Gazing Over the Horizon at Cancer Treatment
“The greatest curse is to be stuck in one’s own time; the greatest power is to see beyond its horizon.”
From the book, The Weight of Ink by Rachel Kadish
It is true that all cancers are in some way genetic, whether by germline (mutations passed down from a parent), sporadic (mutations which develop spontaneously and not passed down from a parent), or by an epigenetic event (a change in gene expression not caused by a change in the underlying DNA). I certainly believe this to be the case. We initially saw the benefits of germline mutation (e.g., BRCA 1 and 2) as well as testing tumor genomics (e.g., Oncotype Dx, MammaPrint). Both assisted in risk assessment and the latter in treatment selection. Much of the benefit of genetic testing comes from a more accurate assessment of risk reduction or the use of chemotherapy. It is also undeniable that the identification of oncogenes such as Her2 has led to the development of new biological treatment options. Unfortunately, biological therapies for breast cancer have not been highly successful when given as monotherapy, all appearing to require more standard courses of multidrug chemotherapy to maximize success.
As these thoughts creep inexorably to gain a peek beyond the horizon, one might conclude that since all cancers are genetic in one way or another, it should follow that eventually, cancer treatment should proceed along a path that takes advantage of this genetic knowledge. It is only in recent years that we began to catch a glimpse of that distant light. At least part of the answer lies in identifying single nucleotide polymorphisms (SNP, also called snips). A SNP is a type of genetic variation that occurs when a single nucleotide (A, C, G, or T) in a specific location in the gene’s DNA is altered in a significant proportion of a population. SNPs can be used to study the genetic basis of disease. For example, SNPs have been used to identify genes associated with cancer, heart disease, and other diseases. SNPs can also be used to develop new drugs and treatments for diseases.
SNP tests are now commercially available to assess breast cancer risk for high-risk but germline mutation-negative patients. Both companies use nearly 100 SNPs plus the Tyrer-Cuzick risk model (TC) to arrive at their risk score. Equally exciting data was presented at the 2019 San Antonio Breast Cancer Symposium. Hughes et al., from Myriad Genetics Laboratory, presented validated data demonstrating the use of SNPs plus TC to assess risk in women testing positive for five of the more common germline mutations. Intuitively, we’ve always known that different mutations in high-risk genes carry other cancer risks. This data from Myriad finally confirms this.
Looking ahead, genetics will continue to play a crucial role beyond simply assessing risk and treating known oncogenes. In my view, the ultimate goal is to develop genetic treatments for existing cancers. If all cancers are indeed genetic, it makes sense to me that genetics should be the focus of treatment efforts. However, the fact that most patients with overexpressed HER-2 require multidrug chemotherapy and targeted biologics suggests there is still a long way to go before we reach this goal.
They gathered for the feast
They stab it with their steely knives
But they just can’t kill the beast
– Don Henley, Glenn Frey. “Hotel California.”
Dr. Alan Stolier, MD, FACS, clinical breast oncologist, shares his expert medical perspective with a series of educational and scientific articles.