R. Warren

An evaluation of octogenarians undergoing percutaneous coronary intervention from the Melbourne Interventional Group registry

The objective of this study was to evaluate the clinical characteristics and outcomes of octogenarians (≥80 years of age) in a contemporary, multi‐centre percutaneous coronary intervention (PCI) registry.

Breast density and breast cancer risk factors in a high-risk population

This study investigates relationships between familial and hormonal risk factors and breast density in women at high risk of developing breast cancer. The subjects are a subset of 102 women from the international breast cancer intervention study (IBIS), for whom a series of repeated measurements of breast density were available. Details of familial and hormonal risk factors for breast cancer were collected at entry and multivariate ordered logistic regression used to identify risk factors for increased breast density. Lower body mass index and nulliparity were associated with high breast density, whereas smoking was associated with lower breast density. It is not yet known whether a reduction in breast density will lead to a corresponding reduction in breast cancer risk, so we propose that changes in breast density be investigated as a potential early indicator of efficacy in chemoprevention trials for breast cancer.

Prevention of breast cancer in the context of a national breast screening programme.

Abstract.  Howell A, Astley S, Warwick J, Stavrinos P, Sahin S, Ingham S, McBurney H, Eckersley B, Harvie M, Wilson M, Beetles U, Warren R, Hufton A, Sergeant J, Newman W, Buchan I, Cuzick J, Evans DG (Genesis Prevention Centre and Nightingale Breast Screening Centre, University Hospital of South Manchester; School of Cancer and Enabling Sciences, University of Manchester, Manchester; Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London; School of Community Based Medicine, University of Manchester, Manchester; Genetic Medicine, Manchester Academic Health Sciences Centre, University of Manchester and Central Manchester Foundation Trust, Manchester; and Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge; UK). Prevention of breast cancer in the context of a national breast screening programme (Review). J Intern Med 2012; 271: 321–330.

Prevention of Breast Cancer on the context of National Breast Screening Programme.

Abstract.  Howell A, Astley S, Warwick J, Stavrinos P, Sahin S, Ingham S, McBurney H, Eckersley B, Harvie M, Wilson M, Beetles U, Warren R, Hufton A, Sergeant J, Newman W, Buchan I, Cuzick J, Evans DG (Genesis Prevention Centre and Nightingale Breast Screening Centre, University Hospital of South Manchester; School of Cancer and Enabling Sciences, University of Manchester, Manchester; Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London; School of Community Based Medicine, University of Manchester, Manchester; Genetic Medicine, Manchester Academic Health Sciences Centre, University of Manchester and Central Manchester Foundation Trust, Manchester; and Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge; UK). Prevention of breast cancer in the context of a national breast screening programme (Review). J Intern Med 2012; 271: 321–330.

Automated breast tissue measurement of women at increased risk of breast cancer

We have analysed data from a subgroup of thirty-nine women who had previously gained more than 10kg in adult life, and who were amongst those recruited from a family history clinic to a study examining the effects of diet and exercise on breast cancer risk. At entry to the study and after 12 months they underwent a series of investigations, including mammography during which markers were attached to the compression plate to allow accurate measurement of breast thickness. A calibrated stepwedge was placed adjacent to the breast to enable quantitative analysis. The proportions of glandular and fatty tissue were calculated at each pixel from the stepwedge and thickness data and from these, the percentage gland in the breast was computed, both by area and by volume. Statistical analysis showed that the volume of glandular tissue was not related to breast size. Over the 12 month period, the majority of the women lost weight, while some gained weight. It was found that weight change was correlated with change in the volume of fat in the breasts, with those women who lost the largest amount of weight showing the greatest reduction in volume. There was little change in volume of glandular tissue for any of the women. Percentage gland is often used as an indication of risk of developing breast cancer. These results suggest that measures of percentage of gland (e.g. Boyd groups) may be dominated by excess breast fat in overweight women.

An audit of assessment procedures in women who develop breast cancer after a negative result

Objectives: A case audit was undertaken to determine the extent to which the early diagnosis of cancer could be improved by better adherence to screening guidelines, and to estimate the effect that this might have on breast cancer survival. Although affecting only a small proportion of the cancers of the screening programme, this exercise had an educational function for screening radiologists. Setting: The East Anglian breast screening programme, a group of seven centres offering screening to a total population of 2.2 million inhabitants. Women were screened every three years between the ages of 50 and 64. Methods: Adherence to the guidelines of the UK National Breast Screening Programme (as published in 2001) was tested in women assessed between the start of screening on 1 April 1989 and 31 December 1999, in cases where the screen was negative but who were subsequently diagnosed with breast cancer. Results: In this period the programme screened 503,493 women, recalled 25,346 and diagnosed 3689 with cancer. 194 cancers in 193 women were reviewed, comprising those cancers that arose at the site of the lesion previously assessed. 96 women (49.5%) had calcifications, 48 (24.7%) had opacities. 139 of 194 cases were judged to have been inadequately assessed. A recurring theme showed that biopsies not undertaken or with false negative findings led to failure to diagnose lesions which were subsequently shown to be cancer. Microcalcifications and opacities were more likely to have been inadequately assessed than spiculate masses, parenchymal deformities, or asymmetric densities. In the earliest time period (1989–1993), there were a larger proportion of inadequately assessed cases than in the period 1994–1999. Conclusion: Scrupulous adherence to good guidelines will result in a greater proportion of cancers being diagnosed. Failure to perform effective percutaneous biopsy was the usual cause of missed diagnoses. Although an infrequent occurrence this may have an effect on subsequent survival from breast cancer.

Change in breast density as a biomarker of breast cancer risk reduction; results from IBIS-1

Background: Numerous studies have documented the importance of mammographic breast density as a risk factor for breast cancer. It has the highest attributable risk of all currently known risk factors, and is modifiable. For mammographic density to be considered a biomarker, however, one would have to demonstrate that the risk reduction induced by a preventive intervention can be predicted by change in density, and that those who experience the largest change are most likely to have benefited. In the IBIS-1 study, tamoxifen reduced the risk of breast cancer by about 40% (Cuzick, et al JNCI 2007). Here we focus on whether the change in breast density after 12-18 months of prophylactic treatment predicts the subsequent impact of tamoxifen on the development of breast cancer. Material and Methods: The entry and 12-18 month mammograms for 120 UK breast cancer cases and 943 controls (women who had not developed breast cancer) who were participants in IBIS-1 were retrieved and mammographic density visually assessed (as a percentage of the total breast area) by a consultant radiologist (RW) using a semi-continuous 21-point categorical scale (0,5, 10,..., 100). Using logistic regression we assessed the univariate and multivariate effects of treatment, mammographic density (change over the first 12-18 months on treatment and at entry), anthropometric, hormonal and familial factors on the risk of developing breast cancer. All analyses were unmatched but adjusted for age at entry to the study. Sub-analyses were performed on the placebo and tamoxifen arms separately. Results: Mammographic density at entry, BMI, breast cancer risk (from the Cuzick-Tyrer model) and change in density during the first 12-18 months of treatment were all significant in the multivariate model. In the tamoxifen arm (N=504, 48 cases and 456 controls), only change in mammographic density was significant (P = 0.05). For the 46% of women in the tamoxifen arm whose density reduced by 10% or more, the risk of breast cancer was reduced by 52% relative to the control group (P = 0.01) while for the 54% of women whose density was not reduced by 10 % there was only a non-significant 8% reduction in breast cancer risk. Discussion: Our findings suggest that the impact of tamoxifen on risk reduction is predictable by the changes it induces on breast density after 12-18 months of treatment. Changes in breast density may therefore constitute an early indicator of treatment efficacy, which would be useful for the evaluation of new chemoprevention therapies. Furthermore, by measuring density changes between baseline and initial follow up mammograms in high risk women receiving tamoxifen, it may be possible to determine which women are actually benefiting from the intervention (and should therefore continue treatment), and those who might benefit more from alternative risk reducing strategies. These findings need confirmation in an independent study.

Evaluation of mammographic surveillance services in women aged 40–49 years with a moderate family history of breast cancer: a single-arm cohort study

BACKGROUND Women with a significant family history of breast cancer are often offered more intensive and earlier surveillance than is offered to the general population in the National Breast Screening Programme. Up to now, this strategy has not been fully evaluated. OBJECTIVE To evaluate the benefit of mammographic surveillance for women aged 40-49 years at moderate risk of breast cancer due to family history. The study is referred to as FH01. DESIGN This was a single-arm cohort study with recruitment taking place between January 2003 and February 2007. Recruits were women aged < 50 years with a family history of breast or ovarian cancer conferring at least a 3% risk of breast cancer between ages 40 and 49 years. The women were offered annual mammography for at least 5 years and observed for the occurrence of breast cancer during the surveillance period. The age group 40-44 years was targeted so that they would still be aged < 50 years after 5 years of surveillance. SETTING Seventy-four surveillance centres in England, Wales, Scotland and Northern Ireland. PARTICIPANTS A total of 6710 women, 94% of whom were aged < 45 years at recruitment, with a family history of breast cancer estimated to imply at least a 3% risk of the disease between the ages of 40 and 50 years. INTERVENTIONS Annual mammography for at least 5 years. MAIN OUTCOME MEASURES The primary study end point was the predicted risk of death from breast cancer as estimated from the size, lymph node status and grade of the tumours diagnosed. This was compared with the control group from the UK Breast Screening Age Trial (Age Trial), adjusting for the different underlying incidence in the two populations. RESULTS As of December 2010, there were 165 breast cancers diagnosed in 37,025 person-years of observation and 30,556 mammographic screening episodes. Of these, 122 (74%) were diagnosed at screening. The cancers included 44 (27%) cases of ductal carcinoma in situ. There were 19 predicted deaths in 37,025 person-years in FH01, with an estimated incidence of 6.3 per 1000 per year. The corresponding figures for the Age Trial control group were 204 predicted deaths in 622,127 person-years and an incidence of 2.4 per 1000 per year. This gave an estimated 40% reduction in breast cancer mortality (relative risk = 0.60; 95% confidence interval 0.37 to 0.98; p = 0.04). CONCLUSIONS Annual mammography in women aged 40-49 years with a significant family history of breast or ovarian cancer is both clinically effective in reducing breast cancer mortality and cost-effective. There is a need to further standardise familial risk assessment, to research the impact of digital mammography and to clarify the role of breast density in this population. TRIAL REGISTRATION National Research Register N0484114809. FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 11. See the HTA programme website for further project information.