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Adding Liquid Biopsy to Breast Imaging Could Improve Accuracy


Including a DNA-methylation analysis could improve early diagnosis for BI-RADS 4 patients.

Liquid biopsy has been emerging in radiology in recent years as a non-invasive alternative to needle biopsy. Now, new evidence shows pairing it with mammography and breast ultrasound imaging could reduce false positives and help patients side-step unnecessary harms.

In a research letter published earlier this month in Molecular Cancer, investigators from China discussed the role that plasma cell-free DNA (cfDNA) could play in more accurately assessing breast lesions that are suspected of malignancy.

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“We performed the first blood-based whole-genome DNA methylation study for detecting early-stage breast cancer from benign tumors at single-based resolution, which suggests that combining the liquid biopsy with the traditional diagnostic imaging can improve the current clinical practice, by reducing the false-positive rate and avoiding unnecessary harms,” said the team led by Jiaqi Liu from the department of breast surgical oncology at the Chinese Academy of Medical Sciences and Peking Union Medical College.

Typically mammograms and ultrasounds are used to detect early-stage breast cancers in asymptomatic women, but they can also produce under-estimation or over-diagnosis. And, for women with BI-RADS 4, the variation for malignancy spans from 3 percent to 94 percent, the team said, potentially leading to unnecessary biopsies. This highlights the need for more accurate assessment tools.

Recently liquid biopsy combined with diagnostic imaging measures have demonstrated good results. Liu’s team wanted to see whether focusing on DNA methylation-based markers could lead to further improvements.

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For their study, they recruited 210 female patients with BI-RADS 4 who were biopsied after mammogram or ultrasound between April 1, 2019, and Aug. 31, 2019, at their Cancer Hospital. They collected 20 tumor samples for whole-genome bisulfite sequencing and examined them with two diagnostic models – one that relied of cfDNA methylation markers alone and one that combined those markers with imaging findings.

Based on their analysis, they determined that the combination technique worked better. The overall detection rate for the combined model for stage I, II, and III cancers was 93.3 percent, 100 percent, and 100 percent, respectively, and specificity was 73.5 percent for all stages. The area under the curve was 0.94.

In contrast, the area under the curve for the cfDNA methylation-only model discovery and validation cohorts were 0.89 and 0.81, respectively. For mammography and ultrasound, it was 0.78 to 0.79.

“This study demonstrated a better performance by this combination strategy, even successful at distinguishing malignant breast lesions from benign ones, especially in stage I and II,” the team said. “Clinical use of the combined approach might reduce the number of unnecessary biopsies in women with BI-RADS category 4 findings.”

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