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Liquid biopsy predictive of survival for metastatic triple-negative breast cancer
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Liquid biopsy feasibly predicted outcomes among patients with metastatic triple-negative breast cancer, study data showed.
“Traditionally, we would need to obtain a tissue biopsy to perform the whole-genome sequencing tests that could reveal potential DNA-level mutations driving a patient’s specific cancer. For metastatic breast cancer patients, however, tissue biopsy can be risky or painful,” Daniel Stover, MD, assistant professor of medicine at The Ohio State University Comprehensive Cancer Center, said in a press release. “Being able to do this type of genomic analysis from a simple blood draw allows us to get a picture of a patient’s specific cancer genomic characteristics in a less invasive way.”
The researchers conducted a retrospective cohort study of 164 patients with biopsy-proven metastatic triple-negative breast cancer. Stover and colleagues carried out genome-wide sequencing of cell-free DNA from plasma samples. All patients had received prior chemotherapy.
Stover and colleagues determined the tumor fraction of cell-free DNA for most patients (96.3%) and somatic copy number alterations for more than half (63.9%).
The researchers noted that primary and metastatic triple-negative breast cancers had “remarkably similar” copy number profiles and percent genome altered.
Certain somatic copy number alterations occurred more frequently for metastatic triple-negative breast cancers than for primary tumors or primary triple-negative breast cancer. These included chromosomal gains in NOTCH2, AKT2 and AKT3.
More than half of patients (64%) had a cell-free DNA tumor fraction of 10% or greater. This threshold was associated with significantly worse metastatic survival compared with patients who had a smaller tumor fraction (median, 6.4 months vs. 15.9 months; P < .001). This association remained significant independent of clinicopathologic factors (HR = 2.14; 95% CI, 1.4-3.8).
“These are exciting and important discoveries that could help us understand how a patient’s cancer is likely to progress and, ultimately, could have the potential to guide treatment decisions based on specific genomic risk factors,” Stover said.
The findings “could have important implications for patient management,” Andjelija Zivanovic Bujak, and Sarah-Jane Dawson, PhD, both of the Peter MacCallum Cancer Centre and University of Melbourne, wrote in an accompanying editorial.
“The era of comprehensive molecular characterization promises to pave the way forward,” they wrote. “In this regard, circulating tumor DNA profiling offers new opportunities to study underlying tumor genomic features while simultaneously providing prognostic information to unravel the complexity of this disease.” – by Andy Polhamus
Disclosures: Stover reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures. Bujak and Dawson report no relevant financial disclosures.
Perspective
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Cell-free DNA consists of DNA fragments shed from tumor cells and normal cells into the bloodstream. Circulating tumor DNA (ctDNA) is the fraction of cell-free DNA that originates from tumor cells. Commonly referred to as liquid biopsies, ctDNA represents a promising blood-based diagnostic. The clinical utility of ctDNA in the management of patients with breast cancer includes prognostication; real-time monitoring of tumor evolution and progression; detection of residual disease in early-stage cancer; and identification of mutations in a rapid, noninvasive way.
The clinical application of ctDNA for improving prognostication of metastatic triple-negative breast cancer is shown in this retrospective cohort study. Stover and colleagues found that a cell-free DNA tumor fraction greater than 10% was independently associated with worse outcomes regardless of clinicopathological features. Median OS was 6.4 months for this group, compared with 15.9 months for patients with a lower tumor fraction.
This study gives us new insight into the genomic characterization of metastatic triple-negative breast cancer based solely from liquid biopsies. Notably, certain genes occurred more frequently in metastatic triple-negative breast cancers than paired primary triple-negative breast cancers — such as NOTCH2, GATA3, AKT2 and AKT3 — and they could serve as new targets for therapy.
The study is certainly informative, but it remains to be seen if measurement of ctDNA can be incorporated into routine clinical care to replace a tumor biopsy and either predict therapeutic response or detect markers of resistance. Moving forward, it would be important to evaluate the predictive potential of ctDNA to guide and change therapy for patients with breast cancer.
The use of ctDNA is particularly relevant for triple-negative breast cancer, as this breast cancer subtype can have multiple genomic alterations that are potentially targetable. The hope is that we can one day have an assay that can help predict benefit of genomically driven treatments in real time.
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