Assessment of MRI-Detected Breast Lesions: A Benign Correlate on Second-Look Ultrasound Can Safely Exclude Malignancy.

INTRODUCTION: Due to the increasing use of dynamic breast MRI and the limited availability of MR-guided interventions, MRI-detected lesions usually undergo a second-look ultrasound (SLUS). We investigated the safety of a negative SLUS and a benign SLUS correlate in excluding malignant and high-risk lesions (B3) and evaluated criteria for the rate of detection on SLUS. METHODS: In the retrospective analysis, all breast MRIs performed between 2011 and 2013 were screened for newly detected lesions. We analyzed the SLUS detection rate dependent on breast density, mass character, lesion size, and histology. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a negative and benign SLUS for malignant lesions (B5) and lesions requiring surgical excision (including high-risk and B5 lesions). RESULTS: We successfully correlated 110 of 397 lesions. The detection rate was significantly higher for mass than for non-mass lesions and correlated with lesion size for mass lesions only. Lesions without/with a benign SLUS correlate were more frequently benign (including B3) or required no further procedure (B2). The sensitivity of SLUS in the detection of B3 and B5 lesions was 58%, and 73% in the detection of B5 lesions. The NPV of a negative or benign SLUS for B3 and B5 lesions was 89%, and 96% for B5 lesions. DISCUSSION: SLUS is a safe diagnostic tool for the management of MRI-detected lesions and can spare patients from undergoing invasive procedures.

Magnetic resonance imaging and ultrasound for prediction of residual tumor size in early breast cancer within the ADAPT subtrials.

BACKGROUND: Prediction of histological tumor size by post-neoadjuvant therapy (NAT) ultrasound and magnetic resonance imaging (MRI) was evaluated in different breast cancer subtypes. METHODS: Imaging was performed after 12-week NAT in patients enrolled into three neoadjuvant WSG ADAPT subtrials. Imaging performance was analyzed for prediction of residual tumor measuring ≤10 mm and summarized using positive (PPV) and negative (NPV) predictive values. RESULTS: A total of 248 and 588 patients had MRI and ultrasound, respectively. Tumor size was over- or underestimated by < 10 mm in 4.4% and 21.8% of patients by MRI and in 10.2% and 15.8% by ultrasound. Overall, NPV (proportion of correctly predicted tumor size ≤10 mm) of MRI and ultrasound was 0.92 and 0.83; PPV (correctly predicted tumor size > 10 mm) was 0.52 and 0.61. MRI demonstrated a higher NPV and lower PPV than ultrasound in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-positive and in HR-/HER2+ tumors. Both methods had a comparable NPV and PPV in HR-/HER2- tumors. CONCLUSIONS: In HR+/HER2+ and HR-/HER2+ breast cancer, MRI is less likely than ultrasound to underestimate while ultrasound is associated with a lower risk to overestimate tumor size. These findings may help to select the most optimal imaging approach for planning surgery after NAT. TRIAL REGISTRATION: Clinicaltrials.gov , NCT01815242 (registered on March 21, 2013), NCT01817452 (registered on March 25, 2013), and NCT01779206 (registered on January 30, 2013).

High-risk breast cancer surveillance with MRI: 10-year experience from the German consortium for hereditary breast and ovarian cancer.

PURPOSE: To report on 10 years of high-risk service screening with annual MRI in the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). METHODS: A cohort of 4,573 high-risk, previously unaffected women (954 BRCA1 carriers, 598 BRCA2 carriers, 3021 BRCA1/2 non-carriers) participating in the GC-HBOC surveillance program was prospectively followed. Screening outcomes for 14,142 screening rounds with MRI between 2006 and 2015 were analyzed and stratified by risk group, type of screening round, and age. RESULTS: A total of 221 primary breast cancers (185 invasive, 36 in situ) were diagnosed within 12 months of an annual screening round with MRI. Of all cancers, 84.5% (174/206, 15 unknown) were stage 0 or I. In BRCA1 carriers, 16.9% (10/59, 5 unknown) of all incident cancers (screen-detected and interval cancers combined) and in BRCA2 carriers 12.5% (3/24, 4 unknown) were stage IIA or higher, compared to only 4.8% (2/42, 2 unknown) in high-risk BRCA1/2 non-carriers. Program sensitivity was 89.6% (95% CI 84.9-93.0) with no significant differences in sensitivity between risk groups or by age. Specificity was significantly lower in the first screening round (84.6%, 95% CI 83.6-85.7) than in subsequent screening rounds (91.1%, 95% CI 90.6-91.7), p < 0.001. Cancer detection rates (CDRs) and as a result positive predictive values were strongly dependent on type of screening round, risk group and patient age. CDRs ranged from 43.5‰ (95% CI 29.8-62.9) for the first screening round in BRCA2 carriers to 2.9‰ (95% CI 1.3-6.3) for subsequent screening rounds in high-risk non-carriers in the age group 30 to 39 years. CONCLUSIONS: High-risk screening with MRI was successfully implemented in the GC-HBOC with high sensitivity and specificity. Risk prediction and inclusion criteria in high-risk non-carriers need to be adjusted to improve CDRs and thus screening efficacy in these patients.

Chemotherapy and Post-traumatic Stress in the Causation of Cognitive Dysfunction in Breast Cancer Patients.

Background: Cancer-related cognitive dysfunction has mostly been attributed to chemotherapy; this explanation, however, fails to account for cognitive dysfunction observed in chemotherapy-naïve patients. In a controlled, longitudinal, multisite study, we tested the hypothesis that cognitive function in breast cancer patients is affected by cancer-related post-traumatic stress. Methods: Newly diagnosed breast cancer patients and healthy control subjects, age 65 or younger, underwent three assessments within one year, including paper-and-pencil and computerized neuropsychological tests, clinical diagnostics of post-traumatic stress disorder (PTSD), and self-reported cognitive function. Analysis of variance was used to compare three groups of participants-patients who did or did not receive chemotherapy and healthy control subjects-on age- and education-corrected cognitive performance and cognitive change. Differences that were statistically significant after correction for false discovery rate were investigated with linear mixed-effects models and mediation models. All statistical tests were two-sided. Results: Of 226 participants (166 patients and 60 control subjects), 206 completed all assessment sessions (attrition: 8.8%). Patients demonstrated overall cognitive decline (group*time effect on composite z -score: -0.13, P = .04) and scored consistently worse on Go/Nogo errors. The latter effect was mediated by PTSD symptoms (mediation effect: B = 0.15, 95% confidence interval = 0.02 to 0.38). Only chemotherapy patients showed declined reaction time on a computerized alertness test. Overall cognitive performance correlated with self-reported cognitive problems at one year ( T = -0.11, P = .02). Conclusions: Largely irrespective of chemotherapy, breast cancer patients may encounter very subtle cognitive dysfunction, part of which is mediated by cancer-related post-traumatic stress. Further factors other than treatment side effects remain to be investigated.

Elucidating pretreatment cognitive impairment in breast cancer patients: the impact of cancer-related post-traumatic stress.

BACKGROUND: Pretreatment cognitive impairment in cancer patients is well established but unexplained. Similar cognitive compromise has been observed in post-traumatic stress disorder (PTSD) patients, and PTSD symptoms are a frequent concomitant of cancer diagnosis. We tested the hypothesis that pretreatment cognitive impairment is attributable to cancer-related post-traumatic stress. METHODS: Women aged 65 years or younger who were diagnosed with breast cancer (case patients) or had undergone negative routine breast imaging (control patients) at one of six participating breast centers underwent traditional and computerized neuropsychological testing, clinician-administered diagnostic assessment of stress disorders, and self-report assessments of cognitive function and depression. To minimize confounding, case patients were evaluated prior to any local or systemic treatment. Cognitive indices of case patients, control patients, and normative samples were compared. The patients' risk of overall cognitive impairment was determined. Linear regression and a mediation model were used to test the study hypothesis. All statistical tests were two-sided. RESULTS: The 166 case patients and 60 well-matched control patients showed near-identical deviations from population norms. Case patients scored worse than control patients on two of 20 cognitive indices (Go/Nogo commission errors, Go/Nogo omission errors). Self-reported cognitive problems were associated with Go/Nogo omission errors and more pronounced in case patients. Only PTSD symptoms (Beta = 0.27, P = .004) and age (Beta = 0.22, P = .04) statistically significantly predicted Go/Nogo errors. The effect of having cancer on Go/Nogo errors was mediated by PTSD symptoms. Case patients did not have an increased risk of overall cognitive impairment. CONCLUSION: Prior to any treatment, breast cancer patients may show limited cognitive impairment that is apparently largely caused by cancer-related post-traumatic stress.

Dual-energy CT for the evaluation of silicone breast implants.

OBJECTIVE: The evaluation of breast implants for rupture is currently the domain of ultrasound and MRI, while mammography is of very limited diagnostic value. Recently, specific visualisation of silicone has become feasible using dual-energy CT. Our objective was to evaluate whether it is feasible to identify silicone in breast implants by dual-energy CT and to reliably diagnose or rule out ruptures. METHODS: Seven silicone breast implant specimens were examined on dual-source CT at 100- and 140-kV tube potential with a 0.8-mm tin filter (collimation 128 × 0.6 mm, current-time products 165 and 140 mAsref with modulation, rotation time 0.28 s, pitch 0.55). Two patients scheduled for implant removal or replacement were examined with identical parameters. RESULTS: The silicone of the implant specimens showed a strong dual-energy signal. In one patient, both implants were intact, while a rupture was identified in the other patient. Ultrasound, MRI, surgical findings and histology confirmed the dual-energy CT diagnosis. CONCLUSION: Dual-energy CT may serve as an alternative technique for speedy evaluation of silicone breast implants. Specific clinical studies are required to determine the diagnostic accuracy and define indications for this technique.

Automated classification of breast parenchymal density: topologic analysis of x-ray attenuation patterns depicted with digital mammography.

OBJECTIVE: We used an algorithm for quantitative image processing to classify breast tissue into the categories fibrosis, involution atrophy, and normal. The algorithm entailed use of Minkowski functionals in topologic analysis of x-ray attenuation patterns on digital mammograms. The results were compared with those of techniques based on evaluation of gray-level histograms. MATERIALS AND METHODS: One hundred digital mammograms were classified by consensus of two experienced readers. A topologic parameter extracted from the Minkowski functional spectra was obtained for retromammilar image sections (512 x 512 pixels). From the gray-level histogram of each of these samples, the 20th percentile, median, and mean were determined. Discriminant analysis was used to assess the predictive value of the methods with respect to correct categorization. RESULTS: The mean gray-level intensity of normal breast tissue was 90 +/- 9, and the 20th percentile was 68 +/- 18. The mean gray-level intensity was 84 +/- 7 for involution and 90 +/- 8 for fibrosis; the 20th percentile was 75 +/- 6 for involution and 73 +/- 10 for fibrosis. The results of discriminant analysis showed that use of the gray-level histogram parameters led to correct classification in 66% of cases. Use of topologic analysis with Minkowski functionals increased the rate of correct classification to 83%. When a combined model of histogram-derived parameters and Minkowski functionals was used, 89% of cases were categorized correctly. CONCLUSION: Topologic analysis of x-ray attenuation patterns on digital mammograms obtained with Minkowski functionals is simple and robust, and the results agree with radiologists' ratings. Because correct classification is significantly higher than with use of density features, our technique may be an objective and quantitative alternative in the evaluation of the parenchymal structure of the breast.

Effects of galactooligosaccharide and long-chain fructooligosaccharide supplementation during pregnancy on maternal and neonatal microbiota and immunity--a randomized, double-blind, placebo-controlled study.

BACKGROUND: Galactooligosaccharides (GOS) and long-chain fructooligosaccharides (lcFOS) proliferate bifidobacteria in infant gut microbiota. However, it is not known how GOS and FOS influence the microbiota of pregnant women and whether a potential prebiotic effect is transferred to the offspring. OBJECTIVES: We aimed to test how supplementation with GOS and lcFOS (GOS/lcFOS) in the last trimester of pregnancy affects maternal and neonatal gut microbiota. Variables of fetal immunity were assessed as a secondary outcome. DESIGN: In a randomized, double-blind, placebo-controlled pilot study, 48 pregnant women were supplemented 3 times/d with 3 g GOS/lcFOS (at a ratio of 9:1) or maltodextrin (placebo) from week 25 of gestation until delivery. Percentages of bifidobacteria and lactobacilli within total bacterial counts were detected by fluorescent in situ hybridization and quantitative polymerase chain reaction in maternal and neonatal (days 5, 20, and approximately 182) stool samples. Variables of fetal immunity were assessed in cord blood by using flow cytometry and cytokine multiplex-array analysis. RESULTS: The proportions of bifidobacteria in the maternal gut were significantly higher in the supplemented group than in the placebo group (21.0% and 12.4%, respectively; P = 0.026); the proportion of lactobacilli did not differ between the groups. In neonates, bifidobacteria and lactobacilli percentages, diversity and similarity indexes, and fetal immune parameters did not differ significantly between the 2 groups. Mother-neonate similarity indexes of bifidobacteria decreased over time. CONCLUSIONS: GOS/lcFOS supplementation has a bifidogenic effect on maternal gut microbiota that is not transferred to neonates. The increased maternal bifidobacteria did not affect fetal immunity as measured by a comprehensive examination of cord blood immunity variables.