Elizabeth S. McDonald

Effectiveness of Digital Breast Tomosynthesis Compared With Digital Mammography: Outcomes Analysis From 3 Years of Breast Cancer Screening

IMPORTANCE Breast cancer screening with digital breast tomosynthesis (DBT) combined with digital mammography (DM) decreases false-positive examinations and increases cancer detection compared with screening with DM alone. However, the longitudinal performance of DBT screening is unknown. OBJECTIVES To determine whether the improved outcomes observed after initial implementation of DBT screening are sustainable over time at a population level and to evaluate the effect of more than 1 DBT screening at the individual level. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of screening mammography metrics was performed for all patients presenting for screening mammography in an urban, academic breast center during 4 consecutive years (DM, year 0; DBT, years, 1-3). The study was conducted from September 1, 2010, to September 30, 2014 (excluding September 2011, which was the transition period from DM to DBT), for a total of 44 468 screening events attributable to a total of 23 958 unique women. Differences in screening outcomes between each DBT year and the DM year, as well as between groups of women with only 1, 2, or 3 DBT screenings, were assessed, and the odds of recall adjusted for age, race/ethnicity, breast density, and prior mammograms were estimated. Data analysis was performed between February 16 and October 26, 2015. EXPOSURE Digital mammography screening supplemented with DBT. MAIN OUTCOMES AND MEASURES Recall rates, cancer cases per recalled patients, and biopsy and interval cancer rates were determined. RESULTS Screening outcome metrics were evaluated for a total of 44 468 examinations attributable to 23 958 unique women (mean [SD] age, 56.8 [11.0] years) over a 4-year period: year 0 cohort (DM0), 10 728 women; year 1 cohort (DBT1), 11 007; year 2 cohort (DBT2), 11 157; and year 3 cohort (DBT3), 11 576. Recall rates rose slightly for years 1 to 3 of DBT (88, 90, and 92 per 1000 screened, respectively) but remained significantly reduced compared with the DM0 rate of 104 per 1000 screened. Reported as odds ratios (95% CIs), the findings were DM vs DBT1, 0.83 (0.76-0.91, P < .001); DM vs DBT2, 0.85 (0.78-0.93, P < .001); and DM vs DBT3, 0.87 (0.80-0.95, P = .003). The cancer cases per recalled patients continued to rise from DM0 rate of 4.4% to 6.2% (P = .06), 6.5% (P = .03), and 6.7% (P = .02) for years 1 to 3 of DBT, respectively. Outcomes assessed for the most recent screening for individual women undergoing only 1, 2, or 3 DBT screenings during the study period demonstrated decreasing recall rates of 130, 78, and 59 per 1000 screened, respectively (P < .001). Interval cancer rates, determined using available follow-up data, decreased from 0.7 per 1000 women screened with the use of DM to 0.5 per 1000 screened with the use of DBT1. CONCLUSIONS AND RELEVANCE Digital breast tomosynthesis screening outcomes are sustainable, with significant recall reduction, increasing cancer cases per recalled patients, and a decline in interval cancers.

Diffusion weighted MRI of the breast: Protocol optimization, guidelines for interpretation, and potential clinical applications

Diffusion-weighted magnetic resonance (MR) imaging (DWI) has shown promise for improving the positive predictive value of breast MR imaging for detection of breast cancer, evaluating tumor response to neoadjuvant chemotherapy, and as a noncontrast alternative to MR imaging in screening for breast cancer. However, data quality varies widely. Before implementing DWI into clinical practice, one must understand the pertinent technical considerations and current evidence regarding clinical applications of breast DWI. This article provides an overview of basic principles of DWI, optimization of breast DWI protocols, imaging features of benign and malignant breast lesions, promising clinical applications, and potential future directions.

Diffusion Weighted Magnetic Resonance Imaging of the Breast: Protocol Optimization, Interpretation, and Clinical Applications

Diffusion-weighted magnetic resonance (MR) imaging (DWI) has shown promise for improving the positive predictive value of breast MR imaging for detection of breast cancer, evaluating tumor response to neoadjuvant chemotherapy, and as a noncontrast alternative to MR imaging in screening for breast cancer. However, data quality varies widely. Before implementing DWI into clinical practice, one must understand the pertinent technical considerations and current evidence regarding clinical applications of breast DWI. This article provides an overview of basic principles of DWI, optimization of breast DWI protocols, imaging features of benign and malignant breast lesions, promising clinical applications, and potential future directions.

Baseline Screening Mammography: Performance of Full-Field Digital Mammography Versus Digital Breast Tomosynthesis

OBJECTIVE Baseline mammography studies have significantly higher recall rates than mammography studies with available comparison examinations. Digital breast tomosynthesis reduces recalls when compared with digital mammographic screening alone, but many sites operate in a hybrid environment. To maximize the effect of screening digital breast tomosynthesis with limited resources, choosing which patient populations will benefit most is critical. This study evaluates digital breast tomosynthesis in the baseline screening population. MATERIALS AND METHODS Outcomes were compared for 10,728 women who underwent digital mammography screening, including 1204 (11.2%) baseline studies, and 15,571 women who underwent digital breast tomosynthesis screening, including 1859 (11.9%) baseline studies. Recall rates, cancer detection rates, and positive predictive values were calculated. Logistic regression estimated the odds ratios of recall for digital mammography versus digital breast tomosynthesis for patients undergoing baseline screening and previously screened patients, adjusted for age, race, and breast density. RESULTS In the baseline subgroup, recall rates for digital mammography and digital breast tomosynthesis screening were 20.5% and 16.0%, respectively (p = 0.002); digital breast tomosynthesis screening in the baseline subgroup resulted in a 22% reduction in recall compared with digital mammography, or 45 fewer patients recalled per 1000 patients screened. Digital breast tomosynthesis screening in the previously screened patients resulted in recall reduction of 14.3% (p < 0.001; p for interaction = 0.21). The recall rate reduction for baseline screening was especially pronounced in women younger than 50 years (p = 0.005). DBT implementation resulted in an increase in cancer detection in the baseline subgroup of 40.5% versus an increase in the previously screened subgroup of 17.4%. DBT implementation resulted in an increase in PPV1 in the baseline subgroup of 85% versus 35.3% in the previously screened subgroup, although the p-interaction was not significant. CONCLUSION If resources are limited, women younger than 50 years who are undergoing baseline screening or do not have prior available mammograms may benefit more from digital breast tomosynthesis than from digital mammography alone.

MR lymphangiography: How i do it.

Lymphedema is a chronic progressive edematous disease that in the United States is most commonly related to malignancy and its treatment. Lymphaticovenular anastomosis is a recently introduced microsurgical treatment option for lymphedema that requires the identification and mapping of individual lymphatic channels. While nuclear medicine lymphoscintigraphy has been the primary imaging modality performed to evaluate suspected lymphedema, lymphoscintigraphy does not provide the spatial information necessary for presurgical planning. High‐resolution dynamic 3D magnetic resonance imaging (MRI) can noninvasively image abnormal lymphatic channels to both diagnose lymphedema and depict the location and number of individual lymphatic channels for surgical planning. MR lymphangiography can be performed at 1.5T or 3.0T using multichannel phased array surface coils. The main components of the exam are a heavily T2‐weighted 3D sequence to define the severity and extent of edema, a high‐resolution dynamic 3D gradient echo imaging after intracutaneous contrast injection to visualize lymphatic channels, and a delayed 3D gradient echo sequence after intravenous contrast to define veins. This article reviews the pathophysiology and microsurgical treatment of lymphedema, presents the imaging protocol used at our institution, and describes exam interpretation and the image postprocessing performed for surgical planning. J. MAGN. RESON. IMAGING 2015;42:1465–1477.

Fully Automated Quantitative Estimation of Volumetric Breast Density from Digital Breast Tomosynthesis Images: Preliminary Results and Comparison with Digital Mammography and MR Imaging

PURPOSE To assess a fully automated method for volumetric breast density (VBD) estimation in digital breast tomosynthesis (DBT) and to compare the findings with those of full-field digital mammography (FFDM) and magnetic resonance (MR) imaging. MATERIALS AND METHODS Bilateral DBT images, FFDM images, and sagittal breast MR images were retrospectively collected from 68 women who underwent breast cancer screening from October 2011 to September 2012 with institutional review board-approved, HIPAA-compliant protocols. A fully automated computer algorithm was developed for quantitative estimation of VBD from DBT images. FFDM images were processed with U.S. Food and Drug Administration-cleared software, and the MR images were processed with a previously validated automated algorithm to obtain corresponding VBD estimates. Pearson correlation and analysis of variance with Tukey-Kramer post hoc correction were used to compare the multimodality VBD estimates. RESULTS Estimates of VBD from DBT were significantly correlated with FFDM-based and MR imaging-based estimates with r = 0.83 (95% confidence interval [CI]: 0.74, 0.90) and r = 0.88 (95% CI: 0.82, 0.93), respectively (P < .001). The corresponding correlation between FFDM and MR imaging was r = 0.84 (95% CI: 0.76, 0.90). However, statistically significant differences after post hoc correction (α = 0.05) were found among VBD estimates from FFDM (mean ± standard deviation, 11.1% ± 7.0) relative to MR imaging (16.6% ± 11.2) and DBT (19.8% ± 16.2). Differences between VDB estimates from DBT and MR imaging were not significant (P = .26). CONCLUSION Fully automated VBD estimates from DBT, FFDM, and MR imaging are strongly correlated but show statistically significant differences. Therefore, absolute differences in VBD between FFDM, DBT, and MR imaging should be considered in breast cancer risk assessment.

Diffusion-Weighted MRI: Association Between Patient Characteristics and Apparent Diffusion Coefficients of Normal Breast Fibroglandular Tissue at 3 T

OBJECTIVE The purpose of this study is to assess associations between patient characteristics and apparent diffusion coefficient (ADC) values of normal breast fibroglandular tissue on diffusion-weighted imaging (DWI) at 3 T. MATERIALS AND METHODS The retrospective study included 103 women with negative bilateral findings on 3-T breast MRI examinations (BI-RADS category 1). DWI was acquired during clinical breast MRI scans using b = 0 and b = 800 s/mm(2). Mean ADC of normal breast fibroglandular tissue was calculated for each breast using a semiautomated software tool in which parenchyma pixels were selected by interactive thresholding of the b = 0 s/mm(2) image to exclude fat. Intrasubject right- and left-breast ADC values were compared and averaged together to evaluate the association of mean breast ADC with age, mammographic breast density, and background parenchymal enhancement. RESULTS Overall mean ± SD breast ADC was 1.62 ± 0.30 × 10(-3) mm(2)/s. Intrasubject right- and left-breast ADC measurements were highly correlated (R(2) = 0.89; p < 0.0001). Increased breast density was strongly associated with increased ADC (p ≤ 0.0001). Age and background parenchymal enhancement were not associated with ADC. CONCLUSION Normal breast parenchymal ADC values increase with mammographic density but are independent of age and background parenchymal enhancement. Because breast malignancies have been shown to have low ADC values, DWI may be particularly valuable in women with dense breasts owing to greater contrast between lesion and normal tissue.

Performance of DWI as a Rapid Unenhanced Technique for Detecting Mammographically Occult Breast Cancer in Elevated-Risk Women With Dense Breasts

OBJECTIVE The objective of our study was to evaluate the performance of DWI to detect mammographically occult breast cancer in elevated-risk women with dense breasts. MATERIALS AND METHODS We retrospectively reviewed all women who underwent screening breast MRI at our institution from January 2007 through May 2013. We created a case-control cohort composed of 48 subjects with mammographically dense breasts: 24 with mammographically occult cancer detected on MRI and 24 healthy women with negative MRI findings who were matched to the subjects with breast cancer patients for age, breast density, and MRI protocol. The contrast-to-noise ratio (CNR), apparent diffusion coefficient (ADC), and conspicuity score (range, 1-5) were assessed on DWI for all malignancies. Lesions and normal tissue were compared using the Wilcoxon signed rank test; associations with clinical characteristics were evaluated using the Mann-Whitney U test. Three experienced breast imagers who were blinded to medical records and contrast-enhanced MRI findings independently evaluated the unenhanced MRI scans of the 48 women for the presence of cancer. RESULTS Mammographically occult breast cancers (invasive carcinoma, n = 16; ductal carcinoma in situ, n = 8) in women with dense breasts typically exhibited higher signal intensity on DWI than normal parenchyma (median CNR of cancers, 1.4; median conspicuity score of cancers, 4) and a lower ADC (median, 1.31 vs 1.79 × 10(-3) mm(2)/s, respectively) (p < 0.0001). The conspicuity score, CNR, and ADC were not associated with patient age, menopausal status, lesion size, morphologic type, or histology (p > 0.05). Average reader performance using unenhanced MRI was 45% sensitivity, 91% specificity, 62% positive predictive value, and 83% negative predictive value. CONCLUSION In elevated-risk women with dense breasts, DWI can reveal cancers in addition to those detected on mammography alone with a low false-positive rate; these results suggest that DWI may have potential as a rapid supplemental screening tool.

Role of PET quantitation in the monitoring of cancer response to treatment: review of approaches and human clinical trials

Positron emission tomography (PET) measures of cancer metabolism and cellular proliferation are increasingly being studied as markers of cancer response to treatment, with the goal of using them as predictors of patient therapeutic outcomes—i.e., as surrogate outcome measures. The primary PET radiotracers so far used for monitoring response of cancer to treatment are 18F-fluorodeoxyglucose (FDG) for studying abnormal energy metabolism and 18F-fluorothymidine (FLT) for examining cell proliferation. Both FDG and FLT PET quantitation of cancer response to treatment have been found to correlate with patient outcomes, mostly in single-center studies. The aim of this review is to summarize the impact of commonly selected PET quantitation methods on the ability of PET measures to quantitate cancer response to treatment. An understanding of the biochemistry and kinetics of FDG and FLT uptake and knowledge of the expected tracer uptake by cancerous processes relative to background uptake are required to select appropriate PET quantitation methods for trial testing for correlations between PET measures and patient outcome. PET measures may eventually serve as predictive biomarkers capable of guiding individualized treatment and improving patient outcomes and quality of life by early identification of ineffective therapies. PET can also potentially identify patients who would be good candidates for molecularly targeted drugs and monitor response to these personalized therapies.

A Radiotracer Strategy to Quantify PARP-1 Expression In Vivo Provides a Biomarker That Can Enable Patient Selection for PARP Inhibitor Therapy.

Despite the availability of PARP inhibitors for cancer therapy, a biomarker to clearly stratify patients for selection of this treatment remains lacking. Here we describe a radiotracer-based method that addresses this issue, using the novel compound [(125)I] KX1: as a PARP-1-selective radiotracer that can accurately measure PARP-1 expression in vitro and in vivo The pharmacologic properties of the PARP radiotracer [(125)I] KX1: was characterized in multiple cell lines where single-agent sensitivity was correlated with [(125)I] KX1: binding to PARP-1. In vivo evaluation of [(125)I] KX1: verified in vitro results, validating PARP radiotracers to define PARP-1 enzyme expression as an in vivo biomarker. Notably, PARP-1 expression as quantified by [(125)I] KX1: correlated positively with the cytotoxic sensitivity of cell lines evaluated with PARP inhibitors. Overall, our results defined a novel technology with the potential to serve as a companion diagnostic to identify patients most likely to respond therapeutically to a PARP inhibitor. Cancer Res; 76(15); 4516-24. ©2016 AACR.