Patient-Derived Xenograft Engraftment and Breast Cancer Outcomes in a Prospective Neoadjuvant Study (BEAUTY).

PURPOSE: Patient-derived xenografts (PDX) are a research tool for studying cancer biology and drug response phenotypes. While engraftment rates are higher for tumors with more aggressive characteristics, it is uncertain whether engraftment is prognostic for cancer recurrence. PATIENTS AND METHODS: In a prospective study of patients with breast cancer treated with neoadjuvant chemotherapy (NAC) with taxane ± trastuzumab followed by anthracycline-based chemotherapy, we report the association between breast cancer events and PDX engraftment using tumors derived from treatment naïve (pre-NAC biopsies from 113 patients) and treatment resistant (post-NAC at surgery from 34 patients). Gray test was used to assess whether the cumulative incidence of a breast cancer event differs with respect to either pre-NAC PDX engraftment or post-NAC PDX engraftment. RESULTS: With a median follow-up of 5.7 years, the cumulative incidence of breast cancer relapse did not differ significantly according to pre-NAC PDX engraftment (5-year rate: 13.6% vs. 13.4%; P = 0.89). However, the incidence of a breast event was greater for patients with post-NAC PDX engraftment (5-year rate: 50.0% vs. 19.6%), but this did not achieve significance (P = 0.11). CONCLUSIONS: In treatment-naïve breast cancer receiving standard NAC, PDX engraftment was not prognostic for breast cancer recurrence. Further study is needed to establish whether PDX engraftment in the treatment-resistant setting is prognostic for cancer recurrence.

Tiger-Striped PASH: Recognition of a Unique Morphology Allows for a Zippered-Up Diagnosis of Pseudoangiomatous Stromal Hyperplasia of Breast.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is histologically characterized by anastomosing and slit-like spaces invested by collagenous stroma and lined by flattened, spindle cells. These clear spaces that may mimic microscopic vascular channels do not contain red blood cells. Immunohistochemistry (IHC) studies may also help to confirm a diagnosis of PASH, with the spindled cells marking positively with CD34 and PR while demonstrating no reactivity with more specific endothelial antigens such as CD31 and ERG. In the current case, a 39-year-old female was diagnosed with cellular PASH of the right breast with unique histological patterns showing "tiger-striped" and "zippered" histologies. To our knowledge, this is the first report of these unique variant PASH morphologies.

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.

Basics of time-driven activity-based costing (TDABC) and applications in breast imaging.

Time-drive activity-based costing (TDABC) is a practical way of calculating costs, decreasing waste, and improving efficiency. Although TDABC has been utilized in other service industries for years, it has only recently gained attention in healthcare. In this review article, we define the basic concepts and steps of TDABC and provide examples for applications in breast imaging.

Utilizing Time-Driven Activity-Based Costing to Increase Efficiency in Ultrasound-Guided Breast Biopsy Practice.

PURPOSE: In this study, we used time-driven activity-based costing to increase efficiency in our ultrasound-guided breast biopsy practice by understanding costs associated with this procedure. METHODS: We assembled a multidisciplinary team of all relevant stakeholders involved in ultrasound-guided breast biopsies, including a radiologist, a lead technologist, a clinical assistant, a licensed practical nurse, and a procedural support assistant. The team mapped each step in an ultrasound-guided breast biopsy from the time of scheduling a biopsy to patient checkout. We completed on average 20 time observations of each step involved in these biopsies from a provider's perspective. Using capacity cost rate, we calculated the cost of all resources including personnel, supply, room, and equipment costs. Several costly steps were identified in the process, which led to the intervention of changing our overlapping biopsy times to staggered biopsy times. Time observations for each step and cost calculations were repeated postintervention. RESULTS: Our postintervention data showed that the total time spent by the radiologist in an ultrasound breast biopsy decreased by 28%, accounting for 56% of the total cost in comparison with 63% pre-intervention. The radiologist's wait time decreased by 38%, accounting for 28% of the total cost in comparison with 35% pre-intervention. Our total cost of the procedure decreased by 20%, and the personnel cost decreased by 25%. CONCLUSIONS: Time-driven activity-based costing is a practical way to calculate costs and identify non-value-added steps, which can foster strategies to improve efficiency and minimize waste.

Assessment of MRI-detected lesions on screening tomosynthesis in patients with newly diagnosed breast cancer.

OBJECTIVES: The purpose of this study is to retrospectively evaluate the presence of screening digital breast tomosynthesis (DBT) correlates for suspicious lesions detected on pre-operative staging magnetic resonance imaging (MRI) in patients with newly diagnosed breast cancer. METHODS: After approval from the institutional review board (IRB), screening DBTs on breast cancer patients with BI-RADS 4 or 5 staging MRI exams between 8/1/17 and 8/1/18 were assessed for presence of DBT correlates for suspicious MRI findings. The pathology of the index lesion, type of additional MRI finding (mass, non-mass enhancement, or focus), correlative finding on tomosynthesis (mass, asymmetry/focal asymmetry, distortion, or calcifications), size on MRI and tomosynthesis, breast density, and pathology of the additional lesion were recorded. The chi-square test of association was used unless otherwise specified. Confidence intervals for proportions were estimated using the Wilson's score method. RESULTS: 17/70 (24%) of additional lesions seen on pre-operative MRI exams in patients with newly diagnosed cancer had a mammographic correlate on corresponding screening DBT. There was no significant relationship between the presence of a mammographic correlate and the type of MRI finding (mass, NME, or focus), breast density, size of lesion, pathology of index cancer, or pathology of the additional lesion (p≥ 0.05). CONCLUSIONS: 76% of additional lesions seen on pre-operative staging MRI in patients with newly diagnosed breast cancer are not seen retrospectively on screening DBT. Since about 24% of MRI-detected additional lesions may have a DBT correlate, DBT exams should be reviewed in patients recalled for further workup of findings seen on pre-operative MRI since this may facilitate DBT-guided biopsy of suspicious lesions, which is preferable to MRI-guided biopsy for cost and patient comfort reasons.

Comparison of 99mTc-Sestamibi Molecular Breast Imaging and Breast MRI in Patients With Invasive Breast Cancer Receiving Neoadjuvant Chemotherapy.

OBJECTIVE. The purpose of this study is to prospectively compare the size of invasive breast cancer before and after neoadjuvant chemotherapy (NAC) at breast MRI and molecular breast imaging (MBI) and to assess the accuracy of post-NAC MBI and MRI relative to pathologic analysis. SUBJECTS AND METHODS. Women with invasive breast cancer greater than or equal to 1.5 cm were enrolled to compare the longest dimension before and after NAC at MRI and MBI. MBI was performed on a dual-detector cadmium zinc telluride system after administration of 6.5 mCi (240 MBq) 99mTc-sestamibi. The accuracy of MRI and MBI in assessing residual disease (invasive disease or ductal carcinoma in situ) was determined relative to pathologic examination. RESULTS. The longest dimension at MRI was within 1.0 cm of that at MBI in 72.3% of cases before NAC and 70.1% of cases after NAC. The difference between the longest dimension at imaging after NAC and pathologic tumor size was within 1 cm for 58.7% of breast MRI cases and 59.6% of MBI cases. Ninety patients underwent both MRI and MBI after NAC. In the 56 patients with invasive residual disease, 10 (17.9%) cases were negative at MRI and 23 (41.1%) cases were negative at MBI. In the 34 patients with breast pathologic complete response, there was enhancement in 10 cases (29.4%) at MRI and uptake in six cases (17.6%) at MBI. Sensitivity, specificity, positive predictive value, and negative predictive value after NAC were 82.8%, 69.4%, 81.4%, and 71.4%, respectively, for MRI and 58.9%, 82.4%, 84.6%, and 54.9%, respectively, for MBI. CONCLUSION. Breast MRI and MBI showed similar disease extent before NAC. MBI may be an alternative to breast MRI in patients with a contraindication to breast MRI. Neither modality showed sufficient accuracy after NAC in predicting breast pathologic complete response to obviate tissue diagnosis to assess for residual invasive disease. Defining the extent of residual disease compared with pathologic evaluation was also limited after NAC for both breast MRI and MBI.

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.

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.

Masses in the era of screening tomosynthesis: Is diagnostic ultrasound sufficient?

METHODS:: All masses recalled from screening digital breast tomosynthesis between July 1, 2017 and December 31, 2017 that were sent either to diagnostic mammography or ultrasound were compared. Size, shape, margins, visibility on ultrasound, diagnostic assessment and pathology of all masses along with breast density were evaluated. RESULTS:: 102/212 digital breast tomosynthesis screen-detected masses were worked up with diagnostic mammography initially and 110/212 were worked up with ultrasound directly. There was no significant difference in ultrasound visibility of masses sent to diagnostic mammography first with those sent to ultrasound first (p = 0.42). 4 (4%) masses sent to mammogram first and 2 (2%) masses sent to ultrasound first were not visualized. There was a significant difference in size between masses that were visualized under ultrasound versus those that were not (p = 0.01), when masses in both groups were assessed cumulatively. CONCLUSIONS:: 98% of digital breast tomosynthesis screen-detected masses sent to ultrasound directly were adequately assessed without diagnostic mammography. ADVANCES IN KNOWLEDGE:: There is potential for avoiding a diagnostic mammogram for evaluation of majority of digital breast tomosynthesis screen-detected masses.

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.

Comparison of Tc-99m maraciclatide and Tc-99m sestamibi molecular breast imaging in patients with suspected breast cancer.

BACKGROUND: Molecular breast imaging (MBI) performed with 99mTc sestamibi has been shown to be a valuable technique for the detection of breast cancer. Alternative radiotracers such as 99mTc maraciclatide may offer improved uptake in breast lesions. The purpose of this study was to compare relative performance of 99mTc sestamibi and 99mTc maraciclatide in patients with suspected breast cancer, using a high-resolution dedicated gamma camera for MBI. Women with breast lesions suspicious for malignancy were recruited to undergo two MBI examinations-one with 99mTc sestamibi and one with 99mTc maraciclatide. A radiologist interpreted MBI studies in a randomized, blinded fashion to assign an assessment score (1-5) and measured lesion size. Lesion-to-background (L/B) ratio was measured with region-of-interest analysis. RESULTS: Among 39 analyzable patients, 21 malignant tumors were identified in 21 patients. Eighteen of 21 tumors (86%) were seen on 99mTc sestamibi MBI and 19 of 21 (90%) were seen on 99mTc maraciclatide MBI (p = 1). Tumor extent measured with both radiopharmaceuticals correlated strongly with pathologic size (99mTc sestamibi, r = 0.84; 99mTc maraciclatide, r = 0.81). The L/B ratio in detected breast cancers was similar for the two radiopharmaceuticals: 1.55 ± 0.36 (mean ± S.D.) for 99mTc sestamibi and 1.62 ± 0.37 (mean ± S.D.) for 99mTc maraciclatide (p = 0.53). No correlation was found between the L/B ratio and molecular subtype for 99mTc sestamibi (r s = 0.12, p = 0.63) or 99mTc maraciclatide (r s = -0.12, p = 0.64). Of 20 benign lesions, 10 (50%) were seen on 99mTc sestamibi and 9 of 20 (45%) were seen on 99mTc maraciclatide images (p = 0.1). The average L/B ratio for benign lesions was 1.34 ±0.40 (mean ±S.D.) for 99mTc sestamibi and 1.41 ±0.52 (mean ±S.D.) for 99mTc maraciclatide (p = 0.75). Overall diagnostic performance was similar for both radiopharmaceuticals. AUC from ROC analysis was 0.83 for 99mTc sestamibi and 0.87 for 99mTc maraciclatide (p = 0.64). CONCLUSIONS: 99mTc maraciclatide offered comparable lesion uptake to 99mTc sestamibi, in both malignant and benign lesions. There was good correlation between lesion extent and uptake measured from both radiopharmaceuticals. 99mTc maraciclatide offered a marginal (but not significant) improvement in sensitivity over 99mTc sestamibi. Our findings did not support an association between the uptake of either radiopharmaceutical and tumor molecular subtype. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00888589.

Background parenchymal uptake on molecular breast imaging as a breast cancer risk factor: a case-control study.

BACKGROUND: Molecular breast imaging (MBI) is a functional test used for supplemental screening of women with mammographically dense breasts. Additionally, MBI depicts variable levels of background parenchymal uptake (BPU) within nonmalignant, dense fibroglandular tissue. We investigated whether BPU is a risk factor for breast cancer. METHODS: We conducted a retrospective case-control study of 3027 eligible women who had undergone MBI between February 2004 and February 2014. Sixty-two incident breast cancer cases were identified. A total of 179 controls were matched on age, menopausal status, and MBI year. Two radiologists blinded to case status independently assessed BPU as one of four categories: photopenic, minimal to mild, moderate, or marked. Conditional logistic regression analysis was performed to estimate the associations (OR) of BPU categories (moderate or marked vs. minimal to mild or photopenic) and breast cancer risk, adjusted for other risk factors. RESULTS: The median age was 60.2 years (range 38-86 years) for cases vs. 60.2 years (range 38-88 years) for controls (p = 0.88). Women with moderate or marked BPU had a 3.4-fold (95 % CI 1.6-7.3) and 4.8-fold (95 % CI 2.1-10.8) increased risk of breast cancer, respectively, compared with women with photopenic or minimal to mild BPU, for two radiologists. The results were similar after adjustment for BI-RADS density (OR 3.3 [95 % CI 1.6-7.2] and OR 4.6 [95 % CI 2.1-10.5]) or postmenopausal hormone use (OR 3.6 [95 % CI 1.7-7.7] and OR 5.0 [95 % CI 2.2-11.4]). The association of BPU with breast cancer remained in analyses limited to postmenopausal women only (OR 3.8 [95 % CI 1.5-9.3] and OR 4.1 [95 % CI 1.6-10.2]) and invasive breast cancer cases only (OR 3.6 [95 % CI 1.5-8.8] and OR 4.4 [95 % CI 1.7-11.1]). Variable BPU was observed among women with similar mammographic density; the distribution of BPU categories differed across density categories (p < 0.0001). CONCLUSIONS: This study provides the first evidence for BPU as a risk factor for breast cancer. Among women with dense breasts, who comprise >40 % of the screening population, BPU may serve as a functional imaging biomarker to identify the subset at greatest risk.

Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

OBJECTIVE: The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. MATERIALS AND METHODS: Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. RESULTS: In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients. CONCLUSION: Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular breast imaging is less likely to show all foci of ILC compared with IDC.

Effect of menstrual cycle phase on background parenchymal uptake at molecular breast imaging.

RATIONALE AND OBJECTIVES: The level of Tc-99m sestamibi uptake within normal fibroglandular tissue on molecular breast imaging (MBI), termed background parenchymal uptake (BPU), has been anecdotally observed to fluctuate with menstrual cycle. Our objective was to assess the impact of menstrual cycle phase on BPU appearance. MATERIALS AND METHODS: Premenopausal volunteers who reported regular menstrual cycles and no exogenous hormone use were recruited to undergo serial MBI examinations during the follicular and luteal phase. A study radiologist, blinded to cycle phase, categorized BPU as photopenic, minimal mild, moderate, or marked. Change in BPU with cycle phase was determined, as well as correlations of BPU with mammographic density and hormone levels. RESULTS: In 42 analyzable participants, high BPU (moderate or marked) was observed more often in luteal phase compared to follicular (P = .016). BPU did not change with phase in 30 of 42 participants (71%) and increased in the luteal phase compared to follicular in 12 (29%). High BPU was more frequent in dense breasts compared to nondense breasts at both the luteal (58% [15 of 26] vs. 13% [2 of 16], P = .004) and follicular phases (35% [9 of 26] vs. 6% [1 of 16], P = .061). Spearman correlation coefficients did not show any correlation of BPU with hormone levels measured at either cycle phase and suggested a weak correlation between change in BPU and changes in estrone and estradiol between phases. CONCLUSIONS: We observed variable effects of menstrual cycle on BPU among our cohort of premenopausal women; however, when high BPU was observed, it was most frequently seen during the luteal phase compared to follicular phase and in women with dense breasts compared to nondense breasts.

Diagnostic workup and costs of a single supplemental molecular breast imaging screen of mammographically dense breasts.

OBJECTIVE: The purpose of this study was to examine additional diagnostic workup and costs generated by addition of a single molecular breast imaging (MBI) examination to screening mammography for women with dense breasts. SUBJECTS AND METHODS: Women with mammographically dense breasts presenting for screening mammography underwent adjunct MBI performed with 300 MBq (99m)Tc-sestamibi and a direct-conversion cadmium-zinc-telluride dual-head gamma camera. All subsequent imaging tests and biopsies were tracked for a minimum of 1 year. The positive predictive value of biopsies performed (PPV3), benign biopsy rate, cost per patient screened, and cost per cancer detected were determined. RESULTS: A total of 1651 women enrolled in the study. Among the 1585 participants with complete reference standard, screening mammography alone prompted diagnostic workup of 175 (11.0%) patients and biopsy of 20 (1.3%) and yielded five malignancies (PPV3, 25%). Results of combined screening mammography plus MBI prompted diagnostic workup of 279 patients (17.6%) and biopsy of 67 (4.2%) and yielded 19 malignancies (PPV3, 28.4%). The benign biopsy rates were 0.9% (15 of 1585) for screening mammography alone and 3.0% (48 of 1585) for the combination (p < 0.001). The addition of MBI increased the cost per patient screened from $176 for mammography alone to $571 for the combination. However, cost per cancer detected was lower for the combination ($47,597) than for mammography alone ($55,851). CONCLUSION: The addition of MBI to screening mammography of women with dense breasts increased the overall costs and benign biopsy rate but also increased the cancer detection rate, which resulted in a lower cost per cancer detected than with screening mammography alone.