Carolyn Nickson

Mammographic Screening and Breast Cancer Mortality: A Case–Control Study and Meta-analysis

Background: Observational studies are necessary to assess the impact of population screening on breast cancer mortality. While some ecological studies have notably found little or no association, case–control studies consistently show strong inverse associations, but they are sometimes ignored, perhaps due to theoretical biases arising from the study design. We conducted a case–control study of breast cancer deaths in Western Australia to evaluate the effect of participation in the BreastScreen Australia program, paying particular attention to potential sources of bias, and undertook an updated meta-analysis of case–control studies. Methods: Our study included 427 cases (women who died from breast cancer), each matched to up to 10 controls. We estimated the association between screening participation and breast cancer mortality, quantifying the effect of potential sources of bias on our findings, including selection bias, information bias, and confounding. We also conducted a meta-analysis of published case–control studies. Results: The OR for participation in the Western Australian BreastScreen program in relation to death from breast cancer was 0.48 [95% confidence interval (CI), 0.38–0.59; P < 0.001]. We were unable to identify biases that could negate this finding: sensitivity analyses generated ORs from 0.45 to 0.52. Our meta-analysis yielded an OR of 0.51 (95% CI, 0.46–0.55). Conclusions: Our findings suggest an average 49% reduction in breast cancer mortality for women who are screened. In practice, theoretical biases have little effect on estimates from case–control studies. Impact: Case–control studies, such as ours, provide robust and consistent evidence that screening benefits women who choose to be screened. Cancer Epidemiol Biomarkers Prev; 21(9); 1479–88. ©2012 AACR.

The predicted impact of HPV vaccination on male infections and male HPV-related cancers in Australia.

Australia implemented a National HPV Vaccination Program in 2007, with routine vaccination of 12-13 year old females and catch-up in females aged 13-26 years to 2009. The aim of this study was to estimate the impact of the current female-only national vaccination program on males, and then to estimate the incremental benefits to males from being included in the program. We used preliminary data to estimate vaccination coverage in females. We then fitted a dynamic model of sexual behaviour and HPV transmission in Australia to local data on female pre-vaccination age-specific HPV prevalence, predicted the corresponding pre-vaccination prevalence in males due to heterosexual transmission, and modelled the short and long term impact of female-only versus female-and-male vaccination programs. The estimated 3-dose female coverage rates were 78% (range 70-80%) for ongoing coverage in 12-13 year old girls; and from 74% (range 70-80%) in 14 year olds, to 25% (range 15-35%) for women aged 26 years old in 2007. The median estimate for age-standardised pre-vaccination HPV 16 prevalence in females and males aged 15-59 years was 3.2% (95% range: 2.4-4.1%) and 3.1% (95% range: 2.2-4.2%), respectively. The current program in females is predicted to result in a 68% reduction in male HPV 16 infections by 2050, leading to an estimated long term reduction of 14% in rates of cancers of the head, neck and anogenital area. The estimated proportion of the maximum possible vaccine-conferred benefit to males from a female-and-male program which will be achieved by female-only vaccination is 73% (range in probabilistic sensitivity analysis: 53-78%). In conclusion, up to three-quarters of the maximum possible vaccination-conferred benefit to males due to reduced heterosexual transmission will be achieved by the existing female-only program.

Prevention of cervical cancer in rural China: evaluation of HPV vaccination and primary HPV screening strategies.

Comprehensive evaluation of the cost-effectiveness of HPV vaccination in China has not previously been performed. The objective of this study was to evaluate vaccination as an alternative or addition to primary HPV screening with careHPV (Qiagen, Gaithersburg, USA), and to assess the threshold total cost per vaccinated girl (CVG) at which strategies involving vaccination would become viable compared to screening-only strategies in rural China. We used data from field studies in Shanxi Province to support modelling of HPV vaccination and screening, including local information on sexual behaviour, HPV prevalence, test accuracy, treatment protocols and costs. We evaluated several strategies involving screening once or twice per lifetime or at regular 5-yearly intervals, with or without vaccination of young females at age 15 years, assuming 70% coverage for both screening and vaccination. We also predicted cross-sectional cancer incidence each year to the year 2050 for a range of strategies. We found that strategies involving vaccination would be cost-effective at CVGs of US

AutoDensity: an automated method to measure mammographic breast density that predicts breast cancer risk and screening outcomes

50-54 or less, but at CVGs >

Using Mammographic Density to Improve Breast Cancer Screening Outcomes

54, screening-only strategies would be more cost-effective. If vaccination of young cohorts is combined with two rounds of careHPV screening for women aged 30-59 years in 2012 and 2027, a predicted indicative 33% reduction in cervical cancer incidence by 2030 would be sustained until 2050, with incidence rates decreasing thereafter. In conclusion, taking into account estimated vaccine delivery costs (for 3 doses), a per-dose HPV vaccine cost of approximately <

Tumour size at detection according to different measures of mammographic breast density.

9-14 would be required for strategies involving vaccination to be cost-effective. Overall, combined screening and vaccination approaches are required to maximise outcomes in rural China.

Cancer incidence and mortality in people aged less than 75 years: changes in Australia over the period 1987-2007.

IntroductionWhile Cumulus – a semi-automated method for measuring breast density – is utilised extensively in research, it is labour-intensive and unsuitable for screening programmes that require an efficient and valid measure on which to base screening recommendations. We develop an automated method to measure breast density (AutoDensity) and compare it to Cumulus in terms of association with breast cancer risk and breast cancer screening outcomes.MethodsAutoDensity automatically identifies the breast area in the mammogram and classifies breast density in a similar way to Cumulus, through a fast, stand-alone Windows or Linux program. Our sample comprised 985 women with screen-detected cancers, 367 women with interval cancers and 4,975 controls (women who did not have cancer), sampled from first and subsequent screening rounds of a film mammography screening programme. To test the validity of AutoDensity, we compared the effect estimates using AutoDensity with those using Cumulus from logistic regression models that tested the association between breast density and breast cancer risk, risk of small and large screen-detected cancers and interval cancers, and screening programme sensitivity (the proportion of cancers that are screen-detected). As a secondary analysis, we report on correlation between AutoDensity and Cumulus measures.ResultsAutoDensity performed similarly to Cumulus in all associations tested. For example, using AutoDensity, the odds ratios for women in the highest decile of breast density compared to women in the lowest quintile for invasive breast cancer, interval cancers, large and small screen-detected cancers were 3.2 (95% CI 2.5 to 4.1), 4.7 (95% CI 3.0 to 7.4), 6.4 (95% CI 3.7 to 11.1) and 2.2 (95% CI 1.6 to 3.0) respectively. For Cumulus the corresponding odds ratios were: 2.4 (95% CI 1.9 to 3.1), 4.1 (95% CI 2.6 to 6.3), 6.6 (95% CI 3.7 to 11.7) and 1.3 (95% CI 0.9 to 1.8). Correlation between Cumulus and AutoDensity measures was 0.63 (P < 0.001).ConclusionsBased on the similarity of the effect estimates for AutoDensity and Cumulus in models of breast density and breast cancer risk and screening outcomes, we conclude that AutoDensity is a valid automated method for measuring breast density from digitised film mammograms.

Intention to claim a Medicare rebate among women receiving private Victorian pregnancy termination services.

It is possible that the performance of mammographic screening would be improved if it is targeted at women at higher risk of breast cancer or who are more likely to have their cancer missed at screening, through more intensive screening or alternative screening modalities. We conducted a case-control study within a population-based Australian mammographic screening program (1,706 invasive breast cancers and 5,637 randomly selected controls). We used logistic regression to examine the effects of breast density, age, and hormone therapy use, all known to influence both breast cancer risk and the sensitivity of mammographic screening, on the risk of small (≤15 mm) and large (>15 mm) screen-detected and interval breast cancers. The risk of small screen-detected cancers was not associated with density, but the risk of large screen-detected cancers was nearly 3-fold for the second quintile and approximately 4-fold for the four highest density categories (third and fourth quintiles and the two highest deciles) compared with the lowest quintile. The risk of interval cancers increased monotonically across the density categories [highest decile odds ratio (OR), 4.65; 95% confidence interval (95% CI), 2.96-7.31]. The risk of small and large screen-detected cancers, but not interval cancers, increased with age. After adjusting for age and density, hormone therapy use was associated with a moderately elevated risk of interval cancers (OR, 1.43; 95% CI, 1.12-1.81). The effectiveness of the screening program could be improved if density were to be used to identify women most likely to have poor screening outcomes. There would be little additional benefit in targeting screening based on age and hormone therapy use. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2818–24)

Optimization of propagation-based x-ray phase-contrast tomography for breast cancer imaging

Objectives Breast cancer prognosis is better for smaller tumours. Women with high breast density are at higher risk of breast cancer and have larger screen-detected and interval cancers in mammographic screening programmes. We assess which continuous measures of breast density are the strongest predictors of breast tumour size at detection and therefore the best measures to identify women who might benefit from more intensive mammographic screening or alternative screening strategies. Setting and methods We compared the association between breast density and tumour size for 1007 screen-detected and 341 interval cancers diagnosed in an Australian mammographic screening programme between 1994 and 1996, for three semi-automated continuous measures of breast density: per cent density, dense area and dense area adjusted for non-dense area. Results After adjustment for age, hormone therapy use, family history of breast cancer and mode of detection (screen-detected or interval cancers), all measures of breast density shared a similar positive and significant association with tumour size. For example, tumours increased in size with dense area from an estimated mean 2.2 mm larger in the second quintile (β = 2.2; 95% Cl 0.4–3.9, P < 0.001) to mean 6.6 mm larger in the highest decile of dense area (β = 6.6; 95% Cl 4.4–8.9, P < 0.001), when compared with first quintile of breast density. Conclusions Of the breast density measures assessed, either dense area or per cent density are suitable measures for identifying women who might benefit from more intensive mammographic screening or alternative screening strategies.

Expenditure and resource utilisation for cervical screening in Australia

BACKGROUND Australia has one of the highest rates of cancer incidence worldwide and, despite improving survival, cancer continues to be a major public health problem. Our aim was to provide simple summary measures of changes in cancer mortality and incidence in Australia so that progress and areas for improvement in cancer control can be identified. METHODS We used national data on cancer deaths and newly registered cancer cases and compared expected and observed numbers of deaths and cases diagnosed in 2007. The expected numbers were obtained by applying 1987 age-sex specific rates (average of 1986-1988) directly to the 2007 population. The observed numbers of deaths and incident cases were calculated for 2007 (average of 2006-2008). We limited the analyses to people aged less than 75 years. RESULTS There was a 28% fall in cancer mortality (7827 fewer deaths in 2007 vs. 1987) and a 21% increase in new cancer diagnoses (13,012 more diagnosed cases in 2007). The greatest reductions in deaths were for cancers of the lung in males (-2259), bowel (-1797), breast (-773) and stomach (-577). Other notable falls were for cancers of the prostate (-295), cervix (-242) and non-Hodgkin lymphoma (-240). Only small or no changes occurred in mortality for cancers of the lung (female only), pancreas, brain and related, oesophagus and thyroid, with an increase in liver cancer (267). Cancer types that showed the greatest increase in incident cases were cancers of the prostate (10,245), breast (2736), other cancers (1353), melanoma (1138) and thyroid (1107), while falls were seen for cancers of the lung (-1705), bladder (-1110) and unknown primary (-904). CONCLUSIONS The reduction in mortality indicates that prevention strategies, improvements in cancer treatment, and screening programmes have made significant contributions to cancer control in Australia since 1987. The rise in incidence is partly due to diagnoses being brought forward by technological improvements and increased coverage of screening and early diagnostic testing.