Christiane M. Hakim's research while affiliated with Magee-Womens Hospital and other places

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.

PURPOSE To assess diagnostic performance of digital breast tomosynthesis (DBT) alone or combined with technologist-performed handheld screening ultrasound (US) in women with dense breasts. METHODS In an institutional review board–approved, Health Insurance Portability and Accountability Act–compliant multicenter protocol in western Pennsylvania, 6,179 women consented to three rounds of annual screening, interpreted by two radiologist observers, and had appropriate follow-up. Primary analysis was based on first observer results. RESULTS Mean participant age was 54.8 years (range, 40-75 years). Across 17,552 screens, there were 126 cancer events in 125 women (7.2/1,000; 95% CI, 5.9 to 8.4). In year 1, DBT-alone cancer yield was 5.0/1,000, and of DBT+US, 6.3/1,000, difference 1.3/1,000 (95% CI, 0.3 to 2.1; P = .005). In years 2 + 3, DBT cancer yield was 4.9/1,000, and of DBT+US, 5.9/1,000, difference 1.0/1,000 (95% CI, 0.4 to 1.5; P < .001). False-positive rate increased from 7.0% for DBT in year 1 to 11.5% for DBT+US and from 5.9% for DBT in year 2 + 3 to 9.7% for DBT+US ( P < .001 for both). Nine cancers were seen only by double reading DBT and one by double reading US. Ten interval cancers (0.6/1,000 [95% CI, 0.2 to 0.9]) were identified. Despite reduction in specificity, addition of US improved receiver operating characteristic curves, with area under receiver operating characteristic curve increasing from 0.83 for DBT alone to 0.92 for DBT+US in year 1 ( P = .01), with smaller improvements in subsequent years. Of 6,179 women, across all 3 years, 172/6,179 (2.8%) unique women had a false-positive biopsy because of DBT as did another 230/6,179 (3.7%) women because of US ( P < .001). CONCLUSION Overall added cancer detection rate of US screening after DBT was modest at 19/17,552 (1.1/1,000; CI, 0.5- to 1.6) screens but potentially overcomes substantial increases in false-positive recalls and benign biopsies.

Objective For breast US interpretation, to assess impact of computer-aided diagnosis (CADx) in original mode or with improved sensitivity or specificity. Methods In this IRB approved protocol, orthogonal-paired US images of 319 lesions identified on screening, including 88 (27.6%) cancers (median 7 mm, range 1–34 mm), were reviewed by 9 breast imaging radiologists. Each observer provided BI-RADS assessments (2, 3, 4A, 4B, 4C, 5) before and after CADx in a mode-balanced design: mode 1, original CADx (outputs benign, probably benign, suspicious, or malignant); mode 2, artificially-high-sensitivity CADx (benign or malignant); and mode 3, artificially-high-specificity CADx (benign or malignant). Area under the receiver operating characteristic curve (AUC) was estimated under each modality and for standalone CADx outputs. Multi-reader analysis accounted for inter-reader variability and correlation between same-lesion assessments. Results AUC of standalone CADx was 0.77 (95% CI: 0.72–0.83). For mode 1, average reader AUC was 0.82 (range 0.76–0.84) without CADx and not significantly changed with CADx. In high-sensitivity mode, all observers’ AUCs increased: average AUC 0.83 (range 0.78–0.86) before CADx increased to 0.88 (range 0.84–0.90), P < 0.001. In high-specificity mode, all observers’ AUCs increased: average AUC 0.82 (range 0.76–0.84) before CADx increased to 0.89 (range 0.87–0.92), P < 0.0001. Radiologists responded more frequently to malignant CADx cues in high-specificity mode (42.7% vs 23.2% mode 1, and 27.0% mode 2, P = 0.008). Conclusion Original CADx did not substantially impact radiologists’ interpretations. Radiologists showed improved performance and were more responsive when CADx produced fewer false-positive malignant cues.

Objective To assess prospectively the interpretative performance of automated breast ultrasound (ABUS) as a supplemental screening after digital breast tomosynthesis (DBT) or as a standalone screening of women with dense breast tissue. Methods Under an IRB-approved protocol (written consent required), women with dense breasts prospectively underwent concurrent baseline DBT and ABUS screening. Examinations were independently evaluated, in opposite order, by two of seven Mammography Quality Standards Act–qualified radiologists, with the primary radiologist arbitrating disagreements and making clinical management recommendations. We report results for 1111 screening examinations (598 first year and 513 second year) for which all diagnostic workups are complete. Imaging was also retrospectively reviewed for all cancers. Statistical assessments used a 0.05 significance level and accounted for correlation between participants’ examinations. Results Of 1111 women screened, primary radiologists initially “recalled” based on DBT alone (6.6%, 73/1111, CI: 5.2%–8.2%), of which 20 were biopsied, yielding 6/8 total cancers. Automated breast ultrasound increased recalls overall to 14.4% (160/1111, CI: 12.4%–16.6%), with 27 total biopsies, yielding 1 additional cancer. Double reading of DBT alone increased the recall rate to 10.7% (119/1111), with 21 biopsies, with no improvement in cancer detection. Double reading ABUS increased the recall rate to 15.2% (169/1111, CI: 13.2%–17.5%) of women, of whom 22 were biopsied, yielding the detection of 7 cancers, including one seen only on double reading ABUS. Inter-radiologist agreement was similar for recall recommendations from DBT (κ = 0.24, CI: 0.14–0.34) and ABUS (κ = 0.23, CI: 0.15–0.32). Integrated assessments from both readers resulted in a recall rate of 15.1% (168/1111, CI: 13.1%–17.4%). Conclusions Supplemental or standalone ABUS screening detected cancers not seen on DBT, but substantially increased noncancer recall rates.

Background Staging newly diagnosed breast cancer by using dynamic contrast material-enhanced MRI is limited by access, high cost, and false-positive findings. The utility of contrast-enhanced mammography (CEM) and 99mTc sestamibi-based molecular breast imaging (MBI) in this setting is largely unknown. Purpose To compare extent-of-disease assessments by using MRI, CEM, and MBI versus pathology in women with breast cancer. Materials and Methods In this HIPAA-compliant prospective study, women with biopsy-proven breast cancer underwent MRI, CEM, and MBI between October 2014 and April 2018. Eight radiologists independently interpreted each examination result prospectively and were blinded to interpretations of findings with the other modalities. Visibility of index malignancies, lesion size, and additional suspicious lesions (malignant or benign) were compared during pathology review. Accuracy of index lesion sizing and detection of additional lesions in women without neoadjuvant chemotherapy were compared. Results A total of 102 women were enrolled and 99 completed the study protocol (mean age, 51 years ± 11 [standard deviation]; range, 32-77 years). Lumpectomy or mastectomy was performed in 71 women (79 index malignancies) without neoadjuvant chemotherapy and in 28 women (31 index malignancies) with neoadjuvant chemotherapy. Of the 110 index malignancies, MRI, CEM, and MBI depicted 102 (93%; 95% confidence interval [CI]: 86%, 97%), 100 (91%; 95% CI: 84%, 96%), and 101 (92%; 95% CI: 85%, 96%) malignancies, respectively. In patients without neoadjuvant chemotherapy, pathologic size of index malignancies was overestimated with all modalities (P = .02). MRI led to overestimation of 24% (17 of 72) of malignancies by more than 1.5 cm compared with 11% (eight of 70) with CEM and 15% (11 of 72) with MBI. MRI depicted more (P = .007) nonindex lesions, with sensitivity similar to that of CEM or MBI, resulting in lower positive predictive value of additional biopsies (13 of 46 [28%; 95% CI: 17%, 44%] for MRI; 14 of 27 [52%; 95% CI: 32%, 71%] for CEM; and 11 of 25 [44%; 95% CI: 24%, 65%] for MBI (overall P = .01). Conclusion Contrast-enhanced mammography, molecular breast imaging, and MRI showed similar detection of all malignancies. MRI depicted more nonindex suspicious benign lesions than did contrast-enhanced mammography or molecular breast imaging, leading to lower positive predictive value of additional biopsies. All three modalities led to overestimation of index tumor size, particularly MRI. © RSNA, 2019 Online supplemental material is available for this article.

Rationale and objectives: To preliminarily asses if Contrast Enhanced Digital Mammography (CEDM) can accurately reduce biopsy rates for soft tissue BI-RADS 4A or 4B lesions. Materials and methods: Eight radiologists retrospectively and independently reviewed 60 lesions in 54 consenting patients who underwent CEDM under Health Insurance Portability and Accountability Act compliant institutional review board-approved protocols. Readers provided Breast Imaging Reporting & Data System ratings sequentially for digital mammography/digital breast tomosynthesis (DM/DBT), then with ultrasound, then with CEDM for each lesion. Area under the curve (AUC), true positive rates and false positive rates, positive predictive values and negative predictive values were calculated. Statistical analysis accounting for correlation between lesion-examinations and between-reader variability was performed using OR/DBM (for SAS v.3.0), generalized linear mixed model for binary data (proc glimmix, SAS v.9.4, SAS Institute, Cary North Carolina), and bootstrap. Results: The cohort included 49 benign, two high-risk and nine cancerous lesions in 54 women aged 34-74 (average 50) years. Reader-averaged AUC for CEDM was significantly higher than DM/DBT alone (0.85 versus 0.66, p < 0.001) or with US (0.85 versus 0.75, p = 0.001). CEDM increased true positive rates from 0.74 under DB/DBT, and 0.89 with US, to 0.90 with CEDM, (p = 0.019 DM/DBT versus CEDM, p = 0.78 DM/DBT + US versus CEDM) and decreased false positive rates from 0.47 using DM/DBT and 0.61 with US to 0.39 with CEDM (p = 0.017 DM/DBT versus CEDM, p = 0.001 DM/DBT+ US versus CEDM). For an expected cancer rate of 10%, CEDM positive predictive values was 20.5% (95% CI: 16%-27%) and negative predictive values 98.3% (95% CI: 96%-100%). Conclusion: Addition of CEDM for evaluation of low-moderate suspicion soft tissue breast lesions can substantially reduce biopsy of benign lesions without compromising cancer detection.