Dr Lipsyc-Sharf on the Use of the Signatera Genome Assay in Breast Cancer Management

“We hope the real-world data will advance simultaneously with the prospective investigational trial [data], so we can learn the best ways to use this test, how often we should be getting this test, and how we can escalate and de-escalate [treatment] based on the results.”

Marla D. Lipsyc-Sharf, MD, a breast medical oncologist with UCLA Health, discussed the clinical role of the Signatera Genome Test in Breast Cancer for circulating tumor DNA (ctDNA) surveillance in patients with breast cancer.

Lipsyc-Sharf began by highlighting technological shifts in the Signatera assay repertoire, noting that although former versions were based on whole-exome sequencing, the development of a whole-genome sequencing–based assay has provided a more sensitive tool for detecting minimal residual disease across breast cancer and other malignancies. She explained that this personalized ctDNA test involves Natera performing whole genome sequencing directly on a patient’s tumor tissue to identify a unique set of genomic alterations. From these data, a targeted, tailored assay is developed to monitor for these alterations within the patient’s plasma over time, allowing oncologists to track the molecular signature of the cancer through routine blood draws.

A critical aspect of this advancement of the Signatera Genome test is its ability to reach a sensitivity threshold below 1 part per million, which Lipsyc-Sharf characterized as a major milestone in identifying breast cancer recurrence at the earliest possible stage. She emphasized that such high sensitivity is vital in breast cancer care due to the long latent periods that often occur between a patient’s initial diagnosis and the eventual emergence of a recurrence.

Currently, the Signatera Genome assay is being used in routine practice across the US and globally, Lipsyc-Sharf stated. This ultrasensitive technology is also being integrated into multiple ongoing clinical trials, she added. Lipsyc-Sharf noted that this research may allow real-world data and prospective trial data to advance in tandem, providing oncologists with the necessary evidence to determine the optimal frequency of testing. Ultimately, she concluded that these insights are expected to guide critical clinical decisions, such as when to escalate or de-escalate treatment based on the presence or absence of molecularly detected disease.