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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.