By Jacob Dayan M.D.

PGY-3 Radiology

Department of Radiology

Rutgers Robert Wood Johnson School of Medicine


For decades biomarkers have been identified and correlated for various types of cancer as an indicator of recurrence, prognosis, or presence of disease. Recently, a team at Johnson Hopkins University School of Medicine led by Victor Velculescu, MD, PhD, has honed a technique to detect early stage breast cancers. Their method, called Targeted Error Correction Sequencing, focuses on circulating tumor DNA (ctDNA) which can be amplified and used to identify cancer related mutations.

Circulating tumor DNA levels may serve an adjunctive function in the future of breast cancer detection to increase the sensitivity and specificity of biopsies. Dr Velculescu’s group examined a cohort of 45 patients with biopsy proven breast cancer. The test spotted cancer-derived mutations in 2 of 3 (67%) patients with stage I disease, 17 of 29 (59%) with stage II disease, and 6 of 13 (46%) with stage III disease.

In January 2016, the United States Preventive Service Task Force released results from a decade long meta-analysis for the effectiveness of screening mammography in preventing breast cancer related deaths. They reported data exhibiting high rates of over-diagnosis and overtreatment in women aged 40-50. Thus, a recommendation was made for mammographic screening to begin biennially for women at age 50. The ACR, citing methodological shortcomings of the USPSTF study, continues to recommend annual mammography beginning at age 40.

Although colloquially referred to as the “gold standard” of diagnosis of indeterminate breast lesions, the biopsy has been shown to yield less than certain results. The Journal of the American Medical Association published an article in March 2015 investigating variances in pathologist interpretations of biopsy results. Cases included invasive breast cancer, Ductal carcinoma in situ, atypical hyperplasia, and a variety of benign subcategories. Overall, 115 pathologists were given the 240 samples representing varying numbers of the aforementioned categories. The analysis demonstrated that 96% of the invasive breast cancer diagnoses matched, whereas only 84% of the DCIS diagnosis matched. Of the benign categories of diagnoses, 87% matched and only 48% of the atypical hyperplasia diagnoses matched. Although there is high concordance with the most aggressive pathology, invasive ductal carcinoma, there appears to be relatively high variability with atypical hyperplasia.

Utilization of ctDNA to identify breast cancer may soon be commercialized in clinics throughout the country with patients who are poor candidates for breast biopsies or elect for less invasive options. The high specificity of ctDNA assays result in a positive predictive value which can be clinically guiding in the absence of a biopsy. However, the sensitivity of these exams are lower, and may pose challenges to the clinician if a negative result is obtained. Ultimately, only time will tell if future iterations of this technology will enable its integration into clinics across the Unites States and beyond.



Dawson SJ, Tsui DW, Murtaza M, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;368:1199-209.

Dillon MF, Quinn CM, McDermott EW, O’Doherty A, O’Higgins N, Hill ADK. Diagnostic accuracy of core biopsy for ductal carcinoma in situ and its implications for surgical practice. Journal of Clinical Pathology. 2006;59(7):740-743. doi:10.1136/jcp.2005.034330.

Elmore JG, Longton GM, Carney PA, Geller BM, Onega T, Tosteson ANA, Nelson HD, Pepe MS, Allison KH, Schnitt SJ, O’Malley FP, Weaver DL. Diagnostic Concordance Among Pathologists Interpreting Breast Biopsy Specimens. JAMA. 2015;313(11):1122–1132. doi:10.1001/jama.2015.1405

Phallen, J. (2017). Direct detection of early-stage cancers using circulating tumor DNA. Science Transnational Medicine , 9(403), 1-12. Retrieved September 2, 17, from

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