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OBJECTIVES: High background parenchymal enhancement (BPE) levels and asymmetric distribution could cause diagnostic uncertainty due to morphological similarity to breast cancer, especially invasive lobular carcinoma (ILC). We investigated BPE in ILC patients, its association with the tumor hormonal profile, and the effect of endocrine treatment (ET). METHODS: The analysis included all MRI examinations performed at our institution between 2010 and 2019 for ILC-diagnosed patients. Baseline study and the first follow-up study were reviewed. Digital medical records were reviewed to retrieve demographics/pathology results/treatment information. BPE and fibroglandular tissue were assessed qualitatively on the contralateral breast according to the criteria of the Breast Imaging Reporting and Data System (BI-RADS). RESULTS: The study included 129 patients. Most (91%) had pure ILC. All received ET; 12% also received chemotherapy; 90% had surgery first; 70% by breast conservation. On the baseline MRI, 70% had mild or moderate BPE; whereas, on the follow-up study, the majority (59%) had minimal BPE. Most BPE reductions were by 2 degrees. In the baseline study, additional biopsies were required in 59% of cases, and in 17%, a short-term follow-up was recommended. In the follow-up study, biopsies were recommended in 10%, and a short-term follow-up was requested in 16%. A correlation between progesterone receptor intensity index and baseline BPE level was observed (r = 0.3, p = 0.004). CONCLUSION: ILC patients usually exhibit high BPE. ET decreases BPE, and therefore may decrease false-positive interpretations. Additional research is needed to explore whether study can be performed on ET without compromising sensitivity. Key points: ∙ High background parenchymal enhancement levels reduces breast MRI sensitivity, yielding high false positive rates especially when reporting cases of invasive lobular carcinoma [ILC]. ∙Treatment of ILC with endocrine therapy reduces background parenchymal enhancement and thus could decrease these false-positive interpretations.

Purpose: To evaluate the total biopsy and positive biopsy rates in women at high risk of breast cancer compared to the general population. Methods: The study group consisted of 330 BRCA mutation carriers attending the dedicated multidisciplinary breast cancer clinic of a tertiary medical center in Israel. Clinical, genetic, and biopsy data were retrieved from the central healthcare database and the medical files. Patients who were at age 50 years or older during follow-up were matched 1:10 to women in the general population referred for routine breast cancer screening at the same age, as recommended in the international guidelines. The groups were compared for rate of biopsy studies performed and percentage of positive biopsy results. Matched analysis was performed to correct for confounders. Results: The matched analysis revealed that the total biopsy rate per 1000 follow-up-years was 61.7 in the study group and 22.7 in the control group (p Citation Format: Adi Pomerantz, Daliah Tsoref, Ahuva Grubstein, Sonya Wadhawker, Yael Rapson, Itay Gadiel, Hadar Goldvaser, Ariel Hammerman, Tzipora Shochat, Eran Sharon, Rinat Yerushalmi. Rate of breast biopsy referrals in BRCA mutation carriers: A retrospective comparative study and matched analysis [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 P2-11-16.

Introduction: Submucosal fat deposition (SMF) in the gastrointestinal tract can be seen in patients treated with vascular endothelial growth factor receptor multitarget tyrosine kinase inhibitors (mtTKIs). We aimed to assess the association between mtTKIs treatment and appearance of SMF on computed tomography (CT). Methods: We performed retrospective evaluation of patients who started mtTKI treatment between 2016 and 2018, with a comparison patient cohort treated with single-target tyrosine kinase inhibitors (stTKIs). SMF amount for each gastrointestinal tract segment (stomach, duodenum, jejunum, ileum, terminal ileum, right colon, left colon) was scored as follows: 0 = none; 1 = low amount (2 mm layer). For each CT, segment scores were aggregated to create an SMF index (SMFI). Maximal increase in SMFI between pretreatment and posttreatment CTs was documented. SMF ⩾3 was defined as positive. Results: Forty patients treated with mtTKIs and 23 patients receiving stTKIs were included. Maximal increase in SMFI during treatment was 0–1 in 56/63 patients (89%) and 3–6 in 7/63 patients (11%). All patients with positive SMFI received mtTKIs compared to 0 patients treated with stTKIs (17.5% vs. 0%; p = 0.04). mtTKI treatment was associated with higher incidence of nausea/vomiting (4/7) and diarrhea (4/7) when positive SMF was noted, as compared to patients with negative SMF (6/33 patients each; p = 0.048). Conclusion: Gastrointestinal tract SMF deposition occurs in a considerable proportion of patients treated with mtTKIs with association to abdominal symptoms. This may be unique to mtTKIs and was not found in patients receiving stTKIs.

Background Breast cancer patients with lymph node (LN) metastases at diagnosis often undergo neoadjuvant therapy (NAT). Identification of a LN which regressed after NAT remains a challenge. Objective To evaluate marking of involved nodes by tattooing with carbon suspension, and identifying these nodes during surgery. Methods A small amount (0.2–0.5 ml) of carbon suspension was injected into one or two axillary LNs under ultrasound guidance at the time of LN biopsy or before or shortly after starting NAT for LN positive breast cancer. During surgery an attempt was made to identify and remove the tattooed LN as a separate specimen. All patients underwent sentinel LN mapping and biopsy and/or axillary LN dissection as mandated by their clinical status. Results Sixty three patients underwent tattooing of axillary LNs with no complications or adverse events. At surgery a tattooed node was identified in 60 patients (95%; 95% CI 87, 98). Of 56 patients who underwent sentinel mapping with Tc99, in 51 (91%; 95% CI 81, 96) at least one radioactive LN was identified. Of 50 patients in whom both radioactivity and tattoo were identified in axillary LNs, in 40 (80%; 95% CI 67, 89) LNs were radioactive and tattooed, however in 10 patients (20%; 95% CI 11, 33), the tattooed LN was not radioactive. Conclusions Tattooing of axillary LNs is safe and easily performed. Tattooing was helpful in identifying the marked LN in the majority of cases. This technique helps to ensure that metastatic LNs are identified and removed at surgery after NAT.

Background: Adjuvant regional nodal irradiation together with whole breast or chest wall irradiation is considered standard of care in most node positive early breast cancer. Existing data on adding internal mammary irradiation (IMNI) to the regional nodal fields are inconsistent. The objective of this study was to conduct a meta-analysis to explore the efficacy and safety of adding IMNI to adjuvant radiotherapy in early-stage, high risk breast cancer. Methods: A search of PubMed and EMBASE identified randomized trials that investigated the addition of IMNI to standard adjuvant radiation in early-stage breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for overall survival (OS), breast cancer specific survival (BCSS), disease-free survival (DFS) and distant-metastasis free survival (DMFS). The odds ratios (ORs) for regional and loco-regional recurrence, non-breast cancer mortality, secondary non-breast cancer, contralateral breast cancer and cardiovascular morbidity and mortality were also extracted. These data where pooled in a meta-analysis using RevMan 5.4. Results: Analysis included 5 trials comprising 10,994 patients. Compared to the control group, IMNI was associated with a small, but statistically significant improvement in OS (HR=0.91, 95% 0.85-0.97, p=0.004), BCSS (HR=0.84, 95%0.77-0.92, p< 0.001), DFS (HR=0.89, 95% CI 0.82-0.98, p= 0.01) and DMFS (HR=0.89, 95% 0.81-0.98, p=0.02). IMNI was also associated with reduced odds for regional (OR=0.58, 95% 0.44-0.75, p< 0.001) and loco-regional recurrence (OR=0.85, 95% CI 0.72-1.00, p=0.04). Subgroup analyses for OS by tumor location (medial/central vs. lateral) and by nodal burden showed similar benefit is all subgroups. The odds for cardiotoxicity were higher, but did not reach statistical significance (OR=1.23, 95% 0.99-1.53, p=0.07). There was no association with cardiovascular mortality (OR=1.00, 95% 0.69-1.46, p=1.00). There were also comparable odds for non-breast cancer mortality (OR=1.05, 95% 0.79-1.41, p=0.74), secondary cancer (OR=0.95, 95% 0.82-1.10, p=0.51) and contra-lateral breast cancer (OR=1.07, 95% 0.77-1.51, p=0.68). Conclusions: Compared to the control group the addition of IMNI in high-risk patients is associated with a statistically significant improvement in survival, albeit with a magnitude of questionable clinical meaningfulness. Non-significant association with increased cardiovascular toxicity requires further study in longer-term studies. Citation Format: Yasmin Korzets, Dina Levitas, Ahuva Grubstein, Ben W Corn, Eitan Amir, Hadar Goldvaser. Efficacy and Safety of the Addition of Internal Mammary Irradiation to Standard Adjuvant Radiation in Early-Stage Breast Cancer: A Systematic Review and Meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-02-03.

Sertraline-associated interstitial lung disease (ILD) is a rare entity. A search of the English medical literature retrieved only 9 such cases. We report herein on an additional 12 patients who developed ILD during treatment with sertraline. The patients met the criteria for drug-induced pulmonary toxicity such as exposure to drug, correlation of the drug with clinical symptoms, lung imaging, lung biopsy findings, exclusion of other potential causes and improvement after drug removal. We review the available data and discuss various aspects of this entity. The possibility of drug-induced ILD should be considered in an individual who during treatment with sertraline develops dyspnea, cough, and radiographic findings compatible with ILD. Further epidemiological studies should be conducted to explore the association of sertraline treatment with ILD, and to delineate, substantiate, and broaden our knowledge of this rare entity.

PurposeTo evaluate the total biopsy and positive biopsy rates in women at high risk of breast cancer compared to the general population.MethodsThe study group consisted of 330 women with pathogenic variants (PVs) inBRCA1/2attending the dedicated multidisciplinary breast cancer clinic of a tertiary medical center in Israel. Clinical, genetic, and biopsy data were retrieved from the central healthcare database and the medical files. Patients aged 50 years or older during follow-up were matched 1:10 to women in the general population referred for routine breast cancer screening at the same age, as recommended by international guidelines. The groups were compared for rate of biopsy studies performed and percentage of positive biopsy results. Matched analysis was performed to correct for confounders.ResultsThe total biopsy rate per 1000 follow-up years was 61.7 in the study group and 22.7 in the control group (p p p ConclusionWomen aged 50 + years with PVs inBRCA1/2attending a dedicated clinic have a 2.7 times higher biopsy rate per 1000 follow-up years, a 13.2 times higher positive biopsy rate per 1000 follow-up years, and a 4.9 times higher positive biopsy percentage than same-aged women in the general population.

Purpose To evaluate the total biopsy and positive biopsy rates in women at high risk of breast cancer compared to the general population. Methods The study group consisted of 330 BRCA mutation carriers attending the dedicated multidisciplinary breast cancer clinic of a tertiary medical center in Israel. Clinical, genetic, and biopsy data were retrieved from the central healthcare database and the medical files. Patients who were at age 50 years or older during follow-up were matched 1:10 to women in the general population referred for routine breast cancer screening at the same age, as recommended in the international guidelines. The groups were compared for rate of biopsy studies performed and percentage of positive biopsy results. Matched analysis was performed to correct for confounders. Results The matched analysis revealed that the total biopsy rate per 1000 follow-up-years was 61.7 in the study group and 22.7 in the control group (p p p BRCA mutation carriers who attend a dedicated clinic, have a 2.7 times higher biopsy rate per 1000 follow-up-years, a 13.2 times higher positive biopsy rate per 1000 follow-up-years, and a 4.9 times higher positive biopsy percentage compared with women in the general population.

Early detection of COVID-19 is key in containing the pandemic. Disease detection and evaluation based on imaging is fast and cheap and therefore plays an important role in COVID-19 handling. COVID-19 is easier to detect in chest CT, however, it is expensive, non-portable, and difficult to dis-infect, making it unfit as a point-of-care (POC) modality. On the other hand, chest X-ray (CXR) and lung ultrasound (LUS) are widely used, yet, COVID-19 findings in these modalities are not always very clear. Here we train deep neural networks to significantly enhance the capability to detect, grade and monitor COVID-19 patients using CXRs and LUS. Collaborating with several hospitals in Israel we collect a large dataset of CXRs and use this dataset to train a neural network obtaining above 90% detection rate for COVID-19. In addition, in collaboration with ULTRa (Ultrasound Laboratory Trento, Italy) and hospitals in Italy we obtained POC ultrasound data with annotations of the severity of disease and trained a deep network for automatic severity grading.

In the midst of the coronavirus disease 2019 (COVID-19) outbreak, chest X-ray (CXR) imaging is playing an important role in the diagnosis and monitoring of patients with COVID-19. Machine learning solutions have been shown to be useful for X-ray analysis and classification in a range of medical contexts. The purpose of this study is to create and evaluate a machine learning model for diagnosis of COVID-19, and to provide a tool for searching for similar patients according to their X-ray scans. In this retrospective study, a classifier was built using a pre-trained deep learning model (ReNet50) and enhanced by data augmentation and lung segmentation to detect COVID-19 in frontal CXR images collected between January 2018 and July 2020 in four hospitals in Israel. A nearest-neighbors algorithm was implemented based on the network results that identifies the images most similar to a given image. The model was evaluated using accuracy, sensitivity, area under the curve (AUC) of receiver operating characteristic (ROC) curve and of the precision-recall (P-R) curve. The dataset sourced for this study includes 2362 CXRs, balanced for positive and negative COVID-19, from 1384 patients (63 +/- 18 years, 552 men). Our model achieved 89.7% (314/350) accuracy and 87.1% (156/179) sensitivity in classification of COVID-19 on a test dataset comprising 15% (350 of 2326) of the original data, with AUC of ROC 0.95 and AUC of the P-R curve 0.94. For each image we retrieve images with the most similar DNN-based image embeddings; these can be used to compare with previous cases., Elisha Goldstein, Daphna Keidar, and Daniel Yaron have made an equal contribution and are equal first authors, listed alphabetically

Neoadjuvant therapy (NAT) is increasingly used in breast cancer (BC), yet, the recommended time interval between NAT completion, preoperative imaging assessment, and breast surgery is not clearly defined. This single-center retrospective study investigated tumor growth between NAT completion and surgery. The analysis included 106 BC patients who received NAT (69% chemotherapy alone, 31% chemotherapy plus anti-HER2 therapy), had post-NAT breast MRI, and definitive surgery between 2012 and 2019. The median time interval between end-of-treatment and surgery was 6 weeks; 90% had surgery within 8 weeks of NAT completion, and 10% had surgery 8-12 weeks after NAT completion. No significant correlation was found between any of the time intervals (i.e., NAT completion-to-surgery, NAT completion-to-MRI, post-NAT MRI to surgery) and the tumor size as captured in the pathology report. The only parameter that was significantly correlated with pathological tumor size was tumor size as measured on the post NAT MRI (P .0001). The difference in tumor size between post NAT MRI and surgical pathology did not correlate with the time interval between end-of-treatment and surgery. The ratio between residual tumor size on post-NAT MRI and the time interval from the end-of-treatment to surgery, significantly correlated with the tumor size on surgical pathology (P .0001) suggesting that NAT has a beneficial effect weeks after end-of-treatment. In conclusion, our results suggest that for patients undergoing neoadjuvant chemotherapy, surgery within 4-8 weeks of completing NAT is reasonable, and is unlikely to result in a clinically significant change in residual tumor size.

INTRODUCTION Breast and chest wall desmoid tumours can cause debilitating symptoms and deformity. The mutilating effects of surgical treatment have prompted a shift to medical treatments and even to a wait-and-see approach. This study sought to highlight specific characteristics of breast and chest wall desmoid tumours on long-term follow-up by sequential MRI scans. METHODS Thirty-two breast MRI scans from six patients with chest wall or breast desmoid tumours followed up for up to 6 years were retrospectively reviewed. RESULTS All patients underwent breast surgery prior to the development of the desmoid tumour. Five of the patients had reconstruction or augmentation using silicone implants. Two desmoids were treated primarily with surgery, three with medical means and one is under wait-and-see approach. On MRI, tumours appeared either oval and lobulated (chest wall) or spiculated with architectural distortion (breast). Chest wall desmoids demonstrated both an enhancing high-T2-signal component and a non-enhancing low-T2- signal component. The histologically defined phases during the course of desmoid tumours (progression, regression, residual disease) could be demonstrated by corresponding MRI changes in each of the components. CONCLUSIONS Magnetic resonance imaging delineates the complex infiltrative features of chest wall and breast desmoid tumours. In tumours with a bright cellular enhancing and dark collagenous non-enhancing component, treatment response may be predicted by changes on serial T2-weighted sequences, beyond the tumour-dimension-based RECIST assessment alone.

Objective The objective of this study is to introduce a single and reproducible tissue-rearrangement oncoplastic technique that is applicable for all quadrants partial-mastectomy defects in small- to medium-sized breasts, using grounds drawn from cosmetic surgery. Methods Eleven small- to medium-sized breast cancer patients with tumor involvement of more than a quarter of the breast were operated on using the chest wall-based flap technique. The procedure is described in detail, and the results are analyzed in terms of both cosmetic and oncological results. Results The flap successfully reached all breast quadrants as necessary, as well as the areola-nipple complex. The resection borders were found to be free of tumor in all cases, and there were no perioperative complications. Patients rated nearly all the cosmetic parameters as "somewhat satisfied" or "very satisfied," and there was no evidence of fat necrosis in the postoperative mammography examinations. Conclusions Applying principles taken from the cosmetic plastic surgery lies at the base of any high standard reconstructive surgery in general and oncoplastic breast surgery in particular. The chest wall-based flap is suitable for the reconstruction of a wide range of breast lumpectomy defects and is feasible for small- to medium-sized breasts, which are usually not easily amenable to tissue rearrangement techniques. The learning curve is short, with replicable results.

Background: The Heme Oxygenase system, along with its catabolism products, is involved in a variety of crucial physiological functions, including cytoprotection, inflammation, anti-oxidative effects, apoptosis, angiogenesis, and vascular regulation. Objectives: To analyze the Heme Oxygenase -1 (HO-1) mediated effect of mild deterioration of pulmonary function testing (PFT) in exposed artificial stone smoking workers. Methods: One hundred stone workers divided into current smokers, ex-smokers and never smokers underwent Low Resolution Computed Tomography, PFT, induced sputum (IS) Particle Size Distribution (PSD) and Real Time PCR in IS samples. Results: Smoking status had no significant effect on PFT results but it altered the IS differential cell counts. There was significantly less decline in PFT over time for the smokers group. There was a significantly lower fraction of small particles (