Thousands of women with breast cancer could be spared unnecessary treatment, thanks to a simple test which can identify whether or not their cancer is likely to return – just two weeks after starting treatment.
The test – which is already approved for clinical use – could have a transformative impact on the treatment of oestrogen receptor positive, human epidermal growth factor receptor 2 positive (ER+/HER2+) breast cancer, which accounts for 200,000 cases per year worldwide.
Subtypes based on molecular differences
A team of scientists from The Institute of Cancer Research, London, identified a set of subtypes of ER+/HER2+ breast cancer that will help clinicians to develop more personalised treatment strategies for the disease – allowing some patients to avoid side effects of unnecessary treatment, and moving other patients onto more intensive therapies at an earlier stage.
One in 10 cases of breast cancer is ER+/HER2+. Patients have varying responses to the same treatment due to the molecular differences in their tumours.
The Institute of Cancer Research (ICR) team analysed tumour samples from 213 patients participating in the phase III POETIC trial, which tested the benefit of hormone therapy before and after surgery – compared with post-surgery alone – to reduce the risk of cancer coming back in women with early-stage, ER+ breast cancer.
Hormone therapy alters the subtype
The POETIC trial – a study co-sponsored by the ICR and The Royal Marsden NHS Foundation Trust and managed by the ICR Clinical Trials and Statistics Unit (ICR-CTSU) – did not suggest a clear benefit of two weeks of hormone therapy before surgery for all patients.
However, this new research shows the hormone therapy can indicate which post-surgery treatment is best for each patient. The researchers are calling for all patients to be offered this short-term hormone therapy.
In research published in the journal eBioMedicine, the team analysed tumour samples taken before and after this short-term treatment, to see how the tumour responds.
The research was funded by the ICR, which is a charity as well as a research institute, Breast Cancer Now and NanoString, which provided genetic profiling technology, and the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at The Royal Marsden and the ICR.
Decisions about ongoing care
The same team previously identified five subtypes of ER+/HER2+ breast cancer based on the molecular and genetic features of the tumours. This current research looked at two subtypes – Luminal A and Luminal B.
In the new study, the team showed that just two weeks of hormone therapy changes the characteristics of some tumours, causing them to shift their subtype.
The subtype of the tumour after treatment was an even stronger predictor of the risk of cancer coming back. Some tumours changed to the less aggressive subtypes, suggesting the treatment is working – which could help guide decisions about ongoing care.
Identify those at highest risk of relapse
Tumours which remained Luminal A after two weeks of treatment – 19 per cent of the tumours analysed – were associated with the lowest risk of relapse. The research team suggests these patients continue with their five years of hormone therapy – the standard of care for all ER+/HER2+ patients.
Of the 213 patient samples analysed, 28 per cent of tumours shifted from Luminal B subtype to the Luminal A subtype, suggesting that the treatment is working, and they should also continue with standard of care hormone therapy.
Patients with the highest risk of their cancer returning at five years had Luminal B tumours that did not change after this short-term hormone therapy. These patients – accounting for 6 per cent of the 213 patients in the study – were at least 1.5 times more likely to relapse than if their tumour shifted to the Luminal A subtype.
The researchers suggest that these patients will require more intensive treatment, such as CDK4/6 inhibitors, to keep their breast cancer at bay.
The study authors say the findings highlight the benefit of two weeks of hormone therapy before surgery to help guide clinical decision-making, providing patients with personalised treatment plans based on how their cancer responds to drugs, not just how tumours are initially classified.
Tailor treatment strategies
Dr Maggie Cheang, leader of the ICR-CTSU Integrative Genomic Analysis in Clinical Trials Team at The Institute of Cancer Research, London, said:
“To deliver truly personalised care, we need to refine how we classify breast cancer, so that each patient receives the treatment most likely to benefit them. While current classification relies on hormone receptor and HER2 status, we know that patients within these groups can respond very differently to the same therapy.
“Our earlier research identified distinct molecular subtypes within HER2-positive, oestrogen receptor–positive breast cancer. In this new study, we’ve shown that these subtypes can shift after just two weeks of hormone therapy.
“This insight helps us identify which patients are likely to respond well and which may show early signs of treatment resistance, offering the opportunity to tailor treatment strategies sooner. Ultimately, our findings move us closer to more precise, patient-centred care for this over-looked breast cancer subtype.”
“The POETIC trial benefited from strong collaboration and dialogue with Independent Cancer Patients’ Voice. I am grateful for the patient advocate group’s input, which was fundamental during the trial’s development. The group brings the views and experience of cancer patients, their families, and carers to the cancer research community.”
Define cancer by its molecular characteristics
Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said:
“We have long moved past defining cancer solely by where it starts in the body – we now know that its complex molecular characteristics will drive its behaviour. By decoding the underlying biology of tumours, we can tailor treatments to individual patients.
“This research offers insight into how the biology of some breast cancers changes in response to hormone therapy. I look forward to seeing how these findings inform treatment decisions in the future – helping some patients avoid unnecessary side effects, while ensuring that those with more aggressive tumours are offered alternative and more effective drugs.”
Professor Marian Knight, Scientific Director for NIHR Infrastructure, said:
"The insights that the researchers at The Institute of Cancer Research have uncovered in this study will help clinicians deliver more personalised breast cancer care that will be transformative for some patients, saving them from unnecessary treatments and their side effects.
"Work like this, which is underpinned by the NIHR's investment in Biomedical Research Centres, is crucial to saving the NHS time and money and, ultimately, moving the dial on patient outcomes."