Chromosomal instability refers to mutations in a person's DNA that means whole chromosomes or parts of chromosomes are duplicated or deleted. This is usually linked to poor treatment outcome in cancer - but Francis Crick Institute researchers have shown in a large validation study that in some breast cancers, extreme chromosomal instability is actually associated with improved outcomes.
Professor Charles Swanton of the Crick (currently based at Lincoln's Inn Fields) said: "Many studies have shown that chromosomal instability is associated with poor response to treatment and poor outcome."
Professor Swanton's team investigated chromosomal instability in over 1,000 samples from breast cancer tumours by looking at two chromosomes that are not usually linked to chromosomal instability in breast cancer.
They found that in patients with a type called oestrogen receptor (ER)-negative breast cancer, which accounts for around a third of patients, extreme chromosomal instability was linked to better outcomes. The outcome measured was disease-free survival, which is the length of time after treatment a patient survives without any sign of the cancer coming back. This paradoxical link was previously shown in a small group of patients, and so the purpose of this study was to validate this link using a much larger group of patients. This is the largest study looking at the link between chromosomal instability and outcome in breast cancer.
Speculating on the reasons for their finding, the scientists suggest that extreme chromosomal instability might be self-limiting and reduce a tumour's ability to keep growing. This could mean that certain drugs, such as those that damage DNA, might be able to increase the level of chromosomal instability in a tumour and therefore improve outcome.
Dr Mariam Jamal-Hanjani of the Crick said: "This finding is important since it highlights the potential value in using chromosomal instability as an indicator of prognosis in ER-negative breast cancer. Identifying patients with extreme chromosomal instability may help distinguish those who have a good prognosis from those who don't, and help in making decisions about treatment."
The paper, Extreme chromosomal instability forecasts improved outcome in
ER-negative breast cancer: a prospective validation cohort study
from the TACT trial, is published in the Annals of
Oncology.
