A cutting-edge technique called cellular barcoding has been used to tag, track and pinpoint cells responsible for the spread of breast cancer from the main tumor into the blood and other organs.

The technique also revealed how chemotherapy temporarily shrinks the number of harmful cells, rather than eliminating them, explaining how the cancer could eventually relapse.

Insights from the study, published in Nature Communications, could lead to new targeted treatments for breast cancer, the most common cancer to affect women. Most deaths from breast cancer are caused by the metastasis, or spread, of cancerous cells from the main tumor site into other organs.

Breast cancers consist of thousands of different cell variants with diverse characteristics that may or may not play a role in the metastasis of the cancer. This makes effective treatment a challenge because it is difficult to know which cells are responsible for driving the spread of cancer.

The author said the ability to pinpoint the 'clones' - subpopulations of cells arising from an original patient tumor - responsible for the spread of cancer was crucial for improving treatments.

"Our study revealed that only a select few clones were actually responsible for the metastasis.

"The barcoding technique enabled us to identify the clones that were able to get into the blood stream and make their way into other organs where they would 'seed' new tumor growth," another author said.

Another author said the technique also allowed the researchers to see what was happening to the clones after chemotherapy was introduced.

The authors find that tumor resection had a major impact on reducing clonal diversity in secondary sites, indicating that most disseminated tumor cells lacked the capacity to ‘seed’, hence originated from ‘shedders’ that did not persist. The few clones that continued to grow after resection i.e. ‘seeders’, did not correlate in frequency with their parental clones in primary tumors.

"We used the chemotherapy agent Cisplatin to treat laboratory models developed using donated breast tumor tissue. While the treatment was able to shrink tumors and the size of individual clones, it did not kill them off completely. All the clones, including the nasty seeders, eventually grew again, accounting for cancer relapse”.

Cisplatin treatment of one BRCA1-mutated PDX model to non-palpable levels had a surprisingly minor impact on clonal diversity in the relapsed tumor yet purged 50% of distal clones. Therefore, clonal features of shedding, seeding and drug resistance are important factors to consider for the design of therapeutic strategies.

Another author said, "Now that we know which clones are involved in the spread of breast cancer, we have the power to really focus our research to block their activity. For instance, we are curious to understand what is unique about these particular clones that enables them to successfully spread, seed and grow the cancer".

https://www.wehi.edu.au/news/cellular-barcoding-reveals-how-breast-cancer-spreads

https://www.nature.com/articles/s41467-019-08595-2