IMPROVED care for triple-negative breast cancer (TNBC) could take place following the discovery that the condition is chemoresistant even before initiation of chemotherapy. The study from the Karolinska Institutet, Solna, Sweden, suggests that identifying therapy-resistant tumour clones could enable a more personalised treatment for this difficult-to-treat and aggressive form of breast cancer.
Resistance to chemotherapy in TNBC is a common problem which can lead to tumour growth and relapse, despite several chemotherapy drugs being effective against the condition. As chemotherapy is the main form of treatment for this cancer, understanding the mechanisms behind the chemoresistance is important.
The team wanted to establish whether the resistance is caused by the presence of resistant groups of cells known as clones in the tumour at the very start, or if it occurs due to the development of new genetic mutations during treatment. Using single-cell sequencing, they analysed the DNA and gene expression (RNA) of all genes in individual cells of the tumour tissue of 20 TNBC patients who had received preoperative chemotherapy to determine the properties and kinship of the cells. The tissue was collected before the therapy began, after the completion of two courses of therapy, and during surgery.
Resistant Tumour Clones
It was found that tumour clones remained after treatment in half of the cases and they existed in the tumour prior to chemotherapy, often as a small proportion of the population of the tumour cell when studied in detail at a single-cell level. Additionally, the team revealed that during treatment the remaining tumour clones had adapted their gene expression to become even more chemoresistant.
Dr Theodoros Foukakis, who co-led the study, commented: “All in all, the study shows that chemoresistance in TNBC is a complex process involving both a selection of resistant clones that existed in the tumour from the start as well as a reprogramming of their gene expression to ensure survival during therapy.”
More Personalised Care
The results could lead to more personalised treatment being given to TNBC patients who respond poorly to chemotherapy and have a worse prognosis through the identification of therapy-resistant tumour clones in future studies.
James Coker, Reporter
For the source and further information about the study, click here.