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Top Line: Does detection of circulating tumor DNA predict early breast cancer relapse?
The Study: With the KATHERINE (T-DM1 for HER2+) and CREATE-X (capecitabine for triple negative) trials, we are seeing the beginnings of adaptive therapy for breast cancer. The decision point is the presence of persistent gross disease after neoadjuvant chemotherapy. But it’s still common to hear patients ask in clinic, “How will I know if the cancer comes back?” For now, our answer isn’t very sophisticated. This study reports data from two prospective ctDNA collection studies in women with breast cancer. They had baseline ctDNA measured before chemotherapy and then every 3 months for 1 year and 6 months for 5 years. How exactly do you detect ctDNA, you say? Well, they ran breast cancer driver gene panels on the breast biopsy samples looking for somatic mutations in those driver genes. In total, 101 patients had driver mutations that were then tracked in plasma samples. Over half of patients had detectable ctDNA before treatment and 16% developed molecular residual disease (MRD) after treatment. Patients with MRD (and even those with detectable ctDNA upfront) had significantly shorter progression-free survival. In fact, over 80% of all relapses were preceded by MRD at a median of over 10 months.
TBL: A large proportion of breast cancer relapse could be preceded by the detection of circulating tumor DNA by as much as 10 months--opening the door to ongoing therapeutic trials. | Garcia-Murillas, JAMA Oncol 2019