One in eight women in the US will develop breast cancer in her lifetime. For nearly 30 percent of them, the cancer will spread, or metastasize. While there has been significant progress in early detection and treatment for primary breast cancer, advances in treatment and prevention of metastasis are lagging behind. Today, an estimated 150,000 to 250,000 women and men in the US alone are living with metastatic breast cancer.
In 2013 BCRF, under the direction of our Scientific Director Dr. Larry Norton and former Chairman of our Scientific Advisory Board Dr. Clifford Hudis, established a dedicated initiative to address the persistent challenges of breast cancer metastasis. This initiative, now known as the Evelyn H. Lauder Founder’s Fund was fueled by an outpouring of support honoring the memory and immutable determination of BCRF’s founder, Evelyn Lauder following her death in 2011.
No topic in cancer medicine is more pressing and no opportunity more significant than understanding and stopping metastasis. The Founder’s Fund is an international, multi-year collaboration focused on dissecting the molecular basis of metastasis. BCRF investigators from around the world are using the most advanced tools of molecular analysis--some developed with BCRF support--to understand real disease in real people in real time. BCRF is committed to finding out why some cancers metastasize and others do not; why some cancers grow quickly and cause problems while others do not, and how to use this knowledge to predict, treat, and even prevent the spread of cancer. To date, BCRF has dedicated $31 million to the Founder’s Fund to fuel research that will accelerate discoveries to improve outcomes for people living with metastatic breast cancer.
The Founder’s Fund has two components: AURORA EU, based in Brussels and conducted under the oversight of Martine Piccart-Gebhart and AURORA US, coordinated by Nancy Davidson with clinical aspects being administered by Antonio Wolff through his leadership of the Translational Breast Cancer Research Consortium (TBCRC).
The objective of AURORA EU is to conduct precise molecular analyses of primary and metastatic breast cancer samples to better understand the evolution of metastasis and the mechanisms of drug resistance that allow tumors to grow and spread. The consortium includes 11 collaborative research groups and 2 independent sites across 14 countries throughout Europe. Over 80 clinical sites will participate with 34 already active. In total, at least 1000 women and men with metastatic breast cancer will be included. Tumor samples, blood, serum, and plasma samples will be used by the investigators to identify major cancer related genes driving metastasis and blood-based biomarkers that can be used as a non-invasive test (instead of a biopsy) to determine tumor progression and response to treatment. These efforts will lead to more efficient clinical trials and better management of metastatic breast cancer based on tumor genomics. The biospecimens collected will provide a valuable resource for future translational studies.
AURORA US utilizes the extensive clinical trial infrastructure of the TBCRC for clinical trial development and molecular and pathological evaluation of metastatic breast cancer samples. The TBCRC is a model clinical trials program uniting the efforts of laboratory scientists and clinical researchers focused on trials that integrate clinical and laboratory studies to accelerate advances in breast cancer care. The AURORA US efforts are being conducted by three integrated working groups that are focused on (i) retrospective analysis of primary and metastatic tumors and (ii) prospective clinical trial development. It is anticipated that 10 sites across the United States will participate in the retrospective and prospective trials. 26 samples have already been submitted for analysis to help determine the features that cause metastasis and/or resistance to treatment. Leading the various efforts of AURORA US are BCRF grantees, Charles Perou, Lisa Carey, Andrea Richardson and W. Fraser Symmans.
In a separate project, BCRF investigator Matthew Ellis is leading a team of 5 investigators at 4 universities to (i) develop an experimental model system that precisely mimics human breast metastases and (ii) an open access online database of metastases models. The team of researchers that include Michael Lewis (Baylor College of Medicine), Shunqiang Li (Washington University, St. Louis), Jorge Reis-Filho (Memorial Sloan Kettering Cancer Center) and Alana Welm (University of Utah, Huntsman Cancer Institute) will develop over 50 models of metastatic disease from patients. The team has already developed 36 models and matched primary metastasis pairs established in 3 cases with 2 more in development. Importantly, the models and data analysis will be made available to researchers for reanalysis and cross-study comparisons.
The creation of an open access database of metastasis models, the PDX cBioPortal, is being led by BCRF investigator, Dr. Jorge Reis-Filho. It is built on the backbone of the MSKCC cBioPortal, which has become a worldwide reference tool for visualization and reanalysis of molecular data. The PDX cBioPortal, will be a one stop shop for the visualization and re-analysis of genomics data derived from PDX models of breast cancer from AURORA US and other researchers around the world. This portal will provide a wealth of information for new discoveries to be made and foster new collaborations to be established. The PDX cBioPortal is expected to go live by the end of October 2016.
The talent and dedication of the international experts involved assure the success of the Evelyn H. Lauder Founder’s Fund Project. Many world-renowned investigators are involved in every step. Thousands of cases of metastatic breast cancer will be thoroughly analyzed and the data and many of the specimens will be available for future research by investigators around the globe.
None of this would be possible without the generous support of BCRF donors. With your help we honor Mrs. Lauder’s vision in the best way possible: research to defeat disease.