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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
Goal: Understanding the determinants of response to estrogen therapy in estrogen receptor-positive breast cancer patients.
Impact: Breast cancer patients that have estrogen receptor (ER)-positive disease receive treatment with anti-estrogen (endocrine) drugs, such as tamoxifen or aromatase inhibitors—these drugs can reduce their chances of dying from breast cancer by about 30-40 percent. Those patients with high levels of ER receive major benefits from estrogen therapy but estrogen receptor levels vary greatly among ER-positive breast cancers. Drs. Smith and Dowsett are determining the level of ER needed to achieve benefit and to therefore avoid both over- and under-treatment of patients with endocrine drugs.
What’s next: The team will analyse the amount of ER expressed on the tumor cells from several hundred patients who received endocrine treatment before their surgery and determine how those levels correlate with the rate of growth of the tumor cells.
Breast cancers that require estrogen to grow respond well to endocrine therapy, which blocks the growth-promoting effects of estrogen. Although patients with ER-positive breast cancer typically respond well to anti-estrogen drugs, some develop resistance which often leads to cancer recurrence and breast cancer deaths. The reasons for this remain unclear. Drs. Smith and Dowsett are pursuing ways to help predict which patients would benefit from endocrine therapy.
Full Research Summary
Research area: Determining the utility of measuring the amount of estrogen receptor on tumor cells to guide endocrine treatment for estrogen receptor-positive breast cancer.
Impact: The majority of breast cancers are called estrogen receptor (ER)-positive because the cancer cells depend on estrogen for growth. Inhibiting the production of estrogens or blocking their effect with anti-estrogen agents such as an aromatase inhibitor or tamoxifen, markedly reduces growth of the ER-positive breast cancers. When taken for at least five years after surgery anti-estogen (endocrine) treatments significantly reduce the likelihood of a recurrent breast cancer. Not all patients respond equally to endocrine therapies, however. This could depend on the relative requirement of the cells for estrogen, which may be determined by the amount of ER on the tumor cells. Drs. Smith and Dowsett are studying ER-positivity as a marker of response to endocrine therapy to better guide treatment strategies for breast cancer patients.
Current investigation: In the coming year, Drs. Dowsett and Smith will define the level of ER needed to achieve benefit and therefore to avoid both over- and under-treatment of patients with endocrine drugs . To accomplish this, the team will analyze tumors from several hundred patients who received treatment with an AI before their surgery, determine the levels of ER in those tumors and determine how those levels affect the rate of growth of the tumor cells.
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.