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Prof Jean Abraham discusses progress on personalised breast cancer medicine ahead of CBC on Virtual Tour talk

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We talk to Prof Jean Abraham about her work in personalised breast cancer medicine ahead of her talk on the subject on Wednesday November 10 - part of a series of free presentations called CBC (Cambridge Biomedical Campus) on Virtual Tour.

Jean Abraham, professor of precision cancer medicine at the University of Cambridge, and academic honorary consultant in medical oncology at Cambridge University Hospitals (52795057)
Jean Abraham, professor of precision cancer medicine at the University of Cambridge, and academic honorary consultant in medical oncology at Cambridge University Hospitals (52795057)

For Professor Jean Abraham, delivering clinical medicine to breast cancer patients while conducting academic research provides an important daily reminder.

“It gives you a really interesting insight into why you are doing what you are doing,” she explains. “It would be very easy with academic studies to just do the research. But if you are seeing patients on a daily basis, you never forget the reason for the research. Your fundamental aim is to make your patients’ lives better.”

Professor of precision cancer medicine at the University of Cambridge, and academic honorary consultant in medical oncology at Cambridge University Hospitals, Jean co-leads the pioneering Personalised Breast Cancer Programme.

Since it launched in 2016, the programme has aimed to improve early diagnosis and tailor treatment by mapping patients’ DNA and RNA.

“The way treatment has changed today is that we focus on particular biological pathways to target. To a certain extent, we’ve always done that – oestrogen receptor positive breast cancer patients have been treated differently to those that are not. But we’re now doing that at a finer level.

“Patients who are not oestrogen receptor positive have always been called ‘triple negative’ breast cancer patients, but triple negative breast cancer has at least four categories, if not more. It’s about understanding the detail and finding the treatments that best match those differences.

“Through the Personalised Breast Cancer Programme, all breast cancer patients of all stages are given the opportunity to have the genes sequenced for free.

“They have their tumour sequenced and a blood sample sequenced which allows them to understand if they have inherited the changes that they have.”

Sequencing of the genome. The sequence of nucleotides in DNA after decryption
Sequencing of the genome. The sequence of nucleotides in DNA after decryption

The programme means this sequencing is now routine in Cambridge – but that is not yet replicated nationwide.

“Nationally, we have genomic laboratory hubs which over time will be doing something probably based on panel testing, rather than whole genome testing, but it will allow patients to have some form of sequencing,” explains Jean.

The importance of adapting treatment is underscored by the fact that we now know that breast cancer is not one disease. But our understanding of how many types there are “depends on which research you talk to”, Jean suggests, as there a number of ways to categorise it.

“You can categorise it clinically – which means you look at oestrogen and progesterone. We are beginning to look at immune markers, although that is not completely routine yet.

“If you look at it from a molecular perspective and depending on the kind and depth of sequencing, and the detail in which you look at the sequencing, you could categorise breast cancer in up to 11 sub-types if you wanted to.

“The usual step for a patient who is diagnosed would be to have an ultrasound mammogram and biopsy done to confirm if it is breast cancer.

“We will take the sample, and the sequencing will take about six to nine weeks to come back. In the meantime, we develop a plan for them based on information we have about their family history, other clinical features and the tests we do with the pathologist.”

When the sequencing results return, they are reviewed by our Onco-Genomics Review Board (ORB) – a group of specialists on both the scientific and clinical side, like Jean, who will looking at the tumour and hereditary components and recommend the best approach.

“Initially, it may be that we need to double-check what we’ve found because this is a research study so we need to validate what we find before it’s implemented,” notes Jean.

“We will feed back the results to the patient, the clinician and the consultant.

“The patient also gets a lay version – a reader-friendly version – of the results they can take away.”

Cambridge breast cancer patients have their DNA sequenced
Cambridge breast cancer patients have their DNA sequenced

Sequencing results are complex and the range of responses to them is varied.

“When you get the sequencing results, the changes in management are not always about treatment,” Jean says.

The DNA findings could prompt prophylactic surgery, for example, as a preventative measure.

“Or somebody may have a drug removed because of the likelihood of toxicity to a particular drug, or they may have a finding that a particular drug could work well.

“There is a whole range of effects the sequencing results could have. Our job is to find the right treatments to fit the patient,” says Jean.

“A lot of these treatments where we find a change are not licensed in a particular breast cancer setting, so we will look for a clinical trial that allows that patient to access that particular agent because they wouldn’t be able to get it under the standard of care and that is usually because the efficacy level is not deemed to be high enough yet.

“Part of our job is to manage expectations patients have when they get sequencing. Sometimes, when you read about it, it can seem like a magic bullet that can sort everything. What it does is give us information and in a lot of patients changes are implemented, but in some patients they aren’t, because a drug isn’t available, or it isn’t needed.

“They may be early breast cancer patients who are being treated appropriately and don’t need it now, but it is something to be aware of if they relapse.”

Cambridge patients benefit from access to a broad range of trials.

A mammogram is carried out (52881454)
A mammogram is carried out (52881454)

“We try to get a clinical trial for as many patients as possible. They are an opportunity to learn more about the disease a patient has, and to help future patients. It is part of the reason that the Cambridge Breast Cancer Research Unit and the Breast Cancer Unit are so at the cutting edge.

“The trials could be in imaging, or surgery, but my particular area is therapeutic, or drug, trials.”

Jean’s early interest in this field prompted her to study pharmacology for her first degree.

“My parents said I should think about studying medicine,” she recalls. “But I was stubborn and did pharmacology, until I realised they were quite right and the bits I enjoyed most were the clinical parts. So I did a second degree in medicine and did my clinical training in Cambridge.”

It is a reminder, she says, to people like her 18-year-old son that decisions you make as a young person do not have to define you for life.

One of the largest drugs trial Jean is currently involved in is PARTNER for patients with triple negative breast cancer – that is cancers that don’t have receptors to oestrogen, progesterone and HER2.

“They have limited treatment options outside of surgery and radiotherapy. Chemotherapy is really their only option,” says Jean.

“This trial gives access to an AstraZeneca drug called olaparib. It has recently been found to have a very positive result in a post-surgical setting. We are trying to see if it has an equally interesting effect in the pre-surgical setting.”

An aerial view of Cambridge Biomedical Campus. Picture: CBC
An aerial view of Cambridge Biomedical Campus. Picture: CBC

There are further options for both patients found to respond to this, and those who do not.

While trials like this gather more invaluable data, there is a broader project going on to bring all the information now being gathered about a patient together.

Jean is leading work along with Prof Richard Gilbertson and others to develop a vision for the future of cancer care, aided by the new hospital coming to the Cambridge Biomedical Campus.

“What we have in Cambridge is a theme called integrated cancer medicine. That theme is looking at all the different strands of research that patients have done – the pathology, the sequencing, the imaging. We are now collecting circulating tumour DNA and then there is the clinical data. We want to look at all those and the importance of them, and integrate them to give us an indicator of how best to treat that patient.

“We are trying to use artificial intelligence and machine learning so this can be done remotely, with algorithms, so that we can help patients who are not in Cambridge.”

A new cancer research hospital is coming to the Cambridge Biomedical Campus. Image: NBBJ
A new cancer research hospital is coming to the Cambridge Biomedical Campus. Image: NBBJ

In years to come, the benefits of this visionary approach could change cancer care well beyond the limits of Cambridge University Hospitals.

“I would hope that all cancer patients will have a really holistic treatment that takes into account all the different facets of their care and wellbeing. It will allow us to spread our expertise beyond Cambridge to the region and internationally. We want to improve healthcare standards for breast cancer patients around the world.”

You can register for Jean’s virtual talk, which runs from 1-2pm on Wednesday, November 10, at Eventbrite. It will also be recorded and posted on the Cambridge University Health Partners website and the Cambridge Biomedical Campus YouTube channel.

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