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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
- 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. Dowsett and Smith 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. Dowsett and Smith 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.
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.