To evaluate the extent and histopathological characteristics of asymptomatic breast cancer detected outside the Norwegian Breast Cancer Screening Program (NBCSP) in women targeted by the programme.
Our study included 568 primary breast cancers (523 invasive and 45 ductal carcinoma in situ) diagnosed in 553 women aged 50-70, residing in Møre og Romsdal County, 2002-2008. The cancers were divided into screening-detected cancers in the NBCSP, interval cancers (ICs) and cancers detected in women not participating in the NBCSP (never participated and lapsed attendees), and further into asymptomatic and symptomatic cancers. Nottingham Prognostic Index (NPI) was used for comparisons across the groups and the distributions were compared using chi-square tests for statistical significance.
Twenty percent (19/97) of the ICs and 32% (69/213) of the breast cancers in non-participants were asymptomatic, with opportunistic screening as the most frequent detection method (42%, 8/19 for ICs and 54%, 37/69 for non-participants). There were no differences in distribution of NPI prognostic categories across subgroups of asymptomatic invasive cancers (screening-detected cancers in the NBCSP, asymptomatic ICs and asymptomatic cancers in non-participants) or between subgroups of symptomatic invasive cancers (symptomatic ICs and symptomatic cancers in non-participants). Asymptomatic cancers had a significantly more favourable distribution of NPI prognostic categories compared with symptomatic cancers (P
To compute a ratio between the estimated numbers of lives saved from breast cancer death and the number of women diagnosed with a breast cancer that never would have been diagnosed during the woman's lifetime had she not attended screening (epidemiologic over-diagnosis) in the Norwegian Breast Cancer Screening Program.
The Norwegian Breast Cancer Screening Program invites women aged 50-69 to biennial mammographic screening. Results from published studies using individual level data from the programme for estimating breast cancer mortality and epidemiologic over-diagnosis comprised the basis for the ratio. The mortality reduction varied from 36.8% to 43% among screened women, while estimates on epidemiologic over-diagnosis ranged from 7% to 19.6%. We computed the average estimates for both values. The benefit-detriment ratio, number of lives saved, and number of women over-diagnosed were computed for different scenarios of reduction in breast cancer mortality and epidemiologic over-diagnosis.
For every 10,000 biennially screened women, followed until age 79, we estimated that 53-61 (average 57) women were saved from breast cancer death, and 45-126 (average 82) were over-diagnosed. The benefit-detriment ratio using average estimates was 1:1.4, indicating that the programme saved about one life per 1-2 women with epidemiologic over-diagnosis.
The benefit-detriment ratio estimates of the Norwegian Breast Cancer Screening Program, expressed as lives saved from breast cancer death and epidemiologic over-diagnosis, should be interpreted with care due to substantial uncertainties in the estimates, and the differences in the scale of values of the events compared.
Objective Fluctuations in the incidence of breast cancer in Norway in the last three decades are partly explained by the use of hormone replacement therapy and mammography screening, but overdiagnosis has also been suggested as a cause. We assessed the trends in breast cancer incidence and overdiagnosis in Norway. Methods We calibrated our microsimulation model to Norwegian Cancer Registration data. The model takes into account the use of mammography (both within and outside the Norwegian Breast Cancer Screening Programme) and of hormone replacement therapy. We obtained a proper fit of breast cancer incidence in recent years, when assuming an increase in the background risk for breast cancer, and estimated overdiagnosis. Results We estimated a 2% overdiagnosis rate as a fraction of all cancers diagnosed in women aged 50-100, and a 3% overdiagnosis rate as a fraction of all cancers diagnosed in women aged 50-70 (i.e. screening age). If all of the increased incidence would be the result of the detection of slow growing tumours, these estimates were 7% and 11%, respectively. Conclusion Besides mammography and hormone replacement therapy use, additional risk factors contributed to the sudden increase in breast cancer incidence in Norway. Overdiagnosis estimates due to screening were within the range of international plausible estimates.
To compare accuracy measures for mammographic screening in Norway, Spain, and the US.
Information from women aged 50-69 years who underwent mammographic screening 1996-2009 in the US (898,418 women), Norway (527,464), and Spain (517,317) was included. Screen-detected cancer, interval cancer, and the false-positive rates, sensitivity, specificity, positive predictive value (PPV) for recalls (PPV-1), PPV for biopsies (PPV-2), 1/PPV-1 and 1/PPV-2 were computed for each country. Analyses were stratified by age, screening history, time since last screening, calendar year, and mammography modality.
The rate of screen-detected cancers was 4.5, 5.5, and 4.0 per 1000 screening exams in the US, Norway, and Spain respectively. The highest sensitivity and lowest specificity were reported in the US (83.1 % and 91.3 %, respectively), followed by Spain (79.0 % and 96.2 %) and Norway (75.5 % and 97.1 %). In Norway, Spain and the US, PPV-1 was 16.4 %, 9.8 %, and 4.9 %, and PPV-2 was 39.4 %, 38.9 %, and 25.9 %, respectively. The number of women needed to recall to detect one cancer was 20.3, 6.1, and 10.2 in the US, Norway, and Spain, respectively.
Differences were found across countries, suggesting that opportunistic screening may translate into higher sensitivity at the cost of lower specificity and PPV.
• Positive predictive value is higher in population-based screening programmes in Spain and Norway. • Opportunistic mammography screening in the US has lower positive predictive value. • Screening settings in the US translate into higher sensitivity and lower specificity. • The clinical burden may be higher for women screened opportunistically.
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From the Cancer Registry of Norway, PO 5313 Majorstuen, 0304 Oslo, Norway (S.H., S. Sagstad, S. Sebuødegård); Department of Pathology, Akershus Universitetssykehus HF, Lorenskog, Norway (Y.C.); Department of Epidemiology and Evaluation, Hospital del Mar Medical Research Institute, Barcelona, Spain (M.R.); and Department of Radiology, University of Washington, Seattle Cancer Care Alliance, Seattle, Wash (C.I.L.).
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
To investigate the probability of breast cancer among women recalled due to abnormal findings on the screening mammograms (PPV-1) and among women who underwent an invasive procedure (PPV-2) by mammographic density (MD), screening mode and age.
We used information about 28,826 recall examinations from 26,951 subsequently screened women in the Norwegian Breast Cancer Screening Program, 1996-2010. The radiologists who performed the recall examinations subjectively classified MD on the mammograms into three categories: fatty (70%). Screening mode was defined as screen-film mammography (SFM) and full-field digital mammography (FFDM). We examined trends of PPVs by MD, screening mode and age. We used logistic regression to estimate odds ratio (OR) of screen-detected breast cancer associated with MD among women recalled, adjusting for screening mode and age.
PPV-1 and PPV-2 decreased by increasing MD, regardless of screening mode (p for trend
Studies comparing analog and digital mammography in breast cancer screening have shown conflicting results. Little is known about the use of digital photon-counting detectors.
To retrospectively compare performance indicators in screen-film (SFM) and full-field digital mammography (FFDM) using a photon-counting detector in a population-based screening program.
The Norwegian Social Science Data Services approved the study, which was part of the Norwegian Breast Cancer Screening Program. The program invites women aged 50–69 years to two-view mammography biannually. The study period was January 2005 to June 2006 for SFM and August 2006 to December 2007 for FFDM. Independent double reading was performed using a five-point rating scale for probability of cancer. Recalls due to abnormal mammography were retrospectively reviewed by an expert panel. Performance indicators for the two techniques were compared. Attendance rate was 83.6% (7442/8901) for SFM and 82.0% (6932/8451) for FFDM.
The recall rate due to abnormal mammography, cancer detection rate and positive predictive value did not differ significantly between SFM and FFDM: recall 2.3% (174/7442) versus 2.4% (168/6932), cancer detection 0.39% (29/7442) versus 0.48% (33/6932), positive predictive value 16.7% (29/174) versus 19.6% (33/168), respectively (P>0.05 for all). The recall rate due to technically inadequate mammograms was 0.3% (19/7442) for SFM and 0.01% (1/6932) for FFDM. In the retrospective review, a significantly higher proportion of calcifications and asymmetric density were categorized as normal or definitively benign in FFDM compared with SFM. The average glandular dose was 2.17 mGy for SFM and 1.25 mGy for FFDM.
Performance indicators show that FFDM using photon-counting detector is suitable for breast cancer screening. The lower radiation dose and lower recalls due to technically inadequate mammograms are of importance in mammography screening.
To analyze discordant and concordant screening-detected breast cancers in a nationwide population-based screening program by using independent double reading with consensus.
The study is a part of the evaluation of the Norwegian Breast Cancer Screening Program and is covered by the Cancer Registry regulation. Analyses were based on prospective initial interpretation scores of 1 033 870 screenings that included 5611 breast cancers. A five-point scale for probability of cancer was used in the initial interpretation. Screening mammograms with a score of 2 or higher by either radiologist were discussed at consensus meetings where the decision whether to recall was made. A score of 1 by one reader and 2 or higher by the other was defined as a discordant interpretation and discordant cancer, whereas a score of 2 or higher by both readers was defined as a concordant recall and cancer.
Discordant interpretation was present in 5.3% (54 447 of 1 033 870) of the screenings, whereas 2.1% (21 928 of 1 033 870) were concordant positive interpretations. Of the screening-detected cancers, 23.6% (1326 of 5611) were diagnosed in women who were recalled because of screenings with discordant interpretation. One hundred seventeen interval breast cancers were diagnosed among the 40 312 screenings that were dismissed at consensus; these were 6.5% of all interval cancers. A significantly higher proportion of microcalcifications alone was present in discordant cancers (24.9% [304 of 1219]) compared with concordant cancers (17.7% [704 of 3972]) (P
Overdiagnosis in breast cancer screening is a topic of debate. Researchers often estimate trends in incidence prior to screening and project these to predict incidence during the screening epoch.
Data was obtained from the Cancer Registry of Norway and the Norwegian Breast Cancer Screening Programme. Using breast cancer incidence prior to screening in Norway (1976-1995), incidence trends were estimated from age-period and age-cohort models. These estimates were used to predict the incidence of breast cancer in five-year age and period groups in the screening epoch (1996-2009).
Excess numbers of cancers in the screening age range (6,876 cancers), and deficits in women above and below the screening age range (1,947 cancers) were observed. However, only part of the observed differences between the observed and the expected incidence can be explained by screening, as evidenced by numbers of excess cancers greater than the numbers of screen-detected cancers in some age groups and time periods.
There are potential errors in estimation of overdiagnosis from screening if individual data on screening exposure and detection mode are not taken into account. For reliable estimates of overdiagnosis, it is necessary to compare excess incidence in the screening period in those actually screened with the corresponding excess in those not screened. This is the subject of ongoing research.