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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.
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.
Researchers at the University of Manchester (UoM) have made a significant impact internationally on improving outcomes for women diagnosed with breast cancer (>49,000 pa in the UK) and on preventing the disease. The changes in clinical practice based on our research are now national guidelines and have helped set international treatment standards. These new approaches have: increased the duration of survival of women with advanced breast cancer; reduced relapse rates and improved survival after surgery for early breast cancer; and prevented disease in women at high risk. The revised treatment has benefited >1.5m women worldwide annually who develop breast cancer and sales of anastrozole, which has replaced tamoxifen as the major endocrine therapy, have grossed over $1bn p.a.
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.
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.
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.
Research at Cardiff University is underpinning the abandonment of the 100-year-old surgical practice of removing all axillary lymph nodes in cases of breast cancer. Such surgery frequently caused arm lymphoedema, loss of arm mobility and lymphatic system damage. Cardiff led the seminal ALMANAC trial which showed that full node clearance was unnecessary if a biopsy of the first draining `sentinel' node was cancer-free. Cardiff then spearheaded the impact on practice through a training and awareness programme for surgeons, primarily in the UK, but also in China, India, Brazil and Turkey. By 2010 these efforts had established the Sentinel Lymph Node Biopsy (SLNB) procedure as standard in the UK, while the study was also cited in USA guidelines. The main beneficiaries of the impact are the 50-75% of breast cancer patients who now enjoy lower levels of pain, shoulder disability and arm lymphoedema. Healthcare providers also benefit financially from a reduced need for extensive surgery.
Research by our group at the University of Manchester has impacted directly on policy addressing inequities in access to treatment for older women with breast cancer, affecting treatment for 10,060 older breast cancer sufferers in England each year. Our research has led to improvements in pre-operative nutrition and screening for malnutrition for nearly 100,000 patients in Greater Manchester. We have contributed directly to international guidelines on post-treatment follow up for breast cancer and management of cough in lung cancer. We have also contributed to development of national vocational rehabilitation, employer support and benefits advisors for cancer survivors, affecting 700,000 survivors across the UK. Our work has led to implementation of family carer support needs assessment in UK hospice services, to date supporting some 4,500 carers per year with wider roll out imminent.