Cell-free DNA detected by “liquid biopsy” as a potential prognostic biomarker in early breast cancer

Abstract

As conventional biomarkers for defining breast cancer (BC) subtypes are not always capable of predicting prognosis, search for new biomarkers which can be easily detected by liquid biopsy is ongoing. It has long been known that cell-free DNA (CF-DNA) could be a promising diagnostic and prognostic marker in different tumor types, although its prognostic value in BC is yet to be confirmed. This retrospective study evaluated the prognostic role of CF-DNA quantity and integrity of HER2, MYC, BCAS1 and PI3KCA, which are frequently altered in BC. We collected 79 serum samples before surgery from women at first diagnosis of BC at Forlì Hospital (Italy) from 2002 to 2010. Twenty-one relapsed and 58 non-relapsed patients were matched by subtype and age. Blood samples were also collected from 10 healthy donors. All samples were analyzed by Real Time PCR for CF-DNA quantity and integrity of all oncogenes. Except for MYC, BC patients showed significantly higher median values of CF-DNA quantity (ng) than healthy controls, who had higher integrity and lower apoptotic index. A difference nearing statistical significance was observed for HER2 short CF-DNA (p = 0.078, AUC value: 0.6305). HER2 short CF-DNA showed an odds ratio of 1.39 for disease recurrence with p = 0.056 (95% CI 0.991-1.973). Our study suggests that CF-DNA detected as liquid biopsy could have great potential in clinical practice once demonstration of its clinical validity and utility has been provided by prospective studies with robust assays.

Liquid biopsy in breast cancer: A comprehensive review

“…It is important to note that in addition to sensitivity, specificity of mutation detection is another significant factor to consider when conducting liquid biopsy. Mutation incident rates in individuals may be increased through various environmental and physiological factors . Spontaneous mutations, which are known to contribute to cancer development, can occur with increasing age although they may not directly cause cancer .…”

“…Furthermore, when looking for the ability of the genes to predict relapse, a univariate conditional logistic model showed that short fragments of HER2 cfDNA had an odds ratio of 1.39 for disease recurrence. The study concluded that analyzing cfDNA through liquid biopsy may have great potential as a prognostic biomarker in clinical settings . Another study by Madic et al explored the correlations of ctDNA and CTC plasma level with the prognosis of triple‐negative breast cancer patients.…”

“…Mutation incident rates in individuals may be increased through various environmental and physiological factors. 155 Spontaneous mutations, which are known to contribute to cancer development, can occur with increasing age although they may not directly cause cancer. 156 Therefore, the utilization of liquid biopsy at pre-symptomatic stages may lead to over-diagnosis of cancer and false-positive results.…”

Plasma C-MYC Level Manifesting As An Indicator in Progression of Breast Cancer

“…Our study showed a consistent result with Escot [21] who first reported C-MYC gene abnormalities in primary breast cancer. However, Ravaioli et al [35] reported that there was no statistical difference of cfDNA quantity and integrity of MYC between breast cancer patients and healthy controls in their research. We speculate that the differences may be due to the diversity in population or race.…”

Liquid Biopsy as Novel Tool in Precision Medicine: Origins, Properties, Identification and Clinical Perspective of Cancer’s Biomarkers

“…However, methodological limitations in recent technological development have allowed much progress in methods to isolate CTCs from blood, taking into account the heterogeneity of the CTCs in relation to surface protein markers and physical characteristics. Therefore, before isolation, to consider the specificity and sensitivity, and the tests that are desired to be performed in CTCs such as quantification, molecular characterization or functional studies are required to improve the clinical utility of LB [32].…”