Over the course of my BRCA Journal posts, I have highlighted emerging technologies and highly tailored therapeutics. These exciting innovations have the potential to change the way cancer is studied and treated. While they advance the trend of personalized medicine, they currently only benefit a small portion of cancer patients. Existing treatments have proven highly effective for many people, particularly in the case of breast cancer. By utilizing existing data on treatment outcomes, however, we can learn much more about who benefits from these widespread treatment options. This information can provide us with quicker and possibly cheaper solutions than highly personalized and experimental therapies. In order to learn about research that is helping us better understand the potential of current treatments, I spoke with BRCA Foundation-supported investigator, Dr. Allison Kurian about her research and passion in helping women with breast cancer.
Dr. Kurian is an Associate Professor of Medicine and of Health Research and Policy at Stanford University School of Medicine and Director of the Stanford Women’s Clinical Cancer Genetics Program. Her research focuses on understanding breast and ovarian cancer risk, and on developing tools to improve early cancer detection, risk reduction, and education. Dr. Kurian initially discussed some of her research in an episode of the BRCA Foundation’s Positive Perspectives podcast. In the podcast, she described the use of observational studies in her research, which utilize real world outcomes to cancer treatments as opposed to outcomes of highly controlled clinical trials. As clinical trial data only represents outcomes for a small sample of people, they often do not represent how a treatment will affect the general population.
I delved into one of Dr. Kurian’s studies in my post, Genetic Testing: A Breakdown of One Study Examining Clinical-Decision Making, which utilized observational studies to analyze clinical treatment in the context of genetic status. The study data emerged from the Surveillance, Epidemiology, and End Results (SEER) Program, which uses many cancer registries across the United States to compile data on cancer incidence and survival rates. During our conversation, Dr. Kurian explained that analysis of cancer registry data allows us to gain insight into trends occurring at the population level, rather than on an individual basis, and can teach us about the general effectiveness of treatments. Some of Dr. Kurian’s recent research is also in collaboration with genetic testing companies, which allows her to associate cancer outcome data with genetic testing data. The combination of these two sets of data will be able to inform us about the effectiveness of certain treatments with even greater resolution.
According to Dr. Kurian, information gained from these studies will, importantly, also inform us about the implementation of new educational tools. The BRCA1 and BRCA2 genes, which I focused on in my posts, represent a unique example of our understanding of cancer susceptibility. BRCA1 and BRCA2 are two of the best-characterized genes in terms of their cancer risk and treatment options. The understanding of breast cancer risk associated with mutations in these genes and the need for genetic testing is significantly greater within the general public than it is for other cancers and cancer-susceptibility genes.
The level and distribution of knowledge about other BRCA1- and BRCA2- associated cancers among various populations also drastically differs from that of breast cancer risk. Dr. Kurian’s research recently indicated that while there are no major racial differences in women who seek genetic testing for breast cancer, these disparities exist for testing in ovarian cancer. She is aiming to understand why disparities in genetic testing exist so tools to remedy this problem may be implemented.
While it is still early in the process of understanding these issues, Dr. Kurian noted steps are already being taken to increase education about cancer risk and genetic testing. She mentioned that web-based decision-making tools are being introduced and efforts to increase the reach of genetic counselors are being implemented. The last few decades have brought an expansion of the role of genetic counselors. As genetic testing becomes more accessible, the volume of people in need of counseling is exceeding the capacity of genetic counselors. Some ways in which genetic counselors are expanding their reach include telephone-based counseling and class-based education and counseling. Developing additional tools that increase the educational reach of genetic counselors will be very important as more people opt for genetic testing.
While increasing rates of genetic testing is important, I wondered what the greatest hurdle for implementing effective cancer treatments would be. Breast cancer treatment has improved dramatically and has reduced mortality rates to approximately 15%. While this improvement in treatment is considered a success, there is still a long way to go in advancing treatment for other cancers, including breast cancer.
Targeted cancer treatments like CAR T-cell therapy and PARP inhibitors are also pushing the field of personalized therapeutics in an exciting direction. While immunotherapy treatments have the potential to be tailored to any type of cancer, they currently only treat a small percentage of patients. Additionally, PARP inhibitors have paved a new path for targeted treatment cancers with known genetic deficiencies through the mechanism of synthetic lethality that I explained in The Power of PARP Inhibition. I wondered, however, if further development of these treatments would be more beneficial for improving outcomes for the majority of patients compared to better implementation of current therapies.
I asked Dr. Kurian her opinion about whether advancing innovative treatment options or better implementation of current treatments has more potential for improving outcomes in the future. She thought both ends of the spectrum will be important. With regard to breast cancer, where a number of successful treatments already exist, one of the major roadblocks is the implementation of treatments such as chemotherapy and mastectomy. Dr. Kurian referred to the Trial Assigning IndividuaLized Options for Treatment (Rx) (TailorX) study as an example of efforts to improve implementation. The TailorX study recently published results indicating many women with early-stage breast cancer do not benefit from chemotherapy. By analyzing how breast cancers with differing genetic properties responded to common treatments including hormone therapy and chemotherapy, researchers determined that many women receive unnecessary treatments. This suggests similar trends are true for the treatment of other types of cancer.
That said, one major roadblock lies in the development of therapies for other cancers. Successful treatment of some cancers may greatly benefit from adaptable treatments such as CAR T-cell therapy. Currently, however, there are hurdles preventing the application of these therapies to all types of cancers, some of which I detailed in CAR T Cell Therapy: Engineering the Immune System to Fight Cancer. While more research in the laboratory may help overcome these barrier, Dr. Kurian pointed out that genetic data analysis provides us with the capability to devise smarter clinical trials, which may also make treatments more effective or applicable to a wider variety of patients.
Our discussion of how we can overcome these barriers covered multiple aspects of how analysis of genetic testing and cancer treatments provide useful information for improving outcomes. These range from improving and expanding education of cancer risk and the importance of genetic testing to improving implementation of treatments. I delved into many of these topics in my previous posts through discussion of the research and scientific concepts behind both the genetic and therapeutic aspects of cancer. My posts spanned the microscopic level, in which I explained the biological processes that BRCA1 and BRCA2 mediate, and the analysis of trends in clinical outcomes on a macroscopic scale. My conversation with Dr. Kurian left me hopeful that as research continues at both the microscopic and macroscopic levels, both the development and implementation of treatments will lead to improved outcomes across the spectrum of cancers.
