̽��ֱ�� of Cambridge - Helena Earl

Back to BRCA: the discovery of a breast cancer risk gene

cjb250 — Mon, 07 Oct 2024 08:00:50 +0000

In 1994, a landmark paper identified a gene – BRCA1 – that significantly increases the risk of breast and ovarian cancers when faulty. Thirty years on, we look at the major impact it has had on how we understand and treat cancer – and why there is still much to learn.

Six months of Herceptin could be as effective as 12 months for some women

cjb250 — Thu, 17 May 2018 11:47:23 +0000

̽��ֱ��PERSEPHONE trial, a £2.6 million study funded by the NIHR with translational research funded by Cancer Research UK, recruited over 4,000 women and compared a six month course of treatment of Herceptin with the current standard of 12 months for women with HER2-positive early-stage breast cancer.

This is the largest trial of its kind examining the impact of shortening the duration of Herceptin treatment. Over the last five years, the NIHR has invested £46.5 million in funding and supporting breast cancer research.

Herceptin, has been a major breakthrough, prolonging and saving the lives of women with breast cancers that carry the HER2 receptor on the surface of their cancer cells. Around 15 out of every 100 women with early breast cancers have HER2 positive disease.

Herceptin is a targeted therapy that works by attaching to the HER2 receptors preventing the cancer cells from growing and dividing. It has rapidly become standard of care and based on clinical research a 12 month treatment course was adopted. However, a further clinical study suggested a shorter duration could be as effective, significantly reducing side effects and cost both to patients and to the NHS.

̽��ֱ��trial, led by a team from the ̽��ֱ�� of Cambridge and Warwick Clinical Trials, the ̽��ֱ�� of Warwick, found that 89.4% of patients taking six months treatment were free of disease after four years compared with 89.8% of patients taking treatment for 12 months. These results show that taking Herceptin for six months is as effective as 12 months for many women.

In addition, only 4% of women in the six month arm stopped taking the drug early because of heart problems, compared with 8% in the 12 month arm. Women also received chemotherapy (anthracycline-based, taxane-based or a combination of both) while enrolled in the trial.

Lead study author Professor Helena Earl, Professor of Clinical Cancer Medicine, ̽��ֱ�� of Cambridge and Cancer Research UK Cambridge Centre, said: “ ̽��ֱ��PERSEPHONE trials team, patient advocates who have worked with us on the study and our investigators are very excited by these results. We are confident that this will mark the first steps towards a reduction of Herceptin treatment to six months in many women with HER2-positive breast cancer.

“However, any proposed reduction in effective cancer treatment will always be complex and very challenging, and women currently taking the medication should not change their treatment without seeking advice from their doctor. There is more research to be done to define as precisely as possible the particular patients who could safely reduce their treatment duration. We are poised to do important translational research analysing blood and tissue samples collected within the trial to look for biomarkers to identify subgroups of different risk where shorter/longer durations might be tailored.”

Professor Hywel Williams, Director of the NIHR Health Technology Assessment Programme that funded the PERSEPHONE study said: “This is a hugely important clinical trial that shows that more is not always better. Women will now have the potential to avoid unnecessary side effects of longer treatment without losing any benefit. In turn, this should help save vital funds for the NHS and prompt more studies in other situations where the optimum duration of treatment is not known. It is unlikely that research like this would ever be done by industry, so I am delighted that the NIHR are able to fund valuable research that has a direct impact on patients.”

Professor Charles Swanton, Cancer Research UK’s chief clinician, said: “This is a critically important study that the breast cancer field has been eagerly awaiting. Targeted therapies, while effective, come at a huge health economic cost to the NHS as well as potentially causing side effects such as heart problems. Despite years of research, we haven’t been able to establish the optimal duration of Herceptin treatment, either to delay cancer coming back or to cure patients with early HER2+ breast cancer following surgery.

“ ̽��ֱ��exciting early key findings from this study show that 6 months of Herceptin might be as effective as 12 months, and it may also be safer and with fewer side effects. By analysing tumour and blood samples, the researchers will now try to understand which patients can stop Herceptin at 6 months and which patients need extended therapy.”

Maggie Wilcox, President of Independent Cancer patients Voice (ICPV) who is the patient lead for the PERSEPHONE trial, said: “I am delighted to have been part of this landmark trial which is an important step to reduce the length of treatment whilst not changing effectiveness. Most trials add novel treatments to standard practice whilst this has set out to reduce duration of Herceptin. ̽��ֱ��collection of the patient reported experiences throughout the trial will greatly inform future practice and benefit patients. ICPV is working with the Persephone team to help disseminate these exciting results’.

̽��ֱ��results of the trial, PERSEPHONE, will be presented at the upcoming 2018 ASCO Annual Meeting in Chicago. ̽��ֱ��full report, which will include analysis to determine the impact of treatment length on quality of life and a detailed cost effectiveness analysis, will publish in the NIHR journals library.

Press release from the NIHR

For women with HER2 positive early-stage breast cancer taking Herceptin for six months could be as effective as 12 months in preventing relapse and death, and can reduce side effects, finds new research.

We are confident that this will mark the first steps towards a reduction of Herceptin treatment to six months in many women with HER2-positive breast cancer.

Helena Earl

Voyagerix

Breast cancer. Female hands make heart on pink ribbon

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New way of predicting kidney function could improve chemotherapy dosing for many cancer patients

cjb250 — Fri, 07 Jul 2017 20:29:03 +0000

Kidneys perform a number of vital functions, including filtering waste and toxins out of the blood, producing vitamin D, and regulating blood pressure. ̽��ֱ��filtration function of the kidneys is measured by the glomerular filtration rate (GFR), the rate at which blood is passed through the glomeruli, the small blood vessel filters in the kidneys.

Determination of the GFR is important because the assessment of kidney function can indicate how a disease is progressing, whether a drug treatment is having adverse side-effects on key bodily functions, and if it is safe to prescribe a drug at a certain dose, a question of particular importance to cancer doctors when prescribing chemotherapy drugs. However, measuring GFR is technically difficult. Doctors therefore often rely on ways to estimate GFR, which can be relatively inaccurate.

“Almost every patient with cancer gets a measurement of their kidney function, reported as estimated GFR, and this value influences many treatment decisions, but until now, we did not know the best way to provide this value for patients with cancer,” says Dr Tobias Janowitz from the Cancer Research UK (CRUK) Cambridge Institute at the ̽��ֱ�� of Cambridge, joint first author. “Given how important this measure is in day-to-day clinical practice, we felt that we should provide an evidence-based model for its calculation in this context.”

Now, in a study published today in the Journal of Clinical Oncology, the authors describe a new and better way to estimate the GFR, which has been developed using data from a large dataset of over 2,500 patients. They used accurate measurements of GFR to provide a gold standard and then statistical modelling methods to find the best mathematical model to estimate GFR. ̽��ֱ��new model also provides a measure of the uncertainty for this estimate.

To test the use of this revised method of estimating GFR, the researchers focused on the precision of chemotherapy dosing, specifically dosing of carboplatin, which is used to treat multiple cancers, such as lung cancer, germ cell tumours, ovarian cancer, and breast cancer. ̽��ֱ��new model reduced the probability of incorrect dosing for carboplatin substantially compared to the current models used in clinical practice, from more than 20% for the currently published models to 11.7% with the new model.

“Accuracy in chemotherapy dosing is very important,” says Edward Williams, joint first author, also from the CRUK Cambridge Institute. “Too much chemotherapy can be toxic and can even be life threatening, but too little chemotherapy may be ineffective against the cancer. Our model should help doctors calculate chemotherapy doses more accurately and thereby reduce the risk of toxicity or treatment failure.”

̽��ֱ��model has been made available for clinicians to access online free of charge.

“We believe this tool, which is based on stringent methodology, could have a positive impact on the care for a great many patients with cancer,” says senior author Professor Helena Earl from the Department of Oncology at Cambridge. “This is why we have made it free and easily accessible.”

“ ̽��ֱ��limitation of our work that we are most aware of is that due to the patient demographics in our data set, our model does not provide guidance on the impact of race on the estimated GFR, though it is well known that race can be a key variable,” explains Dr Janowitz. “This will be addressed in future work. We are also keen to explore how well the new model performs for patients with diseases other than cancers.

“ ̽��ֱ��work is a very good example of scientists from different specialties coming together to provide an advance for the care that we offer to patients with cancer.”

̽��ֱ��study was supported by Cancer Research UK, the Wellcome Trust, and the National Institute of Health Research Cambridge Biomedical Research Centre.

Professor Peter Johnson, Cancer Research UK’s chief clinician, said: “Chemotherapy drugs are very powerful, so having the correct dose makes an enormous difference to how effective they are and how we can avoid unnecessary side effects. This way of measuring how well a patient’s kidneys are working and how quickly chemotherapy drugs like carboplatin leave the body helps to make our treatments more accurate and better suited to each individual.”

Reference
Janowitz, J et al. A new model for estimating glomerular filtration rate in patients with cancer. Journal of Clinical Oncology; 7 July 2017; DOI: 10.1200/JCO.2017.72.7578

Scientists at the ̽��ֱ�� of Cambridge have developed a new statistical model which estimates kidney function in patients with cancer. This is the most accurate model for estimating kidney function yet developed and should help cancer specialists treat their patients more safely and improve the accuracy of chemotherapy dosing. ̽��ֱ��model is now available free online.

Accuracy in chemotherapy dosing is very important. Too much chemotherapy can be toxic and can even be life threatening, but too little chemotherapy may be ineffective against the cancer

Edward Williams

Sir Cam

CRUK Cambridge Institute

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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