Potential new forms of personalised cancer therapeutics continue to emerge. Two recent discoveries may contribute to therapeutic advancement in management of breast cancer.
A study published in the Cell Stem Cell and reported in the New Scientist sheds new light on the origin of most common forms of breast malignant tumours. Till recently, it has been thought that most breast cancers originate from basal stem cells. A team of scientists at the Breakthrough Breast Cancer Centre in London, compared mice expressing mutant versions of the BRCA1 gene (a tumor suppressor gene), which is known to cause breast cancer, in a number of different breast cell types.
They inserted a mutant version of the gene into either basal stem cells or luminal progenitor cells. Both sets of animals developed breast tumours but only tumours derived from the luminal cells mimicked the features of BRCA1- linked cancers in humans, and also so called sporadic basal-like breast cancers, showing aggressive growth and specific genetic markers [Molyneux G et al. (2010) Cell Stem Cell 7(3):403-417]. This accurate identification of the cellular origin of breast cancers constitutes an important step in development of new treatments.
Another important study linking DNA polymorphisms in the estrogen metabolism pathway to breast and endometrial cancer risks has been recently published in PLoS Genetics and discussed at the 2010 conference of the British Society of Human Genetics. This comprehensive genetic study involved more than 7,000 participants from Sweden and Finland and allowed the analysis of a large population of SNPs and the correlation of their potential effects on the production of estrogen and the development of breast and endometrial cancer [Low YL et al. (2010) PLoS Genet. 6:e1001012]
The genes analysed included the CYP19A1 gene encoding the enzyme aromatase, a known candidate target for cancer treatment in postmenopausal women. Although it has long been known that estrogen plays an important role in the breast cancer development, this recent study is the first to give exhaustive evidence of strong links between polymorphisms in genes involved in the estrogen metabolism pathway, and potential development of breast and endometrial cancer. These findings strengthen the scientific rationale for current chemoprophylaxis agents, and provide an opportunity for further advances in estrogen-related cancer treatment.
Prof Edison Liu, director of the Genome Institute of Singapore and lead author of the study, said, “This research raises the possibility of having a test using multiple genetic markers that, when added together, can give an estimate of risk for the most common forms of breast cancer. Previously such genetic risk determination was limited to rare forms of breast cancer. It was the combination of the markers rather than single markers, and our integration of the knowledge of the estrogen metabolism pathways that made the difference” (see press release).
Comment: These two recently reported studies give significant new prospects for novel therapeutic and prophylactic approaches in the battle with breast cancer.