Circulating tumour cells provide genomic snapshot of breast cancer

Tumour 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 suggest that tumour cells circulating in the blood of metastatic patients could give as accurate a genomic read-out as tumour biopsies.

“Counting the number of circulating tumour 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 tumour 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 tumour 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 tumour, this is the first study to look at the genomic signature of individual tumour cells in circulation. In order to isolate single tumour 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 tumour 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 tumour biopsy, however in one patient, some of circulating tumour 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.
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. Thomas Jefferson University (TJU)