2018 Lush Science Prize.

The Lush Prize supports animal-free testing by awarding money prizes of up to £350,000 per year to the most effective projects and individuals who have been working towards the goal of replacing animals in product or ingredient safety testing. Since its inception in 2012, the Lush Prize has distributed almost £2 million. Prizes are awarded for developments in five strategic areas: Science; Lobbying; Training; Public Awareness; and Young Researchers. In 2015, the judges also awarded a Black Box prize for the development of the skin sensitisation Adverse Outcome Pathway and its associated in vitro assays. The Science Prize is awarded to researchers whose work the judging panel believe to have made the most significant contribution, in the preceding year, to the replacement of animal testing. This 2018 Science Background paper outlines the research projects that were presented to the Prize judges as potential candidates for the 2018 Lush Science Prize award. To obtain an overview of developments in the field of animal replacement in toxicity research, recent work by the relevant scientific institutions and projects in this area, including the OECD, CAAT, ECVAM, UK NC3Rs, US Tox21 Programme, the ToxCast programme and EU-ToxRisk, was reviewed. Recent developments in toxicity testing research were investigated by searching the relevant literature. Abstracts from conferences focusing on animal replacement in toxicity testing that were held in the preceding 12 months, were also analysed, including those from the 2017 10th World Congress on Alternatives and Animals in the Life Sciences and the 2018 Society of Toxicology annual conference.

2017 Lush Science Prize.

Now in its sixth year, the Lush Prize supports animal-free testing by awarding money prizes of up to £350,000 to the most effective projects and individuals who have been working towards the goal of replacing animals in product or ingredient safety testing. Prizes are awarded for developments in five strategic areas: Science; Lobbying; Training; Public Awareness; and Young Researchers. In the event of a major breakthrough leading to the replacement of animal tests in the area of 21st Century Toxicology, a Black Box Prize (equivalent to the entire annual fund) is awarded. The Science Prize is awarded to the researchers whose work the judging panel believe has made the most significant contribution to the replacement of animal testing in the preceding year. This Background Paper outlines the research projects that were shortlisted and presented to the judging panel as potential candidates for the 2017 Lush Science Prize. This process involved reviewing recent work of the relevant scientific institutions and projects in this area, such as the OECD, Human Toxome Project, UK NC3Rs, US Tox21 programme, ToxCast programme and the Human Toxicology Project Consortium. Recent developments in toxicity testing research were also identified by searching for relevant published papers in the literature, and analysing abstracts from conferences focusing on animal replacement in toxicity testing that had been held in the preceding 12 months -- for example, the 2016 EUSAAT-Linz conference and the 2017 Society of Toxicology annual conference.

2016 Lush Science Prize.

The Lush Prize supports animal-free testing by awarding monetary prizes totalling £250,000 to the most effective projects and individuals who have been working toward the goal of replacing animals in product or ingredient safety testing. Prizes are awarded for developments in five strategic areas: Science; Lobbying; Training; Public Awareness; and Young Researchers. In the event of a major breakthrough leading to the replacement of animal tests in the area of 21st Century Toxicology, a Black Box Prize (equivalent to the entire annual fund of £250,000) is awarded. The Science Prize is awarded to the researchers whose work the judging panel believe has made the most significant contribution to the replacement of animal testing in the preceding year. This Background Paper outlines the research projects that were shortlisted and presented to the judging panel as potential candidates for the 2016 Lush Science Prize. This process involved reviewing recent work of the relevant scientific institutions and projects in this area, such as the OECD, CAAT, The Hamner Institutes, ECVAM, UK NC3Rs, and the US Tox21 Programme. Recent developments in toxicity testing research were also identified by searching for relevant published papers in the literature, and analysing abstracts from conferences focusing on animal replacement in toxicity testing that had been held in the preceding 12 months - for example the EUSAAT-Linz, Society of Toxicology, and SEURAT-1 conferences.

2015 Lush Science Prize.

The Lush Prize supports animal-free testing by rewarding the most effective projects and individuals who have been working toward the goal of replacing animals in product or ingredient safety testing. Prizes are awarded for developments in five strategic areas: Science; Lobbying; Training; Public Awareness; and Young Researchers. Should there be a major breakthrough in 21st century toxicology, a Black Box Prize equivalent to the entire annual fund of £250,000 is awarded. A Background Paper is prepared each year, prior to the judging process, to provide the panel with a brief overview of current developments in the field of Replacement alternatives, particularly those relevant to the concept of toxicity pathways. The Background Paper includes information on recent work by the relevant scientific institutions and projects in this area, including AXLR8, the OECD, The Hamner Institutes, the Human Toxome Project, EURL ECVAM, ICCVAM, the US Tox21 Programme, the ToxCast programme, and the Human Toxicology Project Consortium. Recent developments in toxicity pathway research are also assessed by reviewing the relevant literature (including conference proceedings), and the abstracts and papers receiving the highest score are presented to the judges for consideration.

Some issues in screening for breast and other cancers.

BACKGROUND: There are some issues in screening for cancer, especially breast cancer, which are worthy of further study. METHODS: We reviewed some approaches to the following issues in breast cancer screening: absolute benefit, overdiagnosis, separation of effects of screening from effects of others on deaths from breast cancer over time and determination of which tumours benefit most from early detection. For separation of screening effects from other effects, we developed a simple analysis of survival by tumour size. For the other issues, we identified methods and results from the literature on the randomized trials of screening and on service screening programmes. We also reviewed screening issues pertaining to other selected cancers, including some cancers common or becoming common in Asia. RESULTS: Published results from the Swedish Two-County Trial showed that for 350 women screened for 10 years, one life would be saved. Results from service screening programmes in Florence and elsewhere suggested that overdiagnosis is a minor phenomenon and mainly confined to ductal carcinoma in situ. Data from before and after the inception of screening in East Anglia suggested that 40-60% of the recent improvement in survival of breast cancer cases was due to early detection. Published data from the Swedish Two-county Trial indicated that the majority of the benefit of breast screening derives from early detection of grades 2 and 3 ductal carcinoma. CONCLUSIONS: Mammographic screening is effective in saving lives from breast cancer. Other cancers, which have strong evidence for a benefit of screening in terms of saving lives from cancer, are cervical and colorectal cancers. There is also evidence of a reduction in mortality associated with ultrasound screening for liver cancer in subjects at very high risk of the disease. There are a number of other cancers that are potential candidates for early detection. There is clearly an opportunity for saving lives from further development and implementation of cancer screening.

Modelling the impact of detecting and treating ductal carcinoma in situ in a breast screening programme.

OBJECTIVES: Screening has substantially increased the detection of carcinoma in situ of the breast (CIS). Opinions vary as to whether this constitutes over-diagnosis or an opportunity to interrupt breast cancer's natural history. In England, incidence of invasive cancer and CIS increased in women of screening age (50-64 years), leading to a subsequent deficit in invasive incidence in women aged 65-69 years immediately beyond the invited age range. We aimed to model underlying incidence of invasive cancer and CIS expected in the absence of screening, and to quantify the likely relative contributions of their early detection to the observed reduction in invasive cancer in women of postscreening age. SETTING: UK NHS breast screening programme in England. METHODS: Poisson regression modelling was used to establish the underlying incidence of invasive and in situ cancers in the absence of screening. We then estimated age- and year-specific excess detection rates attributable to screening. Applying these to population figures we estimated conservatively the relative contributions of early diagnosis of CIS and invasive cancer at 50-64 years of age to the subsequent deficit in invasive cancer in women beyond invitation age (65-69 years), for screening early in the programme and at steady state. RESULTS: Our model estimated a 1.6% annual increase in incidence, giving an estimated deficit of 4.22 invasive cancers per 10,000 women aged 65-69 years in 1996. Carcinoma in situ contributed 13-17% to the deficit, assuming a mean six year lead time and 75-100% progression to invasive cancer. At steady state, with current screening performance and with lead times of 3-4 years (invasive cancer) and 6-9 years (CIS), invasive incidence might be reduced by 5-6 cancers per 10,000 women aged 65-69 years in 2010 (15-20% of underlying incidence), CIS contributing 20-40%. DISCUSSION: The longer lead time associated with CIS attenuates the impact its early detection has on subsequent invasive incidence. At steady state screening, its detection contributes significantly to the deficit in invasive incidence. Our results suggest that, cancer for cancer, there may be just as much benefit in detecting and treating a case of CIS as there is in treating a case of invasive cancer.

Impact of false-positive mammography on subsequent screening attendance and risk of cancer.

BACKGROUND: One area of concern within the largely successful UK National Health Service breast screening programme is the relatively high proportion of women showing mammographic abnormalities who undergo further diagnostic tests that prove negative. Previous studies suggest that, in addition to increasing anxiety, such false-positive mammography is associated with increased risk of subsequent interval cancer. In the present article, we quantify this increased risk, investigate whether it extends to cancers detected at rescreening, and determine whether cancers differ between women who have, and have not, experienced false-positive mammography. METHODS: This was a retrospective cohort study of 140,387 women aged 49-63 years routinely invited for first screening by the East Anglian National Health Service breast screening programme. Proportions reattending, and subsequent risk and pathological attributes of cancer were compared between women who underwent further (negative) assessment following false-positive mammography and women mammographically normal at first screen. RESULTS: At first screen, 108,617 (91.9%) of the screened women were mammographically normal, 4278 (3.6%) were assessed and then judged normal, and 514 (0.4%) underwent benign biopsy. Compared with nonassessed normal women, reattendance was lower among assessed women: 83.1% (95% confidence interval [CI], 82.0-84.1) versus 85.7% (95% CI, 85.5-85.9) (odds ratio [OR], 0.82; 95% CI, 0.76-0.89). Assessed women were at greater risk of interval cancer (rate per 1000 women screened, 9.6 [95% CI, 6.8-12.4] versus 3.0 [95% CI, 2.7-3.4]; OR, 3.19 [95% CI, 2.34-4.35]), and also of cancer detected at second screen (rate per 1000, 8.4 [95% CI, 5.8-10.9] versus 3.9 [95% CI, 3.5-4.3]; OR, 2.15 [95% CI, 1.55-2.98]). More cancers in assessed women measured >or = 20 mm (OR, 1.59; 95% CI, 0.99-2.55). CONCLUSIONS: Women undergoing false-positive mammography at first screen were less likely to reattend for subsequent screens than were nonassessed women, yet they were more likely to develop interval cancers or cancers at second screen, and their cancers were larger. Factors predisposing for false-positive mammography require investigation. Women should be encouraged to continue with screening.