Study examines role of insulin in response to breast cancer treatment
28 January 2026
A new clinical study has been launched to investigate whether insulin levels influence how women with the most common type of breast cancer respond to treatment.
The Trans-EndoNET study will examine the relationship between insulin levels and the response to aromatise inhibitors in women with oestrogen receptor-positive, HER2-negative (ER+HER2-) breast cancer.
Oxford University Hospitals (OUH) is expected to begin recruiting patients in the coming months. It is one of 32 hospitals participating in the study.
The study has been funded by a partnership between the UKRI Medical Research Council (MRC) and the National Institute for Health and Care Research (NIHR).
ER+HER2- breast cancer accounts for the majority of breast cancer diagnoses, particularly among post-menopausal women. In these tumours, oestrogen is a key driver of cancer growth, binding to cancer cells and promoting their proliferation.
Aromatase inhibitors, such as letrozole, tackle this by lowering oestrogen levels; they are given as a standard of care treatment for five to 10 years following surgery for early-stage breast cancer to reduce the risk of recurrence.
However, growing evidence suggests that metabolic factors, including insulin levels, may influence how well patients respond to hormone therapies such as aromatase inhibitors.
Type 2 diabetes and elevated insulin levels have been associated with a higher incidence of breast cancer and increased breast cancer-related mortality. Laboratory studies have also shown that high insulin levels can activate a key biological pathway known to drive resistance to hormone treatments, while lowering insulin levels appears to inhibit this pathway and improve treatment response.
“Insulin resistance and metabolic syndrome are increasingly common, particularly in older adults,” said Dr Simon Lord, Director of Oxford Cancer Trials in the Department of Oncology and Consultant Medical Oncologist at OUH. “The Trans-EndoNET study will help us understand whether insulin levels play a role in determining how well patients respond to aromatase inhibitors, which are among the most widely used treatments in breast cancer.”
It is estimated that around one in three adults over the age of 50 may be affected by insulin resistance or metabolic syndrome, raising important questions about how metabolic health interacts with cancer treatments.
Trans-EndoNET is a sub-study of the Phase III EndoNET trial of women with early-stage ER+HER2- breast cancer who have been through the menopause. The EndoNET trial, conducted by the Surgical Intervention Trials Unit (SITU) at the Nuffield Department of Surgical Sciences, is investigating the clinical benefit of giving part of the five-year course of aromatase inhibitors prior to surgery, with a view to shrinking the breast cancer, to see if this reduces the extent of surgery needed.
Some 250 people are participating in EndoNET in the UK and patients joining the trial will now have the opportunity to participate in both studies.
Trans-EndoNET will use patient samples collected during the main trial to investigate the link between insulin resistance and aromatase inhibitors.
“By analysing tumour samples taken before and after aromatase inhibitor treatment, alongside blood samples measuring insulin levels, this study allows us to directly explore whether insulin resistance could serve as an important clinical marker of resistance to aromatase inhibitors,” said Professor Ramsey Cutress, Professor of Breast Surgery at the University of Southampton and an EndoNET lead investigator.
“Integrating this work within the EndoNET trial gives us a unique opportunity to link biological changes in the tumour with real-world treatment outcomes.”
This study will provide the evidence needed to inform whether future clinical trials exploring dietary or drug-based interventions to lower insulin levels could be used alongside aromatase inhibitors to improve outcomes for people with breast cancer.
Patricia Fairbrother, a patient contributor to the EndoNET trial and trustee of Independent Cancer Patients' Voice (ICPV), said: “Trans-EndoNET is an important study, it’s important to patients and a research priority for post-menopausal women with early breast cancer. Throughout the study, patient representatives will be acting on behalf of participants, advising on patient-facing documents, giving the research more impact, making it more meaningful, and ensuring that along with the trial team, participant’s needs are met.”
