Parkside Oncology Clinic
49, Parkside
Wimbledon
SW19 5NB

Tel: 020 8247 3384
Fax: 020 8247 3385
PA. Ms Hilary Dummer
Email: hdummer@parkside-hospital.co.uk

Most of my clinical research has been directed towards improving the treatment of breast cancer by translation of encouraging laboratory data into clinical trials designed to identify worthwhile clinical activity. The scientific techniques for phase II and III clinical trials have substantially evolved over the last 20 years. While at the Royal Marsden, I lead and directed the Breast Unit clinical research program. During this time I have been principal investigator for a large number of ‘in house’ clinical trials, many of which have been translational from the laboratory and most of which have had associated laboratory projects.

Although we have had a wide ranging and comprehensive research program, my focus has been in four main areas of clinical research.

1. Bone metastases, osteolysis and anti-osteolytic treatments

Following my laboratory work for my PhD, where I showed that use of anti-osteolytic agents could prevent the development of bone metastases in rats, I led a series of clinical trials in patients with metastatic and early breast cancer. We showed that bisphosphonates were more active than other antiosteolytic agents for reducing the complications of bone metastases in women with bone metastases. Following this, I led a double blind placebo controlled trial of the oral bisphosphonate, clodronate as adjuvant therapy patients with operable breast cancer which showed a significant reduction in the risk of development of bone metastases and significantly improvement in survival for these patients.

2. Aromatase inhibitors and other endocrine treatments

I started and led the first trial of aminoglutethamide in Europe and one of the first in the World at the Royal Marsden Hospital in the mid 1970s for treatment of advanced breast cancer, which subsequently included endocrine studies of the mode of action. This was followed by a trial using the very specific aromatase inhibitors, 4 hydroxyandrostenedione. This was the first trial to clearly show a metastatic breast cancer response to such an agent indicating the importance of oestrogen in post menopausal breast cancer growth.

In the late 1970s I started and led a trial of adjuvant aminoglutethamide for patients with operable breast cancer which had to be stopped prematurely because of toxicity. In spite of this the results still showed a significant reduction in relapse. This was the first adjuvant trial of an aromatase inhibitor in the world.

Clinical research into the endocrinology and antitumour activity of aromatase inhibitors has continued as a high priority at the Royal Marsden.

3. Primary medical treatment and molecular markers programme

I started and led one of the first randomised trials of neoadjuvant chemotherapy for patients with operable breast cancer and was the first to show a significant reduction in the requirements for mastectomy for patients who received chemotherapy before surgery and to show that response was associated with better clinical outcomes. Our priority has been to use this modality of treatment to develop discriminating diagnostics in order to identify which patients do or do not require treatment, but to also successfully monitor and optimise treatment. We were one of the first groups to use RNA microarray expression profiling in this context.

4. Endocrine prevention of breast cancer

In 1986, I initiated and start the first clinical trial to evaluate the use of an antioestrogen to prevent breast cancer. This double blind trial of the SERM tamoxifen versus placebo given for 5 to 8 years to 2500 healthy women at increased risk of developing breast cancer, led to other similar trials in Italy, the USA, the UK and elsewhere which recruited over 25,000 women. I was the principal clinical investigator for the IBIS trial based in the UK and with Jack Cusick a meta-analysis of all these trials which indicated that tamoxifen gave rise to a significant risk reduction for breast cancer of about 40%.

I was also an investigator for a double blind, trial of another SERM raloxifene versus placebo, which showed a substantial risk reduction for breast cancer in healthy women who were randomised to raloxifene.

When I started in 1974 at the Royal Marsden Hospital, I was one of the first physicians in the world to specialise in the medical management of breast cancer. My task then was to establish a breast cancer clinical research programme. During this time I have led 35 clinical treatment trials involving over 6000 patients; 11 of these trials were directly translational from laboratory to clinic. We have completed 13 phase III clinical trials, 4 of which were placebo controlled. Most of these trials have had associated diagnostic biochemical and molecular marker projects involving many thousands of patients.

Throughout my time as head of the breast cancer clinical research programme, I have attempted to lead an innovative programme of clinical research aimed at improving the prevention, diagnosis and treatment of breast cancer. I have endeavoured to keep the programmes topical, focused and relevant to improvement in treatment. The primary objective has been to take through innovative ideas and experimental data to full clinical evaluation and my training as an endocrinologist and oncologist together with my PhD in experimental tumour biology has been helpful. Over the last 20 years, the five year relapse rate, for patients on the unit has improved from 60% to over 80%, reflecting the progress that has been made in the treatment of the disease in this time.