Spotlight on Science: Genetics and Side Effects – Dr. Bryan Schneider

One of the most promising new trends in cancer science is the search for personalized medicines – finding treatments that are right for individual patients and identifying those that might not work based on a patient’s genetic makeup and medical history.  In 2009, Komen provided $6 million in research funding to an Indiana University team looking for genetic markers that could predict which patients would respond to a new experimental drug. Soon, the research from this Komen Promise Grant opened promising new doors about genetics and treatment side effects.

The team was led by Indiana University’s Bryan Schneider, M.D. (one of our Komen Scholars) and David Flockhart, M.D., Ph.D., along with patient advocate Mary Lou Smith, Esq., co-founder of Research Advocacy Network. We spoke to Dr. Schneider about this grant to learn more.

Komen: Dr. Schneider, thanks so much for your time and for the important work you do in the fight against breast cancer.  Could you walk us through the ins and outs of your Komen PromiseDr. Bryan Schneider Quote Grant?

Schneider: Of course. The main goal was to deliver better personalized medicine. We did this by leveraging two large randomized trials (involving about 5,000 patients from around the globe), comparing an experimental drug (bevacizumab, or Avastin) to standard treatment with chemotherapy.

Our goal was to use genetic data that we collected from patients to identify those individuals who would benefit from treatment. Along the way, we realized that we also ended up with a great deal of detailed information about the side effects patients suffered from – regardless of which drug they were given.

Komen: How can this study change medicine now?

Schneider: I think we, as researchers, do a great job of determining which drugs will work for which patients, but often overlook serious treatment effects, such as peripheral neuropathy or congestive heart failure. I can tell you from my own experience that some patients fear the word “chemo” more than the word “cancer.” If we can understand who is at increased risk for these life-altering side effects, it could impact how patients receive therapy, or if maybe an alternative therapy or foregoing therapy altogether is a better option.

For now, the most important takeaway is that we will be able to tailor our therapies not just to those we think will benefit, but also to avoid therapies in patients we think may suffer.

Komen: What did you learn about specific side effects?

Schneider: Well, we learned a great deal about this one common side effect called peripheral neuropathy, or inflammation of the nerves. It results in a number of symptoms like numbness or tingling, and it can make seemingly simple tasks (like brushing your teeth) really challenging. And even worse – it can be irreversible.

Our study revealed one biomarker in particular in patients who were more likely to develop this side effect, which could be extremely important information when patients are making treatment decisions.

We also found that African-Americans are much more likely to experience neuropathy. We actually found a gene specific to this population that could indicate which individuals are at increased risk – again, vital information for treatment decisions.

Another serious side effect we discovered a great deal about was congestive heart failure. It’s more rare, but absolutely terrible if it does happen. We were able to identify a biomarker that indicates increased risk of this side effect as well.

Komen: You clearly had patients’ needs at the center of your work. Can you tell us about the role patient advocates played in this study?

Schneider: Having patient advocates on the grant is an amazing asset. They not only help develop the project aims, but keep us grounded about what matters to patients. For example, our initial goal was to identify who might benefit from bevacizumab. Unfortunately, we found that this particular drug probably won’t be important for breast cancer. But, our patient advocates pointed out that we could still use the amazing genetic and treatment data we had gathered to ask other important and meaningful questions, such as who might suffer the most from treatment side effects, and get valuable information for patients.

Komen:  What do you want people to walk away knowing about Komen and this Promise Grant?

Schneider:  None of this work would have happened without Komen’s funding. Komen is one of the few organizations that recognize that it’s not all about discoveries at the molecular level.  The more important question is:  how will we take these findings and make it relevant to patients?  Komen has been amazing at supporting work like this Promise Grant which is directly focused on making an impact in patients’ lives.

As far as what’s next – honestly, we have a long way to go.  I wish we could say we’ve cured cancer and minimized all side effects, but we still have more work to do in terms of understanding how these biomarkers affect treatment regimens, and how we can take this to the patient and into clinics.

Until we get there, we’ll continue to need support from organizations like Komen and individuals everywhere who help make this work possible.