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Research Worth Watching: Using DNA to Optimize Treatment and Reduce Collateral Damage

One major problem from much of our cancer therapy is the collateral damage. Not the side effects, such as nausea and vomiting or hair loss, which are typically transient but the long-term consequences of therapy, such as chemobrain and neuropathy.  Some of these changes will resolve and many will not. In my case, it’s been six years since I received chemotherapy to treat my leukemia, and my sense of taste and smell still haven’t returned.

We’ve long known that not all women diagnosed with breast cancer needed chemotherapy. But we didn’t know who. The OncotypeDX test was developed to help women with early-stage, hormone-sensitive breast cancer answer that question. It allowed patients who had a low score to feel confident that they could skip chemotherapy, and its collateral damage. For those who had a high score, the test added additional information about their tumor that suggested the benefits of chemotherapy outweighed the side effects. But for those in the middle, there was a big question mark. It was unclear for this group whether chemo was necessary, or not. They were left in limbo.

Anyone who knows me know my mantra: the reason we call it research is because we have to keep searching for the right answer.  At any one time we are only making our best guess at the moment.”

To help those women in the middle get answers they needed, a research team sponsored by the National Cancer Institute, launched a clinical trial called TAILORx. The lowest-risk women had hormone therapy; women in the middle, with scores between 11 and 27 were randomized to hormone therapy alone or hormone therapy and chemotherapy, and high scoring women had chemotherapy and hormone therapy. In 2015, the researchers reported that after five years, the women in the low-scoring group that showed overall survival rates of 98 percent—affirming the test’s effectiveness.

At the 2018 American Society for Clinical Oncology (ASCO) meeting, we learned the results for those women in the middle: hormone therapy was as effective as hormone therapy and chemotherapy. Among this group of women, after 9 years of follow-up, the overall survival rates were 93.9 percent for the women who get hormone therapy alone and 93.8 percent for those who had chemo and hormone therapy. The study also looked at invasive disease-free survival—a measure of how many women had a recurrence of invasive breast cancer. At nine years, 83.3 percent of the women who had hormone therapy alone had not had an invasive recurrence compared to 84.3 percent of the group that had hormone therapy and chemotherapy. Since hormone therapy causes much less collateral damage, this was good news. 

Speaking of collateral damage—it was great to see that there was some research on this topic at the meeting. Over the past few years, researchers have begun investigating how we can use precision medicine techniques to not only identify the best drug to treat a patient’s tumor but also the drug that will cause the least collateral damage in that patient. This is an important area of research—and I’m excited to see it taking place. How great would it be if your doctor could do a blood or saliva test to see if you if you are at risk of getting a particular side effect from a specific treatment so they could offer you another option?

At ASCO, I heard about two research studies that are trying to move this area of research forward. The first study was on young men with testicular cancer. For many of these patients, hearing loss from treatment is a significant problem. The study for correlations between certain SNPs (single nucleotide polymorphisms)—variations in a person’s DNA—and hearing loss. They found that young men with a certain SNP (pronounced “snip”) were much more likely to develop significant hearing loss than men who did not have that SNP. The next step will be to figure out whether there may be an alternative drug or dose that could be used in men who have that SNP to help keep them from experiencing hearing loss.

In a second study, researchers looked to see if they could identify SNPs that could predict which women and men were more likely to have sustained skin changes after radiation. These researchers were also able to identify SNPs that correlated with significant skin radiation changes.

It is exciting to see research that expands the definition of personalized from what’s the best treatment to eradicate the tumor to what’s the best way to eradicate the tumor and reduce collateral damage. This is the type of precision we need!