Approximately 140,000 individuals in the United States are diagnosed with metastatic breast cancer annually. Each year, 40,000 people die from the disease.
“Our goal is to understand the biology of metastatic breast cancer and find new treatment strategies,” Nikhil Wagle, MD, of the Dana-Farber Cancer Institute told the ASCO Daily News during the “Cancer Prevention, Genetics, and Epidemiology” Poster Discussion Session on June 6. “One of the ways we can do this is by creating a database of clinical information that is linked to genomic information for patients with metastatic breast cancer and share that with the world so that lots of researchers can use it to make discoveries.”
Dr. Nikhil Wagle
To increase the volume of tumor samples from women with this disease, the Metastatic Breast Cancer Project was designed to capture information from the vast majority of metastatic breast cancer tumors that are not available for research, largely because most patients are cared for in community settings where genomics studies are not conducted.
The MBCP website was developed to allow patients with metastatic breast cancer across the country to participate. Enrolled patients complete a 16-question self-reported survey about their cancer and treatments (LBA1519). Consented patients are sent a saliva collection kit and asked to mail back a saliva sample, which is used to extract germline DNA. Patients also consent to releasing medical records and tumor biopsy. Whole exome and transcriptome sequencing is performed on tumor and germline. Clinically annotated genomic data are used to identify mechanisms of response and resistance to therapies.
Rapid Enrollment, Extraordinary Responders Identified
Since October 2015, more than 2,000 individuals registered with the MBCP; 1,200 of whom have consented to genetic sequencing. As of April 2016, 1,730 patient-reported responses have been received, and 500 saliva kits have been returned with saliva sequencing completed. Approximately 100 medical record cases have been received.
To date, the median age was 53 years (range 24 to 91). MBCP has identified groups of rare or traditionally underrepresented patients. For example, 613 patients (36%) were diagnosed with de novo MBC; 591 (35%) were diagnosed before age 40. 81% of patients had HR-positive tumors, 61% had HER2-positive disease, 11% had triple-negative disease, and 7% had inflammatory breast cancer.
The registry has also identified 946 patients with an “extraordinary response” to a therapy. For example, 117 reported long and/or extraordinary responses to capecitabine; 63 to platinums, and 36 to everolimus. Approximately 100 patients reported having metastatic breast cancer for longer than 10 years, and 632 reported being on a therapy for longer than 2 years.
A Paradigm-Shifting Approach
“We think this approach is paradigm-shifting,” Dr. Wagle said. “It’s a big database where we can hone in on the outliers, such those with extraordinary responses.” He commented that the MBCP subpopulation study is essential to finding answers that will help more people faster and advance precision medicine. Genomic analysis of patients with extraordinary responses and with de novo metastatic breast cancer are underway. The MBCP will be initiating a blood biopsy program this summer to allow for analysis of cell-free DNA. The database is shared widely with researchers. Study updates and discoveries are shared with participants regularly.
“The biggest strength of this kind of research is that it mimics the real world, and it’s a population-based study, which means there is strength in numbers,” Sumithra J. Mandrekar, PhD, of the Mayo Clinic, told the ASCO Daily News when discussing the MBCPinitiative. “You can pick up some rare prevalences, rare phenomenon, or rare patterns that you don’t necessarily get if it’s a prospectively planned clinical trial.”
She cautioned researchers that direct-to-patient registries like this can create an unusual self-selected population base. “It’s very hard to understand what mix of patients will be enrolled on these kinds of registries,” she said. “You just want to make sure you collect key data in a consistent qualitative manner so you do a good job of separating out the noise.”