Improving earlier diagnosis and precision medicine for reduced mortality of breast cancer in Kenya

Data show breast cancer rates are rising in Kenya with scant molecular pathology studies performed. Mortality is high in Kenya compared to the UK and cancer registry data estimate that breast cancer is the second leading cause of cancer death-making it a significant public health problem and loss of economic productivity. Advances in genomic and molecular technologies have transformed our understanding of breast cancer and provide a way to more accurately classify cancers into similar distinct types based on their genetic characteristics. Breast cancer survival has improved significantly in the UK over the last 20 years, but in lower income countries such as Kenya, increasing survival remains a significant challenge likely through a combination of issues. A major barrier to reduce mortality in low and middle-income countries (LMICs), such as Kenya, are multifaceted. However, two major challenges are late stage at diagnosis and limited capacity for accurate molecular tumour subtyping of breast cancer to identify women who would most benefit from endocrine therapies (a form of precision medicine). Hence, a multidisciplinary approach combining expertise in epidemiology, surgery, oncology, pathology, and molecular genetics, could provide new insights into the risk factors of the disease relevant to the Kenya population, as well as new avenues for combatting the high mortality in Kenya. The observation that tumours release DNA into circulating blood, provides a potential means for earlier and more accurate diagnosis of cancer in low and middle resource countries like Kenya. DNA from the tumour that gets in the blood stream could be used as a test to provide minimally invasive diagnosis of cancer. To design effective approaches to improve health-care, consistent with the MRC 2014-2019 strategic plan we aim to 1) Collect data to inform research priorities that are most likely to deliver improved health outcomes, through the use of molecular defined disease datasets including tumour tissues and blood samples; 2)Bring the benefits of excellent research to all sections of society, in collaboration with academic and other research partners; 3) Develop new innovations through the use of new health data-to improve and inform cancer control and treatment programs and enhance economic development in Kenya. This pump-priming award would allow for knowledge exchange and provide a foundation for improved molecular epidemiology studies that would inform development of improved surveillance, diagnostic and treatment paradigms for breast cancer in Kenya. Through this multinational consortium we envision this proposal to provide future opportunities to train and build capacity for molecularly defined health data collection in Kenya and more broadly other countries in sub-Saharan Africa.

Data and key priority setting is desperately needed to inform prevention, diagnosis and improved treatment strategies in Kenya. To tackle the increasing incidence and high mortality of breast cancer in Kenya, this pump-priming award would develop a new UK-Kenya partnership to investigate the molecular epidemiology of breast cancer. Building off a recently funded grant by the Kenya National Research Fund by co-investigator PI: F. Makhoka--Genomic Approaches for Understanding Breast Cancer Progression in Kenyan Patients--this proposal would enhance success of this work by providing key research staff and contemporary methodologies for molecular assays. Specific aims are:

1) Develop a new partnership between the University of Edinburgh and Mount Kenya University. PI: Dr. J. Figueroa has over a decade of experience in molecular epidemiology and pathology studies of breast cancer, including conduct of a large multidisciplinary study in Ghana, west Africa (Brinton...Figueroa International Journal Cancer 2017) .
2) Design data collection pipelines for molecular pathology studies of breast cancer and mortality outcomes--which are desperately needed to inform what the key barriers and challenges are for breast cancer surveillance, diagnosis and treatment.
3) Exchange knowledge of contemporary molecular subtyping methods for breast cancer, and perform a pilot study to assess whether we can collect and quantify cell free DNA (cfDNA) tumour fraction at the time of breast cancer diagnosis and the relationships with clinics-pathological characteristics of breast cancer tumours for (N=100 cases)-for potential earlier diagnosis of breast cancer.
4) Using pilot data collected in this study, engage key stakeholders (e.g. physicians, ministry of health, policy makers) to prioritise the key areas needed for long term planning to enhance capacity to tackle the increasing burden of breast cancer in Kenya

Breast cancer is a model disease showing the impact that targeted treatments and precision medicine can have in reducing the burden and mortality of disease. According to cancer registry data in the UK, mortality rates have decreased by over 30% since the 1970s, a huge success largely due to targeted treatments for tumours that express the oestrogen receptor and/or epidermal growth factor receptor-2 (known as HER2). A major barrier to having similar success in low and middle-income countries (LMICs) such as Kenya are multifaceted, however a big impediment has been late stage at diagnosis and reduced capacity in molecular pathology techniques and timeliness of collection molecular diagnostics for improved diagnosis for treatment especially for women who would most benefit from endocrine therapies. Breast cancer is the second most frequently diagnosed cancer in Kenya and a preventable and highly treatable disease if caught early. This project proposes to implement data collection pipelines / data sharing protocols in Kenya to understand diagnostic pathways for breast cancer, build capacity for molecular pathology studies of cancer; characterise the molecular pathology and aetiology differences by tumour characteristics and mutational patterns in N=100 breast tumours in Kenyan patients; assess the feasibility of detecting breast cancer using circulating tumour nucleic acids using targeted sequencing of gene panels being developed at the University of Edinburgh's Institute of Genomics and Molecular Medicine and state-of-the-art facilities at Edinburgh Genomics. Data from the study will help in developing diagnostics and data management pipelines for not only breast cancer but other cancers in Kenya and the Sub-Saharan region. The Constitution of Kenya, 2010, recognizes the value of Science, Technology and Innovation (ST&I) for national development and prosperity through the Science, Technology, Innovation Policy and Strategy (STIPS), 2009. Our proposal fits well with STIPS and the Kenya National Cancer Control Strategy 2017-2022, including prevention, early detection cancer diagnosis, registration and surveillance. Further, as this study would involve data science, this would enhance Kenya's increasing information technology economic sector-- 'Silicon Savannah'-building a new strategic partnership with the University of Edinburgh- a leader in health data science in the UK. Lastly, through this proposal we would expect to improve efficiency, cost-effectiveness and the impact on equity for current and future programmes on cancer prevention and management; thus, increasing economic development and improving lives.