The presence of circulating tumor DNA (ctDNA) in early-stage, triple-negative breast cancer helped predict the risk of recurrence in women who had undergone surgery after neoadjuvant chemotherapy, according to data presented at the 2019 San Antonio Breast Cancer Symposium (SABCS).
“For patients who have triple-negative breast cancer with residual disease, the risk of recurrence is exceptionally high,” said the study’s senior author, Bryan P. Schneider, MD, professor of Medicine and Medical and Molecular Genetics at Indiana University School of Medicine. “Novel therapies and technologies are critical, including those that can potentially predict the risk of relapse.”
ctDNA, or tumor DNA derived from plasma, is being explored as a way detect cancer, guide treatment, and monitor patients during remission. The presence of ctDNA can signal the presence of cancer.
“If you are a woman with triple-negative breast cancer, after surgery you are in a constant ‘watch and wait’ scenario, in fear of the cancer coming back,” said the study’s first author, Milan Radovich, PhD, associate professor of Surgery and Medical and Molecular Genetics at Indiana University School of Medicine. “We know that a significant proportion of these women will have disease relapse after surgery. ctDNA is a powerful tool to be able to predict recurrence and could help us identify the best ways to manage care for women diagnosed with this disease.”
Conversely, the authors – researchers in the Indiana University Melvin and Bren Simon Cancer Center and the Vera Bradley Foundation Center for Breast Cancer Research – said that superior outcomes for those who did not have ctDNA could potentially set the stage for clinical studies evaluating the ability to reduce post-surgical treatment for these patients.
In this study, the authors and colleagues analyzed plasma samples that had been collected from patients enrolled in the BRE12-158 clinical trial, which studied genomic-directed therapy versus physician’s choice of treatment after preoperative chemotherapy in patients with triple-negative breast cancer. The trial enrolled 196 women, and ctDNA was sequenced in 142 patients using the FoundationOne Liquid Test.
Mutated ctDNA was detected in 90 of the patients, representing 63 percent. TP53 was the most commonly mutated gene, followed by others that are commonly associated with breast cancer.
At 17.2 months of follow-up, detection of ctDNA was significantly associated with inferior distant disease-free survival (DDFS). Patients with ctDNA had a median DDFS of 32.5 months, while the patients without ctDNA had not reached the median.
At 24 months, the DDFS probability was 56 percent in ctDNA-positive patients, compared with 81 percent in ctDNA-negative patients. In multivariate analysis, when the researchers controlled for factors including residual cancer burden; tumor size, grade, and stage; age; and race, detection of ctDNA remained independently associated with inferior DDFS. Overall, ctDNA-positive patients were three times as likely to have distant disease recurrence than ctDNA-negative patients.
Detection of ctDNA was also associated with inferior overall survival; ctDNA-positive patients had 4.1 times increased risk of death compared with ctDNA-negative patients.
“This study establishes that triple-negative breast cancer patients who have ctDNA after neoadjuvant therapy have a higher risk of recurrence,” Schneider said. “This may set the stage for further clinical trials for these high-risk patients, evaluating novel ways to prevent recurrence.”
The authors said a clinical trial expected to begin in 2020 will further examine ctDNA’s potential in guiding therapy for those patients who are at high risk of recurrence. They also noted that sequencing technology is developing rapidly and will likely become more sensitive and more specific over time.
Schneider and Radovich said one limitation of this study is that the follow-up period is still ongoing, so results may change in future analysis.
