​Reducing the bUrden of Breast cancer in Young women (RUBY)

​​​Original Aims: 

1. Genetics: 1) Evaluate the contribution of 25 genes linked to breast cancer causation; and 2) re-assess genetic testing guidelines to determine which genes (other than BRCA1 and BRCA2) should be introduced into clinical genetic testing.
2. ​Lifestyle and modifiable risk factors: Explore associations between increased breast cancer risk for young women and unhealthy lifestyle (i.e., low physical activity, high sedentary behaviour, high caloric intake, low phytoestrogen and micronutrient intake).
3. Fertility: 1) Create a site-specific intervention model to aid discussions about fertility preservation; and 2) determine predictors of premature ovarian failure prior to treatment commencing.
4. Local therapy: Identify modifiable mechanisms during the perioperative period with a focus on the ramifications of treatment delay, impact of breast-conserving therapy, and provision of optimal care through multi-disciplinary care conferences. 

​Aims in the Context of MOHCCN-Generated Data: 

1. Studying Genomic Instability and HRD Status in Breast Cancer: We will have two interconnected studies under this objective.
   • To determine the frequency of homologous recombination deficiency (HRD) in breast cancer tumour samples of patients with a young age of onset and its association with prognosis. This study will investigate the prevalence of HRD in young-onset breast cancer cases and assess its correlation with clinical outcomes, providing insights into its prognostic value and potential therapeutic implications.
   • To determine the HRD status of breast tumors using AI algorithms applied to digitized histology images. AI-driven image analysis of histology slides will be employed to determine HRD status, offering a cost-effective and scalable alternative to traditional genomic testing. This will allow for broader implementation of HRD assessment in routine clinical settings.
2. Investigating Molecular Subtyping and Gene Expression Signatures Predicting Prognosis: We will have two interconnected studies under this objective.
   • ​To determine molecular subtypes of breast cancer in young women and their association with prognosis and treatment response. This study will classify breast cancer cases in young women based on transcriptomic profiling to establish molecular subtypes and evaluate their prognostic relevance.
   • ​To discover a novel gene expression signature that predicts prognosis and response to chemotherapy in young women with breast cancer. By analyzing transcriptomic data, we aim to identify a unique gene expression signature that can predict treatment response and long-term survival, potentially guiding more effective therapeutic strategies.
3. Assessing and Comparing the Prognostic Value of TIL and TIS in Young-Onset Breast Cancer
   • This study will evaluate tumor-infiltrating lymphocytes (TILs) and tumor inflammation scores (TIS) in young breast cancer patients to determine their prognostic significance. By comparing these immune markers with clinical outcomes, we aim to better understand the role of the immune system in young-onset breast cancer and explore their potential as predictive biomarkers.

​​Our program will create a national group of young women with breast cancer to support four key research projects. Each project is led by a Canadian scientist and includes support from other experts across the country. These projects build on what has already been done and use existing systems and tools. Together, they will help create the largest and most complete collection of information, samples, and personal experiences ever gathered from young women with breast cancer. This will support future research in many areas and improve our understanding of what affects this group now and in the future. 

​A previous review identified ten important topics in breast cancer research that need more attention, many of which matter greatly for young women. Our team chose the most urgent of these and has the experience to study them from diagnosis through to life after treatment. Our program includes four related research projects that work together to better understand and respond to the main issues faced by young women with breast cancer. By working as a team, we will make progress in diagnosis, treatment, and support that would not be possible through separate projects alone. 

​We will also create a national network of doctors and researchers across Canada. This network will allow us to: 

1. Enroll young women (aged 40 or younger) recently diagnosed with breast cancer from every province and the Yukon into a national study group. 
2. ​Collect and store blood and tumour samples, along with information on diet, lifestyle, and personal experiences, to help answer important research questions about young women with breast cancer. 

​These efforts will help us tackle the most pressing questions and turn what we learn into better care, improved health outcomes, and a deeper understanding of the disease. We’ve removed unnecessary overlap and created a shared system to support all four research projects. While each project has a specific focus, they will all contribute data to the larger effort. We expect that everyone on the team will share their knowledge across the projects so that our results are stronger together than they would be separately.