Lab research suggests more women could benefit from Herceptin

In collaboration with the Press Association

Herceptin may be effective against more types of breast cancer than previously thought, according to US research.

Herceptin, also known as trastuzumab, is often given to women with breast cancers that test positive for high levels of a protein known as HER2.

But HER2 could help fuel the growth of some breast cancers that are labelled HER2-negative, researchers at the University of Michigan Comprehensive Cancer Center discovered. 

This means Herceptin may be also effective in such cancers, particularly as a way to lower the risk that the cancer will come back (called adjuvant treatment).

Around 20 per cent of breast cancer patients have HER2-positive tumours, and Herceptin has improved the survival in these women.

The new findings - published in the journal Cancer Research - suggest the drug could also have some effect in a further 65 per cent of women with breast cancer.

The research is still at an early stage though, and patients with HER2-negative breast cancer are not advised to take Herceptin.

The scientists wanted to understand previous research indicating that some HER2-negative breast cancers still respond to Herceptin treatment.

They found that the HER2 protein plays an important role in a small pool of treatment-resistant 'cancer stem cells', which are thought to fuel a tumour's growth and spread.

The stem cells represent such a small amount of a tumour's total cells - between one and five per cent - that the level of HER2 is insufficient to meet the threshold for a HER2-positive cancer.

"We can now provide a molecular explanation for the surprising finding that adjuvant Herceptin benefited some women with HER2-negative breast cancer," said study author Professor Max S Wicha.

"If this is confirmed in clinical trials, it could alter our approach to breast cancer treatment," he added.

The team also found that HER2 levels were higher in tumours that had spread to the bone compared with the primary breast tumour in tumours classified as HER2-negative.

Bone is the most frequent site to which breast cancer spreads.

Working with mouse models, researchers found that Herceptin helped to almost completely block bone tumours from growing if administered early, when tumours were very small.

When administered later - once bone tumours were established - the effect of the drug was negligible.

The researchers say that their findings point to a move away from drugs that merely shrink tumours, towards treatments that also target the cancer stem cells and so prevent cancer coming back.

These drugs could then be used in conjunction with traditional chemotherapies, which are still needed to eliminate the primary tumour cells.

Dr John Stingl, a Cancer Research UK expert on breast stem cells, said: "From a biological perspective, this work makes a lot of sense and could be an early step towards many more women benefiting from treatments that target HER2.

"Tests to see if a woman may respond to Herceptin look for abnormally high levels of HER2 in the tumour, but actually this research suggests that much lower levels of HER2 can drive the growth of some breast cancers, particularly once they have spread.

"This presents the tantalising prospect of combating this spread in 'HER2-negative' cancers with Herceptin.

"We don't know yet whether this will work in the clinic, but it will be exciting to see whether this elegant biological explanation means more women could benefit from this life-extending drug."

Copyright Press Association 2013

References

  • Ithimakin, S. et al. HER2 Drives Luminal Breast Cancer Stem Cells in the Absence of HER2 Amplification: Implications for Efficacy of Adjuvant Trastuzumab. Cancer Research doi: 10.1158/0008-5472.CAN-12-3349