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Researchers identify genes responsible for drug resistance in breast cancer
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SAN DIEGO — Seven genes that may play a role in resistance to tamoxifen have been identified by researchers from Erasmus Medical Center in Rotterdam. These genes, some of which are new, could provide therapeutic targets for individualized breast cancer treatment or prevention of drug resistance, according to one of the researchers who presented the findings at the 2008 Annual Meeting of the American Association for Cancer Research.
“We have investigated the principal causes of tamoxifen resistance by performing genome-wide functional genetic screening,” said Lambert Dorssers, PhD, a cell biologist at the department of pathology at Erasmus. “We established that these ‘Breast Cancer Anti-estrogen Resistance’ genes have a role in clinical breast cancer. The results have shown that the majority of genes are indeed associated with clinical tamoxifen resistance and tumor aggressiveness.”
Dorssers presented information about the seven BCAR genes that cause the tamoxifen-resistant phenotype: AKT1, AKT2, BCAR1, BCAR3, EGFR, GRB7 and TRERF1.
After identifying these genes, Dorssers and colleagues then further studied 561 estrogen receptor-positive primary breast cancers for tumor aggressiveness and tamoxifen resistance.
They identified three genes — AKT2, EGFR and TRERF1 — as having an association with metastasis-free survival, the primary endpoint for tumor aggressiveness. In a separate analysis of breast tumor samples from recurrent patients treated with tamoxifen, the researchers found five genes associated with progression-free survival, depending on the level of expression: BCAR3, ERBB2, GRB7, TLE3 and TRERF1.
Moving forward, the researchers are examining how these genes function to pinpoint possible targets for treatment of breast cancer. – by Leah Lawrence
More than 50% of women who are diagnosed with breast cancer express the estrogen receptor and of those approximately 50% respond to treatment. Why do the other 50% not respond? That is the question. Why do women who express the estrogen receptor not respond to hormonal therapies? Why does essentially every woman who gets hormonal therapy who lives long enough eventually become resistant to hormonal therapy? This is a huge problem. Unfortunately, when patients with breast cancer or almost any other solid tumor recur, the prognosis is very bleak in terms of long-term survival. The importance of study is enormous.
– William N. Hait, MD, PhD
Immediate Past President, AACR
For more information:
- Dorssers LCJ. #1582. Presented at: 2008 Annual Meeting of the American Association for Cancer Research; April 12-16, 2008; San Diego.