In this JCO Precision Oncology Article Insights episode, Mitchell Elliot provides a summary on "Serial Postoperative Circulating Tumor DNA Assessment Has Strong Prognostic Value During Long-Term Follow-Up in Patients With Breast Cancer" by Shaw, et al published on May 1st, 2024.

TRANSCRIPT

The guest on this podcast episode has no disclosures to declare. 

Mitchell Elliott: Hello and welcome to the JCO Precision Oncology Article Insights. I'm your host, Mitchell Elliott, an ASCO Journal editorial fellow. Today I will be providing a summary of the article titled, “Serial Postoperative Circulating Tumor DNA Assessment Has Strong Prognostic Value During Long Term Follow up in Patients with Breast Cancer,” by Dr. Jacqueline Shaw and colleagues. 

Circulating tumor DNA is shed readily into the peripheral blood by tumors. ctDNA makes up a small fraction of the total cell free DNA in the peripheral blood and can be detected using highly sensitive assays. ctDNA assays can be tumor-informed where blood samples are tested for the presence of tumor specific mutations, which are selected by sequencing the primary tumor, so the panels are patient specific. Tumor agnostic assays also exist which are typically looking for the presence of cancer driver mutations or cancer derived methylation signals, which are not patient specific but rather cancer specific. Several retrospective analyses of clinical trials and cohorts have demonstrated that the identification of ctDNA in patients in follow-up can predict relapse in breast cancer, lung cancer, and colon cancer. Personalized tumor informed assays have demonstrated high technical specificity, but to date there is no gold standard assay identified and no direct comparison between all of the available assays. While the literature to date has demonstrated that identification of ctDNA prior to clinical relapse is possible, no study has demonstrated that it improves patient outcomes. 

In this specific study, the authors evaluated the Signatera assay, a tumor informed assay based on whole exome sequencing, enabling the design of personalized panels for up to 16 tumor specific variants detected via multiplex PCR next generation sequencing. This was evaluated in the exploratory breast lead interval study or EBLIS, which is a study based out of the United Kingdom. EBLIS is a multicenter prospective cohort study funded by Cancer Research UK and the National Institute of Health Research that opened for recruitment in 2012. This was a retrospective analysis so no results were directly shared with patients or physicians. Patients were eligible if they were 18 years or older, had histologically confirmed breast cancer and must have completed all surgery and chemotherapy within three years of entry into the study. They had to have an adjuvant online risk relapse at greater than 65% or mortality of greater than 50% at 10 years, which defines a very high risk subgroup for study enrollment. 

The results of this study and the baseline patient characteristics reflected the predefined clinical risk. The majority received neoadjuvant or adjuvant chemotherapy. Most patients were diagnosed with invasive ductal carcinoma and were staged 2b to 3c. There were 156 patients identified from this cohort after 28 had insufficient DNA and 3 had unsuccessful whole exome sequencing, which are required for the assay generation. Of the 156 patients, there were 1136 plasma time points evaluated. Of the 1136 plasma time points, ctDNA was identified in 46, which represents approximately 4% of the total time points in this high risk cohort. 34 patients have experienced disease relapse, including 22 with hormone receptor positive HER2 negative disease, three with hormone receptor positive HER2 positive disease, seven with triple negative breast cancer, and two with hormone receptor negative HER2 positive disease. ctDNA was detected in 30 of the 34 patients who had a subsequent relapse with a patient specific sensitivi

Id. d’épisode : 1000657156952

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Date de publication : 29/5/2024 à 13:00:00