Breast cancer screening of women aged 70-74 years: results from a natural experiment across Australia.

There is a lack of evidence regarding the optimal age at which to cease mammographic screening for breast cancer. This ecological study compared Australian state and territory level screening participation rates and cancer outcomes from 1996 to 2005 to identify the extent to which screening women aged 70-74 results in smaller, earlier stage breast cancers. With each 10 % absolute increase in screening participation, there was no significant difference in cancer incidence, but the incidence of large cancers was 8 % lower (IRR = 0.92, 95 % CI 0.90-0.94, p < 0.001); there was some evidence of reduced nodal involvement at diagnosis (IRR 0.97, 95 % CI 0.95-0.99, p = 0.004) but this estimate was sensitive to assumptions regarding missing data. Increased mammographic screening of women aged 70-74 years reduces the incidence of large (>15 mm) cancers-and possibly cancers with nodal involvement-without a concomitant increase in overall cancer incidence.

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

INTRODUCTION: While 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. METHODS: AutoDensity 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. RESULTS: AutoDensity 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). CONCLUSIONS: Based on the similarity of the effect estimates for AutoDensity and Cumulus inmodels 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.

Examining the sensitivity of ultrasound-guided large core biopsy for invasive breast carcinoma in a population screening programme.

INTRODUCTION: To evaluate the sensitivity of ultrasound-guided core-needle biopsy (UCB) in invasive breast carcinoma and to establish causes of false-negative biopsy in a population screening programme. METHOD: We identified 571 consecutive women diagnosed with surgically proven invasive breast cancer. Histology from 14-gauge UCB was compared with surgical histology to identify true-positive and false-negative ultrasound core biopsies. True-positive and false-negative groups were compared for tumour size and histology. On blinded review of UCB images and pathology reports from false negative (n = 20) and a random sample of true-positive cases (n = 80), we compared core sample number and needle visualisation in the lesion. RESULTS: Of 571 carcinomas sampled with UCB, 551 (96.5%) were true positive and 20 (3.5%) were false negative. The mean core number was 2.0 (range 1-3) for false negatives and 2.25 (range 1-4) for true positives (P = 0.27). Mean tumour sizes were 13.3 and 16.2 mm for the false-negative and true-positive groups, respectively (P = 0.25). Tubular carcinomas represented 30% (6/20) of false-negative cases compared with 5.1% (28/551) of the true-positive cases (P < 0.001). On blinded review, needle visualisation within the lesion was demonstrated in 47.4% (9/19) of false-negative cases and 76.3% (61/80) of true-positive cases (P = 0.02). CONCLUSION: We demonstrated a sensitivity of 96.5% with a mean of 2.21 cores. False-negative results were more likely in the absence of post-fire needle position verification and with tubular carcinomas. Neither tumour size nor core number predicted diagnostic accuracy.

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.

Variation in mammographic appearance between projections of small breast cancers compared with radial scars.

AIMS: The study aims to assess variation in appearance between mammographic projections (conspicuity variation) for invasive breast cancers (IBCs) compared with radial scars (RS). Conspicuity variation has been previously described as characteristic of RS. The lesions were also compared with respect to breast density and the proportion of cases detected by one of two readers and required a third (consensus) read. MATERIALS AND METHODS: The study was approved by the BreastScreen Victoria research committee. Mammograms of 75 randomly selected invasive breast cancers, with histological diameter ≤10 mm (IBC), were mixed with 67 consecutively detected RS, all from a double-reading population-based breast cancer screening programme. On blinded review, these 142 lesions were classified for mammographic findings and assessed for marked or minor conspicuity variation between views. We assessed the associations between lesion type, lesion spicules and centres, breast density, conspicuity variation and proportion detected by one reader only. RESULTS: Marked conspicuity variation was common, but not statistically different for IBC and RS (64% vs. 66%, χ(2) = 0.8, P = 0.04). Conspicuity variation did not correlate with spiculation type (long, fine or short, broad based) or lesion centres (lucent or dense) (ρ < 0.05, P = 0.5), and showed no significant change with increasing Breast Imaging Reporting and Data System breast density (IBC, χ(2) = 2.3, P = 0.5; RS, χ(2) = 0.95, P = 0.6). Density did not vary by lesion type. In the screening programme, 29% of IBC (125 of 431) versus 43% of RS (32 of 75) had been detected by one of two readers (χ(2) = 2.7, P = 0.098). CONCLUSIONS: Two-thirds of small IBCs displayed marked conspicuity variation, similar to RS. Therefore, conspicuity variation does not discriminate between IBC and RS.

Using functional data analysis models to estimate future time trends in age-specific breast cancer mortality for the United States and England-Wales.

BACKGROUND: Mortality/incidence predictions are used for allocating public health resources and should accurately reflect age-related changes through time. We present a new forecasting model for estimating future trends in age-related breast cancer mortality for the United States and England-Wales. METHODS: We used functional data analysis techniques both to model breast cancer mortality-age relationships in the United States from 1950 through 2001 and England-Wales from 1950 through 2003 and to estimate 20-year predictions using a new forecasting method. RESULTS: In the United States, trends for women aged 45 to 54 years have continued to decline since 1980. In contrast, trends in women aged 60 to 84 years increased in the 1980s and declined in the 1990s. For England-Wales, trends for women aged 45 to 74 years slightly increased before 1980, but declined thereafter. The greatest age-related changes for both regions were during the 1990s. For both the United States and England-Wales, trends are expected to decline and then stabilize, with the greatest decline in women aged 60 to 70 years. Forecasts suggest relatively stable trends for women older than 75 years. CONCLUSIONS: Prediction of age-related changes in mortality/incidence can be used for planning and targeting programs for specific age groups. Currently, these models are being extended to incorporate other variables that may influence age-related changes in mortality/incidence trends. In their current form, these models will be most useful for modeling and projecting future trends of diseases for which there has been very little advancement in treatment and minimal cohort effects (eg. lethal cancers).

Influence of high-dose estrogen exposure during adolescence on mammographic density for age in adulthood.

High-dose estrogen exposure during adolescence has been hypothesized to increase a woman's breast cancer risk, possibly mediated through an increase in mammographic density, a well-established breast cancer risk factor. In 2006 to 2007, we conducted a retrospective study of women assessed for tall stature as an adolescent between 1959 and 1993. Eligible participants were ages > or =40 years and treated during adolescence with 3 mg diethylstilbestrol or 150 microg ethinyl estradiol daily or untreated. Mammograms from 167 treated and 142 untreated women were digitized. Total breast area, dense area, nondense area, and percent density were measured using a computer thresholding technique. Data on potential determinants were collected from medical records and telephone interview. Treated women had, on average, 17% lower dense area (P = 0.032). Means (95% confidence intervals) adjusted for age and body mass index for treated and untreated women were 24.5 cm(2) (21.8-27.2) and 29.1 cm(2) (26.0-32.4), respectively. There was no difference in adjusted means (95% confidence intervals) between treated and untreated women for nondense area [71.7 cm(2) (66.2-77.7) versus 70.5 cm(2) (64.7-76.9); P = 0.78], percent dense area [24.8% (22.4-27.4) versus 27.7% (24.8-30.7); P = 0.16], or total area [105.6 cm(2) (100.1-111.4) versus 109.3 cm(2) (103.1-115.8); P = 0.41], respectively. High-dose estrogen exposure during adolescence appears to curtail growth of mammographically dense tissue and therefore is unlikely to increase breast cancer risk through mechanisms related to mammographic density.

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

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 (beta = 2.2; 95% CI 0.4-3.9, P < 0.001) to mean 6.6 mm larger in the highest decile of dense area (beta = 6.6; 95% CI 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.

Sexual orientation and weight, body image, and weight control practices among young Australian women.

OBJECTIVES: We compare weight, body image, and weight control practices of young adult Australian women according to sexual orientation. METHODS: Cross-sectional analyses of the second survey of 9683 young adult women in the Australian Longitudinal Study on Women's Health (ALSWH); the weight, weight control practices, and body image of exclusively heterosexual, mainly heterosexual, bisexual, and lesbian women were compared. RESULTS: Lesbians were less likely to be dissatisfied with their body image (body weight: beta -0.64, 95% CI -1.10- -0.18; body shape: beta -0.83, 95% CI -1.27- -0.40; overall: beta -0.74, 95% CI -1.14- -0.32), to cut down on fats and sugars (OR 0.53, 95% CI 0.34-0.85), and to engage in healthy weight control practices overall (OR 0.48, 95% CI 0.29-0.81) compared with exclusively heterosexual women. Compared with exclusively heterosexual women, bisexual women were more likely to weight cycle (OR 2.22, 95% CI 1.22-4.03). Compared with exclusively heterosexual women, mainly heterosexual and bisexual women were more likely to engage in unhealthy weight control practices overall (mainly heterosexual: OR 1.76, 95% CI 1.42-2.17; bisexuals: OR 2.89, 95% CI 1.57-5.33), such as smoking (mainly heterosexuals: OR 1.83, 95% CI 1.38-2.44; bisexuals: OR 3.80, 95% CI 1.94-7.44) and cutting meals (mainly heterosexuals: OR 1.58, 95% CI 1.23-2.02; bisexual women: OR 3.45, 95% CI 1.82-6.54). Mainly heterosexual women were more likely to vomit (mainly heterosexuals: OR 2.41, 95% CI 1.73-3.36) and use laxatives (mainly heterosexuals: OR 1.56, 95% CI 1.12-2.19). CONCLUSIONS: Future research should explore why bisexual and mainly heterosexual women are at higher risk of disordered eating behaviours. Understanding why lesbians have a healthier body image would also provide insights into how to improve the body image of other groups. It is critical that public health policy and practice address less healthy weight control practices of sexual minority groups.

A multilevel study of area socio-economic status and food purchasing behaviour.

OBJECTIVE: The present study examined the association between area socio-economic status (SES) and food purchasing behaviour. DESIGN: Data were collected by mail survey (64.2 % response rate). Area SES was indicated by the proportion of households in each area earning less than $AUS 400 per week, and individual-level socio-economic position was measured using education, occupation and household income. Food purchasing was measured on the basis of compliance with dietary guideline recommendations (for grocery foods) and variety of fruit and vegetable purchase. Multilevel regression analysis examined the association between area SES and food purchase after adjustment for individual-level demographic (age, sex, household composition) and socio-economic factors. SETTING: Melbourne city, Australia, 2003. SUBJECTS: Residents of 2564 households located in fifty small areas. RESULTS: Residents of low-SES areas were significantly less likely than their counterparts in advantaged areas to purchase grocery foods that were high in fibre and low in fat, salt and sugar; and they purchased a smaller variety of fruits. There was no evidence of an association between area SES and vegetable variety. CONCLUSIONS: In Melbourne, area SES was associated with some food purchasing behaviours independent of individual-level factors, suggesting that areas in this city may be differentiated on the basis of food availability, accessibility and affordability, making the purchase of some types of foods more difficult in disadvantaged areas.

Using mammographic density to improve breast cancer screening outcomes.

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) 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.

Urban-rural differences in the management of screen-detected invasive breast cancer and ductal carcinoma in situ in victoria.

BACKGROUND: At least one-third of primary breast cancers in Australia are discovered by population-based mammographic screening. The aim of this study was to determine whether there were any differences in the surgical treatment of women diagnosed with breast cancer by BreastScreen Victoria between urban and rural populations and to investigate temporal changes in their pattern of care. METHODS: An analysis of women diagnosed with breast cancer (invasive and non-invasive) by BreastScreen Victoria from 1993 to 2000 was conducted. Descriptive analyses of the proportion of women undergoing each surgical treatment type over time were carried out. Logistic regression was used to assess the effect of urban-rural residence on each treatment outcome while accounting for possible confounding factors. RESULTS: Rural women with invasive breast cancer were less likely to undergo breast-conserving surgery (BCS) compared with urban women (odds ratio, 0.42; 95% confidence interval, 0.35-0.50). The same was also true for rural women with ductal carcinoma in situ (odds ratio, 0.53; 95% confidence interval, 0.29-0.96). This difference was independent of patient and tumour characteristics, including tumour size, surgeon caseload, patient's age and socioeconomic status. It also persisted over time despite a steady overall increase in use of BCS for both invasive and non-invasive cancers over the study period. CONCLUSIONS: Among Victorian women with screen-detected breast cancer, urban women consistently had higher rates of BCS compared with rural women despite increased overall adoption of BCS. Reasons for this disparity are still unclear and warrant further investigation.

Does gender modify associations between self rated health and the social and economic characteristics of local environments?

OBJECTIVES: To examine whether area level socioeconomic disadvantage and social capital have different relations with women's and men's self rated health. METHODS: The study used data from 15 112 respondents to the 1998 Tasmanian (Australia) healthy communities study (60% response rate) nested within 41 statistical local areas. Gender stratified analyses were conducted of the associations between the index of relative socioeconomic disadvantage (IRSD) and social capital (neighbourhood integration, neighbourhood alienation, neighbourhood safety, political participation, social trust, trust in institutions) and individual level self rated health using multilevel logistic regression analysis before (age only) and after adjustment for individual level confounders (marital status, indigenous status, income, education, occupation, smoking). The study also tested for interactions between gender and area level variables. RESULTS: IRSD was associated with poor self rated health for women (age adjusted p<0.001) and men (age adjusted p<0.001), however, the estimates attenuated when adjusted for individual level variables. Political participation and neighbourhood safety were protective for women's self rated health but not for men's. Interactions between gender and political participation (p = 0.010) and neighbourhood safety (p = 0.023) were significant. CONCLUSIONS: These finding suggest that women may benefit more than men from higher levels of area social capital.

Hormone replacement therapy, percent mammographic density, and sensitivity of mammography.

OBJECTIVE: We examine to what extent the lower mammographic sensitivity found in hormone replacement therapy (HRT) users can be explained by any association of HRT use with higher mammographic density and more difficult to detect cancers. METHODS: We used logistic regression to estimate the odds of a false-negative screen (a breast cancer diagnosed in the 24 months after a negative screening examination) for HRT users and to estimate, and adjust for, mammographic density (measured on a continuous scale, blinded, using a reliable, computer-assisted method), tumor characteristics (size, grade, and morphology), and potential confounders (age, symptom status, family history, and prior screening) among women ages > or =55 years who attended BreastScreen Victoria for first round screening mammography in 1994 and 1995 (1,086 breast cancers) and for subsequent round screening (471 breast cancers) in 1995 and 1996. RESULTS: After adjusting for confounders, HRT users were more likely to have a false-negative screen [first round: odds ratio (OR), 1.99; 95% confidence interval (95% CI), 1.4-2.9; subsequent round: OR, 2.29; 95% CI, 1.4-3.8]. This effect was modestly attenuated by adjusting for mammographic density (first round: OR, 1.54; 95% CI, 1.0-2.3; subsequent round: OR, 1.97; 95% CI, 1.2-3.3). Adjusting for tumor characteristics resulted in a modest increase in the odds of a false negative at first round but had no effect at subsequent round. CONCLUSIONS: Mammographic density only partly explains the effect of HRT on sensitivity. Further research needs to clarify whether hyperemic breast tissue changes affect cancer detectability in HRT users as well as the possibility that the quality of mammography may be poor in some HRT users.

Incidence of invasive breast cancer and ductal carcinoma in situ in a screening program by age: should older women continue screening?

OBJECTIVE: The evidence for the effectiveness of screening is strongest for women ages 50 to 69 years; however, there is variation in the target age group for screening programs between different countries. In particular, there is uncertainty over whether women should continue screening once they reach age 70. We therefore investigated incidence rates for invasive and in situ breast cancer by age as well as prognostic features of tumors within a screening program. METHODS: We studied 474,808 women who attended BreastScreen Victoria from January 1, 1993 to December 31, 2000. Of these women, 5,301 were diagnosed with invasive cancer and 1,127 were diagnosed with ductal carcinoma in situ. We used generalized additive models to model age-incidence rates for invasive cancers and ductal carcinoma in situ separately by users and nonusers of hormone replacement therapy at most recent screen. Nonparametric trends for ordered groups and regression methods were used to investigate trends in size, grade, and nodal involvement for invasive tumors by type of attendance and time since previous negative screen for age group. RESULTS: The incidence of ductal carcinoma in situ among women with a previous negative screen clearly declined after age 70 irrespective of hormone replacement therapy use. At subsequent screen, the age-incidence curve for invasive breast cancer flattened at ages 60 to 75 years and then increased only for women taking hormone replacement therapy. Tumor size at diagnosis declined with age at both first round (P = 0.15) and subsequent round (P = 0.08). The proportion of poorly differentiated tumors also decreased with age, with the smallest proportion of grade III tumors diagnosed in women ages > or = 75 years (P = 0.09 for first screen and P = 0.05 for subsequent screen). The presence of positive nodes at diagnosis declined with age (P < 0.001) for both first and subsequent screening rounds. CONCLUSION: Older age is associated with more favorable prognostic tumor features and a lower incidence of ductal carcinoma in situ among subsequent attenders of screening. When making decisions regarding continuing screening, older women and their physicians should also consider the presence of other comorbid conditions that may mitigate any impact of screening on mortality.

Duration of hormone replacement therapy, breast tumour size and grade in a screening programme.

UNLABELLED: One of the primary adverse effects of long-term use of hormone replacement therapy (HRT) is a modest increase in the risk of breast cancer. Breast tumours that develop in women using HRT have been shown to have prognostically favourable histological features but it is unclear if this is the case for both short- and long-term use. METHODS: We evaluated the association between HRT use with tumour size and histologic grade in a cohort of women aged over 55 years (n = 2200) diagnosed with invasive breast cancer at subsequent screen in BreastScreen Victoria (BSV), Australia between 1993 and 2000. BSV biennially screens women aged over 40 years with the target age group 50-69 years. Multiple linear regression was used to examine predictors of log-transformed tumour size and multinomial logistic regression was used to evaluate associations of HRT with tumour grade. RESULTS: Short-term users of HRT (< or = 5 years), were approximately 50% less likely to develop poorly-differentiated breast tumours OR 0.48 95% CI (0.28-0.82) or node-positive tumours OR 0.57 95% CI (0.35-0.94) than non-users. Long-term users of HRT (> 5 years) were also less likely to develop poorly-differentiated tumours OR 0.36 95% CI (0.24-0.56) but were not more likely to be node-positive than women not on HRT. Duration of HRT use was not significantly associated with tumour size. CONCLUSION: HRT use, regardless of duration, was associated with breast tumours that were better differentiated and not significantly larger than women not on HRT, although only short-term use was associated with fewer node-positive tumours.