Multigene prognostic tests in breast cancer: past, present, future

There is growing consensus that multigene prognostic tests provide useful complementary information to tumor size and grade in estrogen receptor (ER)-positive breast cancers. The tests primarily rely on quantification of ER and proliferation-related genes and combine these into multivariate prediction models. Since ER-negative cancers tend to have higher proliferation rates, the prognostic value of current multigene tests in these cancers is limited. First-generation prognostic signatures (Oncotype DX, MammaPrint, Genomic Grade Index) are substantially more accurate to predict recurrence within the first 5 years than in later years. This has become a limitation with the availability of effective extended adjuvant endocrine therapies. Newer tests (Prosigna, EndoPredict, Breast Cancer Index) appear to possess better prognostic value for late recurrences while also remaining predictive of early relapse. Some clinical prediction problems are more difficult to solve than others: there are no clinically useful prognostic signatures for ER-negative cancers, and drug-specific treatment response predictors also remain elusive. Emerging areas of research involve the development of immune gene signatures that carry modest but significant prognostic value independent of proliferation and ER status and represent candidate predictive markers for immune-targeted therapies. Overall metrics of tumor heterogeneity and genome integrity (for example, homologue recombination deficiency score) are emerging as potential new predictive markers for platinum agents. The recent expansion of high-throughput technology platforms including low-cost sequencing of circulating and tumor-derived DNA and RNA and rapid reliable quantification of microRNA offers new opportunities to build extended prediction models across multiplatform data

Epigenetics in breast cancer: What's new?

Epigenetic changes are critical for development and progression of cancers, including breast cancer. Significant progress has been made in the basic understanding of how various epigenetic changes such as DNA methylation, histone modification, miRNA expression, and higher order chromatin structure affect gene expression. The present review will focus on methylation and demethylation of histones. While the acetylation of histones has been at the forefront of well-characterized post-translational modifications of histones, including the development of inhibitors targeting de-acetylating enzymes, the past few years have witnessed a dramatic increase in knowledge regarding the role of histone methylation/demethylation. This is an exciting and rapidly evolving area of research, with much promise for potential clinical intervention in several cancers including breast cancer. We also summarize efforts to identity DNA methylation signatures that could be prognostic and/or predictive markers in breast cancer, focusing on recent studies using genome-wide approaches. Finally, we briefly review the efforts made by both the National Institutes of Health Epigenome Project and The Cancer Genome Atlas, especially highlighting the study of breast cancer epigenetics, exciting technological advances, potential roadblocks, and future directions. © 2010 BioMed Central Ltd

Neurosurgeons Deliver Similar Quality Care Regardless of First Assistant Type: Resident Physician versus Nonphysician Surgical Assistant

OBJECTIVE: There are limited data evaluating the out-comes of attending neurosurgeons with different types of first assistants. This study considers a common neurosurgical procedure (single-level, posterior-only lumbar fusion surgery) and examines whether attending surgeons deliver equal patient outcomes, regardless of the type of first assistant (resident physician vs. nonphysician surgical assistant [NPSA]), among otherwise exact-matched patients. -METHODS: The authors retrospectively analyzed 3395 adult patients undergoing single-level, posterior-only lumbar fusion at a single academic medical center. Primary outcomes included readmissions, emergency department visits, reoperation, and mortality within 30 and 90 days after surgery. Secondary outcome measures included discharge disposition, length of stay, and length of surgery. Coarsened exact matching was used to match patients on key demographics and baseline characteristics known to independently affect neurosurgical outcomes. -RESULTS: Among exact-matched patients (n [ 1402), there was no significant difference in adverse postsurgical events (readmission, emergency department visits, reoperation, or mortality) within 30 days or 90 days of the index operation between patients who had resident physicians and those who had NPSAs as first assistants. Patients who had resident physicians as first assistants demonstrated a longer length of stay (mean: 100.0 vs. 87.4 hours, P \u3c 0.001) and a shorter duration of surgery (mean: 187.4 vs. 213.8 minutes, P \u3c 0.001). There was no significant difference between the two groups in the percentage of patients discharged home. -CONCLUSIONS: For single-level posterior spinal fusion, in the setting described, there are no differences in short-term patient outcomes delivered by attending surgeons assisted by resident physicians versus NPSAs

Multicenter Us Clinical Experience With the Scepter Mini Balloon Catheter

INTRODUCTION: Distal navigability and imprecise delivery of embolic agents are two limitations encountered during liquid embolization of cerebrospinal lesions. The dual-lumen Scepter Mini balloon (SMB) microcatheter was introduced to overcome these conventional microcatheters\u27 limitations with few small single-center reports suggesting favorable results. METHODS: A series of consecutive patients undergoing SMB-assisted endovascular embolization were extracted from prospectively maintained registries in seven North-American centers (November 2019 to September 2022). RESULTS: Fifty-four patients undergoing 55 embolization procedures utilizing SMB were included (median age 58.5; 48.1% females). Cranial dural arteriovenous fistula embolization was the most common indication (54.5%) followed by cranial arteriovenous malformation (27.3%). Staged/pre-operative embolization was done in 36.4% of cases; and 83.6% of procedures using Onyx-18. Most procedures utilized a transarterial approach (89.1%), and SMB-induced arterial-flow arrest concurrently with transvenous embolization was used in 10.9% of procedures. Femoral access/triaxial setups were utilized in the majority of procedures (65.5% and 60%, respectively). The median vessel diameter where the balloon was inflated of 1.8 mm, with a median of 1.5 cc of injected embolic material per procedure. Technical failures occurred in 5.5% of cases requiring aborting/replacement with other devices without clinical sequelae in any of the patients, with SMB-related procedural complications of 3.6% without clinical sequelae. Radiographic imaging follow-up was available in 76.9% of the patients (median follow-up 3.8 months), with complete occlusion (100%) or \u3e50% occlusion in 92.5% of the cases, and unplanned retreatments in 1.8%. CONCLUSION: The SMB microcatheter is a useful new adjunctive device for balloon-assisted embolization of cerebrospinal lesions with a high technical success rate, favorable outcomes, and a reasonable safety profile

International survey on invasive lobular breast cancer identifies priority research questions

There is growing awareness of the unique etiology, biology, and clinical presentation of invasive lobular breast cancer (ILC), but additional research is needed to ensure translation of findings into management and treatment guidelines. We conducted a survey with input from breast cancer physicians, laboratory-based researchers, and patients to analyze the current understanding of ILC, and identify consensus research questions. 1774 participants from 66 countries respondents self-identified as clinicians (N = 413), researchers (N = 376), and breast cancer patients and advocates (N = 1120), with some belonging to more than one category. The majority of physicians reported being very/extremely (41%) to moderately (42%) confident in describing the differences between ILC and invasive breast cancer of no special type (NST). Knowledge of histology was seen as important (73%) and as affecting treatment decisions (51%), and most agreed that refining treatment guidelines would be valuable (76%). 85% of clinicians have never powered a clinical trial to allow subset analysis for histological subtypes, but the majority would consider it, and would participate in an ILC clinical trials consortium. The majority of laboratory researchers, reported being and very/extremely (48%) to moderately (29%) confident in describing differences between ILC and NST. They reported that ILCs are inadequately presented in large genomic data sets, and that ILC models are insufficient. The majority have adequate access to tissue or blood from patients with ILC. The majority of patients and advocates (52%) thought that their health care providers did not sufficiently explain the unique features of ILC. They identified improvement of ILC screening/early detection, and identification of better imaging tools as top research priorities. In contrast, both researchers and clinicians identified understanding of endocrine resistance and identifying novel drugs that can be tested in clinical trials as top research priority. In summary, we have gathered information from an international community of physicians, researchers, and patients/advocates that we expect will lay the foundation for a community-informed collaborative research agenda, with the goal of improving management and personalizing treatment for patients with ILC

Radiographic and Clinical Outcomes With Particle or Liquid Embolic Agents for Middle Meningeal Artery Embolization of Nonacute Subdural Hematomas

BACKGROUND: Middle meningeal artery (MMA) embolization is an apparently efficacious minimally invasive treatment for nonacute subdural hematomas (NASHs), but how different embolisates affect outcomes remains unclear. Our objective was to compare radiographic and clinical outcomes after particle or liquid MMA embolization. METHODS: Patients who had MMA embolization for NASH were retrospectively identified from a multi-institution database. The primary radiographic and clinical outcomes-50% NASH thickness reduction and need for surgical retreatment within 90 days, respectively-were compared for liquid and particle embolizations in patients treated 1) without surgical intervention (upfront), 2) after recurrence, or 3) with concomitant surgery (prophylactic). RESULTS: The upfront, recurrent, and prophylactic subgroups included 133, 59, and 16 patients, respectively. The primary radiographic outcome was observed in 61.8%, 61%, and 72.7% of particle-embolized patients and 61.3%, 55.6%, and 20% of liquid-embolized patients, respectively (p = 0.457, 0.819, 0.755). Hazard ratios comparing time to reach radiographic outcome in the particle and liquid groups or upfront, recurrent, andprophylactic timing were 1.31 (95% CI 0.78-2.18; p = 0.310), 1.09 (95% CI 0.52-2.27; p = 0.822), and 1.5 (95% CI 0.14-16.54; p = 0.74), respectively. The primary clinical outcome occurred in 8.0%, 2.4%, and 0% of patients who underwent particle embolization in the upfront, recurrent, and prophylactic groups, respectively, compared with 0%, 5.6%, and 0% who underwent liquid embolization (p = 0.197, 0.521, 1.00). CONCLUSIONS: MMA embolization with particle and liquid embolisates appears to be equally effective in treatment of NASHs as determined by the percentage who reach, and the time to reach, 50% NASH thickness reduction and the incidence of surgical reintervention within 90 days

Prognostic utility of the breast cancer index and comparison to Adjuvant! Online in a clinical case series of early breast cancer

Introduction\ud Breast Cancer Index (BCI) combines two independent biomarkers, HOXB13:IL17BR (H:I) and the 5-gene molecular grade index (MGI), that assess estrogen-mediated signalling and tumor grade, respectively. BCI stratifies early-stage estrogen-receptor positive (ER+), lymph-node negative (LN-) breast cancer patients into three risk groups and provides a continuous assessment of individual risk of distant recurrence. Objectives of the current study were to validate BCI in a clinical case series and to compare the prognostic utility of BCI and Adjuvant!Online (AO).\ud \ud Methods\ud Tumor samples from 265 ER+LN- tamoxifen-treated patients were identified from a single academic institution's cancer research registry. The BCI assay was performed and scores were assigned based on a pre-determined risk model. Risk was assessed by BCI and AO and correlated to clinical outcomes in the patient cohort.\ud \ud Results\ud BCI was a significant predictor of outcome in a cohort of 265 ER+LN- patients (median age: 56-y; median follow-up: 10.3-y), treated with adjuvant tamoxifen alone or tamoxifen with chemotherapy (32%). BCI categorized 55%, 21%, and 24% of patients as low, intermediate and high-risk, respectively. The 10-year rates of distant recurrence were 6.6%, 12.1% and 31.9% and of breast cancer-specific mortality were 3.8%, 3.6% and 22.1% in low, intermediate, and high-risk groups, respectively. In a multivariate analysis including clinicopathological factors, BCI was a significant predictor of distant recurrence (HR for 5-unit increase = 5.32 [CI 2.18-13.01; P = 0.0002]) and breast cancer-specific mortality (HR for a 5-unit increase = 9.60 [CI 3.20-28.80; P < 0.0001]). AO was significantly associated with risk of recurrence. In a separate multivariate analysis, both BCI and AO were significantly predictive of outcome. In a time-dependent (10-y) ROC curve accuracy analysis of recurrence risk, the addition of BCI+AO increased predictive accuracy in all patients from 66% (AO only) to 76% (AO+BCI) and in tamoxifen-only treated patients from 65% to 81%.\ud \ud Conclusions\ud This study validates the prognostic performance of BCI in ER+LN- patients. In this characteristically low-risk cohort, BCI classified high versus low-risk groups with ~5-fold difference in 10-year risk of distant recurrence and breast cancer-specific death. BCI and AO are independent predictors with BCI having additive utility beyond standard of care parameters that are encompassed in AO

Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: Predictors of Clinical and Radiographic Failure from 636 Embolizations

Background Knowledge regarding predictors of clinical and radiographic failures of middle meningeal artery (MMA) embolization (MMAE) treatment for chronic subdural hematoma (CSDH) is limited. Purpose To identify predictors of MMAE treatment failure for CSDH. Materials and Methods In this retrospective study, consecutive patients who underwent MMAE for CSDH from February 2018 to April 2022 at 13 U.S. centers were included. Clinical failure was defined as hematoma reaccumulation and/or neurologic deterioration requiring rescue surgery. Radiographic failure was defined as a maximal hematoma thickness reduction less than 50% at last imaging (minimum 2 weeks of head CT follow-up). Multivariable logistic regression models were constructed to identify independent failure predictors, controlling for age, sex, concurrent surgical evacuation, midline shift, hematoma thickness, and pretreatment baseline antiplatelet and anticoagulation therapy. Results Overall, 530 patients (mean age, 71.9 years ± 12.8 [SD]; 386 men; 106 with bilateral lesions) underwent 636 MMAE procedures. At presentation, the median CSDH thickness was 15 mm and 31.3% (166 of 530) and 21.7% (115 of 530) of patients were receiving antiplatelet and anticoagulation medications, respectively. Clinical failure occurred in 36 of 530 patients (6.8%, over a median follow-up of 4.1 months) and radiographic failure occurred in 26.3% (137 of 522) of procedures. At multivariable analysis, independent predictors of clinical failure were pretreatment anticoagulation therapy (odds ratio [OR], 3.23; P = .007) and an MMA diameter less than 1.5 mm (OR, 2.52; P = .027), while liquid embolic agents were associated with nonfailure (OR, 0.32; P = .011). For radiographic failure, female sex (OR, 0.36; P = .001), concurrent surgical evacuation (OR, 0.43; P = .009), and a longer imaging follow-up time were associated with nonfailure. Conversely, MMA diameter less than 1.5 mm (OR, 1.7; P = .044), midline shift (OR, 1.1; P = .02), and superselective MMA catheterization (without targeting the main MMA trunk) (OR, 2; P = .029) were associated with radiographic failure. Sensitivity analyses retained these associations. Conclusion Multiple independent predictors of failure of MMAE treatment for chronic subdural hematomas were identified, with small diameter (\u3c1.5 mm) being the only factor independently associated with both clinical and radiographic failures