Better targeting for breast cancer treatment
Doctors may soon have at their disposal a new test that will help them treat breast cancer patients. European scientists have successfully identified a molecular flag in women with breast cancer who do not respond or have become resistant to the hormone drug tamoxifen.
Tamoxifen is used alongside traditional chemotherapy and radiotherapy, and is designed to prevent breast cancer from coming back. Specifically, the drug blocks the female hormone oestrogen that, in certain breast cancers, is required by the tumour to grow. Its use has been shown to improve cancer survival rates by up to one third.
'Tamoxifen has been shown to be highly effective in some breast cancer patients when used alongside traditional cancer therapies but, in a third of cases, the result has not been what we would hope,' said Professor Göran Landberg who led the study. 'If we can predict which patients will respond to tamoxifen, and those who won't, then this is clearly advantageous as it means the correct treatment is provided instantly which will improve disease outcomes.'
In a 2008 CORDIS article, Professor Sir David Lane spoke highly of the drug. 'Tamoxifen has been a huge success story helping to prevent breast cancer from recurring for many women,' he said. 'Understanding why it occasionally stops working is really important because it allows us to identify new targets for drug development and who will need such treatments.'
Approximately one third of patients with the appropriate type of breast cancer - known as oestrogen receptor positive breast cancer - do not respond to tamoxifen or, worse, develop a resistance to the drug. Oestrogen receptor positive breast cancer is the most common form of the disease accounting for 70 % of cases.
This is why identifying a molecular flag that will help doctors predict which patients will respond best to complementary (adjuvant) hormone therapy with tamoxifen is so vital. 'The identification of molecular flags to classify subgroups of breast cancer and so determine the best treatment for each patient is of increasing importance in cancer therapy,' noted Professor Landberg.
The research looked at the connective tissue surrounding the tumour, which is known to send signals that help the cancer to grow. What they discovered was that fibroblast cells - the cells that make up connective tissue in our bodies - differ in their characteristics from patient to patient and can give clues about tamoxifen treatment response.
Their results have been published in the journal PLOS ONE. Lead author of the article, Dr Susann Busch, spoke about the discovery and its connection to the pERK protein: 'We analysed tissue samples from 564 women with invasive breast cancer, some of whom were given tamoxifen and some who weren't; this allowed us to make a comparison between treatment responses. We discovered that women who had low levels of a protein known as pERK in their cancer-associated fibroblasts did not respond to tamoxifen. Testing patients for the pERK flag could help doctors determine whether tamoxifen is an appropriate treatment for their patient or whether alternative therapies should be explored, so saving time and money.'
Their journal article concludes: 'In summary, our study supports the idea that in addition to conventional tumor markers also stromal biomarkers possess treatment-predictive information and could therefore be highly valuable in identifying patient subgroups benefiting from endocrine treatment.'
The researchers plan to continue to study molecular flags that are characteristic for cancer-associated fibroblasts. Understanding how fibroblasts help the tumour to grow will allow the development of new strategies to block their harmful signals and overcome drug resistance.
Data Source Provider: The University of Manchester; PLOS ONE
Document Reference: Busch, S., et al., 'Low ERK Phosphorylation in Cancer-Associated Fibroblasts Is Associated with Tamoxifen Resistance in Pre-Menopausal Breast Cancer', PLOS ONE, 2012, 7(9), e45669. doi:10.1371/journal.pone.0045669
Subject Index: Coordination, Cooperation; Life Sciences; Medicine, Health; Scientific Research