Understanding exactly how cancer spreads within the body is a new frontier in scientific research as survival rates from all types of tumours continue to increase.
Metastatic cancer, often referred to as stage IV cancer, is when it has travelled from where it started to other parts of the body. As improvements in surgery, radiotherapy and drugs have all contributed to increasing success in treating primary sites of cancer, researchers are focusing on the metastatic form, which is regarded as treatable but generally not curable.
“There is so much hope offered by cancer research, which is really important to patients and their loved ones,” says Dr Claire Kilty, the acting head of research with the Irish Cancer Society. “In the past, four out of 10 patients would survive their cancer and now that number is six out of 10. This is down to the amazing advances in cancer research that we have seen over the last decade.” The National Cancer Registry of Ireland reported at the end of last year that the number of patients living after an invasive cancer diagnosis had exceeded 200,000 for the first time, equivalent to one in 24 people in Ireland.
Every improved cancer treatment in our lifetime is built on the work of many generations of scientists and clinicians, not to mention patients, who came before us. Each generation pushes the boundaries of knowledge forward a little bit more, as young cancer researcher Louise Watson (23) sees even within her own family.
Having recently been awarded the Orla Byrne PhD scholarship by Breast Cancer Ireland (BCI) to research metastatic breast cancer, Louise is the third generation of her family to be involved in the fight against this disease. She graduated from UCD last year with a BSc in genetics and attributes her keen interest in science since an early age to the influence of family members.
Her father, Prof Bill Watson is professor of cancer biology at the UCD School of Medicine. He was inspired by his father, Gordon Watson, who was a breast cancer surgeon at Waterford Regional Hospital (now called University Hospital Waterford), a council member of the Royal College of Surgeons in Ireland (RCSI) and who continues to take an interest in research in retirement. Further back in the family, Louise’s great-great-grandfather and her great-grandfather were, respectively, a teacher of science and a dentist.
Louise’s mother, Chanel Watson, “fell into research” in Toronto, Canada, after training as a nurse in Dublin’s Beaumont Hospital in the early 1990s. When she returned to Dublin and started working as a research nurse in surgery at the Mater, one of the clinical trials she was involved in was looking at optimising treatment strategies for post-menopausal women with breast cancer. She then went into nurse education and has been working at the RCSI as a lecturer since 2006. In another branch of the family tree, Bill’s sister, Penny, is a GP in Tramore, Co Waterford, working alongside her husband, Dr Dermot Nolan, and they have a daughter studying medicine now too.
Bill’s early research specialisation was in the area of inflammation. This is important both in the driving of cancer and in its treatment, he says, with “huge advances in modifying our immune system to fight tumours”. Now he is involved in prostate cancer research at UCD’s Conway Institute.
There’s a sense of symmetry about Louise researching breast cancer and her father working on prostate cancer. “You might think they are very different tumours,” says Bill, “but they are both hormone-regulated tumours: breast tumour is driven through oestrogen and prostate cancer is driven through testosterone. We can use that to our advantage by manipulating those hormones.”
Louise’s project at BCI’s research centre in the RCSI is investigating how breast cancer moves into the brain. “I am focused on looking at how the cells undertake that process; how they adapt to their new environment and communicate within their new environment and what is the cause of them migrating. Also, more specifically, what are the genes involved in that process.”
As the BCI funding for her work is in memory of a woman who died due to metastatic breast cancer, “it really does bring a face to the research”, Louise says. Orla Byrne, of Bohernabreena in Dublin, was just 42 years of age when she died in 2021.
Five years previously Orla had gone to her GP when she noticed that her right breast looked bigger than her left breast, which wasn’t normal for her. Within a couple of weeks she was diagnosed with stage-four inflammatory breast cancer. It had spread from her right breast to her liver, lymph nodes and bone.
Orla, who started on a new clinical trial drug that helped to keep the known cancer cells at bay, took on the role of education and outreach co-ordinator with BCI. She wanted to raise awareness among young women and girls about the importance of understanding good breast health.
After the tumour in her right breast started to grow again in 2019, she had surgery to remove that breast and also underarm lymph nodes. But by mid-2021, the cancer had spread to her brain and she died that November.
In the run-up to World Cancer Day on February 4th, BCI has just launched #MetastaticMatters, (see breastcancerireland.com), a campaign focusing on those living with metastatic breast cancer. It aims to highlight the symptoms of metastatic disease and to increase understanding of how and why this occurs.
The collaborative and global nature of figuring out the very complex puzzle of cancer, which is a term covering a group of more than 100 diseases, is an aspect of scientific research that particularly appeals to Louise. She always enjoyed team sports at school in The King’s Hospital, Dublin, and at UCD, where she was captain of UCD Ladies’ Boat Club for two years.
“In our lab at the moment we have a large number of people working on different projects all towards one main interest, which is breast cancer brain metastasis research,” she says, likening it to being part of one giant jigsaw, to which labs around the world contribute.
“All the time we are reading papers and trying to keep up with relevant research. All these findings go towards to developing our project and informing us how we should continue our research. That’s the really great thing about science, it’s so collaborative.”
Chanel recalls how Louise has had a sense of curiosity and wonder about the world since early childhood. She wouldn’t be happy be with any old answers to her litany of “why?” and always looked for deeper explanations. Participation in events such as the BT Young Scientists over several years, starting when Louise was still in sixth class in primary school, gave “real insight into the conduct of research and the generation of research questions” from a young age, Chanel believes.
“It was the first time I developed a project from start to finish,” Louise agrees, not that she won any prizes then for her efforts. But Chanel can say proudly now: “It is wonderful to see her pursue her passion for research and be awarded the scholarship from Breast Cancer Ireland. No better woman to grab the clinical problem by the horns and to commit herself to producing her piece of the puzzle in understanding breast cancer.”
Listening to her daughter and husband discuss their work, “it’s like a different language to me”, adds Chanel, despite her nursing and research background. Louise, who has one sister studying to be a mental health nurse at Trinity College and another sister still at school, says she and her father try to keep discussions about their work away from the dinner table at home in Lucan, Co Dublin.
“Louise and myself often have conversations about the research she is doing and how that is relevant to my research and other people’s research,” says Bill. “The sharing of information and ideas is so important.”
He is a translational biologist, working at the interface of biology and medicine. Increased understanding of the molecular mechanism of cancer, which is learnt at “the bench”, is then brought to the bedside.
“We also work with clinicians and patients to understand the problems – what are the challenges in the diagnosis and treatment of the disease – and bring those back to the bench. Then [we] bring those solutions back to the bedside.” Academic institutions patent researchers’ discoveries, to sell on to pharmaceutical companies that can fund the extensive and expensive process of multiple phases of clinical trials before any new drug can be licensed.
Considering the size of the country and the limited funding that is put into science, the Irish scientific and clinical community punches far above its weight on the global stage. It was recognised a long time ago, says Bill, that the research institutions here needed to form networks to compete internationally.
“We have the best healthcare in the world – the problem we have is getting into it,” he remarks. “The vast majority of scientists and clinicians have all been abroad to the best institutions in the world and have come back. We are so lucky.”
Cancer research is now getting down to the genetic level of the disease, he explains. “What are the genes that drive it? Then we might be able to come up with drugs that could manipulate it.”
Although there is a vastly improved survival rate for primary cancer, “unfortunately the tumour can adapt and evolve, like evolution, and become metastatic”. That’s why the next stage is to look at how drugs can be developed to target the mechanism by which cancer becomes metastatic.
“We are more successful in giving people a longer period of life with metastatic cancer but can we cure them of it? I don’t think we’re there yet.” However, he believes his daughter’s generation will achieve that.
Meanwhile, he and his scientific peers surround themselves with young people with a “techy mind”, he says. Technology has been developed to do the “heavy lifting” in gathering genetic data. Louise did undergraduate modules in programming so she can write code to help analyse that information, which is “far beyond me”, he comments.
“We will become successful in treating metastatic disease and keeping people alive longer”, Bill adds, “and then something else will emerge”. As life evolves, scientific research follows.
What is metastatic breast cancer?
Metastatic breast cancer, also known as stage IV breast cancer, is cancer that has spread outside of the breast to other areas such as the bones, liver, lung or brain. This process is called metastasis.
What happens when breast cancer spreads? Breast cancer that spreads to the bones, lung or liver, is still breast cancer and does not become bone cancer or liver cancer or lung cancer. Under a microscope, the tumour cells will still look and act like breast cancer and will be treated as breast cancer.
Who gets metastatic breast cancer? Anyone who has had an earlier stage of breast cancer can experience a metastatic recurrence and some women have metastatic disease on their initial diagnosis of cancer, despite mammograms and early detection. As men and women of all age groups can develop breast cancer, metastatic breast cancer can affect younger adults.
Why does breast cancer metastasise? Researchers can’t yet explain exactly why metastatic disease occurs, but they’re working on finding answers.
What is the main difference between early-stage breast cancer and metastatic breast cancer? Metastatic breast cancer is treatable but no longer curable. Treatment is lifelong and focuses on preventing further spread of the disease and managing symptoms.
How is metastatic breast cancer treated? Depending primarily on the kind or subtype of metastatic breast cancer, patients may be on either targeted therapies or systemic chemotherapy. Radiation and surgery are also sometimes used.
How is its progress monitored? Usually metastatic breast cancer is monitored by periodic imaging tests (CT, PET or bone scans or MRIs), blood tests measuring tumour markers and assessment of how the patient is feeling.
- Source: Breast Cancer Ireland’s #MetastatisMatters campaign (breastcancerireland.com)
How the Irish Cancer Society advances research
Cancer research encompasses much more than laboratory studies of the disease itself. Broadly speaking, says Dr Claire Kilty, acting head of research at the Irish Cancer Society (ICS), it spans five main areas. These are: cancer prevention and healthy living; early detection; treating cancer more effectively; research to improve the lives of all people affected by cancer during and after treatment in a holistic sense; and research to improve the experience of those at end of life.
The ICS spreads its annual investment in research, which was €4.3 million in 2021, over all five areas, funding more than 100 researchers across nine institutions in the Republic. There is, she says, particular emphasis on translational research, ie patient-focused biomedical research, the aim of which is to translate existing knowledge about cancer biology into techniques and tools that will accelerate progress towards early detection and treatment.
“Furthermore, we support clinical trials to examine the benefits of new approaches to treatment and care, as well as survivorship-focused research, which seeks to improve the care and outcomes experienced by people living with and beyond cancer.” For example, one of its biggest funding projects is the Irish Cancer Society Women’s Health Initiative, a survivorship research programme based in hospitals in Dublin, Cork and Galway looking at how to improve support for women during and after cancer treatment.
The charity also funds research across strategic priorities such as cancers with significant challenges (cancers with poor prognosis, advanced cancers and rare cancers); children, adolescents and young adults, and innovative research seeking to develop new tools and technologies.
There is a big issue globally with cancer misinformation, says Kilty. People affected by cancer are bombarded by information online from non-reputable sources.
“Cancer research is undertaken by highly trained professionals who have studied accredited research methodology for a long time in universities. It is important, therefore, that members of the public can know that the information they are reading and trusting is evidence-based and undertaken by qualified research professionals, such as the information contained on our own website (cancer.ie).
“If in doubt,” she adds, “I would always recommend an individual to check the information with their own cancer doctor.”