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Ian E. Smith, MD, FRCP, FRCPE
Professor of Cancer Medicine,
The Royal Marsden Hospital and Institute of Cancer Research
Head of the Breast Unit, The Royal Marsden Hospital
London, United Kingdom
- Seeking to reduce recurrence of ER-positive breast cancer with new strategies to prevent resistance to anti-estrogen drugs.
- A novel clinical trial platform is used to identify markers of drug resistance in individual patients following anti-estrogen treatment.
- These studies will lead to better outcomes in early stage breast cancer by identifying biomarkers that can be therapeutically targeted to prevent tumors from coming back.
Breast cancers that require estrogen to grow–called estrogen receptor (ER)-positive breast cancers–are the most frequently diagnosed type of breast cancer. These cancers respond well to therapies that block growth-promoting effects of estrogen – called endocrine therapy. Resistance to endocrine therapy remains a significant clinical challenge, however, and is often the cause of cancer recurrence and breast cancer deaths. Drs. Smith and Dowsett are studying the underlying causes of endocrine resistance so that preventive strategies can be developed.
Full Research Summary
Estrogen receptor (ER)-positive breast cancer makes up more than two-thirds of all breast cancer cases, particularly those that occur after menopause. Although a variety of successful anti-estrogen drugs are available to treat ER-positive cancer, resistance to these therapies remains a significant clinical challenge.
Drs. Smith and Dowsett are analyzing early breast cancers from patients treated with anti-estrogen therapy to identify changes that occur after treatment that lead to drug resistance. They previously found mutations in the ER gene in 16 percent of the tumors that were treated with aromatase inhibitors. This novel finding indicates, for the first time, that such treatment can lead to occurrence of ER mutations even in early breast cancer.
This year, the team will study tumors that occurred in women taking preventive endocrine therapy to determine whether therapy-induced ER mutations may have played a role in their breast cancer.
They continue to conduct studies to understand the biology of endocrine resistance and are working to develop a new method for measuring ER levels in breast cancers. This new method may replace or supplement the universally used method, which is based on staining of sections of the tumor.
Ian E. Smith, MD, FRCP, FRCPE, is Professor of Cancer Medicine at The Royal Marsden Hospital and Institute of Cancer Research, London, United Kingdom. He is also Head of the Breast Unit at The Royal Marsden Hospital.
His initial medical training was in Edinburgh and he came to the Royal Marsden, London, for specialist training in cancer medicine. He spent some time in Boston at the Dana-Farber Cancer Institute, Harvard. His principal clinical research interests have been in breast cancer, lung cancer, and in new drug development. He was involved in the early clinical development of several anticancer drugs that have subsequently proved effective in the clinic, including carboplatin and letrozole. In the last decade he has become increasingly involved in neoadjuvant therapies as a research approach towards individualizing treatment for breast cancer. He is currently Chief Investigator or UK Principal Investigator for several international multicenter breast cancer trials involving in particular targeted therapies and aromatase inhibitors. He publishes and lectures extensively. He was awarded the Susan G Komen for the Cure Brinker Award for Scientific Distinction at the 2009 San Antonio International Breast Cancer Conference.
Professor Smith is Co –Chairman of the ASCO Clinical Guidelines Group for Chemotherapy in Metastatic Breast Cancer, and has just been appointed the first Chair of the newly formed UK Breast Cancer Clinical Reference Group. He is a patron of Breast Cancer Care, the largest UK breast charity for patient support.