Personalized Circulating Tumor DNA Testing for Detection of Progression and Treatment Response Monitoring in Patients...

Despite varying treatment responses and vastly different clinicopathologic characteristics, invasive lobular carcinoma (ILC) is treated similar to other subtypes of breast cancer. Serial personalized and tumor-informed, circulating tumor DNA (ctDNA) analysis may enable real-time treatment monitoring in metastatic ILC (mILC).

In this retrospective analysis of real-world data, we analyzed ctDNA longitudinally in 66 patients with mILC using a clinically validated, personalized, tumor-informed 16-plex polymerase chain reaction-next generation sequencing assay (Signatera). We evaluated the predictive value on survival of a single ctDNA test result and correlated ctDNA detection rates and on-treatment ctDNA dynamics with disease status.

A total of 355 plasma samples were analyzed from 66 patients with mILC (median age at diagnosis, 62.6 years [range, 32.2-79.7 years]). On treatment, ctDNA dynamics correlated well with clinical response to treatment as assessed by imaging. Ninety-two percent (11 of 12) of patients with either ctDNA decrease (6 of 6) or no change in ctDNA levels (5 of 6) while on treatment showed clinical benefit from their prescribed regimen, whereas only 31% (4 of 13) of patients who showed an increase in their ctDNA had a clinical benefit on imaging. Finally, patients with a positive ctDNA test showed a greater probability of death compared with those with negative results, and the positive predictive value of ctDNA testing continued to increase exponentially with each positive result. Similarly, a negative ctDNA result was associated with 97% overall survival at 6 months and remained high (approximately 90%) at the 12-month follow-up.

Serial ctDNA testing in patients with mILC is feasible and may enable personalized surveillance and real-time therapeutic monitoring.