Attendance to screening and breast cancer mortality

Mammographic screening is a method for detecting breast cancer at an early stage of the disease progression, and is thus considered a secondary prevention. The Norwegian Breast Cancer Screening Program invites all women aged 50-69 years to mammographic screening biennially. The benefit of attending screening is evaluated by estimates of reduced breast cancer mortality among women invited and women screened. We introduce causal inference to estimate the benefit of attending screening. As attendance to screening is optional, there is a possible selection bias when comparing women who never attend with women who regularly attend screening. We apply inverse probability weighting (IPW) to compensate for underlying differences between the comparison groups, under the assumption of no unmeasured confounders. A Cox proportional hazard model estimate the risk of breast cancer death to be 63% lower among the women regularly screened (HR=0.37, 95% CI: 0.32-0.43) compared to women never screened. The correction for selection bias by IPW does not have an impact on the estimated effect of mammographic screening, and we conclude that the covariates available do not introduce bias with respect to breast cancer mortality. Further, we are interested in the magnitude of selection bias. We consider an unknown factor representing any beneficial covariates associated with a reduced mortality. This factor needs to be 7 times stronger in women regularly screened compared to women never screened in order to eliminate the estimated effect of mammographic screening on breast cancer mortality. The aim of this thesis is to present a methodological framework in which we can estimate the effect of mammographic screening on breast cancer mortality including a possible effect of the women s screening history. We describe one possible way to achieve the true effect of screening and present the underlying assumptions. The assumption of no unmeasured confounders is violated in the currently available data, and we are thus not able to find the true effect of mammographic screening on breast cancer mortality in this thesis

Breast cancer mortality in participants of the Norwegian Breast Cancer Screening Program

BACKGROUND The Norwegian Breast Cancer Screening Program started in 1996. To the authors' knowledge, this is the first report using individual-based data on invitation and participation to analyze breast cancer mortality among screened and nonscreened women in the program. METHODS Information on dates of invitation, attendance, breast cancer diagnosis, emigration, death, and cause of death was linked by using unique 11-digit personal identification numbers assigned all inhabitants of Norway at birth or immigration. In total, 699,628 women ages 50 to 69 years without prior a diagnosis of breast cancer were invited to the program from 1996 to 2009 and were followed for breast cancer through 2009 and death through 2010. Incidence-based breast cancer mortality rate ratios (MRRs) were compared between the screened and nonscreened cohorts using a Poisson regression model. The MRRs were adjusted for calendar period, attained age, years since inclusion in the cohorts, and self-selection bias. RESULTS The crude breast cancer mortality rate was 20.7 per 100,000 women-years for the screened cohort compared with 39.7 per 100,000 women-years for the nonscreened cohort, resulting in an MRR of 0.52 (95% confidence interval, 0.47-0.59). The mortality reduction associated with attendance in the program was 43% (MRR, 0.57; 95% confidence interval, 0.51-0.64) after adjusting for calendar period, attained age, years after inclusion in the cohort, and self-selection bias. CONCLUSIONS After 15 years of follow-up, a 43% reduction in mortality was observed among women who attended the national mammographic screening program in Norway

A randomized controlled trial of digital breast tomosynthesis versus digital mammography in population-based screening in Bergen: interim analysis of performance indicators from the To-Be trial

Objectives To describe a randomized controlled trial (RCT) of digital breast tomosynthesis including synthesized two-dimensional mammograms (DBT) versus digital mammography (DM) in a population-based screening program for breast cancer and to compare selected secondary screening outcomes for the two techniques. Methods This RCT, performed in Bergen as part of BreastScreen Norway, was approved by the Regional Committees for Medical Health Research Ethics. All screening attendees in Bergen were invited to participate, of which 89% (14,274/15,976) concented during the first year, and were randomized to DBT (n = 7155) or DM (n = 7119). Secondary screening outcomes were stratified by mammographic density and compared using two-sample t-tests, chi-square tests, ANOVA, negative binomial regression and tests of proportions (z tests). Results Mean reading time was 1 min 11 s for DBT and 41 s for DM (p < 0.01). Mean time spent at consensus was 3 min 12 s for DBT and 2 min 12 s for DM (p < 0.01), while the rate of cases discussed at consensus was 6.4% and 7.4%, respectively for DBT and DM (p = 0.03). The recall rate was 3.0% for DBT and 3.6% for DM (p = 0.03). For women with non-dense breasts, recall rate was 2.2% for DBT versus 3.4% for DM (p = 0.04). The rate did not differ for women with dense breasts (3.6% for both). Mean glandular dose per examination was 2.96 mGy for DBT and 2.95 mGy for DM (p = 0.433). Conclusions Interim analysis of a screening RCT showed that DBT took longer to read than DM, but had significantly lower recall rate than DM. We found no differences in radiation dose between the two techniques. Key Points • In this RCT, DBT was associated with longer interpretation time than DM • Recall rates were lower for DBT than for DM • Mean glandular radiation dose did not differ between DBT and DMpublishedVersio

Compression forces used in the Norwegian Breast Cancer Screening Program

Objectives: Compression is used in mammography to reduce breast thickness, which is claimed to improve image quality and reduce radiation dose. In the Norwegian Breast Cancer Screening Program (NBCSP), the recommended range of compression force for full field digital mammography is 11-18 kg (108-177 Newton [N]). This is the first study to investigate the compression force used in the program. Methods: The study included information from 17,951 randomly selected women screened with FFDM at 14 breast centres in the NBCSP, January-March 2014. We investigated the applied compression force on left breast in craniocaudal (CC) and mediolateral oblique (MLO) view for breast centres, mammography machines within the breast centres and for the radiographers. Results: The mean compression force for all mammograms in the study was 116N and ranged from 91 to 147N between the breast centres. The variation in compression force was wider between the breast centres than between mammography machines (range 137-155N) and radiographers (95-143N) within one breast centre. Approximately 59% of the mammograms in the study complied with the recommended range of compression force. Conclusions: A wide variation in applied compression force was observed between the breast centres in the NBCSP. This variation indicates a need for evidence-based recommendations for compression force aimed at optimizing the image quality and individualising breast compression. Advances in knowledge: There was a wide variation in applied compression force between the breast centres in the NBCSP. The variation was wider between the breast centres than between mammography machines and radiographers within one breast centre

Breast cancer mortality after implementation of organized population-based breast cancer screening in Norway.

Background We estimated breast cancer (BC) mortality reduction associated with invitations to a nation-wide population based screening program and changes in treatment, in Norway. Material and methods BreastScreen Norway started in 1996 and became nationwide in 2005. It invites women aged 50–69 to biennial mammographic screening. We retrieved individual-level data for 1,340,333 women from national registries. During 1996–2014 (screening window), women contributed person-years (PY) in non-invited and invited periods. We created comparable periods for 1977–1995 (pre-screening window) by dividing the follow-up time for each woman into a pseudo-non-invited and pseudo-invited periods. We estimated BC mortality for the four periods, using the so-called evaluation model: counting BC deaths in each period for all women diagnosed within the period, counting BC deaths and person-years after screening-age only for women diagnosed within screening-age. We used a multivariable flexible parametric survival model to estimate hazard ratio (HR) for the effect of invitation and improved treatment. Results There were 5818 BC deaths across 16,533,281 PY. Invitations to screening reduced BC mortality by 20% (HR: 0.80, 95%CI: 0.70-0.91) among women ≥50 years old and by 25% (HR: 0.75, 95%CI: 0.65-0.86) among screening-aged women. The treatment effect was 23% (HR: 0.77, 95%CI: 0.65-0.92) for women ≥50 years old, and 17% (HR: 0.83, 95%CI: 0.74-0.94) for screening-aged women. Conclusion We observed a similar reduction in BC mortality associated with invitations to screening and improvements in treatment among women ≥50 years old, during 1977–2014

Mammographic density and histopathologic characteristics of screen-detected tumors in the Norwegian Breast Cancer Screening Program

Background. High mammographic density might mask breast tumors, resulting in delayed diagnosis or missed cancers. Purpose. To investigate the association between mammographic density and histopathologic tumor characteristics (histologic type, size, grade, and lymph node status) among women screened in the Norwegian Breast Cancer Screening Program. Material and Methods. Information about 1760 screen-detected ductal carcinoma in situ (DCIS) and 7366 invasive breast cancers diagnosed among women aged 50–69 years, 1996–2010, was analyzed. The screening mammograms were classified subjectively according to the amount of fibroglandular tissue into fatty, medium dense, and dense by breast radiologists. Chi-square test was used to compare the distribution of tumor characteristics by mammographic density. Odds ratio (OR) of tumor characteristics by density was estimated by means of logistic regression, adjusting for screening mode (screen-film and full-field digital mammography), and age. Results. Mean and median tumor size of invasive breast cancers was 13.8 and 12 mm, respectively, for women with fatty breasts, and 16.2 and 14 mm for those with dense breasts. Lymph node positive tumors were identified among 20.6% of women with fatty breasts compared with 27.2% of those with dense breasts (P < 0.001). The proportion of DCIS was significantly lower for women with fatty (15.8%) compared with dense breasts (22.0%). Women with dense breasts had an increased risk of large (OR, 1.44; 95% CI, 1.18–1.73) and lymph node positive tumors (OR, 1.26; 95% CI, 1.05–1.51) compared with women with fatty and medium dense breasts. Conclusion. High mammographic density was positively associated with tumor size and lymph node positive tumors

Compression forces used in the Norwegian Breast Cancer Screening Program

Objective: Compression is used in mammography to reduce breast thickness, which is claimed to improve image quality and reduce radiation dose. In the Norwegian Breast Cancer Screening Program (NBCSP), the recommended range of compression force for full-field digital mammography (FFDM) is 11–18 kg (108–177 N). This is the first study to investigate the compression force used in the programme. Methods: The study included information from 17,951 randomly selected females screened with FFDM at 14 breast centres in the NBCSP, during January–March 2014. We investigated the applied compression force on the left breast in craniocaudal and mediolateral oblique views for breast centres, mammography machines within the breast centres and for the radiographers. Results: The mean compression force for all mammograms in the study was 116 N and ranged from 91 N to 147 N between the breast centres. The variation in compression force was wider between the breast centres than that between mammography machines (range 137–155 N) and radiographers (95–143 N) within one breast centre. Approximately 59% of the mammograms in the study complied with the recommended range of compression force. Conclusion: A wide variation in applied compression force was observed between the breast centres in the NBCSP. This variation indicates a need for evidence-based recommendations for compression force aimed at optimizing the image quality and individualizing breast compression. Advances in knowledge: There was a wide variation in applied compression force between the breast centres in the NBCSP. The variation was wider between the breast centres than that between mammography machines and radiographers within one breast centre

Mammographic breast density over time among women who have participated in BreastScreen Norway

Background: We analyzed the consistency in absolute and percent density using an automated method for estimating volumetric breast density among women who attended BreastScreen Norway 2007-2015. Material and Methods: We used information from 33,711 women aged 50-69 who underwent two to five full field digital screening examinations biennially, 2007-2015. BMI and HT-use was obtained from a self-administered questionnaire, sent together with the invitation to screening. BMI was categorized into <21.0; 21.0-24.9; ≥25.0 kg/m2, while use of HT was defined as ever versus never used. An automated method estimated fibroglandular volume (cm3), breast volume (cm3) and volumetric breast density (%) for each screening examination. We applied mixed-effects linear models to estimate associations between age, fibroglandular volume, breast volume and volumetric breast density over time including data on BMI and HT. Results: The results models indicated age to be associated with decreased fibroglandular volume and volumetric breast density, and increased breast volume. BMI <21 kg/m2 was associated with higher volumetric breast density, but lower fibroglandular and breast volume. Contrary, BMI ≥25 kg/m2 was associated with lower volumetric breast density and higher fibroglandular and breast volumes. Variation in volumetric breast density and fibroglandular volume within women was rather subtle: this variance did not exceed 10% for either volumetric breast density, fibroglandular volume or breast volume. Conclusion: Automated measures of volumetric breast density and fibroglandular volume software decreased with age among women screened in BreastScreen Norway. Absolute and percent density varied with a maximum of 10% over time, from first to last screening examination

Interval breast cancer rates and histopathologic tumor characteristics after false-positive findings at mammography in a populationbased screening program

Purpose To compare rates and tumor characteristics of interval breast cancers (IBCs) detected after a negative versus false-positive screening among women participating in the Norwegian Breast Cancer Screening Program. Materials and Methods The Cancer Registry Regulation approved this retrospective study. Information about 423 445 women aged 49–71 years who underwent 789 481 full-field digital mammographic screening examinations during 2004–2012 was extracted from the Cancer Registry of Norway. Rates and odds ratios of IBC among women with a negative (the reference group) versus a false-positive screening were estimated by using logistic regression models adjusted for age at diagnosis and county of residence. Results A total of 1302 IBCs were diagnosed after 789 481 screening examinations, of which 7.0% (91 of 1302) were detected among women with a false-positive screening as the most recent breast imaging examination before detection. By using negative screening as the reference, adjusted odds ratios of IBCs were 3.3 (95% confidence interval [CI]: 2.6, 4.2) and 2.8 (95% CI: 1.8, 4.4) for women with a false-positive screening without and with needle biopsy, respectively. Women with a previous negative screening had a significantly lower proportion of tumors that were 10 mm or less (14.3% [150 of 1049] vs 50.0% [seven of 14], respectively; P < .01) and grade I tumors (13.2% [147 of 1114] vs 42.9% [six of 14]; P < .01), but a higher proportion of cases with lymph nodes positive for cancer (40.9% [442 of 1080] vs 13.3% [two of 15], respectively; P = .03) compared with women with a previous false-positive screening with benign biopsy. A retrospective review of the screening mammographic examinations identified 42.9% (39 of 91) of the false-positive cases to be the same lesion as the IBC. Conclusion By using a negative screening as the reference, a false-positive screening examination increased the risk of an IBC three-fold. The tumor characteristics of IBC after a negative screening were less favorable compared with those detected after a previous false-positive screening

Breast compression parameters and mammographic density in the Norwegian Breast Cancer Screening Programme

Objectives To investigate possible associations between breast compression parameters, including compression force, pressure and compressed breast thickness, and mammographic density assessed by an automated software. Methods We obtained data on breast compression parameters, breast volume, absolute and percentage dense volume, and body mass index for 14,698 women screened with two-view (craniocaudal, CC, and mediolateral oblique, MLO) digital mammography, in the Norwegian Breast Cancer Screening Programme, 2014–2015. The Spearman correlation coefficient (ρ) was used to measure correlation between breast compression parameters, breast volume and absolute and percentage dense volume. Linear regression was used to examine associations between breast compression parameters and absolute and percentage dense volume, adjusting for breast volume, age and BMI. Results A fair negative correlation was observed between compression pressure and absolute dense volume (ρ = − 0.37 for CC and ρ = − 0.34 for MLO). A moderate negative correlation was identified for compressed breast thickness and percentage dense volume (ρ = − 0.56 for CC and ρ = − 0.62 for MLO). These correlations were corroborated by the corresponding associations obtained in the adjusted regression analyses. Conclusions Results from this study indicate that breast compression parameters may influence absolute and percentage dense volume measured by the automated software