Incremental Cancer Detection Rate Research Articles

Diagnostic accuracy of digital breast tomosynthesis and digital mammography in women with dense or non-dense breast tissue: A systematic review and meta-analysis.

Despite its excellent screening effectiveness and sensitivity for breast cancer (BC), digital breast tomosynthesis (DBT) is controversial due to its high radiation exposure and long reading time. This study examines the diagnostic accuracy of DBT and digital mammography (DM) for BC screening and diagnosis in women with dense or non-dense breast tissue. PRISMA-compliant searches were performed on Medline, Embase, PubMed, Web of Science, and the Cochrane databases for articles comparing DBT and DM for BC screening until March 2023. Meta-analysis was performed using RevMan sofware, and the Cochrane Risk of Bias Assessment Tool was employed to assess study quality. This meta-analysis included 11 trials with a total of 2,124,018 individuals. Screening with DBT resulted in a greater cancer detection rate, as demonstrated by a risk ratio (RR) of 1.27 (95% confidence interval (95% CI): 1.14-1.41). Digital breast tomosynthesis also had a reduced recall rate, with a RR of 0.88 (95% CI: 0.78-0.99), higher sensitivity and specificity values (pooled sensitivity of 0.91 (95% CI: 0.59-0.99)) and pooled specificity of 0.90 (95% CI: 0.42-1.0)) than DM (pooled sensitivity of 0.86 (95% CI: 0.52-1.0) and pooled specificity of 0.81 (95% CI: 0.12-1.0)). All acquired data exhibited reliability, lack of bias and statistical significance (p < 0.05). Digital breast tomosynthesis is a more effective screening and diagnostic assessment tool for women with dense or non-dense breasts than DM in terms of incremental cancer detection, sensitivity and recall rate.

Addition of Contrast-enhanced Mammography to Tomosynthesis for Breast Cancer Detection in Women with a Personal History of Breast Cancer: Prospective TOCEM Trial Interim Analysis.

Background Digital breast tomosynthesis (DBT) is often inadequate for screening women with a personal history of breast cancer (PHBC). The ongoing prospective Tomosynthesis or Contrast-Enhanced Mammography, or TOCEM, trial includes three annual screenings with both DBT and contrast-enhanced mammography (CEM). Purpose To perform interim assessment of cancer yield, stage, and recall rate when CEM is added to DBT in women with PHBC. Materials and Methods From October 2019 to December 2022, two radiologists interpreted both examinations: Observer 1 reviewed DBT first and then CEM, and observer 2 reviewed CEM first and then DBT. Effects of adding CEM to DBT on incremental cancer detection rate (ICDR), cancer type and node status, recall rate, and other performance characteristics of the primary radiologist decisions were assessed. Results Among the participants (mean age at entry, 63.6 years ± 9.6 [SD]), 1273, 819, and 227 women with PHBC completed year 1, 2, and 3 screening, respectively. For observer 1, year 1 cancer yield was 20 of 1273 (15.7 per 1000 screenings) for DBT and 29 of 1273 (22.8 per 1000 screenings; ICDR, 7.1 per 1000 screenings [95% CI: 3.2, 13.4]) for DBT plus CEM (P < .001). Year 2 plus 3 cancer yield was four of 1046 (3.8 per 1000 screenings) for DBT and eight of 1046 (7.6 per 1000 screenings; ICDR, 3.8 per 1000 screenings [95% CI: 1.0, 7.6]) for DBT plus CEM (P = .001). Year 1 recall rate for observer 1 was 103 of 1273 (8.1%) for (incidence) DBT alone and 187 of 1273 (14.7%) for DBT plus CEM (difference = 84 of 1273, 6.6% [95% CI: 5.3, 8.1]; P < .001). Year 2 plus 3 recall rate was 40 of 1046 (3.8%) for DBT and 92 of 1046 (8.8%) for DBT plus CEM (difference = 52 of 1046, 5.0% [95% CI: 3.7, 6.3]; P < .001). In 18 breasts with cancer detected only at CEM after integration of both observers, 13 (72%) cancers were invasive (median tumor size, 0.6 cm) and eight of nine (88%) with staging were N0. Among 1883 screenings with adequate reference standard, there were three interval cancers (one at the scar, two in axillae). Conclusion CEM added to DBT increased early breast cancer detection each year in women with PHBC, with an accompanying approximately 5.0%-6.6% recall rate increase. Clinical trial registration no. NCT04085510 © RSNA, 2024 Supplemental material is available for this article.

Supplemental Breast Cancer Screening in Women with Dense Breasts and Negative Mammography: A Systematic Review and Meta-Analysis.

Background The best supplemental breast cancer screening modality in women at average risk or intermediate risk for breast cancer with dense breast and negative mammogram remains to be determined. Purpose To conduct systematic review and meta-analysis comparing clinical outcomes of the most common available supplemental screening modalities in women at average risk or intermediate risk for breast cancer in patients with dense breasts and mammography with negative findings. Materials and Methods A comprehensive search was conducted until March 12, 2020, in Medline, Epub Ahead of Print and In-Process and Other Non-Indexed Citations; Embase Classic and Embase; Cochrane Central Register of Controlled Trials; and Cochrane Database of Systematic Reviews, for Randomized Controlled Trials and Prospective Observational Studies. Incremental cancer detection rate (CDR); positive predictive value of recall (PPV1); positive predictive value of biopsies performed (PPV3); and interval CDRs of supplemental imaging modalities, digital breast tomosynthesis, handheld US, automated breast US, and MRI in non-high-risk patients with dense breasts and mammography negative for cancer were reviewed. Data metrics and risk of bias were assessed. Random-effects meta-analysis and two-sided metaregression analyses comparing each imaging modality metrics were performed (PROSPERO; CRD42018080402). Results Twenty-two studies reporting 261 233 screened patients were included. Of 132 166 screened patients with dense breast and mammography negative for cancer who met inclusion criteria, a total of 541 cancers missed at mammography were detected with these supplemental modalities. Metaregression models showed that MRI was superior to other supplemental modalities in CDR (incremental CDR, 1.52 per 1000 screenings; 95% CI: 0.74, 2.33; P < .001), including invasive CDR (invasive CDR, 1.31 per 1000 screenings; 95% CI: 0.57, 2.06; P < .001), and in situ disease (rate of ductal carcinoma in situ, 1.91 per 1000 screenings; 95% CI: 0.10, 3.72; P < .04). No differences in PPV1 and PPV3 were identified. The limited number of studies prevented assessment of interval cancer metrics. Excluding MRI, no statistically significant difference in any metrics were identified among the remaining imaging modalities. Conclusion The pooled data showed that MRI was the best supplemental imaging modality in women at average risk or intermediate risk for breast cancer with dense breasts and mammography negative for cancer. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Hooley and Butler in this issue.

Screening MRI in Women at Intermediate Breast Cancer Risk: An Update of the Recent Literature.

Guidelines issued by the American Cancer Society (ACS) in 2007 recommend neither for nor against screening MRI in women at intermediate breast cancer risk (15%-20%), including those with dense breast tissue, a history of lobular neoplasia or atypical ductal hyperplasia (ADH), or a prior breast cancer, because of scarce supporting evidence about the utility of MRI in these specific patient populations. However, since the issuance of the ACS guidelines in 2007, multiple investigations have found that women at intermediate risk may be suitable candidates for screening MRI, given the high detection rates of early-stage cancers and acceptable false-positive rates. For women with dense breast tissue, the Dense Tissue and Early Breast Neoplasm Screening trial reported that the incremental cancer detection rate (CDR) by MRI exceeded 16 cancers per 1000 examinations but decreased in the second round of screening; this decrease in CDR, however, occurred alongside a marked decrease in the false-positive rate. For women with lobular neoplasia or ADH, single-institution retrospective analyses have shown CDRs mostly ranging from 11 to 16 cancers per 1000 MRI examinations, with women with lobular carcinoma in situ benefitting more than women with atypical lobular hyperplasia or ADH. For patients with a prior breast cancer, the cancer yield by MRI varies widely but mostly ranges from 8 to 20 cancers per 1000 examinations, with certain subpopulations more likely to benefit, such as those with dense breasts. This article reviews and summarizes more recent studies on MRI screening of intermediate-risk women.

Differential detection by breast density for digital breast tomosynthesis versus digital mammography population screening: a systematic review and meta-analysis

BackgroundWe examined whether digital breast tomosynthesis (DBT) detects differentially in high- or low-density screens.MethodsWe searched six databases (2009–2020) for studies comparing DBT and digital mammography (DM), and reporting cancer detection rate (CDR) and/or recall rate by breast density. Meta-analysis was performed to pool incremental CDR and recall rate for DBT (versus DM) for high- and low-density (dichotomised based on BI-RADS) and within-study differences in incremental estimates between high- and low-density. Screening settings (European/US) were compared.ResultsPooled within-study difference in incremental CDR for high- versus low-density was 1.0/1000 screens (95% CI: 0.3, 1.6; p = 0.003). Estimates were not significantly different in US (0.6/1000; 95% CI: 0.0, 1.3; p = 0.05) and European (1.9/1000; 95% CI: 0.3, 3.5; p = 0.02) settings (p for subgroup difference = 0.15). For incremental recall rate, within-study differences between density subgroups differed by setting (p < 0.001). Pooled incremental recall was less in high- versus low-density screens (−0.9%; 95% CI: −1.4%, −0.4%; p < 0.001) in US screening, and greater (0.8%; 95% CI: 0.3%, 1.3%; p = 0.001) in European screening.ConclusionsDBT has differential incremental cancer detection and recall by breast density. Although incremental CDR is greater in high-density, a substantial proportion of additional cancers is likely to be detected in low-density screens. Our findings may assist screening programmes considering DBT for density-tailored screening.

Comparison of Cancers Detected by Screening Breast Ultrasound and Digital Breast Tomosynthesis

Review of outcomes of screening patients imaged with both digital breast tomosynthesis (DBT) and screening ultrasound (US) to compare the cancer detection rates and characteristics of cancers detected by the imaging modalities. This retrospective study reviewed a total of 24,787 screening US exams performed in the time period of January 2013 through December 2017. These exams were in patients with heterogeneously dense or extremely dense breast tissue. In this population, 21,220 (86%) had DBT screening mammography. These cases were further reviewed to identify any pathology-proven malignancy detected with US and/or DBT. The study cohort consisted of 115 breast cancers in patients having screening US and DBT. Of the 115 cancers, 100 were invasive cancers and 15 were ductal carcinoma in situ: 64/115 were seen on DBT, 9 of which were seen only on DBT, and 106 were seen on US, with 51 seen only on US. The cancer detection rate of DBT only was 0.4/1000 (9/21,220) and 3.0/1000 (64/21,220) for those detected on DBT whether with or without additional US, with detection on US only having an incremental cancer detection rate of 2.4/1000 (51/21,220) above DBT detected malignancies. Differences in DBT-detected lesions and US only lesions when comparing median lesion size, lesion type, tumor type (invasive vs noninvasive) and tumor stage were statistically significant (p = 0.0045, p = 0.0113, p = 0.0003, and p = 0.0153, respectively). In review of the outcomes of a screening US program, we found a similar number of breast cancers were detected by DBT and US, and US alone (47.8% vs 44.3%, respectively). Ninety-six percent of the cancers detected by US alone were invasive; 89% of those seen on both modalities were invasive, while most of the breast cancers seen on DBT only were in situ carcinoma. Statistically significant differences between DBT and US, and US alone were found for many lesion characteristics including lesion size, type, tumor size, and tumor stage.

Breast ultrasound in breast cancer surveillance; incremental cancers found at what cost?

PurposeTo determine the diagnostic parameters of breast ultrasound (US) in the setting of routine radiological surveillance after a diagnosis of breast cancer and evaluate costs of the inclusion of breast US as well as any survival benefit of US detected cases of recurrence in surveillance. Methods622 patients underwent breast cancer surgery and follow up at Austin Health from July 2009 to December 2015. Retrospective data analysis was performed to determine; diagnostic parameters, financial costs of US and survival outcomes of US detected cases of recurrence. ResultsPatients underwent 1–9 years of breast cancer surveillance, with a median of 4.24 years. 390 (62.7%) patients underwent additional breast US surveillance to mammography. 232 (38.3%) fit criteria for use of additional breast US. 199 abnormal imaging episodes occurred, leading to 16 screen detected-cases of locoregional recurrence. US alone generated 107 abnormal images and found 9 cancers. US had a sensitivity of 44.1%, specificity of 95.2% and positive predictive value of 11.7% in comparison to mammography; 20.6%, 97.4% and 9.9% respectively. US had a biopsy rate of 4.0% and lead to an incremental cancer detection rate of 0.38%. The cost of incremental cancer found was $31,463.72 AUD. Survival outcomes based on method of detection of recurrence were insignificant (p value = 0.71). ConclusionsBreast US has a sensitivity of 44.1% and detected seven recurrences that were mammographically occult. Breast US has a similar PPV to mammography in surveillance. Breast US generated considerable biopsy rates and costs. Survival analysis was not able to detect any benefit of US detected cases of recurrence.

Diagnostic performance of automated breast ultrasound and handheld ultrasound in women with dense breasts.

As an adjunct to mammography, ultrasound can improve the detection of breast cancer in women with dense breasts. We aimed to evaluate the diagnostic performance of automated breast ultrasound system (ABUS) and handheld ultrasound (HHUS) in Chinese women with dense breasts, both in combination with mammography and separately. This is a cross-sectional multicenter clinical research study. Nine hundred and thirty-seven women with dense breasts underwent ABUS, HHUS, and mammography at one of five tertiary-care hospitals. The diagnostic performance of ABUS and HHUS was evaluated in combination with mammography, or separately in women with mammography-negative dense breasts. The agreement between ABUS and HHUS in breast cancer detection was also assessed. The sensitivity of the combination of ABUS or HHUS with mammography was 99.1% (219/221), and the specificities were 86.9% (622/716) and 84.9% (608/716), respectively. The area under the curve was 0.93 for ABUS combined with mammography and 0.92 for that of HHUS combined with mammography. Statistically significant agreement between ABUS and HHUS in breast cancer detection was observed (percent agreement = 0.94, κ = 0.85). The incremental cancer detection rate in mammography-negative dense breasts was 42.8 per 1000 ultrasound examinations. Both ABUS and HHUS as adjuncts to mammography can significantly improve the breast cancer detection rate in women with dense breasts, and there is a strong correlation between them. Given the high prevalence of dense breasts and the multiple advantages of ABUS over HHUS, such as less operator dependence and reproducibility, ABUS showed great potential for use in breast cancer early detection, especially in resource-limited areas.

Let's Get Real about Molecular Breast Imaging and Radiation Risk.

Let's Get Real about Molecular Breast Imaging and Radiation Risk.

Does three-dimensional functional infrared imaging improve breast cancer detection based on digital mammography in women with dense breasts?

PurposeWe aimed to estimate the incremental cancer detection rate achieved by adding three-dimensional functional infrared imaging (3DIRI) to digital mammography in women with dense breasts.Materials and methodsIn this prospective study conducted between December 2014 and April 2016, 1727 women (median age 56) with percentage volumetric breast density > 6% were recruited at routine screening mammography to undergo additional 3DIRI. The 3DIRI findings were classified as negative or positive. Women with a negative mammography but positive 3DIRI were referred to dynamic contrast-enhanced MRI, whereas all other women underwent routine follow-up based on the mammography finding. Diagnosis of breast cancer was verified by histopathologic examination. The number of women diagnosed with a malignancy formed the basis of our statistical analysis.ResultsMammography detected 7 cancers in 7 women. Of 1692 women with negative mammography, 222 women (13%) had a positive 3DIRI of which 219 underwent MRI. An additional 6 cancers were identified in 5 women, increasing the diagnostic yield from 7 of 1727 (0.41%) to 12 of 1727 (0.69%). The incremental cancer detection rate associated with using 3DIRI to select women for MRI was 5 of 222 (22.5 additional cancers per 1000).ConclusionThe use of 3DIRI to select women for an additional MRI can result in the detection of additional cancers in women with dense breasts, but at the expense of additional false positives and considerably lower positive predictive value of the combined examinations. Additional studies are necessary to evaluate the role of 3DIRI as an adjunct to mammography.Key Points• Use of three-dimensional functional infrared imaging to select women for an MRI in addition to screening mammography has the potential to improve breast cancer detection in women with dense breasts.

Utility of Routine Axillary Ultrasound Surveillance in Breast Cancer Survivors with Previously Diagnosed Metastatic Axillary Adenopathy.

The purpose of this study is to evaluate the utility of routine axillary ultrasound surveillance in asymptomatic T1 or T2 breast cancer patients with 1 to 2 positive axillary nodes that did not undergo axillary lymph node dissection. A retrospective review of our institutional database identified axillary and breast ultrasound examinations performed between February 1, 2011, and August 31, 2017, in asymptomatic T1 or T2 breast cancer patients with 1 to 2 positive axillary nodes that did not undergo axillary lymph node dissection. From the electronic medical record, patient demographics, imaging data, pathology results, and surgical reports were extracted. Positive predictive values (PPVs) 2 and 3 and cancer detection rate (CDR) were calculated with exact 95% confidence intervals (CIs). An average of 2.1 surveillance examinations was performed in 77 unique patients, yielding 160 total examinations. For 7 patients, 7 biopsies were recommended, and 5 biopsies were performed. No malignancy was diagnosed, yielding a PPV2 of 0% (0/7) (95% CI = 0% to 35%); PPV3 of 0% (0/5) (95% CI = 0% to 45%), and CDR of zero per 1000 (0/160) examinations (95% CI = 0 to 19). Given the low frequency of axillary recurrence, routine axillary surveillance ultrasound in women with T1 or T2 breast cancers and 1 to 2 positive lymph nodes would be expected to have a low incremental CDR compared to clinical evaluation alone. Axillary surveillance ultrasound should not be routinely recommended or performed.

Abstract PD4-05: Molecular breast imaging and tomosynthesis to eliminate the reservoir of undetected cancer in dense breasts: The Density MATTERS trial

Abstract Background High mammographic breast density is the primary reason for missed cancers or delayed detection on mammography, and is associated with a higher rate of advanced and interval cancers which increase breast cancer mortality. Digital breast tomosynthesis (DBT) has been shown to reduce false positive findings relative to 2D mammography but does not eliminate the potential for tumor masking in dense breasts due to the similar x-ray attenuation characteristics of tumors and normal fibroglandular tissue. Molecular Breast Imaging (MBI) performed with a dedicated gamma camera to detect functional uptake of a radiotracer, Tc-99m sestamibi, has been shown to reveal breast cancers obscured by density on mammography. In single-institution studies, adding MBI to 2D mammography in women with dense breasts detected an additional 5 to10 invasive cancers per 1000 screened, with modest increases in recall rate (6 to 8%) at a lower cost-per-cancer detected than mammography alone. Despite this promising evidence, the lack of multicenter trial data has limited wider acceptance. Also, MBI has yet to be compared to DBT, which in some centers has replaced 2D mammography screening. We present interim results from a multicenter trial comparing cancer detection rate of DBT and MBI in screening of women with mammographically dense breasts. Methods In this ongoing, prospective, multicenter clinical trial, asymptomatic women aged 40-75 years with dense breasts on prior mammogram and no prior history of supplemental screening are invited to undergo two annual rounds of concurrent DBT and MBI. MBI is performed with injection of 300 MBq Tc-99m sestamibi with a dual-head semiconductor-based gamma camera. Screening tests are interpreted independently. Here, preliminary cancer detection rates (cancers per 1000 women screened), recall rates, and biopsy rates of DBT and MBI for initial screening are reported. Results In 537 women out of a planned 3000 who have completed the first round of screening, 7 cancers were detected: one by DBT only and 6 by MBI only, giving cancer detection rates of 1.9 for DBT vs. 11.2 for MBI and incremental cancer detection rate of 9.3 for MBI. The one DBT-only cancer was a node-negative 0.8 cm invasive lobular carcinoma. All 6 cancers detected by MBI were invasive; 5 of 6 were node negative (median size 1.0 cm; range 0.6 to 2.6 cm). Recall rate was 11% (60/537) for DBT alone; 16% (84/537) for MBI alone, and 21% (115/537) for the combination. Biopsy was prompted by DBT in 13 patients (PPV 8% [1/13]); by MBI in 23 patients (PPV 26% [6/23]); and by the combination of modalities in 33 (PPV 21% [7/33]). Conclusion These preliminary results demonstrate that MBI detects invasive breast cancers occult on DBT in dense breasts. Data from a second screening round will allow calculation of sensitivity and specificity, and determination of the impact of screening MBI in reducing advanced (&amp;gt; 2 cm) and interval cancers. Additional planned analyses will evaluate a denoising algorithm for further reduction in MBI radiation dose to match that of DBT. Citation Format: Rhodes D, Hunt K, Conners A, Zingula S, Whaley D, Ellis R, Gasal Spilde J, Mehta R, Polley M-Y, O'Connor M, Hruska C. Molecular breast imaging and tomosynthesis to eliminate the reservoir of undetected cancer in dense breasts: The Density MATTERS trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD4-05.

Supplemental ultrasound screening in patients with a history of lobular neoplasia.

To investigate the role of ultrasound (US) screening as an adjunct to annual mammography (M) in breast cancer detection in women with a history of lobular neoplasia (LN) diagnosed following core needle or excisional biopsy. A retrospective review of our database was performed between 11/2006 and 11/2011 to identify patients diagnosed with LN, and underwent annual screening. Patients with a lifetime risk >20% per risk modeling were excluded. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and cancer detection rate (CDR) of each screening test were identified. Cancer type and detection modality were recorded. A total of 100 patients who had M and/or US screening were included. Mean patient age was 54.7years (range 33-83). All 100 patients underwent a mean of 3.9 rounds of screening M and 93 (93%) received US screening (mean 3.3 rounds). Of 93 patients who received both M and US screening, 12 (13%) were diagnosed with breast cancer. Mammographic CDR was 4%. Incremental US CDR was 6.5%. The sensitivity, specificity, and NPV for M screening alone was 33% (10%, 65%), 77% (67%, 85%), and 89% (80%, 95%), respectively. US and mammography screening had a combined sensitivity: 83% (52%, 98%), Specificity: 72% (62%, 81%), NPV: 97% (89%, 100%). Supplemental US screening resulted in a significant increase in sensitivity, yielding 6.5% incremental CDR in this high-risk patient subgroup that does not fulfill ACS high-risk MRI screening criteria.

A prospective comparative trial of adjunct screening with tomosynthesis or ultrasound in women with mammography-negative dense breasts (ASTOUND-2)

BackgroundIncreased risk of breast cancer (BC) and increased risk of an interval BC at mammography screening are associated with high mammographic density. Adjunct imaging detects additional BCs not detected at mammography screening in women with dense breasts. AimThe aim is to estimate the incremental cancer detection rate (CDR) and false-positive recall for each of tomosynthesis and ultrasound, as adjunct screening modalities in women with mammography-negative dense breasts. MethodsA multicentre prospective comparative trial of adjunct screening with tomosynthesis or ultrasound in women with mammography-negative dense breasts (ASTOUND-2) recruited asymptomatic women attending Italian breast screening services. All participants had independently interpreted tomosynthesis and ultrasound. Outcomes were ascertained from excision histopathology or completed assessment. Paired binary data were compared using McNemar's test. ResultsWe recruited 5300 screening participants with median age of 50 (interquartile range 43–79) years who had negative mammography and dense breasts (April 2015–September 2017). Adjunct screening detected 29 additional BCs (27 invasive, 2 in situ): 12 detected on both tomosynthesis and ultrasound, 3 detected only on tomosynthesis, 14 detected only on ultrasound. Incremental CDR for tomosynthesis (+15 cancers) was 2.83/1000 screens (95% confidence interval [CI]: 1.58–4.67) versus ultrasound (+26 cancers) with an incremental CDR of 4.90/1000 screens (95% CI: 3.21–7.19), P = 0.015. Mean size of these cancers was 14.2 mm (standard deviation: 7.8 mm), and six had nodal metastases. Incremental false-positive recall was 1.22% (95% CI: 0.91%–1.49%) and differed significantly between tomosynthesis (0.30%) and ultrasound (1.0%), P < 0.001. ConclusionsUltrasound detected more BCs but caused more false positives than tomosynthesis, underscoring trade-offs in screening outcomes when adjunct imaging is used for screening dense breasts.

Contrast-Enhanced Spectral Mammography in Women With Intermediate Breast Cancer Risk and Dense Breasts.

The purpose of this study was to compare the diagnostic performance of contrast-enhanced spectral mammography (CESM) and ultrasound with that of standard digital mammography for breast cancer screening of women at intermediate risk who have dense breasts. In a retrospective cohort of 611 consecutively registered women who underwent screening CESM from 2012 to 2017, BI-RADS scores of the screening modalities were compared with actual disease status, assessed by histopathologic analysis or imaging follow-up. Sensitivity, specificity, and positive and negative predictive values were calculated. Among the 611 women included, 48.3% (295/611) had family or personal history of breast cancer, the BI-RADS breast density score was C or D in 93.1% (569/611). The mean follow-up period was 20 months. Mammography depicted 11 of 21 malignancies, sensitivity of 52.4%, specificity of 90.5% (534/590), positive predictive value of 16.4% (11/67), and negative predictive value of 98.2% (534/544). CESM depicted 19 of 21 malignancies, sensitivity of 90.5%, specificity of 76.1% (449/590), positive predictive value of 11.9% (19/160), and negative predictive value of 99.6% (449/451). Differences in sensitivity (p = 0.008) and specificity (p < 0.001) were statistically significant. Adjunct ultrasound revealed 73 additional suspicious findings; all were false-positive. In 39 women MRI was needed to assess screening abnormalities; two MRI-guided biopsies were performed and yielded one cancer. The incremental cancer detection rate of CESM was 13.1/1000 women (95% CI, 6.1-20.1). Of eight cancers seen only with CESM, seven were invasive (mean size, 9 mm; two of four cancers lymph-node positive). CESM was significantly more sensitive than standard digital mammography for detecting breast cancer in this screening population. No added benefit was found in the performance of ultrasound as an adjunct to CESM screens with negative results. CESM may be a valuable supplemental screening modality for women at intermediate risk who have dense breasts.

Breast Cancer Screening Using Tomosynthesis or Mammography: A Meta-analysis of Cancer Detection and Recall.

Tomosynthesis approximates a 3D mammogram of the breast, reducing parenchymal overlap that masks cancers or creates false "lesions" on 2D mammography, and potentially enabling more accurate detection of breast cancer. We compared breast cancer screening detection and recall in asymptomatic women for tomosynthesis vs 2D mammography. A systematic review and random effects meta-analysis were undertaken. Electronic databases (2009-July 2017) were searched for studies comparing tomosynthesis and 2D mammography in asymptomatic women who attended population breast cancer screening and reporting cancer detection rate (CDR) and recall rate. All statistical tests were two-sided. Seventeen studies (1 009 790 participants) were included from 413 citations. The pooled incremental CDR for tomosynthesis was 1.6 cancers per 1000 screens (95% confidence interval [CI] = 1.1 to 2.0, P < .001, I2 = 36.9%). Incremental CDR was statistically significantly higher for European/Scandinavian studies, all using a "paired" design where women had both tests (2.4 per 1000 screens, 95% CI = 1.9 to 2.9, P < .001, I2 = 0.0%) compared with US ("unpaired") studies (1.1 per 1000 screens, 95% CI = 0.8 to 1.5, P < .001, I2 = 0.0%; P < .001 between strata). The recall rate for tomosynthesis was statistically significantly lower than for 2D mammography (pooled absolute reduction = -2.2%, 95% CI = -3.0 to -1.4, P < .001, I2 = 98.2%). Stratified analyses showed a decrease in US studies (pooled difference in recall rate = -2.9%, 95% CI = -3.5 to -2.4, P < .001, I2 = 92.9%) but not European/Scandinavian studies (0.5% increase in recall, 95% CI = -0.1 to 1.2, P = .12, I2 = 93.5%; P < .001 between strata). Results were similar in sensitivity analyses excluding studies with overlapping cohorts. Tomosynthesis improves CDR and reduces recall; however, effects are dependent on screening setting, with greater improvement in CDR in European/Scandinavian studies (biennial screening) and reduction in recall in US studies with high baseline recall.

Effect of integrating digital breast tomosynthesis (3D-mammography) with acquired or synthetic 2D-mammography on radiologists’ true-positive and false-positive detection in a population screening trial: A descriptive study

BackgroundWe previously reported the Screening with tomosynthesis or standard mammography-2 (STORM-2) trial, showing that tomosynthesis (3D-mammography) screening detected more cancers than 2D-mammography in double-reading practice. In this study, we report reader-specific detection measures for radiologists who performed the screen-reading in this trial. MethodsThis is a sub-study of the STORM-2 trial which prospectively integrated 3D-mammography with acquired or synthetized 2D-mammograms in parallel double-reading arms. Asymptomatic women ≥49 years who attended population-based screening (Trento, 2013–2015) were recruited. Screening participants were recalled at any positive sequential screen-read in either reading arm of the trial. Radiologist-specific detection measures were calculated for each of seven radiologists who performed screen-reads: number of detected cancers, proportion of true-positive (TP) detection, and number and rate of false-positive (FP) recalls (FPR). We estimated incremental cancer detection rate (CDR) from integrating 3D-mammography in screen-reading. ResultsAcross all radiologists, TP detection (relative sensitivity) ranged between: 46% and 100% (median 59.5%) for 2D-mammography; 75% and 100% (median 76%) for integrated 2D/3D-mammography screening; 56% and 76% (median 64%) for 2Dsynthetic; 67% and 88% (median 78%) for 2Dsynthetic/3D-mammography. Integrating 3D-mammography led to incremental CDRs between 0/1000 and 3.5/1000 screens. FPR ranged between: 1.2% and 2.7% (median 2.25%) for 2D-mammography; 1.5% and 3.4% (median 2.75%) for 2D/3D-mammography; 1.6% and 4.6% (median 2.4%) for 2Dsynthetic; and 1.8% and 6.7% (median 3.0%) for 2Dsynthetic/3D-mammography. ConclusionsThere was variability in the magnitude of effect from integrating 3D-mammography (relative to screen-reading with acquired or synthesised 2D-mammography alone) on individual radiologist’s TP and FP detection, although there was an overall pattern of increasing cancer detection and also increasing FP recall for most readers.

Breast cancer screening with tomosynthesis (3D mammography) with acquired or synthetic 2D mammography compared with 2D mammography alone (STORM-2): a population-based prospective study

Breast tomosynthesis (pseudo-3D mammography) improves breast cancer detection when added to 2D mammography. In this study, we examined whether integrating 3D mammography with either standard 2D mammography acquisitions or with synthetic 2D images (reconstructed from 3D mammography) would detect more cases of breast cancer than 2D mammography alone, to potentially reduce the radiation burden from the combination of 2D plus 3D acquisitions. The Screening with Tomosynthesis Or standard Mammography-2 (STORM-2) study was a prospective population-based screening study comparing integrated 3D mammography (dual-acquisition 2D-3D mammography or 2D synthetic-3D mammography) with 2D mammography alone. Asymptomatic women aged 49 years or older who attended population-based screening in Trento, Italy were recruited for the study. All participants underwent digital mammography with 2D and 3D mammography acquisitions, with the use of software that allowed synthetic 2D mammographic images to be reconstructed from 3D acquisitions. Mammography screen-reading was done in two parallel double-readings conducted sequentially for 2D acquisitions followed by integrated acquisitions. Recall based on a positive mammography result was defined as recall at any screen read. Primary outcome measures were a comparison between integrated (2D-3D or 2D synthetic-3D) mammography and 2D mammography alone of the number of cases of screen-detected breast cancer, the cancer detection rate per 1000 screens, the incremental cancer detection rate, and the number and percentage of false-positive recalls. Between May 31, 2013, and May 29, 2015, 10 255 women were invited to participate, of whom 9672 agreed to participate and were screened. In these 9672 participants (median age 58 years [IQR 53-63]), screening detected 90 cases of breast cancer, including 74 invasive breast cancers, in 85 women (five women had bilateral breast cancer). To account for these bilateral cancers in cancer detection rate estimates, the number of screens used for analysis was 9677. Both 2D-3D mammography (cancer detection rate 8·5 per 1000 screens [82 cancers detected in 9677 screens]; 95% CI 6·7-10·5) and 2D synthetic-3D mammography (8·8 per 1000 [85 in 9677]; 7·0-10·8) had significantly higher rates of breast cancer detection than 2D mammography alone (6·3 per 1000 [61 in 9677], 4·8-8·1; p<0·0001 for both comparisons). The cancer detection rate did not differ significantly between 2D-3D mammography and 2D synthetic-3D mammography (p=0·58). Compared with 2D mammography alone, the incremental cancer detection rate from 2D-3D mammography was 2·2 per 1000 screens (95% CI 1·2-3·3) and that from 2D synthetic-3D mammography was 2·5 per 1000 (1·4-3·8). Compared with the proportion of false-positive recalls from 2D mammography alone (328 of 9587 participants not found to have cancer at assessment) [3·42%; 95% CI 3·07-3·80]), false-positive recall was significantly higher for 2D-3D mammography (381 of 9587 [3·97%; 3·59-4·38], p=0·00063) and for 2D synthetic-3D mammography (427 of 9587 [4·45%; 4·05-4·89], p<0·0001). Integration of 3D mammography (2D-3D or 2D synthetic-3D) detected more cases of breast cancer than 2D mammography alone, but increased the percentage of false-positive recalls in sequential screen-reading. These results should be considered in the context of the trade-off between benefits and harms inherent in population breast cancer screening, including that significantly increased breast cancer detection from integrating 3D mammography into screening has the potential to augment screening benefit and also possibly contribute to overdiagnosis. None.

Supplemental Breast Cancer Screening With Molecular Breast Imaging for Women With Dense Breast Tissue.

Molecular breast imaging was implemented in routine clinical practice at a large community-based breast imaging center. The aim of this study was to retrospectively assess the clinical performance of molecular breast imaging as a supplementary screening tool for women with dense breast tissue. Women with dense breasts and negative mammography results who subsequently underwent screening with 300 MBq (8 mCi) (99m)Tc-sestamibi molecular breast imaging were retrospectively analyzed. Outcome measures included cancer detection rate, recall rate, biopsy rate, and positive predictive values (PPVs). Molecular breast imaging screening of 1696 women in this study resulted in the detection of 13 mammographically occult malignancies, of which 11 were invasive, one was node positive, and one had unknown node positivity. The lesion size ranged from 0.6 to 2.4 cm, with a mean of 1.1 cm. The incremental cancer detection rate was 7.7‰ (95% CI, 4.5-13.1‰), the recall rate was 8.4% (95% CI, 7.2-9.8%), and the biopsy rate was 3.7% (95% CI, 2.9%-4.7%). The PPV for recall (PPV 1) was 9.1% (95% CI, 5.4-15.0%), and the PPV for biopsy (PPV 3) was 19.4% (95% CI, 11.4-30.9%). When incorporated into a community-based clinical practice environment, molecular breast imaging yielded a high incremental cancer detection rate of 7.7‰ at an acceptable radiation dose. These results show the utility of molecular breast imaging as a supplementary screening tool to mammography for women with dense breasts.

Adjunct Screening With Tomosynthesis or Ultrasound in Women With Mammography-Negative Dense Breasts: Interim Report of a Prospective Comparative Trial.

Debate on adjunct screening in women with dense breasts has followed legislation requiring that women be informed about their mammographic density and related adjunct imaging. Ultrasound or tomosynthesis can detect breast cancer (BC) in mammography-negative dense breasts, but these modalities have not been directly compared in prospective trials. We conducted a trial of adjunct screening to compare, within the same participants, incremental BC detection by tomosynthesis and ultrasound in mammography-negative dense breasts. Adjunct Screening With Tomosynthesis or Ultrasound in Women With Mammography-Negative Dense Breasts is a prospective multicenter study recruiting asymptomatic women with mammography-negative screens and dense breasts. Eligible women had tomosynthesis and physician-performed ultrasound with independent interpretation of adjunct imaging. Outcome measures included cancer detection rate (CDR), number of false-positive (FP) recalls, and incremental CDR for each modality; these were compared using McNemar's test for paired binary data in a preplanned interim analysis. Among 3,231 mammography-negative screening participants (median age, 51 years; interquartile range, 44 to 78 years) with dense breasts, 24 additional BCs were detected (23 invasive): 13 tomosynthesis-detected BCs (incremental CDR, 4.0 per 1,000 screens; 95% CI, 1.8 to 6.2) versus 23 ultrasound-detected BCs (incremental CDR, 7.1 per 1,000 screens; 95% CI, 4.2 to 10.0), P = .006. Incremental FP recall occurred in 107 participants (3.33%; 95% CI, 2.72% to 3.96%). FP recall (any testing) did not differ between tomosynthesis (FP = 53) and ultrasound (FP = 65), P = .26; FP recall (biopsy) also did not differ between tomosynthesis (FP = 22) and ultrasound (FP = 24), P = .86. The Adjunct Screening With Tomosynthesis or Ultrasound in Women With Mammography-Negative Dense Breasts' interim analysis shows that ultrasound has better incremental BC detection than tomosynthesis in mammography-negative dense breasts at a similar FP-recall rate. However, future application of adjunct screening should consider that tomosynthesis detected more than 50% of the additional BCs in these women and could potentially be the primary screening modality.