High mutation burden of circulating cell‐free DNA in early‐stage breast cancer patients is associated with a poor relapse‐free survival. (29th June 2020)

• Record Type: Journal Article
• Authors: Kujala, Jouni; Hartikainen, Jaana M.; Tengström, Maria; Sironen, Reijo; Kosma, Veli‐Matti; Mannermaa, Arto
• Is Part Of: Cancer medicine. Volume 9:Number 16(2020)
• Page Start: 5922
• Page End: 5931
• Publication Date: 2020-06-29
• Subjects: biomarker -- liquid biopsy -- prognosis -- recurrence -- serum; 616.994005
• DOI: 10.1002/cam4.3258
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Background: High tumor mutation burden is shown to be associated with a poor clinical outcome. As the tumor‐derived fraction of circulating cell‐free DNA (cfDNA) is shown to reflect the genetic spectrum of the tumor, we examined whether the mutation burden of cfDNA could be used to predict the clinical outcomes of early‐stage breast cancer (BC) patients. Methods: We selected a set of 79 Finnish early‐stage BC cases with a good prognosis based on traditional prognostic parameters but some of which still developed relapsed disease during follow‐up. cfDNA was isolated from the serum collected at the time of diagnosis, sequenced, and compared to matched primary tumors, clinical parameters, and survival data. Results: High cfDNA mutation burden was associated with the poor relapse‐free survival (RFS) ( P = .016, HR = 2.23, 95% Cl 1.16‐4.27) when patients were divided into high and low mutation burden according to the median number of somatic variants. A high discordance was observed between the matched tumor and cfDNA samples, thus highlighting the challenges related to the liquid biopsy of early‐stage cancer cases. Despite the low number of detected tumor‐specific variants, the presence of tumor‐specific somatic variants in the cfDNA was associated with the poor RFS ( P = .009, HR = 2.31, 95% Cl 1.23‐4.31). Conclusions: Our results confirm previously observed challenges about the accuracy of liquid biopsy‐based genotyping of early‐stage cancers and support the parallel sequencing of tumor and cfDNA while also demonstrating how the presence of tumor‐specific somatic variants and the high mutation burden in the cfDNA are both associated with the poor RFS, thus indicating the prognostic potential of liquid biopsy in the context of early‐stage cancers. Abstract : High mutation burden and the presence of tumor‐specific mutations in circulating cell‐free DNA in early‐stage breast cancer patients were observed to be associated with a poor relapse‐free survival. Our results suggest that the liquid biopsy of early‐stage cancers might provide potential benefits when making primary prognosis despite the challenges that are associated with the liquid biopsy of early‐stage cancers.