Genes Hold Key to Individualized Therapies for Breast Cancer
At the Podium – November 2006
By Matthew Ellis, MB, BChir, PhD
The prognosis for patients with breast cancer has improved greatly in recent years due to advances in treatment modalities and our understanding of the disease itself. Today, we know that breast cancer is actually several different tumor types with distinct clinical characteristics requiring different treatment approaches. For example, the effectiveness of certain chemotherapy regimens appears to vary greatly according to tumor type.
A consequence of this variable response to treatment is that breast cancer patients may face worrisome “what if” scenarios regarding their care. What if I decide against this therapy because of potentially severe side effects, but in the long run it could have eliminated the disease? What if I sacrifice my quality of life for six months, but the therapy is really no help in fighting my particular cancer?
These troubling questions arise because current treatment recommendations do not fully take into account the reality that every breast cancer is distinct. This uniqueness stems from the almost infinite number of ways the genetic structure of each tumor can be re-coded to “solve” the problem of how to grow abnormally, how to produce a blood supply, how to spread beyond the organ of origin and how to evade treatment. Despite this complexity, tumors do cluster into five to six subtypes.
A means to efficiently determine the key abnormalities that are associated with these different subtypes would be a powerful tool. After undergoing surgery, the patient with a good prognosis could know with certainty that additional expensive, toxic treatments were unnecessary. Alternatively, a patient could embark on the correct chemotherapy, antibody therapy and long-term endocrine therapies knowing that treatment to eradicate cancer cells that have embedded themselves in other organs around her body was absolutely necessary.
Developing a method to efficiently subtype breast cancer using patterns of gene activity to assign tumor categories is the goal of an $8.5 million grant from the National Cancer Institute’s Specialized Program for the Evaluation of Cancer Signatures (SPECS). Through this grant, my colleagues and I at Washington University School of Medicine – along with collaborating institutions in the United States and Canada – are working to develop a new diagnostic and treatment paradigm. Our goal is to use tumor gene activity measurements called real-time quantitative polymerase reaction (qPCR) to identify the different signatures displayed in each breast cancer subtype. In essence, through bioinformatics, we are striving to “bar code” breast cancers in order to distinguish between the different subtypes – some associated with good prognosis, some with bad – which will give us clearer insight into the types of treatment that will provide the best results for each patient.
A key advantage of the qPCR methodology is that it allows retrospective validation, a kind of “cold case” detective work. We are analyzing gene activity in breast tumor tissues banked from patients diagnosed 10 to 15 years ago. By testing the activity of a set of 100 carefully selected genes in each tumor, we should be able to definitively assign genetic signatures to accurately establish the breast tumor subtype. Since patients in the study already have undergone treatment and extensive follow-up, we can compare their signatures to their treatment protocols, quickly resolving the question of which therapies work best for each cancer subtype.
Despite the fact that the complexity of this work is like a New York Times crossword puzzle magnified many times, we are resolute in achieving our long-term goal – developing a broadly applicable subtyping test for all patients with early stage breast cancer. This will be powerful knowledge and a major step forward in the treatment of breast cancer, allowing us to provide patients with highly effective, personalized therapy that improves outcomes and preserves quality of life.
This exciting new technology is not a pipe dream. We are confident that in a short while patients no longer will have to deal with the uncertainty and distress of answering difficult “what if” questions as they undergo breast cancer treatment.