MetARP 2024: Ann and Nicole
Ann and Nicole were delighted to have the chance to attend the Metastases Research Society’s 20th biennial congress in London in 2024. This was unique opportunity for Ann and Nicole to talk through their different experiences of metastatic breast cancer research as patient and scientific researcher. They share why research is important to them, the types of research they are involved with, together with their motivations, successes and challenges.
From Screening to Secondary
Ann was diagnosed with primary breast cancer on her first mammogram, aged 50, in 2013. Her lesion was miniscule and removed by the core biopsy at the screening clinic. She was categorised as low risk and as a result had breast conversing surgery/lumpectomy, followed by 15 sessions of radiotherapy. She was prescribed endocrine therapy for five years. After five years she was discharged from cancer services, considered ‘cured’. Scarcely three months later, she was diagnosed with metastatic breast cancer, the cancer had spread to both lungs, and was now incurable.
Receiving a metastatic diagnosis was a shocking and distressful experience as her case was promoted as an example of ‘EARLY DIAGNOSIS SAVING LIVES’. Ann had fully complied with endocrine therapy throughout the previous 5 years and done everything in her power to rebuild a healthy lifestyle and reduce modifiable risk factors.
Taking control, helped by research
Ann described being in freefall for the first few weeks, initially trying to understand how this had happened, but very quickly she moved to ensuring she had a strong research-focused clinical team and an optimal treatment plan. She knew the biology of her primary tumour, ER+ (8/8), PR-(0/8), HER2+, but pressed for a biopsy in case her subtype had changed, which she knew was a possibility. She was the first patient in Northern Ireland to have a navigational bronchoscopy, which identified the biology of the metastases as the same as her primary cancer.
Whilst conscious that HER2+ was an aggressive sub-type, she took encouragement from the results from clinical trials for her systemic anti-cancer therapies (SACT) and the fact that she was chemotherapy naïve.
Ann also read up on Dr Dennis Slamon, the American scientific researcher whose work identified the HER2+/ neu oncogene and resulting trastuzumab treatment. She read the book, HER2-The Marking of a Herceptin, a Revolutionary Treatment for Breast Cancer by Robert Bazzell, and watched ‘Living Proof’, a dramatization of Dr Slamon’s development of Herceptin. In 2023, Ann was delighted to attend a conference in Dublin and meet Dr Slamon.
She says, ‘from my metastatic breast cancer diagnosis, I researched the different cancer treatments and the trials which brought them into clinical practice. I was also interested in what went before this in terms of the laboratory research and the scientists who painstakingly worked over many years to develop these drugs. Information on current developments, and those in the pipeline, gives a sense of optimism, even though you know in your heart that laboratory research will only benefit those coming behind.’
Ann rebuilt her life. She took control. She informed herself about her disease, the various treatments and side effects to become an ‘expert patient’ . She developed a strong partnership with her oncologist and clinical team, with shared decision-making. Her aim is to live as full and positive a life as possible, despite the limitations imposed by her disease- she wasn’t going to waste a day her cancer treatment was giving her.
Research & advocacy to drive improvements
Ann wanted to give help others. She had a long career in various roles in the NHS and wanted to use her knowledge, skills and experience to make a positive contribution to cancer research and help drive improvements in cancer services. She became a patient advocate and has co-led many research and service improvement initiatives in Northern Ireland (NI), across the island of Ireland and the United Kingdom.
Ann contributed to the development of Northern Ireland’s Cancer Strategy in 2021. This was hugely important as research shows there is a clear link between plans and outcomes. She is the patient representative on the Northern Ireland Cancer Steering Group providing leadership and guidance on the delivery of cancer services throughout Northern Ireland, including the reform and modernisation plans arising from the Cancer Strategy.
Knowing the importance of data, and the shocking fact that there is no information on metastases arising from reoccurrence of the primary disease, she campaigned for a metastatic breast cancer research audit for Northern Ireland. Gaining the support of a cancer charity, she has worked as part of the NI Cancer Registry team to establish a large clinical database covering almost 30 years. Ann says, ‘Despite many setbacks, I am glad I persevered because for the first time in history we know the number of people living with metastatic breast cancer in Northern Ireland. The next steps will be to analyse the database at a breast sub-type level, and look at variation in care. This research is truly groundbreaking.’
Ann also co-produced a research study identifying the needs of metastatic breast cancer patients across the island of Ireland, with the aim of making policy changes, educating clinicians and charities, and helping build greater agency of patients.
Ann is an active member of the Northern Ireland Cancer Research Consumer Forum (NICRCF) and is a co-author on a number of research studies. She is the patient representative on the Northern Ireland Clinical Trials Network Breast Cancer Clinical Study Group working with clinicians to ensure delivery of the highest quality standards of care to patients through leading-edge clinical and translational research.
Ann concludes, ‘Research gave me a real sense of hope in the difficult early days of my diagnosis, and today, as a patient-researcher, it gives a me a real sense of purpose - to drive improvement and help others coming behind.’
From Student to Researcher
Nicole was always passionate about science. For her, science is like a puzzle of which not all pieces have been found to solve it. She studied biochemistry in the University of Wuerzburg in Germany, with her undergraduate and postgraduate studies focusing on research. During this time, she had the chance to visit a laboratory in another country, for which she decided to go to Edinburgh in Scotland. For her research she focused on the clearance of dead cells from the body.
Nicole decided to pursue a PhD in Optical Medical Imaging with Healthcare Innovation and Entrepreneurship at the University of Edinburgh. This interdisciplinary program combined diverse research areas and emphasized translating research from bench to bedside. She conducted her PhD research in Prof. Marc Vendrell’s group, working alongside chemists and biologists to develop probes for detecting dead cells. These probes have broad applications, including monitoring cell death induced by chemotherapy, which can help detect successful therapies before tumor shrinkage occurs. Her work led to the commercialization of the probe by Biolegend, a biomedical company.
Nicole further explored the application of her probe in pre-clinical models during a visit to Prof. Mikala Egeblad’s laboratory in the United States, a leading lab in metastatic research. There, she demonstrated the probe's effectiveness in detecting cell death in cancer cells using intravital imaging. The labs she worked in during her PhD were inspiring places with developing probes to monitor therapy progression and researchers studying why metastatic cancer cells can wake up after being inactive for years and start growing again. Nicole showed that her probe can show when cancer cells die during chemotherapy, using a technique called intravital imaging. This technique lets scientists see what happens to cells in living organisms, which she found incredibly helpful for understanding how treatments work in an intact environment.
Her passion for this work grew, and she resolved to deepen her knowledge of intravital imaging for her future research endeavours. Additionally, the commitment of the researchers she encountered during her PhD to aid cancer patients—whether through the development of new therapies, innovative monitoring techniques, or addressing fundamental biological questions related to disease onset and progression—further fuelled her motivation to pursue a career in this field. She aims to integrate the knowledge gained from her undergraduate and postgraduate studies with her PhD research to explore ways to enhance combination therapies, thereby improving the interaction and destruction of cancer cells by cytotoxic immune cells.
Transition to current research work
Towards the end of her PhD, Nicole secured a prestigious fellowship funded by the Wellcome Trust, allowing her to conduct research in the laboratories of Val Brunton at the Edinburgh Cancer Research Centre in the UK and David Entenberg at the Albert Einstein College of Medicine in New York. These laboratories are renowned for their expertise in cell adhesion and intravital imaging, respectively. This provided Nicole with an optimal environment to investigate changes in the metastatic environment using intravital imaging.
Nicole's current research focuses on understanding how to modulate the metastatic environment to make it more susceptible to immunotherapy. In recent years, it has been shown that successful cancer cell killing by cytotoxic T cells requires multiple prolonged interactions between the T cells and cancer cells. Without these interactions, cancer cells can repair themselves from the damage caused by cytotoxic cells. Despite over 285 clinical trials using immunotherapy for metastatic breast cancer since 2018, only 5-20% of patients have responded, with limited effects on overall and progression-free survival. Factors contributing to this low response rate include a low number of cytotoxic cells, physical barriers, and a highly immunosuppressive environment.
Using intravital imaging, Nicole studies whether changes in the microenvironment can enhance the early infiltration of immune cells into the metastatic site and increase their interactions with cancer cells. Her findings indicate that immunotherapy alone does not significantly enhance these interactions in vivo, but combination therapy does. Nicole's future research aims to understand the specific changes in the microenvironment that facilitate this increase in immune cell-cancer cell interactions.
Nicole's research aims to improve cancer treatment outcomes for patients with metastatic breast cancer, motivated by the limited success of current immunotherapy approaches. She focuses on understanding and modulating the metastatic environment, recognizing its crucial role in treatment resistance. By investigating the interactions between immune cells and cancer cells in vivo, Nicole seeks to uncover new strategies to enhance immunotherapy efficacy. Her dedication is driven by the potential to develop innovative combination therapies that could significantly improve response rates and survival outcomes, shaping her long-term career goals in cancer research and therapeutic development.
Nicole's research embodies a vital intersection of scientific inquiry, aiming to enhance the efficacy of immunotherapy for metastatic breast cancer. By focusing on the intricate dynamics of the metastatic environment, she aspires to develop innovative treatment strategies that could significantly improve patient outcomes and survival rates.
Nicole was deeply inspired by the strength and dedication of Ann and the other patient advocates she met at the Metastases Research Society’s 20th biennial congress in London, and before that at the 10th Annual Metastatic Breast Cancer Research Conference (MBCRC) in Utah in 2023. Hearing their personal stories and understanding their needs reinforced her belief in the importance of aligning research with clinical applicability. She realized that engaging with patient advocates is crucial to ensuring that research efforts are not only scientifically sound, but also practically beneficial for patients. Nicole concludes, ‘these experiences confirm the critical role of patient advocacy in guiding research towards outcomes that can be effectively implemented in clinical setting’.
Ann and Nicole want to acknowledge METarp for facilitating this unique and partnership. They learnt a lot from each other and hope to continue their conversations and gain ongoing benefits going forward.
