Cosmetic breast implants and breast cancer. / Kosmetiske brystimplantater og brystkreft.

BACKGROUND: The number of women with cosmetic breast implants has increased in recent decades in Norway. We compared the risk of detecting breast cancer and histopathological characteristics of the tumours in women with and without implants. MATERIAL AND METHOD: We retrieved information from the Cancer Registry's databases on implants and breast cancer among women who had participated in BreastScreen Norway in the period 1996-2016. Use of the data is pursuant to the Cancer Registry Regulations. We identified 785 706 women, of whom 10 086 (1.3 %) reported that they had an implant. We calculated the incidence rate ratio (IRR) with a 95 % confidence interval (95 % CI) for detected breast cancer and compared histopathological tumour characteristics among women with and without implants with the aid of descriptive analyses. RESULTS: The incidence rate ratio for breast cancer was 30 % lower for women with implants than for women without (IRR 0.70 (95 % CI 0.60-0.81)). Women with implants who had cancer detected had tumours with a larger diameter than women without, and several of these women had metastasis to axillary lymph nodes. INTERPRETATION: Women with implants who participated in BreastScreen Norway had a lower risk of detection of breast cancer, but more advanced disease upon diagnosis than those without implants. This may be due to the difficulty caused by implants in performing and interpreting the mammograms. The women should be informed about this before undergoing augmentation mammoplasty.

Two-view digital breast tomosynthesis versus digital mammography in a population-based breast cancer screening programme (To-Be): a randomised, controlled trial.

BACKGROUND: Digital breast tomosynthesis is an advancement of mammography, and has the potential to overcome limitations of standard digital mammography. This study aimed to compare first-generation digital breast tomo-synthesis including two-dimensional (2D) synthetic mammograms versus digital mammography in a population-based screening programme. METHODS: BreastScreen Norway offers all women aged 50-69 years two-view (craniocaudal and mediolateral oblique) mammographic screening every 2 years and does independent double reading with consensus. We asked all 32 976 women who attended the programme in Bergen in 2016-17, to participate in this randomised, controlled trial with a parallel group design. A study-specific software was developed to allocate women to either digital breast tomosynthesis or digital mammography using a 1:1 simple randomisation method based on participants' unique national identity numbers. The interviewing radiographer did the randomisation by entering the number into the software. Randomisation was done after consent and was therefore concealed from both the women and the radiographer at the time of consent; the algorithm was not disclosed to radiographers during the recruitment period. All data needed for analyses were complete 12 months after the recruitment period ended. The primary outcome measure was screen-detected breast cancer, stratified by screening technique (ie, digital breast tomosynthesis and digital mammography). A log-binomial regression model was used to estimate the efficacy of digital breast tomosynthesis versus digital mammography, defined as the crude risk ratios (RRs) with 95% CIs for screen-detected breast cancer for women screened during the recruitment period. A per-protocol approach was used in the analyses. This trial is registered at ClinicalTrials.gov, number NCT02835625, and is closed to accrual. FINDINGS: Between, Jan 14, 2016, and Dec 31, 2017, 44 266 women were invited to the screening programme in Bergen, and 32 976 (74·5%) attended. After excluding women with breast implants and women who did not consent to participate, 29 453 (89·3%) were eligible for electronic randomisation. 14 734 women were allocated to digital breast tomosynthesis and 14 719 to digital mammography. After randomisation, women with a previous breast cancer were excluded (digital breast tomosynthesis group n=314, digital mammography group n=316), women with metastases from melanoma (digital breast tomosynthesis group n=1), and women who informed the radiographer about breast symptoms after providing consent (digital breast tomosynthesis group n=39, digital mammography group n=34). After exclusions, information from 28 749 women were included in the analyses (digital breast tomosynthesis group n=14 380, digital mammography group n=14 369). The proportion of screen-detected breast cancer among the screened women did not differ between the two groups (95 [0·66%, 0·53-0·79] of 14 380 vs 87 [0·61%, 0·48-0·73] of 14 369; RR 1·09, 95% CI 0·82-1·46; p=0·56). INTERPRETATION: This study indicated that digital breast tomosynthesis including synthetic 2D mammograms was not significantly different from standard digital mammography as a screening tool for the detection of breast cancer in a population-based screening programme. Economic analyses and follow-up studies on interval and consecutive round screen-detected breast cancers are needed to better understand the effect of digital breast tomosynthesis in population-based breast cancer screening. FUNDING: Cancer Registry of Norway, Department of Radiology at Haukeland University Hospital, University of Oslo, and Research Council of Norway.

Digital Mammography versus Digital Mammography Plus Tomosynthesis in Breast Cancer Screening: The Oslo Tomosynthesis Screening Trial.

Background Digital breast tomosynthesis (DBT) is replacing digital mammography (DM) in the clinical workflow. Currently, there are limited prospective studies comparing the diagnostic accuracy of both examinations and the role of synthetic mammography (SM) and computer-aided detection (CAD). Purpose To compare the accuracy of DM versus DM + DBT in population-based breast cancer screening. Materials and Methods This prospective study, performed from November 2010 to December 2012, included 24 301 women (mean age, 59.1 years ± 5.7 [standard deviation]) with 281 cancers, of which 51 were interval cancers. Each examination was independently interpreted with four reading modes: DM, DM + CAD, DM + DBT, and SM + DBT. Sensitivity and specificity were compared for DM versus DM + DBT, DM versus DM + CAD, DM + DBT versus SM + DBT, and DM versus DM + DBT at double reading. Reader-adjusted performance characteristics of reading modes were evaluated on the basis of pre-arbitration (initial interpretation) scores. Statistical analysis was based on cluster bootstrap analysis using 10 000 random resamples. Results Sensitivity was 54.1% (152 of 281) for DM and 70.5% (198 of 281) for DM + DBT. Reader-adjusted difference was 12.6% (95% confidence interval [CI]: 5.2%, 19.7%; P = .001). Specificity was 94.2% (false-positive fraction [FPF], 5.8%; 1388 of 24 020) for DM and 95.0% (FPF, 5.0%; 1209/24 020) for DM + DBT, with a reader-adjusted difference in FPF of -1.2% (95% CI: -1.7%, -0.7%; P < .001). Sensitivity was 69.0% (194 of 281) for SM + DBT and 70.5% (198 of 281) for DM + DBT, with a reader-adjusted difference of 1.0% (95% CI: -6.2%, 8.5%; P = .77). Specificity was 95.4% (FPF, 4.6%; 1111 of 24 020) for SM + DBT and 95.0% (FPF, 5.0%;1209 of 24 020) for DM + DBT, with reader-adjusted 95% CIs for FPF of 4.7%, 5.4% and 5.0%, 5.7%, respectively, and a difference of -0.3% (95% CI: -0.8%, 0.2%; P = .23). Differences in sensitivity and specificity with the addition of CAD were small and not significant (P > .2). Conclusion Addition of digital breast tomosynthesis to digital mammography resulted in significant gains in sensitivity and specificity. Synthetic mammography in combination with digital breast tomosynthesis had similar sensitivity and specificity to digital mammography in combination with digital breast tomosynthesis. © RSNA, 2019 See also the editorial by Lång in this issue.

Screening outcome for consecutive examinations with digital breast tomosynthesis versus standard digital mammography in a population-based screening program.

OBJECTIVES: To retrospectively investigate early performance measures of digital breast tomosynthesis (DBT) versus standard digital mammography (DM) for consecutive screening rounds. METHODS: We included information about 35,736 women screened in BreastScreen Norway, 2008-2016, with at least two consecutive screening examinations. The pair of two consecutive screening examinations was the unit of analysis, and results from the subsequent examination were the measure of interest. Screening technique changed during the study period, resulting in four study groups: DM after DM, DBT after DM, DM after DBT, and DBT after DBT. We compared selected early performance measures between the study groups. RESULTS: Recall for DM after DM was 3.6% and lower for all other study groups (p < 0.001). The rate of screen-detected breast cancer was 4.6/1000 for DM after DM; for DBT after DM and DBT after DBT, it was 9.9/1000 and 8.3/1000, respectively (p < 0.001 relative to DM after DM), and for DM after DBT 4.3/1000. The rate of tubular carcinoma was higher for DBT after DBT or after DM compared with DM after DM (p < 0.01). The rate of histologic grade 1 tumors was higher for DBT after DM compared with DM after DM (p < 0.001). We did not observe any statistical difference in the interval cancer rates. CONCLUSIONS: Lower recall and higher cancer detection rates for screening with DBT were sustainable over two consecutive screening rounds. Positive predictive values were higher for DBT than DM. There were no differences in the interval cancer rates between the study groups. KEY POINTS: • There is limited knowledge about early performance measures for screening with digital breast tomosynthesis beyond one screening round. • A decline in recall rate and an incline in the rate of screen-detected breast cancer were observed for women screened with DBT compared with DM, irrespective of prior screening technique. The interval breast cancer rate did not differ statistically for women screened with DBT versus DM. • Tumor characteristics tended to be prognostic favorable for DBT compared with DM with no differences in rates of more advanced cancers. The clinical significance of increased cancer detection and the potential for future mortality reduction remain unknown.

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 DM.

Performance of breast cancer screening using digital breast tomosynthesis: results from the prospective population-based Oslo Tomosynthesis Screening Trial.

PURPOSE: Digital breast tomosynthesis (DBT) has the potential to overcome limitations of conventional mammography. This study investigated the effects of addition of DBT on interval and detected cancers in population-based screening. METHODS: Oslo Tomosynthesis Screening Trial (OTST) was a prospective, independent double-reading trial inviting women 50-69 years biennially, comparing full-field digital mammography (FFDM) plus DBT with FFDM alone. Performance indicators and characteristics of screen-detected and interval cancers were compared with two previous FFDM rounds. RESULTS: 24,301 consenting women underwent FFDM + DBT screening over a 2-year period. Results were compared with 59,877 FFDM examinations during prior rounds. Addition of DBT resulted in a non-significant increase in sensitivity (76.2%, 378/496, vs. 80.8%, 227/281, p = 0.151) and a significant increase in specificity (96.4%, 57229/59381 vs. 97.5%, 23427/24020, p < .001). Number of recalls per screen-detected cancer decreased from 6.7 (2530/378) to 3.6 (820/227) with DBT (p < .001). Cancer detection per 1000 women screened increased (6.3, 378/59877, vs. 9.3, 227/24301, p < .001). Interval cancer rate per 1000 screens for FFDM + DBT remained similar to previous FFDM rounds (2.1, 51/24301 vs. 2.0, 118/59877, p = 0.734). Interval cancers post-DBT were comparable to prior rounds but significantly different in size, grade, and node status from cancers detected only using DBT. 39.6% (19/48) of interval cancers had positive nodes compared with only 3.9% (2/51) of additional DBT-only-detected cancers. CONCLUSIONS: DBT-supplemented screening resulted in significant increases in screen-detected cancers and specificity. However, no significant change was observed in the rate, size, node status, or grade of interval cancers. ClinicalTrials.gov: NCT01248546.

Interval Breast Cancer Rates and Histopathologic Tumor Characteristics after False-Positive Findings at Mammography in a Population-based 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. © RSNA, 2017 Online supplemental material is available for this article.

Automated Volumetric Analysis of Mammographic Density in a Screening Setting: Worse Outcomes for Women with Dense Breasts.

Purpose To describe screening outcomes from BreastScreen Norway stratified by volumetric breast density (VBD). Materials and Methods This retrospective study included data from 107 949 women aged 50-69 years (mean age ± standard deviation, 58.7 years ± 5.6) who underwent 307 015 screening examinations from 2007 to 2015. Automated software classified mammographic density as nondense (VBD <7.5%) or dense (VBD ≥7.5%). Rates and distributions of screening outcomes (recall, biopsy, screen-detected and interval breast cancer, positive predictive values of recall and of needle biopsy, sensitivity, specificity, and histopathologic tumor characteristics) were analyzed and stratified by density. Tests of proportions, including propensity score and t tests, were used. Results In 28% (87 021 of 307 015) of the screening examinations, the breasts were classified as dense. Recall rates for women with nondense versus dense breasts were 2.7% (5882 of 219 994) and 3.6% (3101 of 87 021); biopsy rates were 1.1% (2359 of 219 994) and 1.4% (1209 of 87 021); rates of screen-detected cancer were 5.5 (1210 of 219 994) and 6.7 (581 of 87 021) per 1000 examinations; and rates of interval breast cancer were 1.2 (199 of 165 324) and 2.8 (185 of 66 674) per 1000 examinations, respectively (P < .001 for all). Sensitivity was 82% (884 of 1083) for nondense breasts and 71% (449 of 634) for dense breasts, whereas specificity was 98% (160 973 of 164 440) and 97% (64 250 of 66 225), respectively (P < .001 for both). For screen-detected cancers, mean tumor diameter was 15.1 mm and 16.6 mm (P = .01), and lymph node-positive disease was found in 18% (170 of 936) and 24% (98 of 417) (P = .02) of women with nondense and dense breasts, respectively. Conclusion Screening examinations of women with dense breasts classified by using automated software resulted in higher recall rate, lower sensitivity, larger tumor diameter, and more lymph node-positive disease compared with women with nondense breasts.

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. KEY POINTS: • A fair correlation was identified between compression pressure and absolute dense volume • A moderate correlation was identified between compressed breast thickness and percentage dense volume • Breast compression may influence automated density estimates.

Optimizing performance of BreastScreen Norway using value of information in graphical models.

This study proposes a method to optimize the performance of BreastScreen Norway through a stratified recommendation of tests including independent double or single reading of the screening mammograms and additional imaging with or without core needle biopsy. This is carefully evaluated by a value of information analysis. An estimated graphical probabilistic model describing the relationship between a set of risk factors and the corresponding risk of breast cancer is used for this analysis, together with a Bayesian network modeling screening test results conditional on the true (but unknown) breast cancer status of a woman. This study contributes towards evaluating a possibility of improving the efficiency of the screening program, where all women aged 50 to 69 are invited every second year, regardless of individual risk factors. Our stratified recommendation of tests is dependent on the probability that an asymptomatic woman has developed breast cancer at the time she is invited to a screening.