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Mitch Dowsett, FMedSci, PhD
Head, Department of Biochemistry and Centre for Molecular Pathology
Professor of Biochemical Endocrinology,
Breakthrough Research Centre
Professor of Translational Research
The Royal Marsden Hospital
Institute of Cancer Research
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. Dowsett and Smith 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. Dowsett and Smith 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. Dowsett and Smith 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.
Professor Mitch Dowsett, FMedSci, PhD, is Head of the Academic Department of Biochemistry and Head of the Centre for Molecular Pathology at the Royal Marsden Hospital; Professor of Biochemical Endocrinology at the Institute of Cancer Research; and Professor of Translational Research in the Breakthrough Breast Cancer Centre, London.
Professor Dowsett’s research focuses almost exclusively on breast cancer and predominantly on hormonal aspects of the disease and biomarkers of response with a research team of about 24 investigators. He was closely involved with the clinical development of aromatase inhibitors and in the creation of national and international standards for steroid receptor and HER2 analysis (ASCO/CAP Guidelines Steering Committees). He co-chairs the International Working Party for Ki67 in Breast Cancer. He was the founding chairman of the UK NCRI Translational Research (subsequently Biomarker and Imaging) Clinical Study Group. In 2004 he founded and continues to chair the Aromatase Inhibitor Overview Group.
He has authored nearly 600 published papers related to breast cancer, and given numerous named lectures including the 2007 William L McGuire Memorial Lecture. He recently rotated off the Executive Board of the Breast International Group (BIG) after seven years, and sits on the Executive/Steering Committees of several clinical trials. He has been a NCRI Senior Clinical Investigator since 2009. In 2013 he was appointed as a Fellow of the Academy of Medical Sciences.