The research, which was led by the University of Leicester and conducted in the HOPE clinical trials facility at Leicester’s Hospitals, found that by identifying variations in two genes that help govern circadian rhythm – the body’s internal ‘clock’ – it may be possible to predict which patients could benefit from receiving their radiotherapy in the afternoon. 

The study analysed the genetic profiles of 879 breast cancer patients across two independent cohorts (LeND and REQUITE). The team found that patients with particular variations in two genes, called PER3 and NOCT, were at greater risk of long-term side effects, including permanent thickening under the skin and chronic pain, and short-term effects such as temporary red, peeling skin, if they were treated in the morning compared to the afternoon.  

If replicated in larger studies, this genetic analysis could allow patients’ radiotherapy treatment to be personalised to reduce its side effects – helping recommend which patients could benefit from being treated in the afternoon, and which could be treated at any time.

Around 55,000 women are sadly diagnosed with breast cancer each year, and most receive radiotherapy after surgery to destroy any remaining tumour cells.

Dr Kotryna Temcinaite, Research Communications Manager at Breast Cancer Now, which helped fund the research, said:

This exciting study suggests that simply altering the time of day that radiotherapy is given could help alleviate its difficult side effects for some patients. If we are to ensure NHS breast cancer patients receive the best possible care, we must focus on personalising therapies to individuals – and the timing of treatment could be important in doing this.

If we are to ensure that by 2050, everyone who develops breast cancer lives, and lives well, not only do we need to develop new and kinder treatments, but we must also find ways to reduce the side effects of existing therapies.

As a cornerstone of breast cancer treatment, thousands of patients each year experience the side effects of radiotherapy, such as burning, redness, and changes to the skin. It’s promising that smarter scheduling of appointments could help improve patients’ quality of life, but first we need to understand the potential mechanisms.

Further, multi-centre trials are now needed to replicate these findings and confirm whether gene tests could help identify patients that may benefit from having their radiotherapy in the afternoon. If confirmed, feasibility studies would then be needed to understand how this research could be translated into a clinical setting.

Professor Paul Symonds, a consultant oncologist at Leicester’s Hospitals and professor of clinical oncology at the University of Leicester said

Our study found that some patients with a particular genetic profile are more at risk of side effects if given radiotherapy in the morning.

This happens because the skin of these particular patients divides earlier in the day than others and dividing cells are more easily damaged by X-rays. This could allow an easy way to personalise treatment just by recommending what time of day a patient should be treated.

Around 90 per cent of operable breast cancer patients are treated with radiotherapy so radiotherapy toxicity is a very real and important issue for these patients.

Dr Christopher Talbot, Senior Lecturer in Medical Genetics, Department of Genetics at University of Leicester, said:

Previously, we and others have found several genetic variants that affect reactions to radiotherapy, especially in the ATM and TNF genes. The REQUITE project set out to find many more. Those variants increase risk for reactions irrespective of time of day and are distinct from the cases in our new report that only affect the time of day response and not risk, as such. It was known before that cancer drugs show different effects according to the time of day, but the evidence was weak for radiotherapy. We now have better evidence but also a way to determine who would benefit.

Where our paper is unique is that through a simple genetic test, we can identify the patients at most risk of side-effects if treated in the morning. Such patients could then be scheduled for afternoon treatment.

Nigel Rose, Chief Executive of Leicester-based charity, Hope Against Cancer, said

We are really excited by the findings of the REQUITE project and its potential to positively benefit patients during and after radiotherapy treatment. As such we have committed to fund a PhD student to further investigate how our genes may affect patient reactions to radiotherapy.

This work was supported by funding from Breast Cancer Now, Hope Against Cancer and the European Union Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 601826 for ‘The REQUITE project: Validating predictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve quality-of-life in cancer survivors’. The paper, ‘Genetic Variants Predict Optimal Timing of Radiotherapy to Reduce Side-effects in Breast Cancer Patients’ is published in Clinical Oncology and is available at Clinical Oncology online.