 2011), and PI3-kinase/mTOR pathway activation (Lopez-Knowles 2014). In the current proposed retrospective study we wish to see if these signatures are “enriched” after neoadjuvant AI treatment (duration approximately 6 months) of postmenopausal women receiving an AI for clinical downstaging of ER+ primary breast cancer prior to surgery.
REC name
East Midlands - Derby Research Ethics Committee
REC reference
17/EM/0145
Date of REC Opinion
18 Apr 2017
REC opinion
Further Information Favourable Opinion