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Breast adenomyoepithelioma (AME) is rare. We sought to evaluate clinical characteristics, treatment, and outcomes of a contemporary patient cohort stratified by histology. We queried health records containing “adenomyoepithelioma” between 2000 and 2018. Histology was confirmed with centralized review and classified into benign, atypical, and malignant. Clinical characteristics, demographics, treatment, and oncologic outcomes were compared. Our query yielded 24 patients with adenomyoethelioma. Histologic diagnosis was confirmed in 12 (benign n = 6, atypical n = 3, malignant n = 3). Excision (n = 11) was the usual initial treatment, with margin status available in 10 patients. Mean follow up was 44 months (range 1–138 months) with no local recurrence observed. Two patients with benign AME presented with concurrent contralateral breast cancer, and one with malignant AME died of metastatic AME. Wide excision of atypical and malignant AME is recommended as local recurrence when excised completely was not observed. Given metastatic potential of malignant AME, multimodal therapy may be warranted. •Unique organization of benign, atypical, malignant AME epidemiology/outcomes.•No local recurrences observed with negative margins in atypical, malignant AME.•Malignant AME carries metastatic potential and may require multimodal therapy.•AME rarity: within 18 years only 12 cases were found after centralized review.•Compares published AME manuscripts in a concise, easy to read table with discussion.

BackgroundResults of an earlier retrospective study from our institution suggested that patients with triple negative breast cancer (TNBC) who had preoperative MRI may have had an improved local recurrence rate (LRR) after breast conserving surgery (BCS). We aimed to clarify the impact of preoperative MRI on surgical outcomes in an expanded TNBC cohort treated by BCS in a contemporary era.MethodsOur study cohort comprised 648 patients with TNBC who underwent BCS between 2009 and 2018. Demographic and clinical characteristics were compared between those with (n = 292, 45.1%) and without (n = 356, 54.9%) preoperative MRI. Multivariable logistic regression was performed to assess the association of preoperative MRI with surgical outcomes.ResultsThe crude LRR of 3.5% was lower than previously reported. Univariable analyses demonstrated that the LRR and re-excision rates in the MRI and no-MRI groups were 3.4 and 3.7%, 21.6% and 27.2%, p = 0.876 and p = 0.10, respectively. Multivariable logistic regression analyses demonstrated that preoperative MRI was not associated with a lower LRR: odds ratio (OR) = 1.42 (p = 0.5). During our study period, new margin guidelines and shave margins practice were adopted in 2014 and 2015. To account for their effects, the year of diagnosis/surgery and other clinical variables were adjusted in multivariable logistic regression and inverse probability weighting models to demonstrate that preoperative MRI remained associated with a lower re-excision risk, OR 0.56, p = 0.04l; and a lower re-excision rate, 23.15% versus 36.0%, p < 0.01, respectively.ConclusionsOur findings suggested that patients with TNBC anticipating BCS may benefit from preoperative MRI.

Purpose This proof-of-concept study investigates gene expression in core needle biopsies (CNB) to predict whether individuals diagnosed with ductal carcinoma in situ (DCIS) on CNB were affected by invasion at the time of diagnosis. Methods Using a QuantiGene Plex 2.0 assay, 14 gene expression profiling was performed in 303 breast tissue samples. Preoperative diagnostic performance of a gene was measured by area under receiver-operating characteristic curve (AUC) with 95% confidence interval (CI). The gene mRNA positivity cutoff was computed using Gaussian mixture model (GMM); protein expression was measured by immunohistochemistry; DNA methylation was evaluated by targeted bisulfite sequencing. Results mRNA from 69% (34/49) mammoplasties, 72% (75/104) CNB DCIS, and 89% (133/150) invasive breast cancers (IBC) were analyzed. Based on pre-and post-surgery DCIS chart reviews, 21 cases were categorized as DCIS synchronous with invasion and 54 DCIS were pure DCIS without pathologic evidence of invasive disease. The ectopic expression of neuronal cadherin CDH2 was probable in 0% mammoplasties, 6% pure DCIS, 29% synchronous DCIS, and 26% IBC. The CDH2 mRNA positivity in preoperative biopsies showing pure DCIS was predictive of a final diagnosis of invasion (AUC = 0.67; 95% CI 0.53–0.80; P  = 0.029). Site-specific methylation of the CDH2 promoter (AUC = 0.76; 95% CI 0.54–0.97; P  = 0.04) and measurements of N-cadherin, a pro-invasive cell–cell adhesion receptor encoded by CDH2 (AUC = 0.8; 95% CI 0.66–0.99; P  < 0.005) had a discriminating power allowing for discernment of CDH2 -positive biopsy. Conclusions Evidence of CDH2 /N-cadherin expression, predictive of invasion synchronous with DCIS, may help to clarify a diagnosis and direct the course of therapy earlier in a patient’s care.

Background Adenoid cystic breast carcinoma (ACC) is a rare subtype of triple-negative breast cancer. We aim to characterize the treatment patterns and clinical outcomes of women diagnosed with ACC at a large medical center. Methods Female patients diagnosed with ACC at our institution between 2009 and 2019 were retrospectively identified. Patients with limited clinicopathologic data were excluded. Results In our final study cohort (n = 9), the majority of ACCs (6/9, 66.7%) were hormone receptor (−) (HR−) and HER-2/neu (−) (HER2−), while 3 ACCs were HR+ HER2−. Two patients received adjuvant chemotherapy, and 4 patients received adjuvant radiotherapy. The crude local and distant recurrence rate of our cohort was 22.2% and 11.1% (median follow-up of 36 months). Conclusions The majority of ACCs were triple negative but some ACCs were HR+. The unadjusted local and distant recurrence rates were not negligible, suggesting that adjuvant chemotherapy and radiotherapy may be warranted in select cases.

IntroductionNational guidelines specify against immediate breast reconstruction (IBR) among inflammatory breast cancer (IBC) patients. However, limited data exist regarding this practice. We report practice patterns and oncologic outcomes among nonmetastatic IBC patients receiving trimodality therapy, with or without IBR.MethodsUsing the National Cancer Database, we identified nonmetastatic IBC patients treated with trimodality therapy from 2004 to 2016. Primary outcome was overall survival (OS), assessed on unadjusted analysis using Kaplan–Meier estimates and on adjusted analysis using multivariable Cox proportional hazards and inverse probability weighting (IPW) models. OS analysis was also conducted with propensity score matched (PSM) cohorts. Secondary outcomes included IBR utilization rates, time to postmastectomy radiotherapy (PMRT), and surgical outcomes.Results6589 women were included, including 5954 (90.4%) non-reconstructed and 635 (9.6%) IBR. Among IBR recipients, 250 (39.4%) underwent autologous reconstruction, 171 (26.9%) underwent implant-based reconstruction, and 214 (33.7%) unspecified. IBR utilization increased from 6.3% to 10.1% from 2004 to 2016 at a 4% average annual growth rate (P < 0.001). Median follow-up was 43 and 45 months for IBR and non-reconstructed patients, respectively (P = 0.29). On Cox multivariable analysis, IBR was associated with improved OS (HR 0.63, 95% CI 0.44–0.90, P = 0.01), but this association was not significant on IPW analysis (P = 0.06). In PSM cohorts, this association remained significant (HR 0.60, 95% CI 0.40–0.92, P = 0.02). Margin status, time to PMRT, 30-day readmission, and 30-/90-day mortality did not differ between groups (all P > 0.05).ConclusionAlthough not endorsed by national guidelines, IBR is increasing among IBC patients; however, more granular data are needed to determine oncologic safety.

Purpose Young adults with isocitrate-dehydrogenase wild-type ( IDH- WT) glioblastoma (GBM) represent a rare, understudied population compared to pediatric high-grade glioma, IDH -mutant GBM, or IDH -WT GBM in older patients. We aimed to explore the prognostic impact of epidermal growth factor receptor copy number gain ( EGFR CN gain), one of the most common genetic alterations in IDH -WT glioma, in young adults with IDH -WT GBM. Methods We performed a retrospective cohort study of patients 18–45 years old with newly diagnosed, IDH -WT GBM whose tumors underwent next-generation sequencing at our institution between 2014 and 2018. The impact of EGFR CN gain on time to tumor progression (TTP) and overall survival (OS) was assessed. A validation cohort of patients 18–45 years old with IDH -WT GBM was analyzed from The Cancer Genome Atlas (TCGA). Results Ten of 28 patients (36%) from our institution had EGFR CN gain, which was associated with shorter TTP (median 6.5 vs. 11.9 months; p = 0.06) and OS (median 16.3 vs. 23.5 months; p = 0.047). The negative prognostic impact of EGFR CN gain on OS persisted in a multivariate model (HR 6.40, 95% CI 1.3–31.0, p = 0.02). In the TCGA cohort (N = 43), EGFR CN gain was associated with shorter TTP and worse OS, although these did not reach statistical significance (TTP, median 11.5 vs. 14.4 months, p = 0.18; OS, median 23.6 vs. 27.8 months; p = 0.18). Conclusions EGFR CN gain may be associated with inferior outcomes in young adults with newly diagnosed, IDH -WT GBM, suggesting a potential role for targeting EGFR in this population.

Cells need to compartmentalize thousands of distinct proteins, but the nanoscale spatial relationship of many proteins to overall intracellular ultrastructure remains poorly understood. Correlated light and electron microscopy approaches can help. Hoffman et al. combined cryogenic super-resolution fluorescence microscopy and focused ion beam–milling scanning electron microscopy to visualize protein-ultrastructure relationships in three dimensions across whole cells. The fusion of the two imaging modalities enabled identification and three-dimensional segmentation of morphologically complex structures within the crowded intracellular environment. The researchers observed unexpected relationships within a variety of cell types, including a web-like protein adhesion network between juxtaposed cerebellar granule neurons. Science , this issue p. eaaz5357 Cryogenic super-resolution fluorescence and electron microscopy reveals protein-ultrastructure relationships in whole cells. Within cells, the spatial compartmentalization of thousands of distinct proteins serves a multitude of diverse biochemical needs. Correlative super-resolution (SR) fluorescence and electron microscopy (EM) can elucidate protein spatial relationships to global ultrastructure, but has suffered from tradeoffs of structure preservation, fluorescence retention, resolution, and field of view. We developed a platform for three-dimensional cryogenic SR and focused ion beam–milled block-face EM across entire vitreously frozen cells. The approach preserves ultrastructure while enabling independent SR and EM workflow optimization. We discovered unexpected protein-ultrastructure relationships in mammalian cells including intranuclear vesicles containing endoplasmic reticulum–associated proteins, web-like adhesions between cultured neurons, and chromatin domains subclassified on the basis of transcriptional activity. Our findings illustrate the value of a comprehensive multimodal view of ultrastructural variability across whole cells.