Scientists have identified a key group of breast cancer patients in whom anti-oestrogen drugs appear exceptionally effective. The subset has multiple copies of the ESR1 gene, which codes for one form of receptor for the hormone oestrogen. The researchers say the discovery could allow the growing arsenal of anti-oestrogen breast cancer treatments to be targeted more effectively.
Oestrogen receptor activation is one of the most important known factors in the development of breast cancer. Drugs such as tamoxifen and Arimidex (anastrozole), which work against oestrogen, can result in a substantial decrease of tumour growth in about 30%-50% of oestrogen receptor–positive patients, and can significantly cut the chances of the disease recurring after surgery.
But now research from University Medical Centre Hamburg suggests that the number of copies of the ESR1 gene a patient possesses is also highly significant. Dr Ronald Simon and colleagues studied the ESR1 gene in 2,000 breast cancer samples. To their surprise, they found that a fifth of the tumours had multiple copies of the gene or “gene amplification.”
To gauge the clinical significance of this, they conducted a small follow-up study of 175 women with breast cancer who were being treated with tamoxifen. They found that women with the amplification survived significantly longer than those who did not.
Better survival
The researchers report in Nature Genetics that survival rates at 100 months were over 95% in the gene amplification group; of the ordinary oestrogen-positive patients around 75% were still alive; while of those without oestrogen receptors, just 50% were still alive.
Team leader Dr Ronald Simon said: “Altogether, these data strongly suggest that ESR1 amplification may identify a subgroup of breast cancers with high oestrogen receptor expression as being particularly likely to respond to anti-oestrogen therapy." He went on to say: "Given the critical role of oestrogen receptor expression for breast cancer therapy and the importance of gene amplification for drug target over-expression, we find it remarkable that the relevance of ESR1 amplification was not discovered until now.”
Significantly, the researchers also found ESR1 amplification in benign and precancerous breast diseases, suggesting that “ESR1 amplification maybe a common mechanism in proliferative breast disease and a very early genetic alteration in a large subset of breast cancers.”
The scientists note that the success of trastuzumab (Herceptin) for treatment of Her2-amplified or Her2-overexpressing breast cancers also shows that amplified genes may be particularly suited as therapeutic targets.
