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Background. Mammographic features on digital breast tomosynthesis (DBT) have not yet been incorporated in any breast cancer risk model. In breast cancer screening, a large proportion of cancers is not detected in screening but develop in between two screening cycles or are missed and detected at later stages. We developed a risk model that identifies women who, after presenting with a negative DBT, are likely to be diagnosed with breast cancer before or at the next screening. Materials and Methods. The study was based on women of multi-ethnic origin attending screening using DBT at four U.S. screening sites in 2014-2019. In a nested case-control study subset, women were followed from last negative DBT through next scheduled screening visit one year later. Breast cancer status was collected from retrospective medical records. An image-based risk model was developed using iCAD artificial intelligence mammographic features (density, masses, microcalcifications), left-right breast differences, and age. Age-adjusted relative risks for mammographic features were estimated using logistic regression and nested cross-validation. Absolute risks were estimated using relative risks, mammographic feature distributions, and U.S. incidence and competing mortality risks. The risk model was validated in four independent sub-cohorts. Results. In all, 5,978 women were included, 805 incident breast cancers and 5,137 healthy women (age 58 +/- 10 years). In the validation set, the risk model reached an area under the curve (AUC) of 0.82 (95% CI 0.79,0.85) at baseline screen. The average 1-year breast cancer incidence rate was 0.28%. By the USPSTF guidelines, 14% of the women were considered at high-risk of breast cancer, Table 1. The high-risk women had a 20-fold increased breast cancer risk compared to the women at general risk. The model showed good fit (le Cessie-Hosmer p = 0.7). In the high-risk group, 83% of the stage 2 and stage 3 cancers and 59% of the stage 0 cancers were observed, p Table 1. Percentages of women at risk using the USPSTF breast cancer risk categorization adapted to 1-year risks.Risk group1Percent women at riskAbsolute 1-year risk (%)Risk stratificationGeneral ( Citation Format: Mikael Eriksson, Stamatia Destounis, Kathy Schilling. A risk tool for digital breast tomosynthesis to predict breast cancer and guide clinical follow-up [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-20.

Objective We investigated the effect of introducing a pressure-based flexible paddle on compression parameters and user and patient experience of digital breast tomosynthesis (DBT) combined with patient-assisted compression or technologist compression. Methods After institutional review board approval, women with a DBT appointment who gave informed consent received pressure-based flexible paddle breast compression. Eight lights on the paddle were illuminated (1.9 kPa per light) as pressure was applied, aiming for an 8–13.9 kPa target range. The compression level was applied by the technologist or the participant utilizing a remote control device. The participant’s and technologist’s experiences were assessed by a questionnaire. Compression parameters were compared to previous examinations. Comparative statistics were performed using t-tests. Results Pressure-based compression (PBC) was judged to be similar or more comfortable compared with previous traditional exams (80%, 83/103), and 87% (90/103) of participants would recommend PBC to friends. Pressure variability decreased for craniocaudal (CC) views (-55%, P < 0.001) and mediolateral oblique (MLO) views (-34%, P < 0.0001). Subgroup analysis showed a similar glandular dose for CC views, while breast thickness was reduced (-3.74 mm, P < 0.0001). For MLO views, both glandular dose (-0.13 mGy, P < 0.0001) and breast thickness were reduced (-6.70 mm, P < 0.0001). Mean compression parameters were similar for technologist compression and patient-assisted examinations. Conclusion Use of the pressure-based flexible paddle in DBT, with or without patient-assisted compression, improved participant and technologist experience and reduced compression pressure variability, mean breast thickness, and glandular dose.

Objective This study sought to determine if a mammogram performed in a multi-sensory environmental upgraded room (UR) is associated with improved image quality when compared to a standard room (SR). Methods A retrospective analysis (interrupted time series design) of compression force and posterior nipple line (PNL) measurements was performed on 303 women (mean age 60.9 years) who underwent screening mammography for 2 consecutive years (year 1 in SR, year 2 in UR) at a single outpatient facility. Using the Picture Archiving Communication System (PACS), craniocaudal (CC) and mediolateral oblique (MLO) images for the two years were reviewed. The PNL was measured for the CC and MLO images bilaterally using the embedded tools in the PACS software. Posterior nipple line and compression force were analyzed using a paired t-test. Bland–Altman plots were used to obtain 95% limits of agreement (LOA) between the UR and SR. Results Image quality as determined by PNL measurement distance was greater in the UR (P < 0.001) when compared with the SR, with similar compression force (P ≥ 0.14). Mean PNL measurement differences ranged from 5.0 to 6.2 mm greater in the UR, whereas mean compression force differences ranged from -2.4 to 1.5 newtons. The 95% LOA suggest that PNL measurement differences between the UR and SR can vary by -11.0 to 27.0 mm. Conclusion Environmentally modifying mammography rooms may improve image quality with regard to PNL measurements without increasing compression force.

An 82-year-old female presented to her breast surgeon with a hard, painful mass in the left breast. Mammography demonstrated a new hyperdense mass with pleomorphic calcifications of trabeculated appearance. Ultrasound-guided biopsy demonstrated a hypoechoic mass with significantly increased vascularity and tissue stiffness as well as additional irregular, hypoechoic masses in the same area. Together these findings suggested multifocal malignancy. The pathology report from the biopsy demonstrated fragments of solid sheets of epithelioid and focally spindled cells with multinucleated osteoclast giant cells. This was found to be most consistent with metaplastic carcinoma showing osteoblastic differentiation. The patient received a left-sided mastectomy. During follow-up with the patient, adjuvant chemotherapy was not advised given the relatively unknown survival advantage in this elderly patient.

Solid tumors can generate a plethora of neurogenesis-related molecules that enhance their growth and metastasis. Among them, we have identified axonal guidance molecule Semaphorin 7A (SEMA7A) in breast cancer. The goal of this study was to determine the therapeutic effect of suppressing SEMA7A levels in the 4T1 murine model of advanced breast carcinoma. We used anti-SEMA7A short hairpin RNA (shRNA) to gene silence SEMA7A in 4T1 mammary tumor cells. When implanted into the mammary fat pads of syngeneic mice, SEMA7A shRNA-expressing 4T1 tumors exhibited decreased growth rates, deferred metastasis and reduced mortality. In vitro, SEMA7A shRNA-expressing 4T1 cells had weakened proliferative, migratory and invasive abilities, and decreased levels of mesenchymal factors. Atomic force microscopy studies showed that SEMA7A shRNA-expressing 4T1 cells had an increase in cell stiffness that corresponded with their decreased malignant potential. Genetic ablation of host-derived SEMA7A further enhanced the antitumor effects of SEMA7A shRNA gene silencing in 4T1 cells. Our preclinical findings demonstrate a critical role for SEMA7A in mediating mammary tumor progression.

Purpose To compare breast cancer detection performance of radiologists reading mammographic examinations unaided versus supported by an artificial intelligence (AI) system. Materials and Methods An enriched retrospective, fully crossed, multireader, multicase, HIPAA-compliant study was performed. Screening digital mammographic examinations from 240 women (median age, 62 years; range, 39-89 years) performed between 2013 and 2017 were included. The 240 examinations (100 showing cancers, 40 leading to false-positive recalls, 100 normal) were interpreted by 14 Mammography Quality Standards Act-qualified radiologists, once with and once without AI support. The readers provided a Breast Imaging Reporting and Data System score and probability of malignancy. AI support provided radiologists with interactive decision support (clicking on a breast region yields a local cancer likelihood score), traditional lesion markers for computer-detected abnormalities, and an examination-based cancer likelihood score. The area under the receiver operating characteristic curve (AUC), specificity and sensitivity, and reading time were compared between conditions by using mixed-models analysis dof variance and generalized linear models for multiple repeated measurements. Results On average, the AUC was higher with AI support than with unaided reading (0.89 vs 0.87, respectively; P = .002). Sensitivity increased with AI support (86% [86 of 100] vs 83% [83 of 100]; P = .046), whereas specificity trended toward improvement (79% [111 of 140]) vs 77% [108 of 140]; P = .06). Reading time per case was similar (unaided, 146 seconds; supported by AI, 149 seconds; P = .15). The AUC with the AI system alone was similar to the average AUC of the radiologists (0.89 vs 0.87). Conclusion Radiologists improved their cancer detection at mammography when using an artificial intelligence system for support, without requiring additional reading time. Published under a CC BY 4.0 license. See also the editorial by Bahl in this issue.

Optoacoustic ultrasound breast imaging is a fused anatomic and functional modality that shows morphologic features, as well as hemoglobin amount and relative oxygenation within and around breast masses. The purpose of this study is to investigate the positive predictive value (PPV) of optoacoustic ultrasound features in benign and malignant masses.In this study, 92 masses assessed as BI-RADS category 3, 4, or 5 in 94 subjects were imaged with optoacoustic ultrasound. Each mass was scored by seven blinded independent readers according to three internal features in the tumor interior and two external features in its boundary zone and periphery. Mean and median optoacoustic ultrasound scores were compared with histologic findings for biopsied masses and nonbiopsied BI-RADS category 3 masses, which were considered benign if they were stable at 12-month follow-up. Statistical significance was analyzed using a two-sided Wilcoxon rank sum test with a 0.05 significance level.Mean and median optoacoustic ultrasound scores for all individual internal and external features, as well as summed scores, were higher for malignant masses than for benign masses (p0.0001). High external scores, indicating increased hemoglobin and deoxygenation and abnormal vessel morphologic features in the tumor boundary zone and periphery, better distinguished benign from malignant masses than did high internal scores reflecting increased hemoglobin and deoxygenation within the tumor interior.High optoacoustic ultrasound scores, particularly those based on external features in the boundary zone and periphery of breast masses, have high PPVs for malignancy and, conversely, low optoacoustic ultrasound scores have low PPV for malignancy. The functional component of optoacoustic ultrasound may help to overcome some of the limitations of morphologic overlap in the distinction of benign and malignant masses.

Preview Although primary care physicians may not actually read patients' mammography films, they play a crucial role in detection and management of breast disease by abiding by screening guidelines. Patient education, reassurance, and guidance in decision making are all important aspects, as pointed out in this article. The authors describe and provide illustrations of findings on breast imaging studies and discuss options for follow-up.

Purpose To compare the diagnostic utility of an investigational optoacoustic imaging device that fuses laser optical imaging (OA) with grayscale ultrasonography (US) to grayscale US alone in differentiating benign and malignant breast masses. Materials and Methods This prospective, 16-site study of 2105 women (study period: 12/21/2012 to 9/9/2015) compared Breast Imaging Reporting and Data System (BI-RADS) categories assigned by seven blinded independent readers to benign and malignant breast masses using OA/US versus US alone. BI-RADS 3, 4, or 5 masses assessed at diagnostic US with biopsy-proven histologic findings and BI-RADS 3 masses stable at 12 months were eligible. Independent readers reviewed US images obtained with the OA/US device, assigned a probability of malignancy (POM) and BI-RADS category, and locked results. The same independent readers then reviewed OA/US images, scored OA features, and assigned OA/US POM and a BI-RADS category. Specificity and sensitivity were calculated for US and OA/US. Benign and malignant mass upgrade and downgrade rates, positive and negative predictive values, and positive and negative likelihood ratios were compared. Results Of 2105 consented subjects with 2191 masses, 100 subjects (103 masses) were analyzed separately as a training population and excluded. An additional 202 subjects (210 masses) were excluded due to technical failures or incomplete imaging, 72 subjects (78 masses) due to protocol deviations, and 41 subjects (43 masses) due to high-risk histologic results. Of 1690 subjects with 1757 masses (1079 [61.4%] benign and 678 [38.6%] malignant masses), OA/US downgraded 40.8% (3078/7535) of benign mass reads, with a specificity of 43.0% (3242/7538, 99% confidence interval [CI]: 40.4%, 45.7%) for OA/US versus 28.1% (2120/7543, 99% CI: 25.8%, 30.5%) for the internal US of the OA/US device. OA/US exceeded US in specificity by 14.9% (P < .0001; 99% CI: 12.9, 16.9%). Sensitivity for biopsied malignant masses was 96.0% (4553/4745, 99% CI: 94.5%, 97.0%) for OA/US and 98.6% (4680/4746, 99% CI: 97.8%, 99.1%) for US (P < .0001). The negative likelihood ratio of 0.094 for OA/US indicates a negative examination can reduce a maximum US-assigned pretest probability of 17.8% (low BI-RADS 4B) to a posttest probability of 2% (BI-RADS 3). Conclusion OA/US increases the specificity of breast mass assessment compared with the device internal grayscale US alone. Online supplemental material is available for this article. © RSNA, 2017.

To compare the performance characteristics of positron emission mammography (PEM) with those of whole-body PET (WBPET) and PET/CT in women with newly diagnosed breast cancer. A total of 178 women consented to PEM for presurgical planning in an IRB-approved protocol and also underwent either WBPET (n = 69) or PET/CT (n = 109) imaging, as per usual care at three centers. Tumor detection sensitivity, positive predictive values, and 18F-fluorodeoxyglucose (FDG) uptake were compared between the modalities. The effects of tumor size, type, and grade on detection were examined. The chi-squared or Fisher’s exact tests were used to compare distributions between groups, and McNemar’s test was used to compare distributions for paired data within subject groups, i.e. PEM versus WBPET or PEM versus PET/CT. The mean age of the women was 59 ± 12 years (median 60 years, range 26–89 years), with a mean invasive index tumor size of 1.6 ± 0.8 cm (median 1.5 cm, range 0.5–4.0 cm). PEM detected more index tumors (61/66, 92 %) than WBPET (37/66, 56 %; p

Mobile interaction with clinical data is becoming increasingly popular as mobile devices, such as smartphones or multi-touch tablets, evolve into personal information hubs. A high number of doctors already own such devices or intend to (Hirschorn 2011). Having access to patient information on the move and being able to answer patient specific questions regardless of one‘s current location is a major advantage and can be a big time-saver. Several software solutions for smartphones and multi-touch tablets, such as Apple‘s iPad, have been available recently. However, for diagnosis and viewing of image data, the available screen space of these devices is very limited. Image comparisons, such as current-prior comparison of patient images or the comparison of different MR sequences are not very meaningful if possible at all. Often, the use of mobile software that has FDA 510(k) clearance is therefore restricted to situations in which no other workstation with calibrated, larger screens is available (FDA 2011). In this article we propose a combination of mobile multi-touch devices and workstation-grade screens or even conventional workstations to provide a workstation-grade reading experience with mobile devices (see Fig. 1). Contrasting to current mobile applications, a highly increased display space and processing power is paired with a more natural and direct interaction on image data, as well as a higher mobility and loFelix Ritter, Jumana Al Issawi, Markus Harz, Simon Benten, Kathy J. Schilling

Molecular imaging, using positron emission tomography (PET), has become an integral step in the evaluation of many patients with malignancy. However, its use in patients with breast cancer has been limited by the lower levels of 18F-fluorodeoxyglucose (FDG) uptake in some breast malignancies compared to other cancers, the small size of many breast cancers, and the need for biopsy under PET guidance. High-resolution breast PET, or positron emission mammography (PEM), with biopsy guidance software, now addresses these issues. We report a prospective, multicenter study designed to test the efficacy and safety of PEM biopsy guidance software in women with FDG-avid breast lesions worrisome for malignancy. The intervention chosen was vacuum-assisted core biopsy. Nineteen subjects underwent a total of 24 PEM-guided biopsies. All lesions were successfully targeted and sampled as determined by post-biopsy image scan evaluation, specimen imaging, and pathologic concordance. Invasive cancer was identified in 13 of 24 lesions (54%), while four (17%) were high-risk lesions and three of these were upgraded to malignancy at excision. No serious adverse events occurred and all patients found the procedure to cause only minimal to mild discomfort. High-resolution PEM-guided breast biopsy is both safe and effective for the sampling of PET-depicted breast lesions.

Today, breast surgeons plan their procedures using pre-operatively placed metal clips or radioactive seeds and radiological images. These images show the breast in a positioning different from the one during surgery. We show a research prototype that eases the surgeon's planning task by providing 3D visualizations based on the radiological images. With a FEM-based deformation simulation, we mimic the real surgical scenario. In particular, we have developed a ligament model that increases the robustness of a fully automatic prone-supine deformation simulation, and we have developed specific visualization methods to aid intra-operative breast lesion localization.

To determine improvement in breast cancer detection by using supplemental three-dimensional (3D) automated breast (AB) ultrasonography (US) with screening mammography versus screening mammography alone in asymptomatic women with dense breasts.Institutional review board approval and written informed consent were obtained for this HIPAA-compliant study. The SomoInsight Study was an observational, multicenter study conducted between 2009 and 2011. A total of 15 318 women (mean age, 53.3 years ± 10 [standard deviation]; range, 25-94 years) presenting for screening mammography alone with heterogeneously (50%-75%) or extremely (75%) dense breasts were included, regardless of further risk characterization, and were followed up for 1 year. Participants underwent screening mammography alone followed by an AB US examination; results were interpreted sequentially. McNemar test was used to assess differences in cancer detection.Breast cancer was diagnosed at screening in 112 women: 82 with screening mammography and an additional 30 with AB US. Addition of AB US to screening mammography yielded an additional 1.9 detected cancers per 1000 women screened (95% confidence interval [CI]: 1.2, 2.7; P.001). Of cancers detected with screening mammography, 62.2% (51 of 82) were invasive versus 93.3% (28 of 30) of additional cancers detected with AB US (P = .001). Of the 82 cancers detected with either screening mammography alone or the combined read, 17 were detected with screening mammography alone. Of these, 64.7% (11 of 17) were ductal carcinoma in situ versus 6.7% (two of 30) of cancers detected with AB US alone. Sensitivity for the combined read increased by 26.7% (95% CI: 18.3%, 35.1%); the increase in the recall rate per 1000 women screened was 284.9 (95% CI: 278.0, 292.2; P.001).Addition of AB US to screening mammography in a generalizable cohort of women with dense breasts increased the cancer detection yield of clinically important cancers, but it also increased the number of false-positive results.

To measure the effect of biopsy device, probe size, mammographic lesion type, lesion size, and number of samples obtained per lesion on the ductal carcinoma in situ (DCIS) underestimation rate.Nonpalpable breast lesions at 16 institutions received a histologic diagnosis of DCIS after 14-gauge automated large-core biopsy in 373 lesions and after 14- or 11-gauge directional vacuum-assisted biopsy in 953 lesions. The presence of histopathologic invasive carcinoma was noted at subsequent surgical biopsy.By performing the chi(2) test, independent significant DCIS underestimation rates by biopsy device were 20.4% (76 of 373) of lesions diagnosed at large-core biopsy and 11.2% (107 of 953) of lesions diagnosed at vacuum-assisted biopsy (P.001); by lesion type, 24.3% (35 of 144) of masses and 12.5% (148 of 1,182) of microcalcifications (P.001); and by number of specimens per lesion, 17.5% (88 of 502) with 10 or fewer specimens and 11.5% (92 of 799) with greater than 10 (P.02). DCIS underestimations increased with lesion size.DCIS underestimations were 1.9 times more frequent with masses than with calcifications, 1.8 times more frequent with large-core biopsy than with vacuum-assisted biopsy, and 1.5 times more frequent with 10 or fewer specimens per lesion than with more than 10 specimens per lesion.

Breast cancer is the most common cancer among American women, and primary care physicians can be instrumental in ensuring a timely diagnosis. Women should be taught breast self-examination by the time they are in their late teens. Patients of all ages should be encouraged to have regular physician-conducted breast examinations and mammographic screening at a high-quality center. The consistent care and individualized follow-up provided in a primary care office are vital components of the total effort toward good breast health.

It is estimated that one in eight women will be diagnosed with breast cancer. Developing an understanding of the tumor microenvironment is critical for developing treatments for breast cancer patients. Poorly differentiated blood vessels can fashion an oxygen-deprived microenvironment that triggers the expression of transcription factor Hypoxia Inducible Factor alpha (HIF-1alpha) that in turn can up regulate genes mediating a pro-tumor effect. Our laboratory has discovered that mammary tumors express Semaphorin7a (SEMA7A), a HIF-1alpha inducible protein. Tumor-derived SEMA7A induces monocytes to secrete proangiogenic chemokines to enhance tumor growth. Decreasing tumor-derived SEMA7A limits tumor growth and the production of angiogenic CXCL-2/MIP-2 and VEGF-A by monocytes. Immune cells also express elevated levels of SEMA7A in tumors, however the role of stromal-derived SEMA7A in tumorigenesis is largely unknown. We hypothesized that SEMA7A may be a hypoxia-inducible factor and that inhibition may deter the effects of hypoxia on tumor and immune cells. Following hypoxic stimuli, WT monocytes increased production of CXCL2, VEGF-A and Chitinase-3-like protein1. However, SEMA7A null monocytes failed to respond to hypoxia, which may be attributed to an impaired MAPK signaling response. Monocytes from SEMA KO tumor bearing mice showed a decreased production of angiogenic molecules. More importantly, we found that SEMA7A KO 4T1 mammary tumor bearing mice showed decreased tumor growth and metastasis compared to WT. Collectively, we show a role for not only a tumor-derived, but also stromal-derived SEMA7A in hypoxia-mediated mammary tumor progression.

Magnetic Resonance Mammography (MRM) has repeatedly been shown to reliably identify breast cancer through the utilization of dynamic imaging techniques that exploit the abnormal vascularity induced by tumors [1]. “Functional” or “molecular” imaging offers the ability to identify cancer directly by identifying cellular abnormalities that are expressed at increased levels by cancer cells. An example of the latter is the increased expression of the GLUT-1 transporter in cancer. This up-regulation of GLUT-1 results in increased uptake of 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG) by breast cancer cells. The gamma rays emitted are used to generate qualitative images and quantitative estimates of this biochemical process [2]. As the metabolic activity, i.e. glucose/FDG uptake, of tumor cells is increased prior to the induction of neo-vascularity, FDG imaging has the theoretic potential to identify cancers earlier than MRM, as well as provide in vivo tumor characterization that may lead to personalized therapy.

We propose a novel paradigm for clinical diagnostic software using a mobile multi-touch device for user interaction and dedicated monitors for image display. We show a demonstrator implementing a workflow-based breast MRI reading system tailored to multi-touch interaction. The demonstrator explores the feasibility of touch interaction for diagnostic reading of MRI patient cases. We show a patient-centric, workflow-oriented concept that is arranged around a multi-touch capable hybrid input-output device. In this contribution we introduce clinically useful concepts of the demonstrator. Firstly, a mechanism that we dubbed location awareness takes care of security issues. Reading is supported by (1) a patient browser with graphical patient history and cancer risk factors; (2) a workflow concept using hanging protocols; (3) dedicated ROI definition, annotation, and measurement tools using multi-touch gestures. Gesture concepts and interaction paradigms are introduced for intuitive user experiences while maintaining accuracy.

The objective of our study was to compare the performance of positron emission mammography (PEM) with that of MRI in the evaluation of the contralateral breast of women with newly diagnosed cancer.Four hundred seventy-two women with newly diagnosed breast cancer offered breast-conserving surgery from September 2006 through November 2008 consented to participate in a multicenter protocol. Participants underwent contrast-enhanced breast MRI and 18F-FDG PEM in randomized order, and the examinations were interpreted independently. The performance characteristics of the imaging modalities were compared using the McNemar test and generalized estimating equations. A retrospective blinded review of PEM images was performed by four experienced observers to understand the reasons for false-negatives.Three hundred sixty-seven women (median age, 58 years; age range, 26-93 years) eligible for analysis completed the appropriate follow-up for study inclusion. Fifteen women (4.1%) were found to have contralateral cancer (11 invasive [mean tumor size, 12 mm; median, 10 mm; range, 1-22 mm] and four ductal carcinoma in situ). Of the 15 cases, both PEM and MRI showed three (20%), only MRI showed 11 (73%), and one (6.7%) was found at prophylactic mastectomy. MRI sensitivity at 14 of 15 (93%; 95% CI, 66-94) was higher than PEM at three of 15 (20%; 95% CI, 5.3-46) (p0.001). On PEM, three additional cancers were seen prospectively but were considered probably benign and two other cancers were visible in retrospect at the site. Of 352 contralateral breasts without cancer, findings were negative or benign on PEM for 335 (95.2%; 95% CI, 92.2-97.0), which is more than MRI at 315 (89.5%; 95% CI, 85.7-92.4; p=0.002). The positive predictive value (PPV) of PEM-prompted biopsies (3/14 [21%]) was not significantly different from the PPV of MRI (15/54 [28%], p=0.58). On blinded retrospective PEM review of the 15 contralateral cancers, PEM findings for 11 (73%) were considered suspicious.Contralateral cancer was found in 15 of 367 women (4.1%), with MRI showing 14 (93%). Eleven contralateral cancers (73%) were visible on PEM, but only three (20%) were recognized prospectively as suspicious. Lesions that are visible on PEM should be viewed as suspicious unless known to be benign by prior breast imaging or biopsy.

Molecular imaging, using positron emission tomography (PET), has become an integral step in the evaluation of many patients with malignancy. However, its use in patients with breast cancer has been limited by the lower levels of (18) F-fluorodeoxyglucose (FDG) uptake in some breast malignancies compared to other cancers, the small size of many breast cancers, and the need for biopsy under PET guidance. High-resolution breast PET, or positron emission mammography (PEM), with biopsy guidance software, now addresses these issues. We report a prospective, multicenter study designed to test the efficacy and safety of PEM biopsy guidance software in women with FDG-avid breast lesions worrisome for malignancy. The intervention chosen was vacuum-assisted core biopsy. Nineteen subjects underwent a total of 24 PEM-guided biopsies. All lesions were successfully targeted and sampled as determined by post-biopsy image scan evaluation, specimen imaging, and pathologic concordance. Invasive cancer was identified in 13 of 24 lesions (54%), while four (17%) were high-risk lesions and three of these were upgraded to malignancy at excision. No serious adverse events occurred and all patients found the procedure to cause only minimal to mild discomfort. High-resolution PEM-guided breast biopsy is both safe and effective for the sampling of PET-depicted breast lesions.

Overall, 61 (16%) of 388 participants had an appropriate change in surgical management based on MR findings—more than the 41 (11%) participants with an appropriate change based on positron emission mammography (PEM) findings (P = .003) and fewer than the 71 (18%) participants with an appropriate change based on combined PEM and MR findings (P = .004 for comparison with MR imaging alone); 25 (6.4%) women had excessive excisions on the basis of MR findings compared with 19 (4.9%) women who had them on the basis of PEM findings (P = .26) and 32 (8.2%) women who had them after undergoing combined PEM and MR imaging (P = .023 for comparison with MR imaging alone).

A novel method for the deformable image registration of follow-up breast magnetic resonance (MR) images is proposed, aimed at an automatic synchronization of temporal images. To compensate potentially large breast deformations and differences among device coordinates, an initial linear alignment of each individual breast, a combination of both transformations using thin-plate splines, as well as a subsequent linear-elastic registration are performed in sequence. Complementary to algorithmic details, an overview of modality-specific factors influencing follow-up registration accuracy is given. The proposed method was evaluated on 20 clinical datasets annotated with landmarks by an expert radiologist. Despite large variations among the MR images, accuracy of the method was sufficient to allow spatial synchronization, with remaining target registration errors of < 32%. Concluding, potential enhancements to further increase robustness and accuracy are discussed.

We describe a group of concepts that facilitate reading of multi-modality breast imaging data in a single workplace and discuss their use and limitations Our concepts comprise intelligent preprocessing, spatial referencing and dedicated workflow tools and aim at homogenizing and simplifying the multi-modality workplace, at improving the standardization across modalities and vendors, at supporting cross-modality information linkage, and at reducing required user interaction and waiting times, all at a high level of flexibility for the user to access the available imaging information at any time required As a result, many situations where information from multiple modalities and time points must be assessed, both qualitatively and quantitatively, are expected to be handled more efficiently and reliably.

Manufacturers of digital mammography systems include proprietary and unique post-processing algorithms to enhance the image contrast for diagnostic presentation We use a wavelet-based enhancement method to both automatically and interactively adjust the contrast of these previously processed mammograms Apart from enhancing small but relevant structures in dense breast tissue, this method allows for the automatic homogenization of cross-vendor contrast appearance, supporting current-prior comparison tasks in the screening and diagnostic setting when different systems were used for acquisition An optional smooth crossfading between originally processed and enhanced images can be used interactively to adapt the presentation view to individual situations, for example to facilitate the detection or interpretation of mammographic features in dense breast tissue A user preference study with experienced readers revealed that our work might positively impact prior-current comparisons and the diagnosis of mammographic images.

BACKGROUND. Percutaneous, vacuum-assisted, large-gauge core needle biopsy (VACNB) provides an alternative to open surgical biopsy as an initial diagnostic tool for breast lesions, yet rates of underestimating malignant diagnoses remain sufficiently high to warrant surgical biopsy in some cases. The current study was performed to determine if the Breast Lesion Excision System (BLES) provides a feasible alternative to VACNB. METHODS. A retrospective review was conducted of 742 consecutive mammographic lesions with microcalcifications classified as Breast Imaging Reporting and Data System (BIRADS) IV or V that had stereotactic percutaneous biopsy using BLES. Initial diagnoses obtained from the histopathologic examination of tissues retrieved at biopsy were compared with the histopathologic examination of tissues received from surgical excision or lumpectomy. Underestimation rates for atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) were recorded if open surgical biopsy revealed DCIS or invasive cancer, and invasive cancer, respectively. RESULTS. Of the 742 breast lesions, 34 displayed ADH upon biopsy with the BLES device. Two patients did not receive open surgical biopsy. Of the 32 patients who had open surgical excision, 3 (9.4%) had DCIS or invasive cancer. There were 119 diagnoses of DCIS upon biopsy with the BLES device. Four patients did not receive open surgical biopsy. Of the 115 patients who had open surgical excision, 6 (5.2%) had invasive cancer. CONCLUSIONS. Breast biopsy can be performed accurately using the BLES device. Compared with VACNB, it does not alter the need for surgical excision in women diagnosed with ADH or DCIS at core biopsy. Cancer 2006;107:945–9. � 2006 American Cancer Society.

The objective of our study was to assess the incremental value of contrast-enhanced MRI in the diagnosis and treatment planning using both a three-time point kinetic and morphologic analysis in addition to mammography and sonography in patients thought to have early-stage breast cancer.Contrast-enhanced bilateral breast MRI was performed prospectively on 65 patients with highly suspicious imaging findings (BI-RADS category 4 or 5). All enrolled patients were believed to be candidates for breast conservation on the basis of clinical examination, mammography, and sonography. The primary index lesion's characteristics, size, and extent were assessed. Also, additional lesions detected by MRI that could represent potential malignancies in both the ipsilateral and contralateral breast were evaluated. Morphologic assessment and kinetic analysis were performed on each lesion using dedicated postprocessing and display software. The patients were reevaluated as to whether they were still candidates for breast-conservation therapy after the MRI examination and subsequent biopsies.There were 46 patients (71%) whose primary breast lesion (detected by mammography, sonography, or both) was found to be malignant (39 invasive breast cancers, five intraductal cancers, and two lymphomas). For the primary index lesions, the sensitivity for MRI was 100% (44/44) for predicting a breast malignancy and the specificity was 73.7% (14/19) for predicting benign lesions. MRI detected an additional 37 lesions, of which 23 were cancerous, beyond those suspected on mammography or sonography. One or more additional ipsilateral breast cancers were detected in 32% (14/44) of breast cancer patients and contralateral breast cancers in 9% (4/44) of the breast cancer patients. MRI also resulted in an incremental recommendation of mastectomy in 18% (8/44) of the pathologically confirmed breast cancer patients. MRI resulted in additional biopsy of only 14 benign lesions, six of which were shown to be atypical ductal hyperplasia.When added to the standard evaluation of clinical examination, mammography, and sonography in patients thought to have early-stage breast cancer, contrast-enhanced MRI using both a kinetic and morphologic analysis will often result in changes in recommended patient management and better treatment planning and will result in no significant increase in biopsies of benign lesions. In addition, there is a significant detection rate of occult contralateral breast cancers.

The potential of distance learning technology to deliver educational programs in which instruction and evaluation are of a consistent and high standard across multiple settings is hampered by a lack of instructional design models. In response, we developed the HEAL (Heuristic for Electronic Asynchronous Learning) model for designing online curricula.HEAL is based on the theories that learning is facilitated by independent problem solving, investigation, and discovery (heuristics); collaboration between students fosters learning; and the proven educational cycle of practice, feedback, and reflection is integral to the interrelated domains of skill development and personal awareness.(1) The HEAL model is defined by synergistic online learning activities integrated with real patient care. It is applicable to all medical education levels. We applied this innovative design template to an online curriculum that augments our conventional six-week third-year clerkship. Our students, who were placed in distant family physician offices, needed more interaction and learning from peers and faculty. The three elements of HEAL, and implementation in the "online clerkship," are: (1) Didactic modules teach and illustrate concepts. Students study modules (HTML pages) on management of diabetes (DM), and complete five modules on evidence-based medicine (EBM). They do EBM literature searches reviewed online by peers, faculty, and librarians, who provide feedback. (2) A problem-based case discussion promotes application of concepts from modules (horizontal curricular integration). Students view streamed video of a patient with a history suggestive of diabetes, review her medical chart online, and suggest evidence-based management in an asynchronous discussion group. The case progresses weekly to mimic 12 months of continuity of care. (3) A collaborative journal activity explores the results of applying elements one and two to real patients (vertical integration). Additional elements advance reflection, professionalism, and medical humanism. Participation in the journal discussion group, stimulated by online readings, enhances self-awareness, informs psychosocial aspects of element 2, and promotes generalization of learning objectives to real patients. We use BlackBoard software. Students log in two to three times per week. Faculty who are trained in online moderation facilitate the threaded discussion groups and provide feedback.Students in alternating clerkship blocks complete the online clerkship. Their performance is compared with that of students who complete a face-to-face diabetes curriculum, but no curriculum on EBM or medical humanism. After nearly a year (105 students), compared with the non-online group, students completing the online clerkship demonstrated greater gains in reported EBM skills from preto post-clerkship, larger increases in mean score (from pre to post) on a medical-humanism aptitude scale, and higher scores on a post-clerkship diabetes management assessment (all comparisons p.05). The online clerkship will become a permanent part of our clerkship and we have begun to use HEAL to design other online courses, including continuing education courses.

The study of breast cancer relies heavily upon the identification of tumor-associated proteins that are involved with tumor growth and development. Our lab has discovered that mammary tumor cells express high levels of a novel protein known as Semaphorin7A (SEMA7A). After analyzing breast tissue samples collected at Boca Raton Regional Hospital, we have found that normal human mammary epithelial cells express negligible mRNA levels of SEMA7A, while the malignant mammary tumor cells express elevated levels of SEMA7A. Additionally, our laboratory has established a murine model of mammary cell lines that parallels our human findings. Currently, we have correlated high levels of SEMA7A with increasing tumor malignancy and metastasis. However, it is still unknown what factors could induce the production of SEMA7A in mammary tumors. Recent studies have proven that the expression and induction of SEMA7A in normal endothelial cells is regulated under a hypoxic-response element in the promoter of its gene. Although hypoxia is an established tumorigenic factor, it is unknown if the increased hypoxic conditions in breast tumors could induce SEMA7A. In this study we have investigated if exposing mammary cells to hypoxia induces the expression of pro-tumorgenic SEMA7A. Our results show that SEMA7A is up-regulated in 4T07 and 4T1 mammary tumor cells after hypoxic exposure via TGF-β activation of the PI3/AKT pathway. Furthermore, we have found that shRNA silencing of the SEMA7A in 4T1 mammary cells attenuates the activation of pro-angiogenic and mesenchymal genes even after hypoxic stimuli. In vivo, these cells show a reduced proliferation and metastatic potential. We therefore postulate an exciting new role for SEMA7A as a TGF-β effector that promotes tumorigenesis during breast cancer progression. Citation Format: Ramon A. Garcia-Areas, Stephania Libreros, Samantha Amat, Camila Castro-Silva, Kathy Schilling, Vijaya Iragavarapu-Charyulu. Hypoxia induced TGF-β regulates Semaphorin7A to promote a pro-tumorigenic mesenchymal phenotype in mammary cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2007. doi:10.1158/1538-7445.AM2014-2007

The goal of this study was to show that one can safely remove all sonographic evidence of masses in the breast less than or equal to 1.5 cm in greatest dimension using the 11-gauge handheld Mammotome, thereby reducing the possibility of a false-negative diagnosis and other shortcomings of the automated core biopsy device.Over a 12-week period (May 3--July 31, 2000), 124 sonographically guided breast biopsies were performed in 113 patients, using a new handheld directional vacuum-assisted biopsy device. All lesions that were less than or equal to 1.5 cm were biopsied using a handheld Mammotome; an attempt was made to continue the biopsy until no sonographic evidence of the lesion remained.Of these 124 lesions, 14 had infiltrating ductal carcinomas, four had infiltrating ductal carcinomas with associated ductal carcinoma in situ, one had infiltrating lobular carcinoma, one had ductal carcinoma in situ, three had atypical ductal hyperplasias, one had atypical lobular hyperplasia, and one had phyllodes tumor. Only one infiltrating ductal carcinoma was entirely removed histologically at Mammotome biopsy. There were no underestimates of disease. No cases of epithelial displacement were observed in any of the surgical excisions of malignancies. The remaining 99 lesions were benign.The handheld Mammotome diminishes the shortcomings of the automated core biopsy device. It reduces the possibility of false-negatives and underestimation of disease. It eliminates the need for multiple insertions and reduces the likelihood of epithelial displacement. As a result, we now use this device for all sonographically guided biopsies of breast masses smaller than 1.5 cm and recommend that others consider it for such use.

Reactivation of embryogenesis related processes such as neurogenesis is a powerful mechanism used by tumor cells to enhance their survival and propagation. Recent studies have shown that many types of solid tumors express neurogenic molecules independent of the tumor's geography. Semaphorins are a compelling example of these pleiotropic neuronal molecules. Semaphorins were originally characterized for their role in axonal guidance and several of them have been found to play a role in cancer and other inflammatory diseases. Of the Semaphorins, Semaphorin7A (Sema7A) has not yet been studied in the context of cancer. It has however been associated with fibrosis, inflammation and immune modulation. Most semaphorins are repellent cues and inhibit cellular migration, but Sema7A is the only vertebrate semaphorin that serves as an axon chemoattractant. Sema7A also promotes dendricity, adhesion and motility during neuronal development, monocyte differentiation and osteoclast development. All these cellular properties have been attributed to Sema7A's ability to activate p38 mitogen-activated protein kinase pathway (MAP-kinase) through α1β1 integrins. We have recently discovered that Sema7A is over-expressed in the tumor tissue of breast cancer patients compared to the adjacent normal tissue. Within the tumor tissue, the mesenchymal cancer stem cells had the highest expression of Sema7A. We have also found that breast cancer cell lines of a mesenchymal phenotype express high levels of Sema7A and that transforming growth factor beta-1 can induce Sema7A expression in breast epithelial cells. Further, we show that mice bearing Sema7A gene silenced mammary tumors had decreased tumor growth and metastasis with enhanced survival compared to the control tumors. Our studies aim to unravel the functional role of Sema7A in breast cancer progression. We hypothesize that Sema7A expression in tumor cells may lead to increased tumor cell dendricity, migration, and adhesion through the activation of the MAP-kinase pathway and mediating epithelial to mesenchymal transition (EMT). Similar to its role in neurogenesis, in the tumor microenvironment Sema7A could contribute to tumor cell migration and tissue remodeling. Therefore, Sema7A could prove to be a novel therapeutic target to limit tumor growth and metastasis not only for breast cancer but for other solid tumors as well. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 346. doi:1538-7445.AM2012-346

Purpose The objective of this study was to compare the performance characteristics of 18F-fluorodeoxyglucose (FDG) positron emission mammography (PEM) with breast magnetic resonance imaging (MRI) as a presurgical imaging and planning option for index and ipsilateral lesions in patients with newly diagnosed, biopsy-proven breast cancer. Methods Two hundred and eight women >25 years of age (median age = 59.7 ± 14.1 years) with biopsy-proven primary breast cancer enrolled in this prospective, single-site study. MRI, PEM, and whole-body positron emission tomography (WBPET) were conducted on each patient within 7 business days. PEM and WBPET images were acquired on the same day after intravenous administration of 370 MBq of FDG (median = 432.9 MBq). PEM and MRI images were blindly evaluated, compared with final surgical histopathology, and the sensitivity determined. Substudy analysis compared the sensitivity of PEM versus MRI in patients with different menopausal status, breast density, and use of hormone replacement therapy (HRT) as well as determination of performance characteristics for additional ipsilateral lesion detection. Results Two hundred and eight patients enrolled in the study of which 87% (182/208) were analyzable. Of these analyzable patients, 26.4% (48/182), 7.1% (13/182), and 64.2% (120/182) were pre-, peri-, and postmenopausal, respectively, and 48.4% (88/182) had extremely or heterogeneously dense breast tissue, while 33.5% (61/182) had a history of HRT use. Ninety-two percent (167/182) underwent core biopsy for index lesion diagnosis. Invasive cancer was found in 77.5% (141/182), while ductal carcinoma in situ (DCIS) and/or Paget’s disease were found in 22.5% (41/182) of patients. Both PEM and MRI had index lesion depiction sensitivity of 92.8% and both were significantly better than WBPET (67.9%, p