Why Do Some Breast Cancers Become Resistant to Chemotherapy?

Researchers may have determined why some triple-negative breast cancers (TNBC) become resistant to chemotherapy, according to a new study published in Cell. The findings could help to improve patient outcomes and identify which patients could benefit from chemotherapy.

Led by a team at The University of Texas MD Anderson Cancer Center, the study findings indicated breast cancer cell resistance to chemotherapy may be pre-existing and the cells may even adapt to become resistant when confronted by the chemotherapy itself.

Neo-adjuvant chemotherapy (NAC) is standard of care for many patients with triple-negative breast cancers. Although the therapy can be effective, approximately half will develop chemotherapy resistance, which could lead to poor outcomes, the researchers noted.

In the study, the researchers evaluated 20 TNBC patients treated with NAC and examined genetic changes by deeply sequencing the coding regions of genes across the genome.

“What we found were 2 distinct classes of clonal dynamics—extinction and persistence,” study author Nicholas Navin, PhD, associate professor of Genetics, said in a press release. “In the clonal extinction patients, NAC eliminated the tumor cells, leaving only normal cell types post-treatment. Clonal persistent patients harbored a larger number of residual tumor cells with genotypes and phenotypes that were altered in response to NAC.”

The researchers used single-cell DNA and RNA sequencing to analyze 8 clonal persistent patients, measuring miniscule portions of DNA and RNA. The data indicated chemoresistance in which both adaptive and acquired evolution work to establish chemo-resistant tumor mass.

Additionally, the researchers believe that pre-existence of chemoresistant genotypes in tumors means there could be diagnostic opportunities for detecting chemoresistant clones in TNBC patients before they are treated with NAC. According to the researchers, the findings may be applicable to patient outcomes or survival.

“Lastly, our data raise the possibility of therapeutic strategies to overcome chemoresistance by targeting pathways identified in this study,” Dr Navin said in the press release. “Future work will need to be performed in a large group of TNBC patients to fully understand this evolutionary model and gene-related chemoresistance.”

Reference

Study may explain why some triple-negative breast cancers are resistant to chemotherapy [news release]. MD Anderson’s website. https://www.mdanderson.org/newsroom/2018/04/study-may-explain-why-some-triple-negative-breast-cancers-are-resistant-to-chemotherapy.html. Accessed April 20, 2018.