Multicenter Development and Prospective Validation of eCARTv5: A Gradient Boosted Machine Learning Early Warning Score.

Rationale: Early detection of clinical deterioration using early warning scores may improve outcomes. However, most implemented scores were developed using logistic regression, only underwent retrospective internal validation, and were not tested in important patient subgroups. Objectives: To develop a gradient boosted machine model (eCARTv5) for identifying clinical deterioration and then validate externally, test prospectively, and evaluate across patient subgroups. Methods: All adult patients hospitalized on the wards in seven hospitals from 2008- 2022 were used to develop eCARTv5, with demographics, vital signs, clinician documentation, and laboratory values utilized to predict intensive care unit transfer or death in the next 24 hours. The model was externally validated retrospectively in 21 hospitals from 2009-2023 and prospectively in 10 hospitals from February to May 2023. eCARTv5 was compared to the Modified Early Warning Score (MEWS) and the National Early Warning Score (NEWS) using the area under the receiver operating characteristic curve (AUROC). Measurements and Main Results: The development cohort included 901,491 admissions, the retrospective validation cohort included 1,769,461 admissions, and the prospective validation cohort included 46,330 admissions. In retrospective validation, eCART had the highest AUROC (0.835; 95%CI 0.834, 0.835), followed by NEWS (0.766 (95%CI 0.766, 0.767)), and MEWS (0.704 (95%CI 0.703, 0.704)). eCART's performance remained high (AUROC ≥0.80) across a range of patient demographics, clinical conditions, and during prospective validation. Conclusions: We developed eCARTv5, which accurately identifies early clinical deterioration in hospitalized ward patients. Our model performed better than the NEWS and MEWS retrospectively, prospectively, and across a range of subgroups.

Breast Cancer Mode of Detection in a Population-Based Cohort.

OBJECTIVE: To evaluate how breast cancers come to clinical attention (mode of detection [MOD]) in a population-based cohort, determine the relative frequency of different MODs, and characterize patient and tumor characteristics associated with MOD. PATIENTS AND METHODS: We used the Rochester Epidemiology Project to identify women ages 40 to 75 years with a first-time diagnosis of breast cancer from May 9, 2017, to May 9, 2019 (n=500) in a 9-county region in Minnesota. We conducted a retrospective medical record review to ascertain the relative frequency of MODs, evaluating differences between screening mammography vs all other MODs by breast density and cancer characteristics. Multiple logistic regression was conducted to examine the likelihood of MOD for breast density and stage of disease. RESULTS: In our population-based cohort, 162 of 500 breast cancers (32.4%) were detected by MODs other than screening mammography, including 124 (24.8%) self-detected cancers. Compared with women with mammography-detected cancers, those with MODs other than screening mammography were more frequently younger than 50 years of age (P=.004) and had higher-grade tumors (P=.007), higher number of positive lymph nodes (P<.001), and larger tumor size (P<.001). Relative to women with mammography-detected cancers, those with MODs other than screening mammography were more likely to have dense breasts (odds ratio, 1.87; 95% CI, 1.20 to 2.92; P=.006) and advanced cancer at diagnosis (odds ratio, 3.58; 95% CI, 2.29 to 5.58; P<.001). CONCLUSION: One-third of all breast cancers in this population were detected by MODs other than screening mammography. Increased likelihood of nonmammographic MODs was observed among women with dense breasts and advanced cancer.

PPV of the Molecular Breast Imaging Lexicon.

BACKGROUND. Molecular breast imaging (MBI) is used for various breast imaging indications. An MBI lexicon has been developed, although the likelihood of malignancy of the lexicon descriptors has not been assessed to our knowledge. OBJECTIVE. The purpose of this article was to evaluate the PPV for malignancy of the MBI lexicon imaging descriptors. METHODS. This retrospective study included MBI examinations performed from August 1, 2005, through August 31, 2017, that were positive (BI-RADS analogous categories 0, 3, 4, 5, or 6) according to the clinical report and had an available reference standard. Examinations were performed using dual-detector cadmium zinc telluride MBI systems after injection of 99mTc sestamibi. Category 3 lesions had pathologic correlation, at least 2 years of imaging follow-up, or final resolution on follow-up imaging as category 1 or 2; category 4 and 5 lesions had pathologic correlation. MBI examinations were reviewed by one of two radiologists to assess lesions on the basis of the published MBI lexicon for type (mass vs nonmass uptake), distribution (if nonmass uptake), uptake intensity, and number of MBI views on which the lesion was seen. PPV for malignancy was summarized. RESULTS. The analysis included 643 lesions (479 benign, 164 malignant; 83 mass, 560 nonmass uptake) in 509 patients (median age, 56 years). PPV was 73.5% (61/83) for masses and 18.4% (103/560) for nonmass uptake. Among the nonmass uptake lesions, PPV was 36.2% (17/47) for segmental, 20.1% (77/384) for focal, 30.8% (4/13) for diffuse, and 4.3% (5/116) for regional or multiple regional distribution. PPV was 5.3% (5/94) for one view, 15.2% (32/210) for two views, 14.6% (13/89) for three views, and 45.4% (113/249) for four views showing the lesion. PPV was 14.0% (43/307) for mild, 22.4% (51/228) for moderate, and 64.8% (70/108) for marked uptake intensity. CONCLUSION. The MBI lexicon lesion descriptors are associated with likelihood of malignancy. PPV was higher for masses, lesions seen on multiple MBI views, and lesions with marked uptake intensity. Among nonmass uptake lesions, PPV was highest for those with segmental distribution. CLINICAL IMPACT. Insight into the likelihood of malignancy associated with the MBI lexicon descriptors can inform radiologists' interpretations and guide potential future incorporation of the MBI lexicon into the ACR BI-RADS Atlas.

Breast Density Knowledge and Awareness Among Latinas in a Low-Resource Setting.

PURPOSE: Latinas in low-resource settings face additional barriers to understanding mammographic breast density (MBD) implications. The authors compared MBD awareness and knowledge in Latinas from a safety-net clinic in Arizona with a national sample. METHODS: Latinas 40 to 74 years of age were recruited within a safety-net clinic during screening mammography appointments from 2016 to 2019 (AZ cohort) and from a nationally representative online panel in 2017 (NS cohort). Surveys completed in either English or Spanish assessed awareness and knowledge of MBD. Chi-square tests and logistic regression were used for comparisons. RESULTS: The NS cohort (n = 152) was older, more educated, more likely to have undergone prior mammography, and more likely to prefer English compared with the AZ cohort (n = 1,327) (P ≤ .03 for all) The NS cohort was more likely to be aware of MBD (32.6% versus 20.7%). Of those aware, the NS cohort was more likely to understand MBD's effect on masking (67.8% versus 37.0%) and breast cancer risk (72.2% versus 32.6%) compared with the AZ cohort (P ≤ .001 for all). Adjusting for age, education, screening history, and language, MBD awareness was similar between the two cohorts (adjusted odds ratio [ORadj], 0.95; P = .83), but knowledge of MBD as a masking factor (ORadj, 2.8; P = .03) and risk factor (ORadj, 7.2; P < .001) remained higher in the NS cohort compared with the AZ cohort. CONCLUSIONS: Differences in MBD awareness, but not knowledge, between Latinas in a low-resource setting compared with a national sample could be explained by age, education, screening history, and language preference, underscoring the need for tailored approaches to MBD education among Latinas.

Evaluating educational interventions to increase breast density awareness among Latinas: A randomized trial in a Federally Qualified Health Center.

BACKGROUND: The objective of this randomized trial was to evaluate the short-term effect of bilingual written and interpersonal education regarding mammographic breast density (MBD). METHODS: Latinas aged 40 to 74 years who were presenting for screening mammography were recruited and randomized 1:1:1 to receive a letter with their mammogram and MBD results (usual care [UC]), a letter plus a brochure (enhanced care [ENH]), or a letter plus a brochure and telephonic promotora education (interpersonal care [INT]). Surveys were administered at enrollment (T0 ) and 2 weeks to 6 months after intervention delivery (T1 ). Differences were assessed with χ2 , Kruskal-Wallis, and McNemar tests and pairwise comparisons as appropriate. INT metrics and audio recordings were analyzed with descriptive statistics and qualitative content analysis. RESULTS: Between October 2016 and October 2019, 943 of 1108 Latina participants (85%) completed both surveys. At T1 , INT participants were more likely (P < .001) to report seeing their MBD results in the letter (70.2%) than UC (53.1%) or ENH participants (55.1%). The percentage of INT women who reported speaking with a provider about MBD (29.0%) was significantly greater (P < .001) than the percentage of UC (14.7%) or ENH participants (15.6%). All groups saw significant (P < .001) but nondifferential improvements in their knowledge of MBD as a masking and risk factor. In the INT group, the promotora delivered education to 77.1% of the 446 participants randomized to INT and answered questions at 28.3% of the encounters for an average of $4.70 per participant. CONCLUSIONS: Among Latinas in a low-resource setting, MBD knowledge may increase with written or interpersonal education, but with modest investment, interpersonal education may better improve MBD awareness and prompt patient-provider discussions.

Background Parenchymal Uptake on Molecular Breast Imaging and Breast Cancer Risk: A Cohort Study.

BACKGROUND. Background parenchymal uptake (BPU) on molecular breast imaging (MBI) was identified in a case-control study as a breast cancer risk factor beyond mammographic density. To our knowledge, this finding has not yet been confirmed in a cohort study. OBJECTIVE. The objectives of this study were to examine the association of BPU with breast cancer and to estimate the absolute risk and discriminatory accuracy of BPU in a cohort study. METHODS. A retrospective cohort was established that included women without a history of breast cancer who underwent MBI from 2004 to 2015. Radiologists who were blinded to future breast cancer diagnoses assessed BPU on baseline MBI examinations as low (photopenic or minimal) or elevated (mild, moderate, or marked). Associations of BPU with breast cancer were estimated using multivariable Cox proportional hazards models of the time to diagnosis. The 5-year absolute risk was calculated for study subgroups. The discriminatory accuracy of BPU was also assessed. RESULTS. Among 2992 women (mean age, 56.3 years; SD, 10.6 years) who underwent MBI, breast cancer events occurred in 144 women (median follow-up, 7.3 years). Median time to diagnosis after MBI was 4.2 years (range, 0.5-11.6 years). Elevated BPU was associated with a greater breast cancer risk (hazard ratio [HR], 2.39; 95% CI, 1.68-3.41; p ≤ .001). This association remained in postmenopausal women (HR, 3.50; 95% CI, 2.31-5.31; p < .001) but was not significant in premenopausal women (HR, 1.29; 95% CI, 0.72-2.32; p = .39). The 5-year absolute risk of breast cancer was 4.3% (95% CI, 2.9-5.7%) for women with elevated BPU versus 2.5% (95% CI, 1.8-3.1%) for those with low BPU. Postmenopausal women with dense breasts and elevated BPU had a 5-year absolute risk of 8.1% (95% CI, 4.3-11.8%) versus 2.8% (1.8-3.8%) for those with low BPU. Among postmenopausal women, discriminatory accuracy for invasive cancer was improved with the addition of BPU versus use of the Gail risk score alone (C statistic, 65.1 vs 59.1; p = .04) or use of the Breast Cancer Surveillance Consortium risk score alone (C statistic, 66.4 vs 60.4; p = .04). CONCLUSION. BPU on MBI is an independent risk factor for breast cancer, with the strongest association observed among postmenopausal women with dense breasts. In postmenopausal women, BPU provides incremental discrimination in predicting breast cancer when combined with either the Gail model or the Breast Cancer Surveillance Consortium model. CLINICAL IMPACT. Observation of elevated BPU on MBI may identify a subset of women with dense breasts who would benefit most from supplemental screening or preventive options.

Evaluation of Germline Genetic Testing Criteria in a Hospital-Based Series of Women With Breast Cancer.

PURPOSE: To determine the sensitivity and specificity of genetic testing criteria for the detection of germline pathogenic variants in women with breast cancer. MATERIALS AND METHODS: Women with breast cancer enrolled in a breast cancer registry at a tertiary cancer center between 2000 and 2016 were evaluated for germline pathogenic variants in 9 breast cancer predisposition genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53). The performance of the National Comprehensive Cancer Network (NCCN) hereditary cancer testing criteria was evaluated relative to testing of all women as recommended by the American Society of Breast Surgeons. RESULTS: Of 3,907 women, 1,872 (47.9%) meeting NCCN criteria were more likely to carry a pathogenic variant in 9 predisposition genes compared with women not meeting criteria (9.0% v 3.5%; P < .001). Of those not meeting criteria (n = 2,035), 14 (0.7%) had pathogenic variants in BRCA1 or BRCA2. The sensitivity of NCCN criteria was 70% for 9 predisposition genes and 87% for BRCA1 and BRCA2, with a specificity of 53%. Expansion of the NCCN criteria to include all women diagnosed with breast cancer at ≤ 65 years of age achieved > 90% sensitivity for the 9 predisposition genes and > 98% sensitivity for BRCA1 and BRCA2. CONCLUSION: A substantial proportion of women with breast cancer carrying germline pathogenic variants in predisposition genes do not qualify for testing by NCCN criteria. Expansion of NCCN criteria to include all women diagnosed at ≤ 65 years of age improves the sensitivity of the selection criteria without requiring testing of all women with breast cancer.

Dose Reduction in Molecular Breast Imaging With a New Image-Processing Algorithm.

OBJECTIVE. The purpose of this study was to determine whether application of a proprietary image-processing algorithm would allow a reduction in the necessary administered activity for molecular breast imaging (MBI) examinations. MATERIALS AND METHODS. Images from standard-dose MBI examinations (300 MBq 99mTc-sestamibi) of 50 subjects were analyzed. The images were acquired in dynamic mode and showed at least one breast lesion. Half-dose MBI examinations were simulated by summing one-half of the dynamic frames and were processed with the algorithm under study in both a default and a preferred filter mode. Two breast radiologists independently completed a set of two-alternative forced-choice tasks to compare lesion conspicuity on standard-dose images, half-dose images, and the algorithm-processed half-dose images in both modes. RESULTS. Relative to the standard-dose images, the half-dose images were preferred in 4, the default-filtered half-dose images in 50, and preferred-filtered half-dose images in 76 of 100 readings. Compared with standard-dose images, in terms of lesion conspicuity, the half-dose images were rated better in 2, equivalent in 6, and poorer in 92 of 100 readings. The default-filtered half-dose images were rated better, equivalent, or poorer in 13, 73, and 14 of 100 readings. The preferred-filtered half-dose images were rated as better, equivalent, or poorer in 55, 34, and 11 of 100 readings. CONCLUSION. Compared with that on standard-dose images, lesion conspicuity on images obtained with the algorithm and acquired at one-half the standard dose was equivalent or better without compromise of image quality. The algorithm can also be used to decrease imaging time with a resulting increase in patient comfort and throughput.

Breast Density Awareness, Knowledge, and Attitudes Among US Women: National Survey Results Across 5 Years.

PURPOSE: To assess changes in breast density (BD) awareness, knowledge, and attitudes among US women over a period of 5 years. METHODS: Using a probability-based web panel representative of the US population, we administered an identical BD survey in 2012 and 2017 to women aged 40 to 74 years. RESULTS: In 2017, 65.8% had heard of BD (versus 57.5% in 2012; P = .0002). BD awareness in both 2012 and 2017 was significantly associated with race, income, and education. Among women aware of BD in 2017, 76.5% had knowledge of BD's relationship to masking (versus 71.5% in 2012; P = .04); 65.5% had knowledge of BD's relationship to cancer risk (versus 58.5%; P = .009); and 47.3% had discussed BD with a provider (versus 43.1% in 2012; P = .13). After multivariable adjustment, residence in a state with BD legislation was associated in 2017 with knowledge of BD's relationship to risk but not to masking. Most women wanted to know their BD (62.5% in 2017 versus 59.8% in 2012; P = .46); this information was anticipated to cause anxiety in 44.8% (versus 44.9% in 2012; P = .96); confusion in 35.9% (versus 43.0%; P = .002); and feeling informed in 89.7% (versus 90.4%; P = .64). Over three-quarters supported federal BD legislation in both surveys. Response rate to the 2017 survey was 55% (1,502 of 2,730) versus 65% (1,506 of 2,311) in 2012. CONCLUSION: Although BD awareness has increased, important disparities persist. Knowledge of BD's impact on risk has increased; knowledge about masking and BD discussions with providers have not. Most women want to know their BD, would not feel anxious or confused as a result of knowing, and would feel empowered to make decisions. The federal BD notification legislation presents an opportunity to improve awareness and knowledge and encourage BD conversations with providers.

Supplemental screening in the dense breast: does molecular breast imaging have a role?

With the passage of a 2019 US federal law directing FDA to ensure that mammography facilities provide a summary to patients categorizing their breast density and explaining how it can influence mammography accuracy, providers will increasingly be called on to discuss the options for supplemental screening. Numerous studies have elucidated the extent of masking that occurs with mammography screening in dense breasts when mammography is compared with other supplemental screening modalities. Despite this evidence, there is currently no consensus among experts or imaging societies as to whether or with what supplemental screening should be performed, leaving providers to counsel patients regarding the balance of benefits and harms.

Behavioral and psychological impact of returning breast density results to Latinas: study protocol for a randomized clinical trial.

BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer mortality among Latinas. As more is learned about the association between mammographic breast density (MBD) and breast cancer risk, a number of U.S. states adopted legislation and now a federal law mandates written notification of MBD along with mammogram results. These notifications vary in content and readability, though, which may limit their effectiveness and create confusion or concern, especially among women with low health literacy or barriers to screening. The purpose of this study is to determine whether educational enhancement of MBD notification results in increased knowledge, decreased anxiety, and adherence to continued mammography screening among Latina women in a limited-resources setting. METHODS: Latinas LEarning About Density (LLEAD) is a randomized clinical trial (RCT) comparing the impact of three notification approaches on behavioral and psychological outcomes in Latina women. Approximately 2000 Latinas undergoing screening mammography in a safety-net community clinic will be randomized 1:1:1 to mailed notification (usual care); mailed notification plus written educational materials (enhanced); or mailed notification, written educational materials, plus verbal explanation by a promotora (interpersonal). The educational materials and verbal explanations are available in Spanish or English. Mechanisms through which written or verbal information influences future screening motivation and behavior will be examined, as well as moderating factors such as depression and worry about breast cancer, which have been linked to diagnostic delays among Latinas. The study includes multiple psychological measures (anxiety, depression, knowledge about MBD, perceived risk of breast cancer, worry, self-efficacy) and behavioral outcomes (continued adherence to mammography). Measurement time points include enrollment, 2-4 weeks post-randomization, and 1 and 2 years post-randomization. Qualitative inquiry related to process and outcomes of the interpersonal arm and cost analysis related to its implementation will be undertaken to understand the intervention's delivery and transferability. DISCUSSION: Legislation mandating written MBD notification may have unintended consequences on behavioral and psychological outcomes, particularly among Latinas with limited health literacy and resources. This study has implications for cancer risk communication and will offer evidence on the potential of generalizable educational strategies for delivering information on breast density to Latinas in limited-resource settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02910986. Registered on 21 September 2016. Items from the WHO Trial Registration Data Set can be found in this protocol.

Impact of short-term low-dose tamoxifen on molecular breast imaging background parenchymal uptake: a pilot study.

BACKGROUND: High background parenchymal uptake (BPU) on molecular breast imaging (MBI) has been identified as a breast cancer risk factor. We explored the feasibility of offering a short-term intervention of low-dose oral tamoxifen to women with high BPU and examined whether this intervention would reduce BPU. METHODS: Women with a history of high BPU and no breast cancer history were invited to the study. Participants had an MBI exam, followed by 30 days of low-dose oral tamoxifen at either 5 mg or 10 mg/day, and a post-tamoxifen MBI exam. BPU on pre- and post-tamoxifen MBI exams was quantitatively assessed as the ratio of average counts in breast fibroglandular tissue vs. average counts in subcutaneous fat. Pre-tamoxifen and post-tamoxifen BPU were compared with paired t tests. RESULTS: Of 47 women invited, 22 enrolled and 21 completed the study (10 taking 5 mg tamoxifen, 11 taking 10 mg tamoxifen). Mean age was 47.7 years (range 41-56 years). After 30 days low-dose tamoxifen, 8 of 21 women (38%) showed a decline in BPU, defined as a decrease from the pre-tamoxifen MBI of at least 15%; 11 of 21 (52%) had no change in BPU (within ± 15%); 2 of 21 (10%) had an increase in BPU of greater than 15%. Overall, the average post-tamoxifen BPU was not significantly different from pre-tamoxifen BPU (1.34 post vs. 1.43 pre, p = 0.11). However, among women taking 10 mg tamoxifen, 5 of 11 (45%) showed a decline in BPU; average BPU was 1.19 post-tamoxifen vs. 1.34 pre-tamoxifen (p = 0.005). In women taking 5 mg tamoxifen, 2 of 10 (20%) showed a decline in BPU; average BPU was 1.51 post-tamoxifen vs.1.53 pre-tamoxifen (p = 0.99). CONCLUSIONS: Short-term intervention with low-dose tamoxifen may reduce high BPU on MBI for some patients. Our preliminary findings suggest that 10 mg tamoxifen per day may be more effective than 5 mg for inducing declines in BPU within 30 days. Given the variability in BPU response to tamoxifen observed among study participants, future study is warranted to determine if BPU response could predict the effectiveness of tamoxifen for breast cancer risk reduction within an individual. TRIAL REGISTRATION: ClinicalTrials.gov NCT02979301 . Registered 01 December 2016.

Molecular breast imaging detected invasive lobular carcinoma in dense breasts: A case report.

This case highlights the role of molecular breast imaging (MBI) in evaluating persistent clinical concerns after a negative diagnostic mammogram and ultrasound. MBI is especially useful in the diagnosis of invasive lobular carcinoma due to its occult nature on conventional imaging modalities.

Classification of Background Parenchymal Uptake on Molecular Breast Imaging Using a Convolutional Neural Network.

PURPOSE: Background parenchymal uptake (BPU), which describes the level of radiotracer uptake in normal fibroglandular tissue on molecular breast imaging (MBI), has been identified as a breast cancer risk factor. Our objective was to develop and validate a deep learning model using image convolution to automatically categorize BPU on MBI. METHODS: MBI examinations obtained for clinical and research purposes from 2004 to 2015 were reviewed to classify the BPU pattern using a standardized five-category scale. Two expert radiologists provided interpretations that were used as the reference standard for modeling. The modeling consisted of training and validating a convolutional neural network to predict BPU. Model performance was summarized in data reserved to test the performance of the algorithm at the per-image and per-breast levels. RESULTS: Training was performed on 24,639 images from 3,133 unique patients. The model performance on the withheld testing data (6,172 images; 786 patients) was evaluated. Using direct matching on the predicted classification resulted in an accuracy of 69.4% (95% CI, 67.4% to 71.3%), and if prediction within one category was considered, accuracy increased to 96.0% (95% CI, 95.2% to 96.7%). When considering the breast-level prediction of BPU, the accuracy remained strong, with 70.3% (95% CI, 68.0% to 72.6%) and 96.2% (95% CI, 95.3% to 97.2%) for the direct match and allowance for one category, respectively. CONCLUSION: BPU provided a robust target for training a convolutional neural network. A validated computer algorithm will allow for objective, reproducible encoding of BPU to foster its integration into risk-stratification algorithms.

Molecular Breast Imaging in Patients with Suspicious Calcifications.

OBJECTIVE: We evaluated the accuracy of molecular breast imaging (MBI)-a nuclear medicine technique that employs dedicated dual-detector, cadmium zinc telluride gamma cameras to image the functional uptake of a radiopharmaceutical (typically Tc-99m sestamibi) in the breast-in patients with suspicious calcifications on mammography. METHODS: Women scheduled for stereotactic biopsy of calcifications detected on 2D digital mammography were prospectively enrolled to undergo MBI before biopsy. Molecular breast imaging was performed with injection of Tc-99m sestamibi and a dual-detector, cadmium zinc telluride gamma camera. Positive findings on either modality were biopsied. High-risk and malignant biopsy findings were excised. RESULTS: In 71 participants, 76 areas of calcifications were recommended for biopsy after mammography, and 24 (32%) were malignant, including 20 cases of ductal carcinoma in situ (DCIS) and 4 cases of invasive ductal cancer. Prebiopsy MBI was positive in 17 of the 76 (22%) calcifications, including 10 of 20 (50%) DCISs and 2 of 4 (50%) invasive cancers. The median pathologic size for MBI-positive cancers was 1.5 cm (range 0.5-3.2 cm) compared with 0.9 cm (range 0.1-2.0 cm) for MBI-negative cancers (P = 0.09).Non-mass uptake on MBI led to additional biopsies of 6 sites in 6 patients, and 2 of 6 (33%) MBI-detected incidental lesions showed malignancy; both DCIS contralateral to the mammographically detected calcifications. The overall per-lesion positive and negative predictive values of MBI in this prebiopsy setting were 61% (14 of 23) and 80% (47 of 59), respectively. CONCLUSION: Molecular breast imaging has insufficient negative predictive value to identify calcifications in which biopsy could be avoided. However, among women presenting for biopsy of suspicious calcifications, MBI revealed additional sites of mammographically occult breast cancer.To avoid biopsy of suspicious calcifications on mammography, negative findings on MBI should not be used.

Patient Acceptance of Half-dose Vs. Half-time Molecular Breast Imaging.

OBJECTIVE: A number of strategies have been implemented at our institution to allow reductions in the administered dose or imaging time for molecular breast imaging (MBI). In this work, we examine patient opinions of whether dose reduction or time reduction is preferred. METHODS: Sixty female volunteers were randomized to undergo MBI at either half-dose (150 MBq Tc-99m sestamibi; images acquired for 10 minutes per view) or half-time (300 MBq Tc-99m sestamibi; images acquired for 5 minutes per view). A survey was then performed to assess patient comfort and examination preferences. Survey responses were compared between groups using Fisher's exact test. RESULTS: No differences were observed between groups regarding opinions of radiation dose, duration of examination, examination comfort, and willingness to undergo MBI in the future. Of those who responded, most women (39/55 [70%]) indicated a preference for the examination type they underwent, either half-dose or half-time MBI, rather than the other protocol. CONCLUSIONS: Survey findings support that MBI, whether performed at half-time or half-dose, is well accepted by patients.

Quantitative background parenchymal uptake on molecular breast imaging and breast cancer risk: a case-control study.

BACKGROUND: Background parenchymal uptake (BPU), which refers to the level of Tc-99m sestamibi uptake within normal fibroglandular tissue on molecular breast imaging (MBI), has been identified as a breast cancer risk factor, independent of mammographic density. Prior analyses have used subjective categories to describe BPU. We evaluate a new quantitative method for assessing BPU by testing its reproducibility, comparing quantitative results with previously established subjective BPU categories, and determining the association of quantitative BPU with breast cancer risk. METHODS: Two nonradiologist operators independently performed region-of-interest analysis on MBI images viewed in conjunction with corresponding digital mammograms. Quantitative BPU was defined as a unitless ratio of the average pixel intensity (counts/pixel) within the fibroglandular tissue versus the average pixel intensity in fat. Operator agreement and the correlation of quantitative BPU measures with subjective BPU categories assessed by expert radiologists were determined. Percent density on mammograms was estimated using Cumulus. The association of quantitative BPU with breast cancer (per one unit BPU) was examined within an established case-control study of 62 incident breast cancer cases and 177 matched controls. RESULTS: Quantitative BPU ranged from 0.4 to 3.2 across all subjects and was on average higher in cases compared to controls (1.4 versus 1.2, p < 0.007 for both operators). Quantitative BPU was strongly correlated with subjective BPU categories (Spearman's r = 0.59 to 0.69, p < 0.0001, for each paired combination of two operators and two radiologists). Interoperator and intraoperator agreement in the quantitative BPU measure, assessed by intraclass correlation, was 0.92 and 0.98, respectively. Quantitative BPU measures showed either no correlation or weak negative correlation with mammographic percent density. In a model adjusted for body mass index and percent density, higher quantitative BPU was associated with increased risk of breast cancer for both operators (OR = 4.0, 95% confidence interval (CI) 1.6-10.1, and 2.4, 95% CI 1.2-4.7). CONCLUSION: Quantitative measurement of BPU, defined as the ratio of average counts in fibroglandular tissue relative to that in fat, can be reliably performed by nonradiologist operators with a simple region-of-interest analysis tool. Similar to results obtained with subjective BPU categories, quantitative BPU is a functional imaging biomarker of breast cancer risk, independent of mammographic density and hormonal factors.

BEST PRACTICES IN MOLECULAR BREAST IMAGING: A GUIDE FOR TECHNOLOGISTS.

Molecular breast imaging (MBI) technologists are required to possess a combination of nuclear medicine skills and mammographic positioning techniques. Currently, no formal programs offer this type of hybrid technologist training. The purpose of this perspective is to provide a best practices guide for technologists performing MBI. Familiarity with best practices may aid in obtaining high-quality MBI examinations by decreasing the likelihood of image artifacts, positioning problems and other factors that contribute to false negative or false positive findings.