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The ATAC trial was conceived, designed and implemented by UCL investigators, and has resulted in a dramatic, global change in the management of breast cancer. It directly compared tamoxifen, the standard treatment for breast cancer for 25 years, with anastrozole, a novel aromatase inhibitor. It convincingly demonstrated superiority for the new agent, in terms of both progression-free survival and adverse effect profile. Tamoxifen had been the world's most widely prescribed anti-cancer drug but was supplanted by anastrozole as a consequence of this trial.
Approximately 80% of all breast cancer is hormone receptor positive localised cancer in postmenopausal women. For 30 years the universal standard adjuvant endocrine treatment for these women was five years of tamoxifen, but side effects and recurrences limited its usefulness. Results from the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial led to a major worldwide change in the standard recommended treatment, from tamoxifen to anastrozole (an aromatase inhibitor). From 2009 this treatment became UK national policy (recommended by NICE), and guidance in other countries (eg Australia, USA) has also been revised. Anastrozole is now routinely offered to women with hormone receptor positive breast cancer in UK and (extrapolating from trial data) we estimate over a thousand are spared a recurrence in UK annually.
Laboratory research at Imperial College supported the concept of switching adjuvant treatment of breast cancer (i.e. tamoxifen for 2-3 years to exemestane for 2-3 years) which has now been shown in Imperial-led clinical trials to improve overall survival of breast cancer patients for at least 5 years post-switching. In association with this, the effects of switching on endometrial, skeletal and joint function have shown few long-term deleterious effects. This way of treating breast cancer has now gained acceptance worldwide, as being more efficacious and resulting in fewer longterm, serious side effects. It is the recommended treatment in international guidelines.
Aromatase inhibitors (AIs) significantly improve survival from breast cancer but are associated with increases in osteoporotic fractures and bone mineral density loss. Research at the University of Manchester (UoM) has provided key evidence that has contributed to preventing debilitating bone demineralisation safely in breast cancer patients undergoing adjuvant therapy with AIs. UoM findings have led to an international consensus on guidelines recommending Dual-energy X-ray Absorptiometry (DEXA) scanning to identify patients at risk of bone loss as well as the use of bisphosphonates where bone loss has been identified. Further guidelines advise against the use of HRT to treat bone loss as a result of its association with breast cancer recurrence.
The primary treatment for ductal carcinoma in situ (DCIS, cancer confined to the milk ducts of the breast) is surgery, and breast-conserving surgery is increasingly preferred over mastectomy. The UK/ANZ DCIS trial, co-led by Queen Mary researchers, showed that following surgery, women with DCIS are significantly less likely to develop invasive disease if given radiotherapy, and that this protection persists long term. NICE recommends that, following adequate breast conserving surgery, adjuvant radiotherapy should be offered to patients with DCIS. This recommendation is also current in the United States, Canada, Australia, and many European countries. Based on current figures, we estimate that in UK alone, around 260 women each year are spared a recurrence of breast cancer as a result of this research.
Research from UCL Division of Surgery has transformed the breast cancer treatment paradigm so women can complete their local treatment intraoperatively (~30 min), with reduced toxicity. Our work has challenged the dogma of giving several weeks of whole breast radiotherapy (EBRT) after lumpectomy for breast cancer with our idea of irradiating only the tumour bed in selected cases; we have developed and evaluated new technology called TARGeted Intraoperative radioTherapy (TARGIT) within the novel approach of risk-adapted radiotherapy. To date, TARGIT has saved 180,000 hospital visits and could save £60M(UK)/ $280M(USA)/year.
Governments, industry and the public have benefitted from research on the potential role of parabens, which are used widely as preservatives in personal care products, in the development of breast cancer. The research, conducted at the University of Reading since the 1990s, has established the oestrogenic activity of parabens in human cells, confirmed and quantified the presence of parabens in human breast tissue and established that parabens can stimulate the proliferation of human breast cancer cells at concentrations measured in the breast tissue. The findings of this research have received widespread media coverage, which has raised public awareness of the issue. As a result, producers and retailers of natural and organic cosmetic products have benefitted through the adoption of these research findings into marketing information available to their customers. Scientific Committees have used the research findings to inform their opinions on the risk of parabens that have been submitted to the European Commission. As well, non-government organisations have benefitted from having scientific evidence to support their public awareness initiatives and campaigns to invoke change in policy.
The Million Women Study of 1.3 million UK women over the age of 50, coordinated by the Cancer Epidemiology Unit at Oxford, has established the relationship between hormone replacement therapy (HRT) and breast, endometrial, and ovarian cancer, and has had a dramatic effect on HRT prescription patterns and prescription guidelines worldwide. This has had a major impact on women's health. Prior to the study, one third of UK women aged 50-64 were using HRT. The marked decline in HRT use following publication of the study's findings has led to a reduction in the incidence of breast cancer among menopausal women.
As a result of research at Queen Mary, an estimated 2,500-3,000 additional women per year in UK have a breast cancer detected early through two-view mammography at the NHS Breast Screening Programme, and similar country-wide benefits have occurred abroad. From 1988 the NHS Breast Screening Programme offered women aged 50-64 three-yearly one-view mammography. In 1995, results from the UKCCCR Randomised Trial of One and Two View Mammography (led by Queen Mary researchers) showed that including a second view increased breast cancer detection by 24% and reduced recall rate by 15%. On the basis of this evidence, the Department of Health immediately issued an Executive Letter requiring all breast screening units to move to two-view mammography for the prevalent screen. Changes were rapidly and widely implemented. By 2004, two-view mammography had become the policy at all screens, prevalent and incident. Two-view mammography remains national policy and its benefits continue to the present day.
Impact: Health and welfare; additional effective therapy for women with advanced, HER2+ breast cancer.
Significance: Allows approximately 10,000 patients a year, whose disease is no longer being controlled by trastuzumab, to receive a more effective therapy than chemotherapy with capecitabine alone.
Beneficiaries: Patients with incurable metastatic HER2+ subtype breast cancer; policy-makers; commerce.
Attribution: Cameron (UoE) was joint chief-investigator on the global pivotal registration trial that led to the marketing authorisation of the drug lapatinib in combination with capecitabine.
Reach: World-wide: the drug is approved in >100 countries and generated >£650M in sales for manufacturer GlaxoSmithKline.