‘Unstable’ breast cancers give clues for tackling the disease

Breast cancer cell (credit: LRI EM Unit)

In March we wrote about Professor Charles Swanton’s exciting work looking at cancers with ‘unstable’ chromosomes – genetic changes that can give cancer cells the power to resist drug treatments.

Last week Professor Swanton and his colleagues published their latest research in the scientific journal Cancer Epidemiology, Biomarkers & Prevention, this time focusing on breast cancer. Surprisingly, they’ve found that some women whose breast cancer cells have very unstable chromosomes tend to respond better to treatment.

At first glance this seems to contradict previous studies, which show that unstable cancers are often harder to treat. So what’s going on?

Oestrogen receptors

The new research compared two types of breast cancer – ER-positive and ER-negative cancers. Breast cancers can be divided into these two groups depending on whether their cells contain proteins called ‘oestrogen receptors’ – or ER for short.

Breast tumours whose cells contain high levels of the oestrogen receptor protein are called ‘ER-positive’. The receptors’ presence allows oestrogen – the female sex hormone – to fuel the cancer cells’ growth, meaning these cancers can be treated with hormone-blocking drugs like tamoxifen and anastrozole.

Breast tumours that have no oestrogen receptors (or very low numbers of them) are called ER-negative tumours. There are fewer treatment options available for these tumours.

Professor Swanton and his colleagues used breast cancer cell samples from 246 patients, together with information about how each patient’s disease had progressed. They examined each cell sample, measuring the instability of the chromosomes, to get an overall idea of how unstable each cancer type tended to be. The team also used data from a previous study which examined samples from 356 patients with ER-negative breast cancer and 832 patients with ER-positive cancer.

A double-edged sword

The results showed that ER-negative cancers tended to have more unstable chromosomes than ER-positive cancers. And by looking at the patient records, the researchers could see that women whose ER-negative cancers were really unstable tended to survive for longer. But in contrast, women with unstable ER-positive cancers tended to do worse.

These are important findings. Researchers are constantly searching for better ways to predict how a patient’s cancer will progress, so they can identify the treatments that will work best. At the moment, predictive tests based on genetic changes are much more accurate for ER-positive breast cancers than for those that are ER-negative. So this research has yielded a valuable clue – testing the instability of an ER-negative cancer could help doctors to treat the patient more effectively.

Instability is clearly a double-edged sword for cancer cells. Sometimes it can help them to adapt and escape the drugs designed to destroy them, but in the case of ER-negative breast cancer it could be that the really unstable cells have so much genetic damage that they’re easier to kill, meaning patients are more likely to survive.

It’s not yet clear how instability can have such paradoxical effects, but Professor Swanton and his colleagues are already working to solve this puzzle. Their work is bringing personalised treatments closer to reality – it’s an area of cancer research that’s becoming more exciting by the day.

Nell Barrie

References

Roylance R et al (2011). Relationship of Extreme Chromosomal Instability with Long-term Survival in a Retrospective Analysis of Primary Breast Cancer. Cancer epidemiology, biomarkers & prevention PMID: 21784954

Carter SL et al (2006). A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. Nature genetics, 38 (9), 1043-8 PMID: 16921376

Birkbak NJ et al (2011). Paradoxical relationship between chromosomal instability and survival outcome in cancer. Cancer research, 71 (10), 3447-52 PMID: 21270108

Pusztai, L. (2009). Gene expression profiling of breast cancer Breast Cancer Research, 11 (Suppl 3) DOI: 10.1186/bcr2430