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Breast Cancer Res Treat. 2016 Jan;155(1):139-49. doi: 10.1007/s10549-015-3635-5. Epub 2015 Dec 14.

Cell-free DNA as a molecular tool for monitoring disease progression and response to therapy in breast cancer patients.

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Department of Surgery, Houston Methodist Hospital, 6550 Fannin St, Smith Tower 1661, Houston, TX, 77030, USA.
Houston Methodist Research Institute, Houston Methodist Hospital, 6670 Bertner Ave., Houston, TX, 77030, USA.
Houston Methodist Cancer Center, 6445 Main Street OPC 24, Houston, TX, 77030, USA.
Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China.
Houston Methodist Cancer Center, 6445 Main Street OPC 24, Houston, TX, 77030, USA.


Due to the spatial and temporal genomic heterogeneity of breast cancer, genomic sequencing obtained from a single biopsy may not capture the complete genomic profile of tumors. Thus, we propose that cell-free DNA (cfDNA) in plasma may be an alternate source of genomic information to provide comprehensive data throughout a patient's clinical course. We performed a retrospective chart review of 100 patients with stage 4 or high-risk stage 3 breast cancer. The degree of agreement between genomic alterations found in tumor DNA (tDNA) and cfDNA was determined by Cohen's Kappa. Clinical disease progression was compared to mutant allele frequency using a two-sided Fisher's exact test. The presence of mutations and mutant allele frequency was correlated with progression-free survival (PFS) using a Cox proportional hazards model and a log-rank test. The most commonly found genomic alterations were mutations in TP53 and PIK3CA, and amplification of EGFR and ERBB2. PIK3CA mutation and ERBB2 amplification demonstrated robust agreement between tDNA and cfDNA (Cohen's kappa = 0.64 and 0.77, respectively). TP53 mutation and EGFR amplification demonstrated poor agreement between tDNA and cfDNA (Cohen's kappa = 0.18 and 0.33, respectively). The directional changes of TP53 and PIK3CA mutant allele frequency were closely associated with response to therapy (p = 0.002). The presence of TP53 mutation (p = 0.0004) and PIK3CA mutant allele frequency [p = 0.01, HR 1.074 (95 % CI 1.018-1.134)] was excellent predictors of PFS. Identification of selected cancer-specific genomic alterations from cfDNA may be a noninvasive way to monitor disease progression, predict PFS, and offer targeted therapy.


Breast cancer; Cell-free DNA; Clinical markers

[Indexed for MEDLINE]

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