Triple negative breast cancer (TNBC) is a devastating form of breast cancer that has left researchers scrambling to find weapons against its high recurrence rate, lower survival rate than other forms of the disease and confusion about how to best treat it—and Indiana is leading the charge. As a nerve center for TNBC research, the Indiana University School of Medicine (IUSM) recently wrapped a clinical trial giving doctors nationwide the most clarity yet about how to treat it. The discoveries are opening the door to a new trial launching now with a laser focus on the highest risk women and uncovering their path to survival.
TNBC is especially difficult to treat, because the cancer cells lack the three common receptors that open the door to methods to kill them. The aggressive cancer accounts for about one in five breast cancers in the U.S. and has a high rate of recurrence, which is often fatal.
The standard treatment is chemotherapy while the tumor is still in the breast, followed by surgery to remove the cancer. Despite enduring this grueling treatment path, about half to two-thirds of these women will have cancer left behind, which causes their survival rate to plummet to 50%.
“This is a group of patients that has been through a lot in terms of chemo and surgery, but then are told by their treating oncologist you still have about a 50/50 chance of this recurring and probably claiming your life,” says IUSM Vera Bradley Chair of Oncology Dr. Bryan Schneider. “This is the population [my research team] and this trial has focused on to try to improve outcomes.”
Schneider’s most recent findings from the clinical trial are recognized as highly impactful in the field and were recently published in the prominent Journal of Clinical Oncology. In addition to leading the study, IU also had the highest enrollment of patients among study sites throughout the U.S.
“We embarked on this trial in 2014, and at that time, the standard of care for that population was no therapy,” says Schneider, who was the principal investigator for BRE12-158. “Talk about a tough situation, telling a patient she has a 50/50 chance of recurrence, and by the way, we don’t really have any therapy for you.”
The trial was designed to see if, by using cutting edge precision medicine, a weakness or vulnerability in the tumor could be identified, and doctors could use some sort of targeted drug to improve the cure rate. The other half of patients would not use precision medicine (a “non-guided approach”) and instead do the “treatment of physician’s choice.”
While the trial was still underway, two new drugs arrived on the market to treat TNBC, including a chemotherapy pill called capecitabine. The completion of the trial revealed that, surprisingly, the targeted approach did not beat the standard approach, which now included capecitabine.
“[The trial] gave validation that using some sort of therapy would indeed improve outcomes in this population. Interestingly, if you also look at the group of patients receiving targeted therapy, that also improved outcomes, versus no therapy,” says Schneider. “So it set the stage to say that doing some sort of therapy in this setting is absolutely critical, and we may not have yet mastered what that perfect combination is.”
Building on its legacy of TNBC research, Schneider is now launching a new trial called PERSEVERE that aims to further improve cure rates by leveraging another discovery Schneider made during the first trial. It involves circulating tumor DNA (ctDNA), “meaning the tumor has the ability to shed its blueprint in the bloodstream,” which can be detected by a blood test. Schneider found that, after chemotherapy and surgery, women who had ctDNA had an incredibly high risk of relapse, and patients who didn’t have ctDNA had a much better chance of being cured.
Five women are enrolled at IU’s trial site, and 20 more locations throughout the U.S. plan to join. With the new knowledge that ctDNA now provides, the trial will zero in on the women with the highest risk—those with ctDNA—and provide treatment that doctors now know is more effective, even if the perfect combination is still ambiguous.
“Part of getting better [cure rates] is understanding which group is really at risk,” says Schneider. “Understanding who is ctDNA positive and has a really, really high risk of recurrence, and focusing our efforts on that group, is going to allow us to best move the needle in an efficient way.”
While much work remains, Schneider is encouraged by the progress and hopeful about new treatment insights. Reflecting on when he started the earlier trial in 2017, Schneider says this population had no therapy options and a 50/50 chance of survival was the best that oncologists could offer patients.
“Now we have immunotherapy, we know the drug capecitabine works…so when you look at the number of tools that have evolved over a very short period of time, and improvements in outcome, to me this is incredibly exciting,” says Schneider. “Now that we’re starting to see momentum, that typically builds on itself. I will not be surprised at all if in the next couple of years, we continue to see marked improvements. I think this is a really exciting time for a really important disease.”
Schneider says, interestingly, the completed trial also showed that this aggressive form of cancer impacted black and white women equally, unlike other forms of breast cancer.