Circulating Tumor Cells Provide Genomic Snapshot of Breast Cancer

Tumor cells isolated from the blood of patients with triple negative breast cancer reveal similar cancer-driving mutations as those detected from standard biopsy, suggesting that circulating cells could one day replace tissue biopsies

The genetic fingerprint of a metastatic cancer is constantly changing, which means that the therapy that may have stopped a patient’s cancer growth today, won’t necessarily work tomorrow. Although doctors can continue to biopsy the cancer during the course of the treatment and send samples for genomic analysis, not all patients can receive repeat biopsies. Taking biopsies from metastatic cancer patients is an invasive procedure that it is frequently impossible due to the lack of accessible lesions.  Research published October 10th in the journal Breast Cancer Research suggest that tumor cells circulating in the blood of metastatic patients could give as accurate a genomic read-out as tumor biopsies.

“Counting the number of circulating tumor cells (CTCs) can tell us whether a patient’s cancer is aggressive, or whether it is stable and responding to therapy,” says the article’s first author Sandra V. Fernandez, Ph.D., assistant professor of Medical Oncology at Thomas Jefferson University. “Our work suggests that these cancer cells in the blood also accurately reflect the genetic status of the parent tumor or its metastases, potentially giving us a new and easy to source of genomic information to guide treatment.”

First discovered for their diagnostic potential in 2004, circulating tumor cells are beginning to be used in the clinic to help guide treatment decisions and track a patient’s progress as the cancer progresses. Although other studies have pooled the collected CTCs and compared their collective genetic signature to that of the primary tumor, this is the first study to look at the genomic signature of individual tumor cells in circulation. In order to isolate single tumor cells from the blood, the authors used a new technology, DEPArrayTM , in their laboratory.

The researchers compared tissue biopsies surgically removed from two patients with inflammatory breast cancer with circulating tumor cells (CTCs). Breast tissue samples from both patients showed a specific mutation in a region of a cancer-driving gene, p53. The authors studied this mutation in several CTCs isolated from both patients. They found that in several of the CTCs collected, the mutations matched with the tumor biopsy, however in one patient, some of circulating tumor cells had an additional mutation. “Since inflammatory breast cancer is a very rapidly changing disease, we think this additional mutation may have been acquired after the original surgical biopsy was taken,” said Dr. Fernandez. In the case where an additional p53 mutation was found, the blood to isolate CTCs were drawn one year later than the breast tissue biopsy was taken.

exosome rna

Although further work analyzing a greater number of genes and samples is needed, the work shows that CTCs offer the possibility of capturing the most current genomic information in an easy-to-obtain sample such as blood, thus helping guide treatment decisions. It also suggests that it may be necessary to test more than one cell for the most accurate reading, as the CTC population appears to be heterogenous.

The authors report no conflict of interest. Authors of this manuscript are Sandra V. Fernandez, Catherine Bingham, Patricia Fittipaldi, Laura Austin, Juan Palazzo, Gary Palmer, Katherine Alpaugh and Massimo Cristofanilli. This work was supported by PA Breast Cancer Coalition (PI: Fernandez) and NIH RO1 CA138239-02 (PI: Cristofanilli).

For more information, contact Edyta Zielinska, 215-955-5291,

About Jefferson

Thomas Jefferson University (TJU), the largest freestanding academic medical center in Philadelphia, is nationally renowned for medical and health sciences education and innovative research.   Thomas Jefferson University includes the Sidney Kimmel Medical College (SKMC), one of the largest private medical schools in the country and ranked among the nation’s best medical schools by U.S. News & World Report, the Graduate School of Biomedical Sciences and the Jefferson Schools of Nursing, Pharmacy, Health Professions, and Population Health.  Jefferson University Physicians is TJU’s multi-specialty physician practice consisting of the full-time faculty of SKMC.  Thomas Jefferson University partners with its clinical affiliate, Thomas Jefferson University Hospitals.

Research article

S.V. Fernandez, et al., “TP53 mutations detected in circulating tumor cells present in the blood of metastatic triple negative breast cancer patients,” Breast Cancer Research, 16:445, 2014. [article]

Source  – Thomas Jefferson University

Leave a Reply

Your email address will not be published. Required fields are marked *