Online and Offline Prioritization of Chemicals of Interest in Suspect Screening and Non-targeted Screening with High-Resolution Mass Spectrometry.

Recent advances in high-resolution mass spectrometry (HRMS) have enabled the detection of thousands of chemicals from a single sample, while computational methods have improved the identification and quantification of these chemicals in the absence of reference standards typically required in targeted analysis. However, to determine the presence of chemicals of interest that may pose an overall impact on ecological and human health, prioritization strategies must be used to effectively and efficiently highlight chemicals for further investigation. Prioritization can be based on a chemical's physicochemical properties, structure, exposure, and toxicity, in addition to its regulatory status. This Perspective aims to provide a framework for the strategies used for chemical prioritization that can be implemented to facilitate high-quality research and communication of results. These strategies are categorized as either "online" or "offline" prioritization techniques. Online prioritization techniques trigger the isolation and fragmentation of ions from the low-energy mass spectra in real time, with user-defined parameters. Offline prioritization techniques, in contrast, highlight chemicals of interest after the data has been acquired; detected features can be filtered and ranked based on the relative abundance or the predicted structure, toxicity, and concentration imputed from the tandem mass spectrum (MS2). Here we provide an overview of these prioritization techniques and how they have been successfully implemented and reported in the literature to find chemicals of elevated risk to human and ecological environments. A complete list of software and tools is available from https://nontargetedanalysis.org/.

Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget's disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.

Exploration of Patient Retention in Seeking a Second Opinion: A Retrospective Cohort Study.

INTRODUCTION: It is common for cancer patients to seek a second opinion for a variety of reasons. Understanding what drives patients to choose to receive treatment with their second opinion provider may uncover opportunities to improve the second opinion process. Therefore, we sought to identify the patient, disease, and treatment characteristics that were associated with second opinion retention rates in patients seeking a second surgical opinion for breast, colon, and pancreatic cancer. METHODS: We conducted a retrospective cohort study to evaluate patients who sought a second opinion within a large academic health-care system for breast, colon, and pancreatic cancer. Electronic medical records were reviewed for second opinions. Patient demographics and characteristics were collected and compared between the retained group and the nonretained groups. RESULTS: A total of 237 patients obtained second opinions for breast, colorectal, and pancreatic cancer. Patients that were offered a different treatment plan at their second opinion were more likely to be retained for systemic therapy (P = 0.009) for pancreatic cancer and any treatment for colon cancer (P = 0.003). Seeing a radiation oncologist (P = 0.007) or a plastic surgeon (P = 0.02) during the multidisciplinary consultation increased retention rates for breast cancer. CONCLUSIONS: Surgeons can better identify patients that are more likely to be retained after a second opinion by the individual patient characteristics and treatment factors. Understanding the factors that lead to retention for these three cancer types may help physicians provide the best possible resources for most patients presenting for second opinion evaluations.

Analyte and matrix method extension of per- and polyfluoroalkyl substances in food and feed.

The development and expansion of analytical methods for per- and polyfluoroalkyl substances (PFAS) in food are essential for the continued monitoring of the United States (US) food supply and assessments of dietary exposure. In March 2022, the European Union Reference Laboratory for Halogenated Persistent Organic Pollutants in Feed and Food (EURL POPs) released a guidance document covering priority PFAS of interest, including analytical method parameters and limits of quantification (LOQs). As a result, the Food and Drug Administration (FDA) began method extension work to incorporate ten new additional analytes to method C-010.02 including long-chain perfluorosulfonic acids, fluorotelomer sulfonates, and perfluorooctane sulfonamide. Four long-chain carboxylic acids were also validated across all foods, which were previously added to C-010.02 but only validated in seafood. In December 2022, the European Union published Commission Regulation 2022/2388, establishing maximum levels for perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) in certain foodstuffs, primarily fish, molluscs, crustaceans, and eggs. As a result, the FDA method was evaluated for performance in reaching LOQs defined in Commission Regulation (EU) 2022/1431. The FDA method was found to be able to reach all required LOQs for analytes in matrices with established maximum levels. Currently, method detection limits (MDLs), which are used by the FDA as the lower limit for reporting PFAS in surveillance samples, were in the same range as defined indicative levels. With further method modifications, required LOQs could be met in fruits, vegetables, and milk. Reaching the lower targeted LOQs for these food matrices will require moving the method to an instrument that can provide increased signal:noise gains at the lower limits of quantification.

PFAS ghosts: how to identify, evaluate, and exorcise new and existing analytical interference.

With increasing public awareness of PFAS, and their presence in biological and environmental media across the globe, comes a matching increase in the number of PFAS monitoring studies. As more matrices and sample cohorts are examined, there are more opportunities for matrix interferents to appear as PFAS where there are none (i.e., "seeing ghosts"), impacting subsequent reports. Addressing these ghosts is vital for the research community, as proper analytical measurements are necessary for decision-makers to understand the presence, levels, and potential risks associated with PFAS and protect human and environmental health. To date, PFAS interference has been identified in several matrices (e.g., food, shellfish, blood, tissue); however, additional unidentified interferents are likely to be observed as PFAS research continues to expand. Therefore, the aim of this commentary is several fold: (1) to create and support a publicly available dataset of all currently known PFAS analytical interferents, (2) to allow for the expansion of that dataset as more sources of interference are identified, and (3) to advise the wider scientific community on how to both identify and eliminate current or new analytical interference in PFAS analyses.

NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024.

The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly. These NCCN Guidelines Insights provide a summary of recent updates regarding the systemic therapy recommendations for recurrent or metastatic disease.

Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology.

Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.

Breast cancer brain metastases localization and risk of hydrocephalus: a single institution experience.

PURPOSE: Brain metastases occur in up to one-third of patients with breast cancer. aromatase, a marker for estrogen activity that has been shown to promote such metastasis, heavily concentrates in certain midline structures of brain. We hypothesize that breast cancer metastasizes more often to brain areas with higher aromatase activity and that these patients have a higher risk of developing obstructive hydrocephalus. METHODS: In our retrospective review of 709 patients who underwent stereotactic radiosurgery (January 2014-May 2020), we identified 358 patients treated for metastatic breast or lung cancer. The MRI scan that first showed evidence of brain metastases was reviewed and number of metastases counted by location. Procedures used to treat obstructive hydrocephalus were recorded. Chi square test was used for statistical analysis. RESULTS: Of 358 patients, 99 patients with breast cancer had 618 brain metastases and 259 patients with lung cancer had 1487 brain metastases. Compared with expected distribution of brain metastases based on regional brain volumes and metastatic lung carcinoma as a control, patients with breast cancer more often had metastases to the cerebellum, diencephalon, medulla, and parietal lobe, and underwent significantly more neurosurgical interventions for treatment of obstructive hydrocephalus. CONCLUSION: Brain metastases in patients with breast cancer occurred more often along midline structures of the brain, which we believe may be associated with the increased estrogen activity in these structures. This finding is important for physicians who treat patients with metastatic breast cancer given the higher possibility of developing obstructive hydrocephalus.

Prospective Clinical Prognostication of Endometrial Carcinomas Based on Next-Generation Sequencing and Immunohistochemistry-Real-World Implementation and Results at a Tertiary Care Center.

Based on findings from The Cancer Genome Atlas and the Proactive Molecular Risk Classifier for Endometrial Cancer algorithm, endometrial carcinoma can now be stratified into 4 prognostically distinct subgroups based on molecular alterations and immunohistochemical (IHC) aberrations. In this study, we describe the de novo adoption and clinical reporting of prognostic subgroup classification based on next-generation sequencing (NGS) and IHC analyses of all endometrial carcinoma resections at a single institution, framed by the Exploration, Preparation, Implementation, and Sustainment model. Results from the first 13 months show 188 tumors underwent analysis by a combination of IHC and a medium-sized (56 analyzed genes) NGS-based assay. All cases were assigned as either POLE (POLE-mutated) (5.3%), mismatch repair deficient (27.7%), no specific molecular profile (45.7%), or p53 abnormal (21.3%) inclusive of multiple-classifier cases. NGS-based analysis revealed additional distinctions among the subgroups, including reduced levels of PI3K pathway activation in the p53 abnormal subgroup, an increased rate of CTNNB1 activating mutation in the no specific molecular profile subgroup, and lower TP53 mutation variant allele frequencies in POLE and mismatch repair deficient subgroups compared with the p53 abnormal subgroup. Overall, we describe the testing protocol, reporting, and results of a combination of NGS and IHC to prospectively prognosticate endometrial carcinomas at a single tertiary care center.

Exploring chemical space in non-targeted analysis: a proposed ChemSpace tool.

Non-targeted analysis (NTA) using high-resolution mass spectrometry allows scientists to detect and identify a broad range of compounds in diverse matrices for monitoring exposure and toxicological evaluation without a priori chemical knowledge. NTA methods present an opportunity to describe the constituents of a sample across a multidimensional swath of chemical properties, referred to as "chemical space." Understanding and communicating which region of chemical space is extractable and detectable by an NTA workflow, however, remains challenging and non-standardized. For example, many sample processing and data analysis steps influence the types of chemicals that can be detected and identified. Accordingly, it is challenging to assess whether analyte non-detection in an NTA study indicates true absence in a sample (above a detection limit) or is a false negative driven by workflow limitations. Here, we describe the need for accessible approaches that enable chemical space mapping in NTA studies, propose a tool to address this need, and highlight the different ways in which it could be implemented in NTA workflows. We identify a suite of existing predictive and analytical tools that can be used in combination to generate scores that describe the likelihood a compound will be detected and identified by a given NTA workflow based on the predicted chemical space of that workflow. Higher scores correspond to a higher likelihood of compound detection and identification in a given workflow (based on sample extraction, data acquisition, and data analysis parameters). Lower scores indicate a lower probability of detection, even if the compound is truly present in the samples of interest. Understanding the constraints of NTA workflows can be useful for stakeholders when results from NTA studies are used in real-world applications and for NTA researchers working to improve their workflow performance. The hypothetical ChemSpaceTool suggested herein could be used in both a prospective and retrospective sense. Prospectively, the tool can be used to further curate screening libraries and set identification thresholds. Retrospectively, false detections can be filtered by the plausibility of the compound identification by the selected NTA method, increasing the confidence of unknown identifications. Lastly, this work highlights the chemometric needs to make such a tool robust and usable across a wide range of NTA disciplines and invites others who are working on various models to participate in the development of the ChemSpaceTool. Ultimately, the development of a chemical space mapping tool strives to enable further standardization of NTA by improving method transparency and communication around false detection rates, thus allowing for more direct method comparisons between studies and improved reproducibility. This, in turn, is expected to promote further widespread applications of NTA beyond research-oriented settings.

Evaluating anthracycline + taxane versus taxane-based chemotherapy in older women with node-negative triple-negative breast cancer: a SEER-Medicare study.

PURPOSE: Adjuvant chemotherapy reduces recurrence in early-stage triple-negative breast cancer (TNBC). However, data are lacking evaluating anthracycline + taxane (ATAX) versus taxane-based (TAX) chemotherapy in older women with node-negative TNBC, as they are often excluded from trials. The purpose of this study was to evaluate the effect of adjuvant ATAX versus TAX on cancer-specific (CSS) and overall survival (OS) in older patients with node-negative TNBC. PATIENTS AND METHODS: Using the SEER-Medicare database, we selected patients aged ≥ 66 years diagnosed with Stage T1-4N0M0 TNBC between 2010 and 2015 (N = 3348). Kaplan-Meier survival curves and adjusted Cox proportional hazards models were used to estimate 3-year OS and CSS. Multivariant Cox regression analysis was used to identify independent factors associated with use of ATAX compared to TAX. RESULTS: Approximately half (N = 1679) of patients identified received chemotherapy and of these, 58.6% (N = 984) received TAX, 25.0% (N = 420) received ATAX, and 16.4% (N = 275) received another regimen. Three-year CSS and OS was improved with any adjuvant chemotherapy from 88.9 to 92.2% (p = 0.0018) for CSS and 77.2% to 88.6% for OS (p < 0.0001). In contrast, treatment with ATAX compared to TAX was associated with inferior 3-year CSS and OS. Three-year CSS was 93.7% with TAX compared to 89.8% (p = 0.048) for ATAX and OS was 91.0% for TAX and 86.4% for ATAX (p = 0.032). CONCLUSION: While adjuvant chemotherapy was associated with improved clinical outcomes, the administration of ATAX compared to TAX was associated with inferior 3-year OS and CSS in older women with node-negative TNBC. The use of adjuvant ATAX should be considered carefully in this patient population.

Characterizing impact of positive lymph node number in endometrial cancer using machine-learning: A better prognostic indicator than FIGO staging?

BACKGROUND: Number of involved lymph nodes (LNs) is a crucial stratification factor in staging of numerous disease sites, but has not been incorporated for endometrial cancer. We evaluated whether number of involved LNs provide improved prognostic value. PATIENTS AND METHODS: Patients diagnosed with node-positive endometrial adenocarcinoma without distant metastasis were identified in the National Cancer Database. We trained a machine-learning based model of overall survival. Shapley additive explanation values (SHAP) based on the model were used to identify cutoffs of number of LNs involved. Results were validated using a Cox proportional hazards regression model. RESULTS: We identified 11,381 patients with endometrial cancer meeting the inclusion criteria. Using the SHAP values, we selected the following thresholds: 1-3 LNs, 4-5 LNs, and 6+ LNs. The 3-year OS was 82.0% for 1-3 LNs, 74.3% for 4-5 LNs (hazard ratio [HR] 1.38; p < 0.001), and 59.9% for 6+ LNs (HR 2.23; p < 0.001). On univariate Cox regression, PA nodal involvement was a significant predictor of OS (HR 1.20; p < 0.001) but was not significant on multivariate analysis when number of LNs was included (HR 1.05; p = 0.273). Additionally, we identified an interaction between adjuvant therapy and number of involved LNs. Patients with 1-3 involved LNs had 3-year OS of 85.2%, 78.7% and 74.2% with chemoradiation (CRT), chemotherapy, and radiation, respectively. Patients with 6+ involved LNs had 3-yr OS of 67.8%, 49.6%, and 48.9% with CRT, chemotherapy, and radiation, respectively (p < 0.001). CONCLUSION: Number of involved LNs is a stronger prognostic and predictive factor compared to PA node involvement.

Approaches for assessing performance of high-resolution mass spectrometry-based non-targeted analysis methods.

Non-targeted analysis (NTA) using high-resolution mass spectrometry has enabled the detection and identification of unknown and unexpected compounds of interest in a wide range of sample matrices. Despite these benefits of NTA methods, standardized procedures do not yet exist for assessing performance, limiting stakeholders' abilities to suitably interpret and utilize NTA results. Herein, we first summarize existing performance assessment metrics for targeted analyses to provide context and clarify terminology that may be shared between targeted and NTA methods (e.g., terms such as accuracy, precision, sensitivity, and selectivity). We then discuss promising approaches for assessing NTA method performance, listing strengths and key caveats for each approach, and highlighting areas in need of further development. To structure the discussion, we define three types of NTA study objectives: sample classification, chemical identification, and chemical quantitation. Qualitative study performance (i.e., focusing on sample classification and/or chemical identification) can be assessed using the traditional confusion matrix, with some challenges and limitations. Quantitative study performance can be assessed using estimation procedures developed for targeted methods with consideration for additional sources of uncontrolled experimental error. This article is intended to stimulate discussion and further efforts to develop and improve procedures for assessing NTA method performance. Ultimately, improved performance assessments will enable accurate communication and effective utilization of NTA results by stakeholders.

Analysis of per- and poly-fluoroalkyl substances (PFAS) in processed foods from FDA's Total Diet Study.

Additional occurrence data are needed to better understand human exposure to per- and poly-fluoroalkyl substances (PFAS) from commercially available foods in the United States. The Food and Drug Administration's (FDA) Total Diet Study (TDS) collects foods that are both nationally and regionally distributed. In 2018, 172 processed foods were collected from grocery stores around Lenexa, KS, as part of the TDS national collection. A previously developed method for the analysis of PFAS in foods as part of the TDS regional collection was modified and optimized for these samples. This method was single lab validated using 5 different matrices and method detection limits were calculated. During the analysis of these samples, challenges arose with method blanks and further investigation into statistical methods to distinguish between blank and sample concentrations were done. The confirmation of two short chain PFAS, perfluorobutanoic acid (PFBA) and perfluoropentanoic acid (PFPeA), was not possible using triple quadrupole mass spectrometry and a confirmation method was developed using high-resolution mass spectrometry. This technique was also used to investigate potential detections and interferents that fell within the retention time criteria for positive detections. In the national collection, positive detections of perfluorooctanesulfonic acid (PFOS) and perfluorononanoic acid (PFNA) were found in frozen fish sticks/patties, PFOS and perfluorodecanoic acid (PFDA) in canned tuna, and PFOS in protein powder. Concentrations were all below 150 ppt, and no other detects were confirmed above the method detection limits in any other foods.

Elementary School Nurses' Perceptions Regarding Menstruation Education: An Exploratory Study.

Menarche can be a difficult transition for young people. With appropriate education, youth can feel more positively about the menstrual experience. Since many elementary teachers are not equipped with menstrual health knowledge, the education falls to the school nurse. However, it is unknown if school nurses feel comfortable communicating about menstruation with young people. The purpose of this study was to explore school nurses' perceptions regarding menstrual health education in elementary schools (grades K-5).An online mixed-methods survey was established using Qualtrics. Through snowball sampling, 30 elementary school nurses responded. Using the Integrated Behavioral Model (IBM) as a framework, a deductive semantic thematic analysis was used to identify themes for each question.Data suggested that elementary school nurses would participate in professional development regarding menstrual health and hygiene. School health nurses are receiving limited knowledge/skills surrounding pedagogy and are not familiar with cultural differences when it comes to menstrual health.

Tetravalent Rabies-Vectored Filovirus and Lassa Fever Vaccine Induces Long-term Immunity in Nonhuman Primates.

BACKGROUND: The objective of this study is to evaluate the immunogenicity of adjuvanted monovalent rabies virus (RABV)-based vaccine candidates against Ebola virus (FILORAB1), Sudan virus (FILORAB2), Marburg virus (FILORAB3), Lassa virus (LASSARAB1), and combined trivalent vaccine candidate (FILORAB1-3) and tetravalent vaccine candidate (FILORAB1-3 and LASSARAB) in nonhuman primates. METHODS: Twenty-four Macaca fascicularis were randomly assigned into 6 groups of 4 animals. Each group was vaccinated with either a single adjuvanted vaccine, the trivalent vaccine, or the tetravalent vaccine at days 0 and 28. We followed the humoral immune responses for 1 year by antigen-specific enzyme-linked immunosorbent assays and RABV neutralization assays. RESULTS: High titers of filovirus and/or Lassa virus glycoprotein-specific immunoglobulin G were induced in the vaccinated animals. There were no significant differences between immune responses in animals vaccinated with single vaccines vs trivalent or tetravalent vaccines. In addition, all vaccine groups elicited strong rabies neutralizing antibody titers. The antigen-specific immune responses were detectable for 1 year in all groups. CONCLUSIONS: In summary, this study shows the longevity of the immune responses up to 365 days for a pentavalent vaccine-against Ebola virus, Sudan virus, Marburg virus, Lassa virus, and RABV-using a safe and effective vaccine platform.

A Proposed Quality Control Standard Mixture and Its Uses for Evaluating Nontargeted and Suspect Screening LC/HR-MS Method Performance.

Nontargeted (NTA) and suspect screening analyses (SSA) aim to detect and identify unknown compounds of interest from a given sample. The complexity and diversity of NTA and SSA methodologies necessitate the use of a comprehensive quality control standard mixture to determine if methods are fit for purpose, but to our knowledge, such a standard has not been developed that can be used by multiple disciplines, nor is one readily available. This work describes the development and analysis of a proposed nontargeted standard/quality control mixture for NTA and SSA applications using liquid chromatography/electrospray ionization-high resolution-mass spectrometry. Considerations in its development included achieving diversity of compounds with respect to elemental composition, molecular weight, retention time, and ionization in positive and/or negative ion modes, which resulted in the inclusion of 89 compounds. The utility of the standard mixture was applied on our own NTA and SSA workflows where sample preparation efficiency and potential sources of error due to instrumental and data processing methods were evaluated. Some areas in need of improvement were identified, such as hydrophilic compound detection and molecular formula generation for compounds containing fluorine. However, our overall methodology was found to be fit for purpose and we were able to establish thresholds to increase reliability and throughput of reported results.

An Introduction to the Benchmarking and Publications for Non-Targeted Analysis Working Group.

Non-targeted analysis (NTA) encompasses a rapidly evolving set of mass spectrometry techniques aimed at characterizing the chemical composition of complex samples, identifying unknown compounds, and/or classifying samples, without prior knowledge regarding the chemical content of the samples. Recent advances in NTA are the result of improved and more accessible instrumentation for data generation and analysis tools for data evaluation and interpretation. As researchers continue to develop NTA approaches in various scientific fields, there is a growing need to identify, disseminate, and adopt community-wide method reporting guidelines. In 2018, NTA researchers formed the Benchmarking and Publications for Non-Targeted Analysis Working Group (BP4NTA) to address this need. Consisting of participants from around the world and representing fields ranging from environmental science and food chemistry to 'omics and toxicology, BP4NTA provides resources addressing a variety of challenges associated with NTA. Thus far, BP4NTA group members have aimed to establish a consensus on NTA-related terms and concepts and to create consistency in reporting practices by providing resources on a public Web site, including consensus definitions, reference content, and lists of available tools. Moving forward, BP4NTA will provide a setting for NTA researchers to continue discussing emerging challenges and contribute to additional harmonization efforts.

Real-world evidence from a University Hospital system regarding the uptake of adjuvant pertuzumab and/or neratinib before and after their FDA approval.

PURPOSE: Adjuvant pertuzumab and neratinib are independently FDA-approved for treatment of early-stage HER2-positive breast cancer in combination with or following trastuzumab for one year, respectively. Both agents reduce the risk of recurrence; however, the absolute benefit is modest for many patients with added risk of adverse effects. The purpose of this study was to evaluate the clinical use of adjuvant pertuzumab and neratinib in patients with early-stage HER2-positive breast cancer. METHODS: Patients diagnosed with stage I-III HER2-positive breast cancer treated with trastuzumab at four University of Colorado Health hospitals between July 2016 and April 2019 were identified. Patient demographics, cancer stage, treatment, and administration of pertuzumab and/or neratinib were obtained. RESULTS: We identified a total of 350 patients who received adjuvant trastuzumab for stage I-III HER2-positive breast cancer; 253 (73.1%) had tumors that were ≥ T2 or node-positive disease. The rate of adjuvant pertuzumab use increased following FDA approval; pertuzumab was administered to the majority of patients with node-positive HER2-positive breast cancer. The use of adjuvant pertuzumab was associated with younger age, premenopausal status, and node-positive disease. Rates of administration of adjuvant neratinib were lower, with only 15.2% of patients receiving this therapy within 3 months of completing adjuvant trastuzumab. CONCLUSION: In our cohort of patients treated within a diverse healthcare network, the majority of patients with node-positive HER2-positive breast cancer received adjuvant pertuzumab following FDA approval. The use of adjuvant neratinib was less common, potentially as a result of adverse effects, prolongation of therapy, previous administration of adjuvant pertuzumab, and modest benefit.

New Persistent Opioid and Benzodiazepine Use After Curative-Intent Treatment in Patients With Breast Cancer.

BACKGROUND: Opioid and benzodiazepine use and abuse is a national healthcare crisis to which patients with cancer are particularly vulnerable. Long-term use and risk factors for opioid and benzodiazepine use in patients with breast cancer is poorly characterized. METHODS: We conducted a retrospective population-based study of patients with breast cancer diagnosed between 2008 and 2015 undergoing curative-intent treatment identified through the SEER-Medicare linked database. Primary outcomes were new persistent opioid use and new persistent benzodiazepine use. Factors associated with new opioid and benzodiazepine use were investigated by univariate and multivariable logistic regression. RESULTS: Among opioid-naïve patients, new opioid use was observed in 22,418 (67.4%). Of this group, 611 (2.7%) developed persistent opioid use at 3 months and 157 (0.7%) at 6 months after treatment. Risk factors for persistent use at 3 and 6 months included stage III disease (odds ratio [OR], 2.16; 95% CI, 1.49-3.12, and OR, 3.48; 95% CI, 1.58-7.67), surgery plus chemotherapy (OR, 1.44; 95% CI, 1.10-1.88, and OR, 2.28; 95% CI, 1.40-3.71), surgery plus chemoradiation therapy (OR, 1.47; 95% CI, 1.10-1.96, and OR, 2.34; 95% CI, 1.38-3.96), and initial tramadol use (OR, 2.66; 95% CI, 2.05-3.46, and OR, 3.12; 95% CI, 1.93-5.04). Among benzodiazepine-naïve patients, new benzodiazepine use was observed in 955 (10.3%), and 111 (11.6%) developed new persistent use at 3 months. Tamoxifen use was statistically significantly associated with new persistent benzodiazepine use at 3 months. CONCLUSIONS: A large percentage of patients receiving curative-intent treatment of breast cancer were prescribed new opioids; however, only a small number developed new persistent opioid use. In contrast, a smaller proportion of patients received a new benzodiazepine prescription; however, new persistent use after completion of treatment was more likely and particularly related to concurrent treatment with tamoxifen.