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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.
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.
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.
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.
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.
The MRC Conventional versus Laparoscopic-Assisted Surgery In Colorectal Cancer trial (CLASICC) is the largest and most successful UK trial of a technology applied to general surgery. It addressed an area of huge clinical uncertainty, providing a rigorous evaluation of a new technology and enabling its safe and widespread implementation. The impact of CLASICC has been global, confirming the advantages for patients (quicker recovery) and healthcare providers (cost-effectiveness) and so influencing national and international policy in favour of the laparoscopic technique. It informed NICE guidance and led to a major DH initiative that has seen the UK become one of the largest providers in the world of laparoscopic colorectal cancer surgery. CLASICC is regarded as a benchmark surgical trial, combining high quality trial design with rigorous quality assurance, which has informed the design of many subsequent colorectal cancer studies.
Clinical research led by The Institute of Cancer Research (ICR) has resulted in new standardised curative radiotherapy dose-fractionation regimens being adopted across the UK for over 25,000 women per year with early breast cancer. As a direct result of the trials led by the ICR, NICE introduced new guidance in 2009 recommending a 15-fractions-over-3-weeks radiotherapy regimen (hypofractionation) instead of the previous 25-fractions-over-5-weeks schedule. Patient welfare is substantially improved with savings in travel time and costs for attending treatment, and the NHS benefits from reduced treatment costs. This new treatment schedule is now being adopted internationally.
Colorectal cancer is a common disease, which frequently causes death or morbidity, either because of failure to control the primary tumour or failure to prevent distant metastases. Leeds researchers have devised new treatment approaches using chemotherapy and radiotherapy and tested them in large randomised controlled trials which have led to major changes in clinical practice in the management of rectal cancer and advanced colorectal cancer (aCRC), driving clinical decision-making and improving outcomes for patients. This includes better-evidenced treatment for elderly patients and patient stratification on the basis of molecular biomarkers.
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.