Pre-treatment peripheral blood immunophenotyping and response to neoadjuvant chemotherapy in operable breast cancer.

BACKGROUND: Tumor immune infiltration and peripheral blood immune signatures have prognostic and predictive value in breast cancer. Whether distinct peripheral blood immune phenotypes are associated with response to neoadjuvant chemotherapy (NAC) remains understudied. METHODS: Peripheral blood mononuclear cells from 126 breast cancer patients enrolled in a prospective clinical trial (NCT02022202) were analyzed using Cytometry by time-of-flight with a panel of 29 immune cell surface protein markers. Kruskal-Wallis tests or Wilcoxon rank-sum tests were used to evaluate differences in immune cell subpopulations according to breast cancer subtype and response to NAC. RESULTS: There were 122 evaluable samples: 47 (38.5%) from patients with hormone receptor-positive, 39 (32%) triple-negative (TNBC), and 36 (29.5%) HER2-positive breast cancer. The relative abundances of pre-treatment peripheral blood T, B, myeloid, NK, and unclassified cells did not differ according to breast cancer subtype. In TNBC, higher pre-treatment myeloid cells were associated with lower pathologic complete response (pCR) rates. In hormone receptor-positive breast cancer, lower pre-treatment CD8 + naïve and CD4 + effector memory cells re-expressing CD45RA (TEMRA) T cells were associated with more extensive residual disease after NAC. In HER2 + breast cancer, the peripheral blood immune phenotype did not differ according to NAC response. CONCLUSIONS: Pre-treatment peripheral blood immune cell populations (myeloid in TNBC; CD8 + naïve T cells and CD4 + TEMRA cells in luminal breast cancer) were associated with response to NAC in early-stage TNBC and hormone receptor-positive breast cancers, but not in HER2 + breast cancer. TRIAL REGISTRATION: NCT02022202 . Registered 20 December 2013.

A Survey of Patient Experience During Molecular Breast Imaging.

Molecular breast imaging (MBI) is one of several options available to patients seeking supplemental screening due to mammographically dense breasts. Patient experience during MBI may influence willingness to undergo the test but has yet to be formally assessed. We aimed to assess patient comfort level during MBI, to compare MBI comfort with mammography comfort, to identify factors associated with MBI discomfort, and to evaluate patients' willingness to return for future MBI. Methods: A 10-question survey was sent by e-mail to patients undergoing MBI between August and December 2022 to obtain quantitative assessments and qualitative opinions about MBI. Results: Of 561 invited patients, 209 (37%) completed the survey and provided study consent. Their average age was 60.1 y (range, 40-81 y). Of the 209 responders, 202 (97%) were presenting for screening MBI, 195 (94%) had dense breasts, and 46 (22%) had a personal history of breast cancer. The average rating of MBI comfort was 2.9 (SD, 1.5; median, 3.0) on a 7-point scale (1 indicating extremely comfortable and 7 indicating extremely uncomfortable). The rating distribution was as follows: 140 (67%) comfortable (rating, 1-3); 24 (12%) neither comfortable nor uncomfortable (rating, 4); and 45 (22%) uncomfortable (rating, 5 or 6). No responders gave a 7 rating. The most frequently mentioned sources of discomfort included breast compression (n = 16), back or neck discomfort (n = 14), and maintaining position during the examination (n = 14). MBI comfort was associated with responder age (74% ≥55 y old were comfortable, versus 53% <55 y old [P = 0.003]) and history of MBI (71% with prior MBI were comfortable, versus 61% having a first MBI [P = 0.006]). Of 208 responders with a prior mammogram, 148 (71%) said MBI is more comfortable than mammography (a significant majority [P < 0.001]). Of 202 responders to the question of whether they were willing to return for a future MBI, 196 (97%) were willing. A notable factor in positive patient experience was interaction with the MBI nuclear medicine technologist. Conclusion: Most responders thought MBI to be a comfortable examination and more comfortable than mammography. Patient experience during MBI may be improved by ensuring back support and soliciting patient feedback at the time of positioning and throughout the examination. Methods under study to reduce imaging time may be most important for improving patient experience.

Molecular Breast Imaging Biopsy with a Dual-Detector System.

Purpose To develop a molecular breast imaging (MBI)-guided biopsy system using dual-detector MBI and to perform initial testing in participants. Materials and Methods The Stereo Navigator MBI Accessory biopsy system comprises a lower detector, upper fenestrated compression paddle, and upper detector. The upper detector retracts, allowing craniocaudal, oblique, or medial or lateral biopsy approaches. The compression paddle allows insertion of a needle guide and needle. Lesion depth is calculated by triangulation of lesion location on the upper detector at 0° and 15° and relative lesion activity on upper and lower detectors. In a prospective study (July 2022-June 2023), participants with Breast Imaging Reporting and Data System category 2, 3, 4, or 5 breast lesions underwent MBI-guided biopsy. After injection of 740 MBq technetium 99m sestamibi, craniocaudal and mediolateral oblique MBI (2-minute acquisition per view) confirmed lesion visualization. A region of interest over the lesion permitted depth calculation in the system software. Upper detector retraction allowed biopsy device placement. Specimen images were obtained on the retracted upper detector, confirming sampling of the target. Results Of 21 participants enrolled (mean age, 50.6 years ± 10.1 [SD]; 21 [100%] women), 17 underwent MBI-guided biopsy with concordant pathology. No lesion was observed at the time of biopsy in four participants. Average lesion size was 17 mm (range, 6-38 mm). Average procedure time, including preprocedure imaging, was 55 minutes ± 13 (range, 38-90 minutes). Pathology results included invasive ductal carcinoma (n = 1), fibroadenoma (n = 4), pseudoangiomatous stromal hyperplasia (n = 6), and fibrocystic changes (n = 6). Conclusion MBI-guided biopsy using a dual-head system with retractable upper detector head was feasible, well tolerated, and efficient. Keywords: Breast Biopsy, Molecular Breast Imaging, Image-guided Biopsy, Molecular Breast Imaging-guided Biopsy, Breast Cancer Clinical trial registration no. NCT06058650 © RSNA, 2024.

PPV of the Molecular Breast Imaging Lexicon.

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

Molecular Breast Imaging in the Screening Setting.

Early detection of breast cancer through screening mammography saves lives. However, the sensitivity of mammography for breast cancer detection is reduced in women with dense breast tissue. Imaging modalities for supplemental breast cancer screening include MRI, whole breast US, contrast-enhanced mammography, and molecular breast imaging (MBI). Molecular breast imaging with 99mTc-sestamibi is a functional imaging test to identify metabolically active areas in the breast with positioning analogous to mammography. Since 2011, there have been six large, published studies of screening MBI as a supplement to mammography involving over 6000 women from four different institutions. A multicenter, prospective clinical trial of 3000 women comparing breast cancer detection using screening digital breast tomosynthesis alone or in combination with MBI recently completed enrollment. This review focuses on the current evidence of MBI use for supplemental breast cancer screening, the strengths and limitations of MBI, and recent technological advances.

Work of breathing at different tidal volume targets in newborn infants with congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) results in varying degrees of pulmonary hypoplasia. Volume targeted ventilation (VTV) is a lung protective strategy but the optimal target tidal volume in CDH infants has not previously been studied. The aim of this study was to test the hypothesis that low targeted volumes would be better in CDH infants as determined by measuring the work of breathing (WOB) in CDH infants, at three different targeted tidal volumes. A randomised cross-over study was undertaken. Infants were eligible for inclusion in the study after surgical repair of their diaphragmatic defect. Targeted tidal volumes of 4, 5, and 6 ml/kg were each delivered in random order for 20-min periods with 20-min periods of baseline ventilation between. WOB was assessed and measured by using the pressure-time product of the diaphragm (PTPdi). Nine infants with a median gestational age at birth of 38 + 4 (range 36 + 4-40 + 6) weeks and median birth weight 3202 (range 2855-3800) g were studied. The PTPdi was higher at 4 ml/kg than at both 5, p = 0.008, and 6 ml/kg, p = 0.012. CONCLUSION: VTV of 4 ml/kg demonstrated an increased PTPdi compared to other VTV levels studied and should be avoided in post-surgical CDH infants. WHAT IS KNOWN: • Lung injury secondary to mechanical ventilation increases the mortality and morbidity of infants with CDH. • Volume targeted ventilation (VTV) reduces 'volutrauma' and ventilator-induced lung injury in other neonatal intensive care populations. WHAT IS NEW: • A randomised cross-over trial was carried out investigating the response to different VTV levels in infants with CDH. • Despite pulmonary hypoplasia being a common finding in CDH, a VTV of 5ml/kg significantly reduced the work of breathing in infants with CDH compared to a lower VTV level.

Volumetric capnography pre- and post-surfactant during initial resuscitation of premature infants.

BACKGROUND: Volumetric capnography allows for continuous monitoring of expired tidal volume and carbon dioxide. The slope of the alveolar plateau of the capnogram (SIII) could provide information regarding ventilation homogeneity. We aimed to assess the feasibility of measuring SIII during newborn resuscitation and determine if SIII decreased after surfactant indicating ventilation inhomogeneity improvement. METHODS: Respiratory function traces of preterm infants resuscitated at birth were analysed. Ten capnograms were constructed for each infant: five pre- and post-surfactant. If a plateau was present SIII was calculated by regression analysis. RESULTS: Thirty-six infants were included, median gestational age of 28.7 weeks and birth weight of 1055 g. Average time between pre- and post-surfactant was 3.2 min. Three hundred and sixty capnograms (180 pre and post) were evaluated. There was adequate slope in 134 (74.4%) capnograms pre and in 100 (55.6%) capnograms post-surfactant (p = 0.004). Normalised for tidal volume SIII pre-surfactant was 18.89 mmHg and post-surfactant was 24.86 mmHg (p = 0.006). An increase in SIII produced an up-slanting appearance to the plateau indicating regional obstruction. CONCLUSION: It was feasible to evaluate the alveolar plateau pre-surfactant in preterm infants. Ventilation inhomogeneity increased post-surfactant likely due to airway obstruction caused by liquid surfactant present in the airways. IMPACT: Volumetric capnography can be used to assess homogeneity of ventilation by SIII analysis. Ventilation inhomogeneity increased immediately post-surfactant administration during the resuscitation of preterm infants, producing a characteristic up-slanting appearance to the alveolar plateau. The best determinant of alveolar plateau presence in preterm infants was the expired tidal volume.

Leveling the Workload for Radiologists in Diagnostic Mammography: Application of Lean Principles and Heijunka.

To facilitate the delivery of accurate and timely care to patients in complex environments, process improvement methodologies such as Lean can be very effective. Lean is a quality improvement methodology that seeks to add value for patients and employees by continuously improving processes and eliminating waste. At our institution, Lean principles were applied to improve efficiency and minimize waste in the diagnostic breast imaging reading room. This paper describes how we applied Lean principles, including plan-do-study-act testing, level-loading (heijunka), and visual management, to level the workload of the diagnostic radiologists in our practice. Implementation of these principles to improve the diagnostic workflow in breast imaging is described along with examples from our practice, including challenges and future opportunities.

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.

Breast cancers observed in transplant patients in a single institution.

OBJECTIVE: Document occurrence of breast cancer in females after liver, kidney, or pancreas transplantation seen at a tertiary medical center. METHODS: Medical records of adult female patients with liver, kidney, or pancreas transplants from 1/1/1995 to 4/4/2014 were retrospectively reviewed. Patients with a history of breast cancer, no mammogram post-transplant, or no research authorization were excluded. Mammogram findings and pathology results were reviewed and recorded. Cancer rates could not be measured in patients followed up outside the institution. Descriptive statistics summarized the cohort. Occurrence rates were estimated using Poisson regression. RESULTS: 1095 women were included and 33 were diagnosed with breast cancer post-transplant. Median age at diagnosis was 58 years. Average interval from transplant to cancer diagnosis was 82.6 months. Observed occurrence of invasive and in-situ breast cancer (reported as per 100,000 person-years [95% confidence interval]) was 353 [243-496]. Liver transplant patients showed the lowest rate (181 [95% CI 73-372]), vs. kidney (476 [305-708]) or pancreas (467 [57-1688]). Patients with the highest breast density showed increased occurrence despite younger age (1001 [367-2178]) compared to those with lower breast density (range 239 [109-454] to 372 [186-666]). CONCLUSIONS: Female patients after organ transplant experienced increased breast cancer occurrence in this observational study. Those who developed breast cancer also had increased breast density. The findings underscore the importance of breast cancer screening in this population.

USMLE Step 3 Scores Have Value in Predicting ABR Core Examination Outcome and Performance: A Multi-institutional Study.

RATIONALE AND OBJECTIVES: We analyzed multi-institutional data to determine if Step 3 performance tiers can identify radiology residents with increased risk of Core examination failure and submean performance. MATERIALS AND METHODS: We collected Step 3 scores (USMLE Step 3 or COMLEX Level 3) and American Board of Radiology (ABR) Core examination outcomes and scores for anonymized residents from 13 different Diagnostic Radiology residency programs taking the ABR Core examination between 2013 and 2019. Step 3 scores were converted to percentiles based on Z-score, with Core outcome and performance analyzed for Step 3 groups based on 50th percentile and based on quintiles. Core outcome was scored as fail when conditionally passed or failed. Core performance was measured by the percent of residents with scores below the mean. Differences between Step 3 groups for Core outcome and Core performance were statistically evaluated. RESULTS: Data were available for 342 residents. The Core examination failure rate for 121 residents with Step 3 scores <50th percentile was 19.8% (fail relative risk = 2.26), significantly higher than the 2.7% failure rate for the 221 other residents. Of 42 residents with Step 3 scores in the lowest quintile, the Core failure rate increased to 31.0% (fail relative risk = 3.52). Core performance improved with higher Step 3 quintiles. CONCLUSION: Step 3 licensing scores have value in predicting radiology resident performance on the ABR Core examination, enabling residency programs to target higher risk residents for early assessment and intervention.

Molecular Breast Imaging: A Scientific Review.

Molecular breast imaging (MBI) is a nuclear medicine technique that has evolved considerably over the past two decades. Technical advances have allowed reductions in administered doses to the point that they are now acceptable for screening. The most common radiotracer used in MBI, 99mTc-sestamibi, has a long history of safe use. Biopsy capability has become available in recent years, with early clinical experience demonstrating technically successful biopsies of MBI-detected lesions. MBI has been shown to be an effective supplemental screening tool in women with dense breasts and is also utilized for breast cancer staging, assessment of response to neoadjuvant chemotherapy, problem solving, and as an alternative to breast MRI in women who have a contraindication to MRI. The degree of background parenchymal uptake on MBI shows promise as a tool for breast cancer risk stratification. Radiologist interpretation is guided by a validated MBI lexicon that mirrors the BI-RADS lexicon. With short interpretation times, a fast learning curve for radiologists, and a substantially lower cost than breast MRI, MBI provides many benefits in the practices in which it is utilized. This review will discuss the current state of MBI technology, clinical applications of MBI, MBI interpretation, radiation dose associated with MBI, and the future of MBI.

Mastitis and More: A Pictorial Review of the Red, Swollen, and Painful Breast.

Clinically, acute mastitis presents as a red, swollen, and painful breast. Targeted ultrasound can be performed to evaluate the extent of infection and for an underlying abscess. Noncomplicated mastitis or a small fluid collection may respond to oral antibiotics without further intervention, but a larger or more complex abscess may require single or serial percutaneous aspiration. Breast infections, particularly those complicated by an abscess, can have a prolonged clinical course, and close follow-up is required. Since the clinical presentation and imaging features of acute infectious mastitis can overlap with other etiologies, such as inflammatory breast cancer and idiopathic granulomatous mastitis, a percutaneous biopsy may be indicated to accurately diagnose patients.

The Relationship Between ACR Diagnostic Radiology In-Training Examination Scores and ABR Core Examination Outcome and Performance: A Multi-Institutional Study.

PURPOSE: We analyzed multi-institutional data to understand the relationship of ACR Diagnostic Radiology In-Training Examination (DXIT) scores to ABR Core examination performance. METHODS: We collected DXIT rank scores and ABR Core examination outcomes and scores for anonymized residents from 12 different diagnostic radiology residency programs taking the ABR Core examination between 2013 and 2019. DXIT scores were grouped into quintiles based on rank score for residency year 1 (R1), residency year 2 (R2), and residency year 3 (R3) residents. Core outcome was scored as fail when conditionally passed or failed. Core performance was grouped using SD from the mean and measured by the percent of residents with scores below the mean. Differences between DXIT score quintiles for Core outcome and Core performance were statistically evaluated. RESULTS: DXIT and Core outcome data were available for 446 residents. The Core examination failure rate for the lowest quintile R1, R2, and R3 DXIT scores was 20.3%, 34.2%, and 38.0%, respectively. Core performance improved with higher R3 DXIT quintiles. Only 2 of 229 residents with R3 DXIT score ≥ 50th percentile failed the Core examination, with both failing residents having R2 DXIT scores in the lowest quintile. CONCLUSIONS: DXIT scores are useful evaluation metrics to identify a subgroup of residents at significantly higher risk for Core examination failure and another subgroup of residents at significantly lower risk for Core examination failure, with increasing predictive power with advancing residency year. These scores enable identification of approximately one-half of R3 residents whose risk of Core examination failure is negligible.

Molecular Breast Imaging in Clinical Practice.

OBJECTIVE. The purpose of this article is to review clinical uses and image interpretation of molecular breast imaging (MBI) and clarify radiation risks. CONCLUSION. MBI detects additional cancers compared with conventional imaging in women with dense breasts and those with elevated risk of breast cancer. Its role as an imaging biomarker of cancer risk and in assessing neoadjuvant chemotherapy response is growing. Radiation risk is minimal; benefit-to-risk ratio is similar to that of mammography. MBI is low cost, well tolerated, and easily adapted into clinical practice.

Prediction of extubation success using the diaphragmatic electromyograph results in ventilated neonates.

Objectives Extubation failure is common in infants and associated with complications. Methods A prospective study was undertaken of preterm and term born infants. Diaphragm electromyogram (EMG) was measured transcutaneously for 15-60 min prior to extubation. The EMG results were related to tidal volume (Tve) to calculate the neuroventilatory efficiency (NVE). Receiver operating characteristic curves (ROC) were constructed and areas under the ROCs (AUROC) calculated. Results Seventy-two infants, median gestational age 28 (range 23-42) weeks were included; 15 (21%) failed extubation. Infants successfully extubated were more mature at birth (p=0.001), of greater corrected gestational age (CGA) at extubation (p<0.001) and heavier birth weight (p=0.005) than those who failed extubation. The amplitude and area under the curve of the diaphragm EMG were not significantly different between those who were and were not successfully extubated. Those successfully extubated required a significantly lower inspired oxygen and had higher expiratory tidal volumes (Tve) and NVE. The CGA and Tve had AUROCs of 0.83. A CGA of >29.6 weeks had the highest combined sensitivity (86%) and specificity (80%) in predicting extubation success. Conclusions Although NVE differed significantly between those who did and did not successfully extubate, CGA was the best predictor of extubation success.