Why is renal impairment associated with poorer cancer specific survival in breast cancer patients?: a comparison with patients with other comorbidities.

BACKGROUND: Our aim is to assess whether the poor breast cancer specific survival (BCSS) seen in women with breast cancer and impaired renal function can be explained by associations with other prognostic factors. METHODS: The study group was a consecutive series of patients undergoing breast ultrasound (US) who had invasive breast cancer (n = 1171). All women had their US diameter and mean stiffness (kPa) at shear wave elastography (SWE) recorded. The core biopsy grade and receptor status were noted. Core biopsy of abnormal axillary nodes and the patient referral source was also noted. Survival including cause of death was ascertained. Comorbidities at diagnosis were recorded. Patients were divided into those with a GFR<60 ("renal group"), those with other comorbidities and those with none. BCSS was assessed using Kaplan-Meier survival curves and Cox proportional hazards regression. RESULTS: One thousand, one hundred and forty-one patients constituted the study group. 107 (9%) patients had impaired renal function, 182 (16%) had other comorbidities while 852 (75%) had no comorbidities. Mean follow-up was 5.8 years. 109 breast cancer and 122 non-breast cancer deaths occurred. BCSS in the renal group was significantly worse than the other groups. Women with renal comorbidity were older, more likely to present symptomatically, have a pre-operative diagnosis of axillary metastases, and have larger and stiffer cancers. Cox proportional hazards regression showed that renal impairment maintained independent significance. CONCLUSION: The poor BCSS in women with impaired renal function is partially explained by advanced tumour stage at presentation. However, impaired renal function maintains an independent prognostic effect.

Pre-operative stromal stiffness measured by shear wave elastography is independently associated with breast cancer-specific survival.

INTRODUCTION: With the increased use of neoadjuvant therapy for breast cancer, there is a need for pre-operative prediction of prognosis. We aimed to assess the prognostic value of tumour stiffness measured by ultrasound shear wave elastography (SWE). METHODS: A consecutive cohort of patients with invasive breast cancer underwent breast ultrasound (US) including SWE. The following were recorded prospectively: US diameter, stiffness at SWE, presentation source, core biopsy grade, oestrogen receptor (ER) status and pre-operative nodal status. Breast cancer-specific survival (BCSS) was analysed with regard to US size and stiffness, tumour grade on core biopsy, ER status, presentation mode and pre-operative nodal status. Analysis used Cox proportional hazards regression. RESULTS: Of the 520 patients, 42 breast cancer and 53 non-breast cancer deaths were recorded at mean follow-up of 5.4 years. Hazard ratios (HR) for tertiles of stiffness were 1, 4.8 and 8.1 (P = 0.0001). HR for 2 groups based on US size < or ≥ 20 mm were 1 and 5.1 (P < 0.0001). HR for each unit increase in tumour grade on core biopsy was 3.9 (P < 0.0001). The HR for ER positivity compared to ER negativity was 0.21 (P < 0.001). BCSS was also associated with presentation mode and pre-operative nodal status. In a multivariable model, stiffness, US size and ER status were independently associated with BCSS. CONCLUSION: Multiple pre-operative factors including stromal stiffness at SWE have independent prognostic significance. A larger dataset with longer follow-up could be used in the future to construct a pre-operative prognostic model to guide treatment decisions.

Mammographic surveillance after breast cancer.

Early detection of local recurrence has been shown to improve survival. What is unclear is how frequently mammography should be performed, how long surveillance should continue and how the answers to these questions vary with tumour pathology, patients age, and surgery type. Many of these questions are not directly answerable from the current literature. While some of these questions will be answered by the Mammo-50 study, evidence from local recurrence rates, tumour biology, and the lead time of mammography can be used to guide policy. Young age is the strongest predictor of local recurrence and given the short lead time of screening in women under 50, these women require annual mammography. Women over 50 with HER-2 positive and triple negative breast cancer have higher rates of local recurrence after breast conserving surgery than women with luminal cancers. Women with HER-2 positive and triple negative breast cancer also have a higher rate of recurrence in years 1-3 post surgery. Annual mammography in year 1-4 would appear justified. Women over 50 with luminal cancers have low rates of local recurrence and no early peak. Recurrence growth will be low due to tumour biology and hormone therapy. Biennial mammography after year 2 would seem appropriate. Women over 50 following mastectomy have no early peak in contralateral cancers so the frequency should be determined by the lead time of screening. This would suggest 2 yearly mammography for women aged 50-60 while 3 yearly mammography may suffice for women over 60.

Upstaging of urothelial cancer at the time of radical cystectomy: factors associated with upstaging and its effect on outcome.

UNLABELLED: What's known on the subject? and What does the study add? The reported discordance between staging on transurethral bladder resection and on radical cystectomy pathology in the literature ranges from 20 to 80%.Correct staging in bladder cancer has direct implications for its management. The upstaging from organ-confined (OC) to non-organ-confined (nOC) disease has been reported in 40% of cases. Lymphovascular invasion (LVI) is a factor known to be associated with poor clinical outcome. Pathological upstaging was observed in our cohort in 40% of cases and most cases (80%) were upstaged from OC to nOC disease. During the study period the frequency of upstaging observed increased. We found LVI (hazard ratio [HR]= 5.07, 95% CI = 3.0-8.3, P < 0.001) and any histological variant variant (HR = 2.77, 95% CI = 1.6-4.8, P < 0.001) to be strong independent predictors of upstaging. Patients with clinical T2 bladder cancer found with upstaging at the time of radical cystectomy had a poorer outcome than patients with no upstaging. Identification of patients at high risk of upstaging at radical cystectomy is key to improving their management and outcome. OBJECTIVES: To analyse the details of bladder cancer (BC) staging in a large combined radical cystectomy (RC) database from two academic centres. To study rate and time trends, as well as risk factors for upstaging, especially clinical factors associated with staging errors after RC. PATIENTS AND METHODS: Characteristics of patients undergoing RC at University Health Network, Toronto, Canada (1992-2010) and University of Turku, Turku, Finland (1986-2005) were analysed. RESULTS: Among 602 patients undergoing RC, 306 (51%) had a discordance in clinical and pathological stages. Upstaging occurred in 240 (40%) patients and 192 (32%) patients were upstaged from organ-confined (OC) to non-organ-confined (nOC) disease. During the study period, upstaging became more common in both centres. In multivariate analyses, T2 disease at initial presentation (P= 0.001, odds ratio [OR]= 2.62, 95% confidence interval [CI]: 1.44-4.77), high grade disease (P= 0.01, OR = 2.85, 95% CI: 1.21-6.7), lymphovascular invasion (LVI) (P < 0.001, OR = 5.17, 95% CI: 3.48-7.68), female gender (P= 0.038, OR = 0.6, 95% CI: 0.38-0.97, and histological variants (P < 0.001, OR = 2.77, 95% CI: 1.6-4.8) were associated with a risk of upstaging from OC to nOC disease. Upstaged patients had worse survival rates than patients with correct staging. This was especially significant among patients with carcinoma invading bladder muscle before undergoing RC (16% vs 46% 10-year disease-specific mortality, P < 0.001). CONCLUSIONS: Upstaging is a common problem and unfortunately no improvements have been observed during the last two decades. LVI and the presence of histological variants are strong predictors of upstaging at the time of RC. Pathologists should be encouraged to report LVI and any histological variant at the time of TURBT.

The value of prognostic ultrasound features of breast cancer in different molecular subtypes with a focus on triple negative disease.

The ultrasound (US) features of breast cancer have recently been shown to have prognostic significance. We aim to assess these features according to molecular subtype. 1140 consecutive US visible invasive breast cancers had US size and mean stiffness by shearwave elastography (SWE) recorded prospectively. Skin thickening (> 2.5 mm) overlying the cancer on US and the presence of posterior echo enhancement were assessed retrospectively while blinded to outcomes. Cancers were classified as luminal, triple negative (TN) or HER2 + ve based on immunohistochemistry and florescent in-situ hybridization. The relationship between US parameters and breast cancer specific survival (BCSS) was ascertained using Kaplan-Meier survival curves and ROC analysis. At median follow-up 6.3 year, there were 117 breast cancer (10%) and 132 non-breast deaths (12%). US size was significantly associated with BCSS all groups (area under the curve (AUC) 0.74 in luminal cancers, 0.64 for TN and 0.65 for HER2 + ve cancers). US skin thickening was associated most strongly with poor prognosis in TN cancers (53% vs. 80% 6 year survival, p = 0.0004). Posterior echo enhancement was associated with a poor BCSS in TN cancers (63% vs. 82% 6 year survival, p = 0.02). Mean stiffness at SWE was prognostic in the luminal and HER2 positive groups (AUC 0.69 and 0.63, respectively). In the subgroup of patients with TN cancers receiving neo-adjuvant chemotherapy posterior enhancement and skin thickening were not associated with response. US skin thickening is a poor prognostic indicator is all 3 subtypes studied, while posterior enhancement was associated with poor outcome in TN cancers.

A pre-operative prognostic model predicting all cause and cause specific mortality for women presenting with invasive breast cancer.

PURPOSE: The aim of this study is to develop a pre-operative prognostic model based on known pre-operative factors. METHODS: A database of ultrasound (US) lesions undergoing biopsy documented US lesion size, stiffness, and patient source prospectively. Women with invasive cancer presenting between 2010 and 2015 were the study group. Breast and axillary core results and ER, PR and HER receptor status were collected prospectively. Assessment of US skin thickening, US distal enhancement and presence of chronic kidney disease (CKD) was performed retrospectively. Patient survival and cause of death were ascertained from computer records. Predictive models for (i) all-cause mortality (ACM) and (ii) breast cancer death (BCD) were built and then validated using bootstrap k-fold cross-validation. A comparison of predictive performance was made between a full cause-specific Cox model, a sub cause-specific Cox model, and a full Fine-Gray sub-distribution hazard model. RESULTS: 1136 patients were included in the study. The median follow-up time was 6.2 years. 125 (11%) women died from breast cancer and 155 (14%) died from other causes. For the prediction of BCD, the cause-specific Cox sub-model performed the best. The time dependent AUC begins above 0.91 in year one to 3 reducing to 0.83 in year 6. The factors included in the Cox sub model were tumour size, skin thickening, source of detection, tumour grade, ER status, pre-operative nodal metastasis and CKD. CONCLUSION: We have shown that a model based on preoperative factors can predict BCD. Such prediction if externally validated and incorporating treatment data could be useful for treatment planning and patient counselling.

The prognostic impact of mode of detection of axillary metastases for women with invasive breast cancer: A retrospective observational study.

AIM: To identify the breast cancer specific survival (BCSS) associated with nodal metastasis identified by axillary core biopsy (ACB), and by sentinel node biopsy (SNB) compared with node negative patients. A further aim was to assess the prognostic effects of axillary ultrasound (US) features and amount of tumour in ACB specimens. METHODS: Consecutive patients with cancer were identified from a database of US lesions undergoing breast biopsy. The three study groups were: a) those with metastasis identified by ACB, b) those undergoing immediate surgery with positive SNB and c) those undergoing immediate surgery with a negative SNB. US features and the amount of tumour in the ACB specimen were assessed by review of US images and pathological reports. BCSS was assessed using Kaplan Meier survival curves. RESULTS: 967 patients were included, with mean follow-up of 6.0 yrs. There were 90 breast cancer deaths: 26% of those with a positive ACB, 11% with a positive SNB and 4% of those with a negative SNB. BCSS was significantly different between the groups (p < 0.001) with hazard ratio, compared with the negative SNB group, of 7.8 (95% CI 4.4-13.7) for patients with positive ACB and 2.5 (95% CI 1.3-4.6) for positive SNB. Axillary US findings and assessment of the amount of tumour in the ACB did not influence survival. CONCLUSION: This study suggests that women with a positive ACB have a worse BCSS compared to those with a positive SNB. This should be borne in mind when systemic therapy is being considered.

Development and validation of a novel measure of adverse patient positioning in mammography.

PURPOSE: The primary aim was to develop and validate a novel mammography positioning measure, specifically incorporating parameters which might relate to mammography pain. We then explored relationships between the new adverse positioning score and (1) pain; (2) patient and technique factors. METHODS: A 15-item instrument incorporating positioning features with potential to relate to mammography pain was developed. Participants' mammograms (n = 310) were reviewed for presence of these features. Validity was investigated using the Rasch model. Scores produced by the resultant measure were investigated for associations with patients' pain scores and relevant patient and technique factors, using Pearson correlation, analysis of variance, and multiple linear regression. RESULTS: Statistical indices within the Rasch measurement framework provided good evidence that the measure reflected a coherent construct of adverse positioning. Thus, the scores produced with the measurement instrument were valid for use in further statistical analysis. There is, however, scope for improvement of the measure's discriminatory properties. Adverse positioning scores were higher for greater breast volumes (r = 0.12, p=.0391) and body mass index (BMI) (r = 0.13, p=.0349), and varied by mammographer (F(11,298) 2.38, p = .0078). The relationships with BMI and mammographer persisted in regression modelling. No relationship was found between adverse positioning and pain. CONCLUSIONS: Evidence from Rasch analysis suggests that this novel measure is valid for quantifying a coherent "adverse positioning" construct in mammography. Adverse positioning scores varied by mammographer and were related to higher patient BMI but not to mammography pain. The measure warrants expansion, further refinement, and testing in larger studies.

Are baseline mammographic and ultrasound features associated with metastasis free survival in women receiving neoadjuvant chemotherapy for invasive breast cancer?

OBJECTIVES: To identify associations between baseline ultrasound (US) and mammographic features and metastasis free survival (MFS) in women receiving neo-adjuvant chemotherapy (NACT) for breast cancer. METHODS: The data were collected as part of an ethically approved prospective study. Women with invasive breast cancer receiving NACT who were metastasis free at diagnosis were included. Baseline US and mammography were performed. Imaging was assessed by an experienced breast radiologist who was blinded to outcomes. US imaging features documented included posterior effect, skin thickening, size and stiffness using shear wave elastography (SWE). The mammographic features documented were spiculation and microcalcification. The development of metastatic disease was ascertained from computer records. Statistical analysis was performed using Kaplan Meier survival curves and Receiver Operator Characteristic (ROC) analysis. RESULTS: 171 women with 172 cancers were included in the study and 55 developed metastatic disease. Mean follow-up was 6.0 years. Women with mammographic calcification had significantly poorer metastasis free survival (MFS) compared to women without calcification (p = 0.043, 6 yr MFS 50 % vs 69 %). Women bearing cancer with distal shadowing had poorer MFS than women without shadowing (p = 0.025, 6 yr MFS 47 % vs. 73 %). Women with US skin thickening had poorer MFS compared to women without skin thickening (p = 0.032, 6 yr MFS 52 % vs. 68 %). Mammographic spiculation, US size and stiffness at SWE had no significant association with MFS. CONCLUSION: We have identified mammographic and US features associated with MFS in women receiving NACT. Such information may be useful when counselling patients about the benefits and risks of NACT.

Application of the Rasch measurement framework to mammography positioning data.

The purpose of this article is to provide raw data and measure-validation data pertaining to a co-submission published in European Journal of Radiology and entitled: Development and validation of a novel measure of adverse patient positioning in mammography. This Data in Brief article serves not only to provide greater detail than its companion article but also as an educational worked example of the Rasch measurement framework. Rasch measurement is a form of modern psychometric technique and our articles provide the first known example of its use in the evaluation of clinical radiological image quality. The data consist of observations of mammographic images, plus limited participant parameters relevant to the measure validation process. Also provided are validation indices produced by subjecting the primary data to Rasch analysis. An expert observer generated the primary data by reviewing mammographic images to judge the presence or absence of a set of features developed through theory and consultation with other experts. The validation data were generated through Rasch analysis, performed using Winsteps® software, which mathematically models the probability of having a correct response (or a present feature in this dataset) to an item in a given measurement instrument (e.g. questionnaire), as a function of the participant's ability/position on the underlying construct under study. The data can be reused by anyone wishing to learn and practice psychometric validation techniques. They can also form a basis for researchers wishing to build on our preliminary measure for the assessment of mammographic clinical image quality.

Triple-negative breast cancer: distinguishing between basal and nonbasal subtypes.

PURPOSE: Triple-negative (TN; estrogen receptor, progesterone receptor, and HER-2 negative) cancer and basal-like breast cancer (BLBC) are associated with poor outcome and lack the benefit of targeted therapy. It is widely perceived that BLBC and TN tumors are synonymous and BLBC can be defined using a TN definition without the need for the expression of basal markers. EXPERIMENTAL DESIGN: We have used two well-defined cohorts of breast cancers with a large panel of biomarkers, BRCA1 mutation status, and follow-up data to compare the clinicopathologic and immunohistochemical features of TN tumors expressing one or more of the specific basal markers (CK5/6, CK17, CK14, and epidermal growth factor receptor; BLBC) with those TN tumors that express none of these markers (TN3BKE-). RESULTS: Here, we show that although the morphologic features of BLBC are not significantly different from that of TN3BKE- tumors, BLBC showed distinct clinical and immunophenotypic differences. BLBC showed a statistically significant association with the expression of the hypoxia-associated factor (CA9), neuroendocrine markers, and other markers of poor prognosis such as p53. A difference in the expression of cell cycle-associated proteins and biomarkers involved in the immunologic portrait of tumors was seen. Compared with TN3BKE- tumors, BLBC was positively associated with BRCA1 mutation status and showed a unique pattern of distant metastasis, better response to chemotherapy, and shorter survival. CONCLUSION: TN breast cancers encompass a remarkably heterogeneous group of tumors. Expression of basal markers identifies a biologically and clinically distinct subgroup of TN tumors, justifying the use of basal markers (in TN tumors) to define BLBC.

Are baseline ultrasound and mammographic features associated with rates of pathological completes response in patients receiving neoadjuvant chemotherapy for breast cancer?

BACKGROUND: Increasing numbers of breast cancer patients receive neoadjuvant chemotherapy (NACT). We seek to investigate whether baseline mammographic and ultrasound features are associated with complete pathological response (pCR) after NACT. METHODS: A database of NACT patients was reviewed. Baseline imaging parameters assessed were ultrasound: posterior effect; echo pattern; margin and lesion diameter; mammography: spiculation and microcalcification. Core biopsy grade and immunophenotype were documented. Data were analysed for the whole study group and by immunophenotype. RESULTS: Of the 222 cancers, 83 (37%) were triple negative (TN), 61 (27%) ER positive/HER-2 negative and 78 (35%) HER-2 positive. A pCR occurred in 46 of 222 cancers (21%). For the whole group, response was associated with high core biopsy grade (grade 3 vs. grade 1 or 2) (26% vs. 9%, p = 0.0044), absence of posterior shadowing on ultrasound (26% vs. 10%, p <  0.001) and the absence of mammographic spiculation (26 vs. 6%, p <  0.001). Within the HER-2 positive group; the absence of shadowing and spiculation remained highly associated with pCR, in addition to small ultrasound size (AUC = 0.71, p < 0.001) and the absence of microcalcification (39% vs. 21%, p < 0.02). On multivariable analysis absence of spiculation and core grade remained significant for the whole cohort, size and absence of spiculation remained significant for HER-2 positive tumours. No feature predicted pCR in TN tumours. CONCLUSION: A pCR is less likely when there is mammographic spiculation. Small ultrasound size is associated with pCR in HER-2 positive tumours. These findings may be helpful when discussing NACT and surgical options with patients. TRIAL REGISTRATION: UK Clinical Trials Gateway: registration number 16712.

Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years' follow-up: a randomised controlled trial.

BACKGROUND: The efficacy of screening by mammography has been shown in randomised controlled trials in women aged 50 years and older, but is less clear in younger women. A meta-analysis of all previous trials showed a 15% mortality reduction in invited women aged 40-49 years at study entry, but this finding could be due in part to screening of women after age 50 years. The Age trial was designed to study the effect on mortality of inviting women for annual mammography from age 40 years. METHODS: 160,921 women aged 39-41 years were randomly assigned in the ratio 1:2 to an intervention group of annual mammography to age 48 years or to a control group of usual medical care. The trial was undertaken in 23 NHS breast-screening units in England, Wales, and Scotland. The primary analysis was based on the intention-to-treat principle and compared mortality rates in the two groups at 10 years' follow-up. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN24647151. FINDINGS: At a mean follow-up of 10.7 years there was a reduction in breast-cancer mortality in the intervention group, in relative and absolute terms, which did not reach statistical significance (relative risk 0.83 [95% CI 0.66-1.04], p=0.11; absolute risk reduction 0.40 per 1000 women invited to screening [95% CI -0.07 to 0.87]). Mortality reduction adjusted for non-compliance in women actually screened was estimated as 24% (RR 0.76, 95% CI 0.51-1.01). INTERPRETATION: Although the reduction in breast-cancer mortality observed in this trial is not significant, it is consistent with results of other trials of mammography alone in this age-group. Future decisions on screening policy should be informed by further follow-up from this trial and should take account of possible costs and harms as well as benefits.

Overdiagnosis in breast imaging.

The main harm of overdiagnosis is overtreatment. However a form of overdiagnosis also occurs when foci of cancer are found by imaging in addition to the symptomatic lesion when this leads to additional treatment which does not benefit the patient. Even if overtreatment is avoided, knowledge of the diagnosis can still cause psychological harm. Overdiagnosis is an inevitable effect of mammographic screening as the benefit comes from diagnosing breast cancer prior to clinical detectability. Estimates of the rate of overdiagnosis at screening are around 10%. DCIS represents 20% of cancers detected by screening and is the main focus in the overdiagnosis debate. Detection and treatment of low grade DCIS and invasive tubular cancer would appear to represent overdiagnosis in most cases. Supplementary screening with tomosynthesis or US are both likely to increase overdiagnosis as both modalities detect predominantly low grade invasive cancers. MRI causes overdiagnosis because it is so sensitive that it detects real tumour foci which after radiotherapy and systemic therapy do not, in many cases go on and cause local recurrence if the women had had no MRI and undergone breast conservation and adjuvant therapy with these small foci left in situ.

Shear-wave elastography and greyscale assessment of palpable probably benign masses: is biopsy always required?

OBJECTIVE: To establish if palpable breast masses with benign greyscale ultrasound features that are soft on shear-wave elastography (SWE) (mean stiffness <50 kPa) have a low enough likelihood of malignancy to negate the need for biopsy or follow-up. METHODS: The study group comprised 694 lesions in 682 females (age range 17-95 years, mean age 56 years) presenting consecutively to our institution with palpable lesions corresponding to discrete masses at ultrasound. All underwent ultrasound, SWE and needle core biopsy. Static greyscale images were retrospectively assigned Breast Imaging Reporting and Data System (BI-RADS) scores by two readers blinded to the SWE and pathology findings, but aware of the patient's age. A mean stiffness of 50 kPa was used as the SWE cut-off for calling a lesion soft or stiff. Histological findings were used to establish ground truth. RESULTS: No cancer had benign characteristics on both modalities. 466 (99.8%) of the 467 cancers were classified BI-RADS 4a or above. The one malignant lesion classified as BI-RADS 3 was stiff on SWE. 446 (96%) of the 467 malignancies were stiff on SWE. No cancer in females under 40 years had benign SWE features. 74 (32.6%) of the 227 benign lesions were BI-RADS 3 and soft on SWE; so, biopsy could potentially have been avoided in this group. CONCLUSION: Lesions which appear benign on greyscale ultrasound and SWE do not require percutaneous biopsy or short-term follow-up, particularly in females under 40 years. ADVANCES IN KNOWLEDGE: None of the cancers had benign characteristics on both greyscale ultrasound and SWE, and 32% of benign lesions were BI-RADS 3 and soft on SWE; lesions that are benign on both ultrasound and SWE may not require percutaneous biopsy or short-term follow-up.

Evidence of multifocality of telomere erosion in high-grade prostatic intraepithelial neoplasia (HPIN) and concurrent carcinoma.

Mechanisms underlying prostate cancer (CaP) initiation and progression are poorly understood. A chromosomal instability mechanism leading to the generation of numerical and structural chromosomal changes has been implicated in the preneoplastic and neoplastic stages of CaP. Telomere dysfunction is one potential mechanism associated with the onset of such instability. To determine whether there was alteration in telomere length and chromosome number, 15 paraffin-embedded prostatectomy specimens were investigated using quantitative peptide nucleic acid (PNA) FISH analysis of representative foci of carcinoma, putative precancerous lesions (high-grade prostatic intraepithelial neoplasia, HPIN) and nondysplastic prostate epithelium. A significant decrease in telomere length was shown in both HPIN and CaP in comparison with normal epithelium. In addition, elevated rates of aneusomy suggested that increased levels of chromosomal aberrations were associated with decreased telomere length. Moreover, multiple foci of HPIN were shown to have a heterogeneous overall reduction of telomere length. This reduction was more evident in the histologic regions of the prostate containing CaP. Such observations lend support to the hypothesis that telomere erosion may be a consistent feature of CaP oncogenesis and may also be associated with the generation of chromosomal instability that characterizes this malignancy.

The diagnosis and management of pre-invasive breast disease: radiological diagnosis.

Pre-invasive disease is most frequently diagnosed in asymptomatic women following detection of microcalcification at mammography. The vast majority is ductal carcinoma in situ. This article summarizes the radiological features of pre-invasive disease and indicates which features are helpful in differentiating between benign and malignant conditions. The value of finding ductal carcinoma in situ at screening, predicting the presence of an invasive focus and methods of percutaneous biopsy of calcification are also addressed.

The effect of mammography pain on repeat participation in breast cancer screening: a systematic review.

Uptake is crucial to reducing breast cancer mortality through screening. This review synthesised all available evidence on mammography pain as a deterrent to subsequent breast screening. Ten databases were searched. Studies containing empirical data relating mammography pain to breast screening re-attendance were included (n = 20). In the most robust studies asking women why they had not re-attended, 25%-46% cited pain, equivalent to approximately 47,000-87,000 women per year in England. The most robust evidence for an association between pain experienced at a previous mammogram and subsequent rates of re-attendance suggests that women who previously experienced pain are more likely than those who did not to fail to re-attend: RR 1.34 (95% CI: 0.94-1.91). The complexity of the pain phenomenon and of screening behaviours must be recognised. However, there is sufficient evidence to conclude that painful mammography contributes to non-re-attendance. Given the importance of cumulative participation, effective pain-reducing interventions in mammography are needed.

Predicting impacts of climate change on Fasciola hepatica risk.

Fasciola hepatica (liver fluke) is a physically and economically devastating parasitic trematode whose rise in recent years has been attributed to climate change. Climate has an impact on the free-living stages of the parasite and its intermediate host Lymnaea truncatula, with the interactions between rainfall and temperature having the greatest influence on transmission efficacy. There have been a number of short term climate driven forecasts developed to predict the following season's infection risk, with the Ollerenshaw index being the most widely used. Through the synthesis of a modified Ollerenshaw index with the UKCP09 fine scale climate projection data we have developed long term seasonal risk forecasts up to 2070 at a 25 km square resolution. Additionally UKCIP gridded datasets at 5 km square resolution from 1970-2006 were used to highlight the climate-driven increase to date. The maps show unprecedented levels of future fasciolosis risk in parts of the UK, with risk of serious epidemics in Wales by 2050. The seasonal risk maps demonstrate the possible change in the timing of disease outbreaks due to increased risk from overwintering larvae. Despite an overall long term increase in all regions of the UK, spatio-temporal variation in risk levels is expected. Infection risk will reduce in some areas and fluctuate greatly in others with a predicted decrease in summer infection for parts of the UK due to restricted water availability. This forecast is the first approximation of the potential impacts of climate change on fasciolosis risk in the UK. It can be used as a basis for indicating where active disease surveillance should be targeted and where the development of improved mitigation or adaptation measures is likely to bring the greatest benefits.