Solveig Hofvind

Comparison of Digital Mammography Alone and Digital Mammography Plus Tomosynthesis in a Population-based Screening Program

PURPOSE To assess cancer detection rates, false-positive rates before arbitration, positive predictive values for women recalled after arbitration, and the type of cancers detected with use of digital mammography alone and combined with tomosynthesis in a large prospective screening trial. MATERIALS AND METHODS A prospective, reader- and modality-balanced screening study of participants undergoing combined mammography plus tomosynthesis, the results of which were read independently by four different radiologists, is under way. The study was approved by a regional ethics committee, and all participants provided written informed consent. The authors performed a preplanned interim analysis of results from 12,631 examinations interpreted by using mammography alone and mammography plus tomosynthesis from November 22, 2010, to December 31, 2011. Analyses were based on marginal log-linear models for binary data, accounting for correlated interpretations and adjusting for reader-specific performance levels by using a two-sided significance level of .0294. RESULTS Detection rates, including those for invasive and in situ cancers, were 6.1 per 1000 examinations for mammography alone and 8.0 per 1000 examinations for mammography plus tomosynthesis (27% increase, adjusted for reader; P = .001). False-positive rates before arbitration were 61.1 per 1000 examinations with mammography alone and 53.1 per 1000 examinations with mammography plus tomosynthesis (15% decrease, adjusted for reader; P < .001). After arbitration, positive predictive values for recalled patients with cancers verified later were comparable (29.1% and 28.5%, respectively, with mammography alone and mammography plus tomosynthesis; P = .72). Twenty-five additional invasive cancers were detected with mammography plus tomosynthesis (40% increase, adjusted for reader; P < .001). The mean interpretation time was 45 seconds for mammography alone and 91 seconds for mammography plus tomosynthesis (P < .001). CONCLUSION The use of mammography plus tomosynthesis in a screening environment resulted in a significantly higher cancer detection rate and enabled the detection of more invasive cancers. Clinical trial registration no. NCT01248546.

Two-View Digital Breast Tomosynthesis Screening with Synthetically Reconstructed Projection Images: Comparison with Digital Breast Tomosynthesis with Full-Field Digital Mammographic Images

PURPOSE To compare the performance of two versions of reconstructed two-dimensional (2D) images in combination with digital breast tomosynthesis (DBT) versus the performance of standard full-field digital mammography (FFDM) plus DBT. MATERIALS AND METHODS This trial had ethical committee approval, and all participants gave written informed consent. Examinations (n = 24 901) in women between the ages of 50 and 69 years (mean age, 59.2 years) were interpreted prospectively as part of a screening trial that included independent interpretations of FFDM plus DBT and reconstructed 2D images plus DBT. Reconstructed 2D images do not require radiation exposure. Using analyses for binary data that accounted for correlated interpretations and were adjusted for reader-specific volume, two versions (initial and current) of reconstructed 2D images used during trial periods 1 (from November 22, 2010, to December 21, 2011; 12 631 women) and 2 (from January 20, 2012, to December 19, 2012; 12 270 women) were compared in terms of cancer detection and false-positive rates with the corresponding FFDM plus DBT interpretations. RESULTS Cancer detection rates were 8.0, 7.4, 7.8, and 7.7 per 1000 screening examinations for FFDM plus DBT in period 1, initial reconstructed 2D images plus DBT in period 1, FFDM plus DBT in period 2, and current reconstructed 2D images plus DBT in period 2, respectively. False-positive scores were 5.3%, 4.6%, 4.6%, and 4.5%, respectively. Corresponding reader-adjusted paired comparisons of false-positive scores revealed significant differences for period 1 (P = .012) but not for period 2 (ratio = 0.99; 95% confidence interval: 0.88, 1.11; P = .85). CONCLUSION The combination of current reconstructed 2D images and DBT performed comparably to FFDM plus DBT and is adequate for routine clinical use when interpreting screening mammograms.

The cumulative risk of a false‐positive recall in the Norwegian Breast Cancer Screening Program

Biennial breast cancer screening for women ages 50–69 years is recommended by the World Health Organization. It has been claimed that the cumulative risk of a false‐positive recall is a significant disadvantage in breast cancer screening programs. The primary objective of this study was to estimate the cumulative risk of a false‐positive recall during a screening period of 20 years in women ages 50–51 years who are screened biennially in a population‐based screening program. A secondary objective was to estimate the cumulative risk of undergoing fine‐needle aspiration cytology, core needle biopsy, and open biopsy with benign morphology in the same group of women.

Mammographic screening programmes in Europe: organization, coverage and participation

Objectives To summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe. Methods We used the European Network for Information on Cancer (EUNICE), a web-based data warehouse (EUNICE Breast Cancer Screening Monitoring, EBCSM) for breast cancer screening, to obtain information on programme characteristics, coverage and participation from its initial application in 10 national and 16 regional programmes in 18 European countries. Results The total population targeted by the screening programme services covered in the report comprised 26.9 million women predominantly aged 50–69. Most of the collected data relates to 2005, 2006 and/or 2007. The average participation rate across all programmes was 53.4% (range 19.4–88.9% of personally invited); or 66.4% excluding Poland, a large programme that initiated personal invitations in 2007. Thirteen of the 26 programmes achieved the European Union benchmark of acceptable participation (>70%), nine achieved the desirable level (>75%). Despite considerable invitation coverage across all programmes (79.3%, range 50.9–115.2%) only 48.2% (range 28.4–92.1%) of the target population were actually screened. The overall invitation and examination coverage excluding Poland was 70.9% and 50.3%, respectively. Conclusions The results demonstrate the feasibility of European-wide screening monitoring using the EBCSM data warehouse, although further efforts to refine the system and to harmonize standards and data collection practices will be required, to fully integrate all European countries. The more than three-fold difference in the examination coverage should be taken into account in the evaluation of service screening programmes.

False-positive results in mammographic screening for breast cancer in Europe: a literature review and survey of service screening programmes

Objective To estimate the cumulative risk of a false-positive screening result in European mammographic screening programmes, and examine the rates and procedures of further assessment. Methods A literature review was conducted to identify studies of the cumulative risk of a false-positive result in European screening programmes (390,000 women). We then examined aggregate data, cross-sectional information about further assessment procedures among women with positive results in 20 mammographic screening programmes from 17 countries (1.7 million initial screens, 5.9 million subsequent screens), collected by the European Network for Information on Cancer project (EUNICE). Results The estimated cumulative risk of a false-positive screening result in women aged 50–69 undergoing 10 biennial screening tests varied from 8% to 21% in the three studies examined (pooled estimate 19.7%). The cumulative risk of an invasive procedure with benign outcome ranged from 1.8% to 6.3% (pooled estimate 2.9%). The risk of undergoing surgical intervention with benign outcome was 0.9% (one study only). From the EUNICE project, the proportions of all screening examinations in the programmes resulting in needle biopsy were 2.2% and 1.1% for initial and subsequent screens, respectively, though the rates differed between countries; the corresponding rates of surgical interventions among women without breast cancer were 0.19% and 0.07%. Conclusion The specific investigative procedures following a recall should be considered when examining the cumulative risk of a false-positive screening result. Most women with a positive screening test undergo a non-invasive assessment procedure. Only a small proportion of recalled women undergo needle biopsy, and even fewer undergo surgical intervention.

Comparing Screening Mammography for Early Breast Cancer Detection in Vermont and Norway

BACKGROUND Most screening mammography in the United States differs from that in countries with formal screening programs by having a shorter screening interval and interpretation by a single reader vs independent double reading. We examined how these differences affect early detection of breast cancer by comparing performance measures and histopathologic outcomes in women undergoing opportunistic screening in Vermont and organized screening in Norway. METHODS We evaluated recall, screen detection, and interval cancer rates and prognostic tumor characteristics for women aged 50-69 years who underwent screening mammography in Vermont (n = 45 050) and in Norway (n = 194 430) from 1997 through 2003. Rates were directly adjusted for age by weighting the rates within 5-year age intervals to reflect the age distribution in the combined data and were compared using two-sided Z tests. RESULTS The age-adjusted recall rate was 9.8% in Vermont and 2.7% in Norway (P < .001). The age-adjusted screen detection rate per 1000 woman-years after 2 years of follow-up was 2.77 in Vermont and 2.57 in Norway (P = .12), whereas the interval cancer rate per 1000 woman-years was 1.24 and 0.86, respectively (P < .001). Larger proportions of invasive interval cancers in Vermont than in Norway were 15 mm or smaller (55.9% vs 38.2%, P < .001) and had no lymph node involvement (67.5% vs 57%, P = .01). The prognostic characteristics of all invasive cancers (screen-detected and interval cancer) were similar in Vermont and Norway. CONCLUSION Screening mammography detected cancer at about the same rate and at the same prognostic stage in Norway and Vermont, with a statistically significantly lower recall rate in Norway. The interval cancer rate was higher in Vermont than in Norway, but tumors that were diagnosed in the Vermont women tended to be at an earlier stage than those diagnosed in the Norwegian women.

A pooled analysis of interval cancer rates in six European countries.

The objective of this study was to assess detection rates and interval breast cancer (IC) rates from eight programmes in the European Breast Cancer Screening Network. A common data collection protocol was used to explore differences in IC rates among programmes and discuss their potential determinants. Pooled analysis was used to describe IC rates by age, compliance in screening, recall rate, screening detection (SD) rate and expected breast cancer incidence. Participation in screening averaged 77.9% (range 42.6–88.7%), recall rate 5.4% (range 3.3–17.7%) in the initial and 3.4% (range 1.8–8.9%) in the subsequent screening rounds, and SD rate was 60.4 (range 41.6–91) per 10 000 women in initial and 38.5 (range 31.3–62.6) in subsequent screens. IC rate during first 12 months after screening was 5.9 (range 2.1–7.3) per 10 000 women screened negative and 12.6 (range 6.3–15) in the second year of the interval. IC comprised 28% of the IC and SD cancers. The ratio between IC rate and expected incidence was 0.29 for the first 12 months and 0.63 for the 13–24 months period. Sensitivity was higher for the ages 60–69 years and for initial tests than subsequent tests. There were distinct differences in the IC rates between programmes. The results of this study reveal large variations in screening sensitivity and performance. Pooled evaluation of some process indicators within the European breast cancer screening programmes proved to be feasible and is likely to be useful for the future, particularly if it is performed regularly and extensively.

Trends in incidence of ductal carcinoma in situ: The effect of a population-based screening programme

BACKGROUND The incidence of ductal carcinoma in situ (DCIS) has increased substantially in the western world in recent decades. The aim of this study was to investigate the incidence according to grade distribution, age, and implementation of a population-based screening programme. METHODS Cases of primary pure DCIS (n = 3167) were obtained from the Cancer Registry of Norway. Poisson regression was used to estimate trends in incidence. RESULTS Age-adjusted incidence of DCIS increased from 4 to 11 per 100, 000 women-years from 1993 to 2007, in parallel with the implementation of screening. Higher incidence was observed among prevalent (IRR 3.3) and subsequent (IRR 2.8) invited women compared with those not invited. The proportion of DCIS among breast malignancies increased throughout the period, most markedly in the age range of screening. CONCLUSION The increased proportion of DCIS during the study period is probably due to improved diagnostics resulting from the implementation of population-based screening.

Interval cancers in the Norwegian breast cancer screening program: Frequency, characteristics and use of HRT

Breast cancers diagnosed between screening examinations among women who attend a breast cancer screening program are defined as interval cancers. The Norwegian Breast Cancer Screening Program started as a pilot project in 1996, and data from the first 2‐year interval are available. Our study quantifies interval cancers in the pilot project and explores characteristics and factors that may be associated with interval cancer. Interval cancers in the screening population were identified through the Cancer Registry of Norway. The frequency of invasive interval cancer was calculated as cases per 10,000 screened and as observed/expected ratio. Characteristics of the interval cancers were compared to screening‐detected and clinical cancers. Breast density was assessed in a blinded review of 3 categories of screening mammograms. Information on hormone replacement therapy (HRT) use was collected from a questionnaire. The frequency of invasive interval cancers was 18.2 (15.9–20.7) per 10,000 screened and the observed/expected ratio was 0.49 (0.43–0.56). The frequency in the second year of the interval was higher than reported from other programs. The median tumor size of the interval cancers was 19.5 mm and 44.0% of the patients had affected axillary lymph nodes. The interval cancer cases had higher proportions of dense breasts and reported use of HRT compared to screen normal and screening‐detected cases. The reported frequency of interval cancers is similar to comparable programs. The interval cancers differed significantly from the cancers detected in the first screening round and were more similar to clinical cancers. Interval cancer was associated with dense breasts and use of HRT. Screening programs must keep these associations in focus.

Overdiagnosis among women attending a population-based mammography screening program

Increased incidence of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC) after introduction of organized screening has prompted debate about overdiagnosis. The aim was to examine the excess in incidence of DCIS and IBC during the screening period and the deficit after women left the program, and thereby to estimate the proportion of overdiagnosis. Women invited to the Norwegian Breast Cancer Screening Program were analyzed for DCIS or IBC during the period 1995–2009. Incidence rate ratios (IRRs) were calculated for attended vs. never attended women. The IRRs were adjusted by Mantel‐Haenszel (MH) method and applied to a set of reference rates and a reference population to estimate the proportion of overdiagnosis during the womens lifespan after the age of 50 years. A total of 702,131 women were invited to the program. An excess of DCIS and IBC was observed among women who attended screening during the screening period; prevalently invited women aged 50–51 years had a MH IRR of 1.86 (95% CI 1.65–2.09) and subsequently invited women aged 52–69 years had a MH IRR of 1.56 (95% CI 1.45–1.68). In women aged 70–79 years, a deficit of 30% (MH IRR 0.70, 95% CI 0.62–0.80) was observed 1–10 years after they left the screening program. The estimated proportion of overdiagnosis varied from 10 to 20% depending on outcome and whether the women were invited or actually screened. The results highlight the need for individual data with longitudinal screening history and long‐term follow‐up as a basis for estimating overdiagnosis.