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In evidence-based medicine frameworks, the highest level of evidence is derived from quantitative synthesis of double-masked, high-quality, randomly assigned controlled trials. Meta-analyses of randomly assigned controlled trials have demonstrated that screening mammography reduces breast cancer deaths. In the United States, every major guideline-producing organization has recommended screening mammography in average-risk women; however, there are controversies about age and frequency. Carefully controlled observational research studies and statistical modeling studies can address evidence gaps and inform evidence-based, contemporary screening practices. As breast imaging radiologists develop and evaluate existing and new screening tests and technologies, they will need to understand the key methodological considerations and scientific criteria used by policy makers and health service researchers to support dissemination and implementation of evidence-based screening tests. The Wilson and Jungner principles and the U.S. Preventive Services Task Force general analytic framework provide structured evaluations of the effectiveness of screening tests. Key considerations in both frameworks include public health significance, natural history of disease, cost-effectiveness, and characteristics of screening tests and treatments. Rigorous evaluation of screening tests using analytic frameworks can maximize the benefits of screening tests while reducing potential harms. The purpose of this article is to review key methodological considerations and analytic frameworks used to evaluate screening studies and develop evidence-based recommendations., (© Society of Breast Imaging 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Breast cancer has been associated with monogenic, polygenic, and epidemiologic (clinical, reproductive, and lifestyle) risk factors, but studies evaluating the combined effects of these factors have been limited., Methods: We extended previous work in breast cancer risk modeling, incorporating pathogenic variants (PV) in six breast cancer predisposition genes and a 105-SNP polygenic risk score (PRS), to include an epidemiologic risk score (ERS) in a sample of non-Hispanic White women drawn from prospective cohorts and population-based case-control studies, with 23,518 cases and 22,832 controls, from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium., Results: The model predicts 4.4-fold higher risk of breast cancer for postmenopausal women with no predisposition PV and median PRS, but with the highest versus lowest ERS. Overall, women with CHEK2 PVs had >20% lifetime risk of breast cancer. However, 15.6% of women with CHEK2 PVs and a family history of breast cancer, and 45.1% of women with CHEK2 PVs but without a family history of breast cancer, had low (<20%) predicted lifetime risk and thus were below the threshold for MRI screening. CHEK2 PV carriers at the 10th percentile of the joint distribution of ERS and PRS, without a family history of breast cancer, had a predicted lifetime risk similar to the general population., Conclusions: These results illustrate that an ERS, alone and combined with the PRS, can contribute to clinically relevant risk stratification., Impact: Integrating monogenic, polygenic, and epidemiologic risk factors in breast cancer risk prediction models may inform personalized screening and prevention efforts., (©2024 American Association for Cancer Research.)

Importance: Information on long-term benefits and harms of screening with digital breast tomosynthesis (DBT) with or without supplemental breast magnetic resonance imaging (MRI) is needed for clinical and policy discussions, particularly for patients with dense breasts., Objective: To project long-term population-based outcomes for breast cancer mammography screening strategies (DBT or digital mammography) with or without supplemental MRI by breast density., Design, Setting, and Participants: Collaborative modeling using 3 Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer simulation models informed by US Breast Cancer Surveillance Consortium data. Simulated women born in 1980 with average breast cancer risk were included. Modeling analyses were conducted from January 2020 to December 2023., Intervention: Annual or biennial mammography screening with or without supplemental MRI by breast density starting at ages 40, 45, or 50 years through age 74 years., Main Outcomes and Measures: Lifetime breast cancer deaths averted, false-positive recall and false-positive biopsy recommendations per 1000 simulated women followed-up from age 40 years to death summarized as means and ranges across models., Results: Biennial DBT screening for all simulated women started at age 50 vs 40 years averted 7.4 vs 8.5 breast cancer deaths, respectively, and led to 884 vs 1392 false-positive recalls and 151 vs 221 false-positive biopsy recommendations, respectively. Biennial digital mammography had similar deaths averted and slightly more false-positive test results than DBT screening. Adding MRI for women with extremely dense breasts to biennial DBT screening for women aged 50 to 74 years increased deaths averted (7.6 vs 7.4), false-positive recalls (919 vs 884), and false-positive biopsy recommendations (180 vs 151). Extending supplemental MRI to women with heterogeneously or extremely dense breasts further increased deaths averted (8.0 vs 7.4), false-positive recalls (1088 vs 884), and false-positive biopsy recommendations (343 vs 151). The same strategy for women aged 40 to 74 years averted 9.5 deaths but led to 1850 false-positive recalls and 628 false-positive biopsy recommendations. Annual screening modestly increased estimated deaths averted but markedly increased estimated false-positive results., Conclusions and Relevance: In this model-based comparative effectiveness analysis, supplemental MRI for women with dense breasts added to DBT screening led to greater benefits and increased harms. The balance of this trade-off for supplemental MRI use was more favorable when MRI was targeted to women with extremely dense breasts who comprise approximately 10% of the population.

Objective: There are limited data about food insecurity within the cancer screening setting. To inform the potential need for food insecurity interventions, our study evaluated the association between food security and mammographic screening among eligible participants., Methods: Female respondents aged 40 to 74 years in the 2019 National Health Interview Survey without history of breast cancer were included. Food insecurity was assessed using the Six-Item Food Security Scale developed by the National Center for Health Statistics. The proportion of patients who reported mammographic screening within the last year was estimated, stratified by food security. Multiple variable logistic regression analyses evaluated the association between food security and mammography screening, adjusted for potential confounders. All analyses were performed accounting for complex survey design features., Results: In all, 8,956 weighted survey respondents met inclusion criteria; 90.1% were classified as having high or marginal food security, of whom 56.6% reported screening; 6.1% were classified with low food security, of whom 42.1% reported screening; and 3.8% were classified with very low food security, of whom 43.1% reported screening. In our unadjusted analyses, participants with low food security (P < .001) and very low food security (P < .001) were less likely to report screening within the last year. In our adjusted analyses, participants with food insecurity (P = .009) were less likely to report screening., Discussion: In a nationally representative cross-sectional survey, participants with food insecurity were less likely to report mammography screening. Radiology practices should consider screening patients for food insecurity and social determinants of health. Evidence-based food insecurity interventions may increase adherence to mammography screening., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: The technical aspects of cancer surgery have a significant impact on patient outcomes. To monitor surgical quality, in 2020, the Commission on Cancer (CoC) revised its accreditation standards for cancer surgery and introduced the synoptic operative reports (SORs). The standardization of SORs holds promise, but successful implementation requires strategies to address key implementation barriers. This study aimed to identify the barriers and facilitators to implementing breast SOR within diverse CoC-accredited programs., Methods: In-depth semi-structured interviews were conducted with 31 health care professionals across diverse CoC-accredited sites. The study used two comprehensive implementation frameworks to guide data collection and analysis., Results: Successful SOR implementation was impeded by disrupted workflows, surgeon resistance to change, low prioritization of resources, and poor flow of information despite CoC's positive reputation. Participants often lacked understanding of the requirements and timeline for breast SOR and were heavily influenced by prior experiences with templates and SOR champion relationships. The perceived lack of monetary benefits (to obtaining CoC accreditation) together with the significant information technology (IT) resource requirements tempered some of the enthusiasm. Additionally, resource constraints and the redirection of personnel during the COVID-19 pandemic were noted as hurdles., Conclusions: Surgeon behavior and workflow change, IT and personnel resources, and communication and networking strategies influenced SOR implementation. During early implementation and the implementation planning phase, the primary focus was on achieving buy-in and initiating successful roll-out rather than effective use or sustainment. These findings have implications for enhancing standardization of surgical cancer care and guidance of future strategies to optimize implementation of CoC accreditation standards., (© 2024. The Author(s).)

Background: Patient engagement in decision making can improve satisfaction with care. Studies demonstrate that patients' emotional states can be significant barriers to engaging in shared decision making., Objective: We sought to examine how emotion associated with a breast cancer diagnosis impacts patient experiences during the surgical consultation, and explore opportunities for surgeons to mitigate the impact of emotion., Methods: We conducted 30 semi-structured interviews with patients who participated in the decision aid arm of Alliance A231701CD, had low engagement, and experienced barriers to engagement. We used qualitative content analysis to analyze the interview data and organize it into overarching themes., Results: Participants recalled strong emotions with their diagnosis, describing it as devastating and shocking. Although several participants said that their emotional reaction to the diagnosis lessened over time, others expressed still feeling very anxious. Participants described ways in which their surgeon helped to de-escalate their emotional state, beginning with the establishment of rapport and continuing through treatment planning. Participants valued surgeons who they perceived to be personable and compassionate, treated them as an individual, provided reassuring and matter-of-fact information about their cancer, and efficiently communicated plans for next steps., Conclusions: Patients with breast cancer are often emotionally overwhelmed during their surgical consults, which impedes their ability to listen and participate in decision making. However, surgeon behaviors can help de-escalate emotions. Addressing emotion is critical to support patients in reaching a decision for breast cancer surgery and is likely to improve patient satisfaction with the decision process., Clinical Trials Registration: ClinicalTrials.gov identifier: NCT03766009., (© 2024. Society of Surgical Oncology.)

Drugs that perturb microtubules are commonly used to treat breast cancers of all subtypes in both early stage and metastatic disease, but they are effective in only approximately 50% of patients. High concentrations of microtubule-targeting agents can elicit mitotic arrest in cell culture models; however, recent evidence from primary and metastatic breast cancers has revealed that these agents only accumulate at intratumoral levels capable of inducing abnormal multipolar mitotic spindles, not mitotic arrest. Although the maintenance of multipolar spindles can generate cytotoxic rates of chromosomal instability (CIN), focusing of aberrant multipolar spindles into normal bipolar spindles can dramatically reduce CIN and confer resistance to microtubule poisons. Here, we showed that inhibition of the mitotic kinesin centromeric-associated protein-E (CENP-E) overcomes resistance caused by focusing multipolar spindles. Clinically relevant microtubule-targeting agents used a mechanistically conserved pathway to induce multipolar spindles without requiring centrosome amplification. Focusing could occur at any point in mitosis, with earlier focusing conferring greater resistance to antimicrotubule agents. CENP-E inhibition increased CIN on focused spindles by generating chromosomes that remained misaligned at spindle poles during anaphase, which substantially increased death in the resulting daughter cells. CENP-E inhibition synergized with diverse, clinically relevant microtubule poisons to potentiate cell death in cell lines and suppress tumor growth in orthotopic tumor models. These results suggest that primary resistance to microtubule-targeting drugs can be overcome by simultaneous inhibition of CENP-E. Significance: The increased incidence of polar chromosomes induced by inhibition of the mitotic kinesin CENP-E exacerbates chromosomal instability, reduces daughter cell viability, and improves sensitivity to microtubule-targeting therapies., (©2024 American Association for Cancer Research.)

Background and Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome side effect in patients exposed to taxanes in the treatment of cancer and may affect quality of life dramatically. Here we assessed whether serum levels of neurofilament light (NfL) and tau (two neuroaxonal injury biomarkers) and glial fibrillary acidic protein (GFAP, a biomarker for astrocytic activation) correlate with the development of CIPN in the adjuvant setting of early breast cancer., Materials and Methods: Using ultrasensitive single molecule array technology, serum levels of NfL, GFAP, and tau were measured before and every 3 weeks in 10 women receiving adjuvant EC (epirubicin 90 mg/m² and cyclophosphamide 600 mg/m²) every 3 weeks × 3, followed by weekly paclitaxel 80 mg/m² × 9-12 weeks after surgery due to early breast cancer. CIPN was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) and the questionnaire EORTC QLQ CIPN-20., Results: Serum levels of GFAP increased successively during cycles of EC. NfL increased instead in response to the treatment of paclitaxel. NfL and GFAP continued to rise throughout exposure of cumulatively higher doses of paclitaxel and were reduced 3 months after the end of chemotherapy. Serums levels of tau were marginally affected by exposure to chemotherapy. Women with worse symptoms of CIPN had higher concentrations of NfL than women with mild symptoms of CIPN., Interpretation: NfL and GFAP are promising biomarkers to identify women at risk of developing CIPN. Larger prospective studies are now needed.

Coactivator-associated arginine methyltransferase 1 (CARM1) is a protein arginine methyltransferase that deposits asymmetrical dimethylation marks on both histone and nonhistone substrates. The regulatory role of CARM1 in transcription was first identified in estrogen receptor positive (ER+) breast cancer. Since then, the mechanism of CARM1 in activating ER-target genes has been further interrogated. CARM1 is expressed at the highest level in ER negative (ER-) breast cancer and higher expression correlates with poor prognosis, suggesting an oncogenic role of CARM1. Indeed, in ER- breast cancer, CARM1 can promote proliferation and metastasis at least partly through methylation of proteins and activation of oncogenes. In this review, we summarize the mechanisms of transcriptional activation by CARM1 in breast cancer. The methyltransferase activity of CARM1 is important for many of its functions; here, we also highlight the nonenzymatic roles of CARM1. We also cover the biological processes regulated by CARM1 that are often deregulated in cancer and the ways to harness CARM1 in cancer treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Purpose: Although patients with metastatic breast cancer (MBC) have been living longer with the advent of more effective treatments such as targeted therapy and immunotherapy, the disease remains incurable, and most patients will undergo therapy indefinitely. When beginning therapy, patients are typically prescribed dose often based upon the maximum tolerated dose identified in phase I clinical trials. However, patients' perspectives about tolerability and willingness to discuss individualized dosing of drugs upon initiation of a new regimen and throughout the course of treatment have not been comprehensively evaluated., Methods: Patient advocates and medical oncologists from the Patient-Centered Dosing Initiative (PCDI) developed a survey to ascertain the prevalence and severity of MBC patients' treatment-related side effects, the level of patient-physician communication, mitigation strategies, perception about the relative efficacy of higher versus lower doses, and willingness to discuss alternative dosing. The PCDI distributed the anonymous confidential online survey in August 2020 to individuals with self-reported MBC., Results: One thousand and two hundred twenty-one patients with MBC completed the survey. 86.1% (n = 1,051) reported experiencing at least one significant treatment-related side effect, and of these, 20.3% (n = 213) visited the emergency room/hospital and 43.2% (n = 454) missed at least one treatment. Nearly all patients with side effects (97.6%, n = 1,026) informed their doctor and 81.7% (n = 838) received assistance. Of the 556 patients given a dose reduction for side-effect mitigation, 82.6% (n = 459) reported relief. Notably, majority of patients (53.3%, n = 651) do not believe that higher dose is always more effective than lower dose, and 92.3% (n = 1,127) would be willing to discuss flexible dosing options with their physicians based upon personal characteristics to optimize quality of life., Conclusion: Given that the majority of patients with MBC experienced at least one substantial treatment-related side effect and most patients given a dose reduction reported improvement, innovative dosage-related strategies are warranted to sustain and improve patients' well-being. Patient-physician discussions in which the patient's unique attributes and circumstances are assessed upon initiation of new treatment and throughout the course of therapy may facilitate the identification of the most favorable dose for each patient, and the majority of patients would be receptive to this approach.

Ductal carcinoma in situ (DCIS) is a heterogeneous breast disease that remains challenging to treat due to its unpredictable progression to invasive breast cancer (IBC). Contemporary literature has become increasingly focused on extracellular matrix (ECM) alterations with breast cancer progression. However, the spatial regulation of the ECM proteome in DCIS has yet to be investigated in relation to IBC. We hypothesized that DCIS and IBC present distinct ECM proteomes that could discriminate between these pathologies. Tissue sections of pure DCIS, mixed DCIS-IBC, or pure IBC ( n = 22) with detailed pathological annotations were investigated by multiplexed spatial proteomics. Across tissues, 1,005 ECM peptides were detected in pathologically annotated regions and their surrounding extracellular microenvironments. A comparison of DCIS to IBC pathologies demonstrated 43 significantly altered ECM peptides. Notably, eight fibrillar collagen peptides could distinguish with high specificity and sensitivity between DCIS and IBC. Lesion-targeted proteomic imaging revealed heterogeneity of the ECM proteome surrounding individual DCIS lesions. Multiplexed spatial proteomics reported an invasive cancer field effect, in which DCIS lesions in closer proximity to IBC shared a more similar ECM profile to IBC than distal counterparts. Defining the ECM proteomic microenvironment provides novel molecular insights relating to DCIS and IBC.

Importance: The effects of breast cancer incidence changes and advances in screening and treatment on outcomes of different screening strategies are not well known., Objective: To estimate outcomes of various mammography screening strategies., Design, Setting, and Population: Comparison of outcomes using 6 Cancer Intervention and Surveillance Modeling Network (CISNET) models and national data on breast cancer incidence, mammography performance, treatment effects, and other-cause mortality in US women without previous cancer diagnoses., Exposures: Thirty-six screening strategies with varying start ages (40, 45, 50 years) and stop ages (74, 79 years) with digital mammography or digital breast tomosynthesis (DBT) annually, biennially, or a combination of intervals. Strategies were evaluated for all women and for Black women, assuming 100% screening adherence and "real-world" treatment., Main Outcomes and Measures: Estimated lifetime benefits (breast cancer deaths averted, percent reduction in breast cancer mortality, life-years gained), harms (false-positive recalls, benign biopsies, overdiagnosis), and number of mammograms per 1000 women., Results: Biennial screening with DBT starting at age 40, 45, or 50 years until age 74 years averted a median of 8.2, 7.5, or 6.7 breast cancer deaths per 1000 women screened, respectively, vs no screening. Biennial DBT screening at age 40 to 74 years (vs no screening) was associated with a 30.0% breast cancer mortality reduction, 1376 false-positive recalls, and 14 overdiagnosed cases per 1000 women screened. Digital mammography screening benefits were similar to those for DBT but had more false-positive recalls. Annual screening increased benefits but resulted in more false-positive recalls and overdiagnosed cases. Benefit-to-harm ratios of continuing screening until age 79 years were similar or superior to stopping at age 74. In all strategies, women with higher-than-average breast cancer risk, higher breast density, and lower comorbidity level experienced greater screening benefits than other groups. Annual screening of Black women from age 40 to 49 years with biennial screening thereafter reduced breast cancer mortality disparities while maintaining similar benefit-to-harm trade-offs as for all women., Conclusions: This modeling analysis suggests that biennial mammography screening starting at age 40 years reduces breast cancer mortality and increases life-years gained per mammogram. More intensive screening for women with greater risk of breast cancer diagnosis or death can maintain similar benefit-to-harm trade-offs and reduce mortality disparities.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Breast cancer is often treated with chemotherapy. However, the development of chemoresistance results in treatment failure. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been shown to contribute to chemoresistance in breast cancer cells. In studying the transcriptional regulation of NEAT1 using multi-omics approaches, we showed that NEAT1 is up-regulated by 5-fluorouracil in breast cancer cells with wild-type cellular tumor antigen p53 but not in mutant-p53-expressing breast cancer cells. The regulation of NEAT1 involves mediator complex subunit 12 (MED12)-mediated repression of histone acetylation marks at the promoter region of NEAT1. Knockdown of MED12 but not coactivator-associated arginine methyltransferase 1 (CARM1) induced histone acetylation at the NEAT1 promoter, leading to elevated NEAT1 mRNAs, resulting in a chemoresistant phenotype. The MED12-dependent regulation of NEAT1 differs between wild-type and mutant p53-expressing cells. MED12 depletion led to increased expression of NEAT1 in a wild-type p53 cell line, but decreased expression in a mutant p53 cell line. Chemoresistance caused by MED12 depletion can be partially rescued by NEAT1 knockdown in p53 wild-type cells. Collectively, our study reveals a novel mechanism of chemoresistance dependent on MED12 transcriptional regulation of NEAT1 in p53 wild-type breast cancer cells., (© 2024 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

The Hippo pathway effectors Yes-associated protein 1 (YAP) and its homolog TAZ are transcriptional coactivators that control gene expression by binding to TEA domain (TEAD) family transcription factors. The YAP/TAZ-TEAD complex is a key regulator of cancer-specific transcriptional programs, which promote tumor progression in diverse types of cancer, including breast cancer. Despite intensive efforts, the YAP/TAZ-TEAD complex in cancer has remained largely undruggable due to an incomplete mechanistic understanding. Here, we report that nuclear phosphoinositides function as cofactors that mediate the binding of YAP/TAZ to TEADs. The enzymatic products of phosphoinositide kinases PIPKIα and IPMK, including phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ) and phosphatidylinositol 3,4,5-trisphosphate (P(I3,4,5)P 3 ), bridge the binding of YAP/TAZ to TEAD. Inhibiting these kinases or the association of YAP/TAZ with PI(4,5)P 2 and PI(3,4,5)P 3 attenuates YAP/TAZ interaction with the TEADs, the expression of YAP/TAZ target genes, and breast cancer cell motility. Although we could not conclusively exclude the possibility that other enzymatic products of IPMK such as inositol phosphates play a role in the mechanism, our results point to a previously unrecognized role of nuclear phosphoinositide signaling in control of YAP/TAZ activity and implicate this pathway as a potential therapeutic target in YAP/TAZ-driven breast cancer., (© 2024. The Author(s).)

Background: Expansion of genome-wide association studies across population groups is needed to improve our understanding of shared and unique genetic contributions to breast cancer. We performed association and replication studies guided by a priori linkage findings from African ancestry (AA) relative pairs., Methods: We performed fixed-effect inverse-variance weighted meta-analysis under three significant AA breast cancer linkage peaks (3q26-27, 12q22-23, and 16q21-22) in 9241 AA cases and 10 193 AA controls. We examined associations with overall breast cancer as well as estrogen receptor (ER)-positive and negative subtypes (193,132 SNPs). We replicated associations in the African-ancestry Breast Cancer Genetic Consortium (AABCG)., Results: In AA women, we identified two associations on chr12q for overall breast cancer (rs1420647, OR = 1.15, p = 2.50×10-6; rs12322371, OR = 1.14, p = 3.15×10-6), and one for ER-negative breast cancer (rs77006600, OR = 1.67, p = 3.51×10-6). On chr3, we identified two associations with ER-negative disease (rs184090918, OR = 3.70, p = 1.23×10-5; rs76959804, OR = 3.57, p = 1.77×10-5) and on chr16q we identified an association with ER-negative disease (rs34147411, OR = 1.62, p = 8.82×10-6). In the replication study, the chr3 associations were significant and effect sizes were larger (rs184090918, OR: 6.66, 95% CI: 1.43, 31.01; rs76959804, OR: 5.24, 95% CI: 1.70, 16.16)., Conclusion: The two chr3 SNPs are upstream to open chromatin ENSR00000710716, a regulatory feature that is actively regulated in mammary tissues, providing evidence that variants in this chr3 region may have a regulatory role in our target organ. Our study provides support for breast cancer variant discovery using prioritization based on linkage evidence., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Estrogen receptor positive breast cancer is frequently treated with anti-hormonal treatment such as aromatase inhibitors (AI). Interestingly, a high body mass index has been shown to have a negative impact on AI efficacy, most likely due to disturbances in steroid metabolism and adipokine production. Here, we propose a mathematical model based on a system of ordinary differential equations to investigate the effect of high-fat diet on tumor growth. We inform the model with data from mouse experiments, where the animals are fed with high-fat or control (normal) diet. By incorporating AI treatment with drug resistance into the model and by solving optimal control problems we found differential responses for control and high-fat diet. To the best of our knowledge, this is the first attempt to model optimal anti-hormonal treatment for breast cancer in the presence of drug resistance. Our results underline the importance of considering high-fat diet and obesity as factors influencing clinical outcomes during anti-hormonal therapies in breast cancer patients., (© 2024. The Author(s).)

Purpose: This guideline provides evidence-based recommendations on appropriate indications and techniques for partial breast irradiation (PBI) for patients with early-stage invasive breast cancer and ductal carcinoma in situ., Methods: ASTRO convened a task force to address 4 key questions focused on the appropriate indications and techniques for PBI as an alternative to whole breast irradiation (WBI) to result in similar rates of ipsilateral breast recurrence (IBR) and toxicity outcomes. Also addressed were aspects related to the technical delivery of PBI, including dose-fractionation regimens, target volumes, and treatment parameters for different PBI techniques. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality. Recommendations were created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength., Results: PBI delivered using 3-dimensional conformal radiation therapy, intensity modulated radiation therapy, multicatheter brachytherapy, and single-entry brachytherapy results in similar IBR as WBI with long-term follow-up. Some patient characteristics and tumor features were underrepresented in the randomized controlled trials, making it difficult to fully define IBR risks for patients with these features. Appropriate dose-fractionation regimens, target volume delineation, and treatment planning parameters for delivery of PBI are outlined. Intraoperative radiation therapy alone is associated with a higher IBR rate compared with WBI. A daily or every-other-day external beam PBI regimen is preferred over twice-daily regimens due to late toxicity concerns., Conclusions: Based on published data, the ASTRO task force has proposed recommendations to inform best clinical practices on the use of PBI., Competing Interests: Disclosures All task force members’ disclosure statements were reviewed before being invited and were shared with other task force members throughout the guideline's development. Those disclosures are published within this guideline. Where potential conflicts were detected, remedial measures to address them were taken. Bethany Anderson: American Board of Radiology (ABR) (board examiner), Brachytherapy Journal (section editor), Clinical Breast Cancer Journal (associate editor), International Journal of Radiation Oncology, Biology, Physics (breast section associate editor), School of Breast Oncology (honoraria); Douglas Arthur: Advanced Radiation Therapy (consultant); Jose Bazan: ABR (board examiner), ASTRO VA Breast Panel (honoraria), International Journal of Radiation Oncology, Biology, Physics (breast section associate editor), Intraop Medical (institutional research); Jennifer Bellon: American Board of Radiology (ABR) (oral exam chair-ended 8/2023), Leidos Pharmaceutical (honoraria), National Cancer Institute (NCI) (research; BOLD task force on breast cancer co-chair), Oncoclinicas (honoraria), PER (honoraria), Prosigna (research), UpToDate (honoraria), Varian (honoraria); Charlotte Coles: Breast Cancer Now (research), Cancer Research UK (research), Lancet Breast Cancer Commission (chair), National Institutes of Health and Care Research (NIHR) (research; IMPORT LOW trial chief investigator); Naamit Gerber: Accuray (advisory board-ended 10/2023), Invus Group (consultant), John Theurer Cancer Center (consultant), Mount Sinai Icahn School of Medicine (honoraria-ended 8/2022), PreludeDX (research); Leonard Kim: American Associations of Physicists in Medicine (subcommittee/working group chair), ABR (board examiner), Elekta (MR-Linac Consortium, institutional representative), The Greeley Company (consultant-ended 5/2022); Christine Laronga (Society of Surgical Oncology [SSO]representative): SSO Breast Disease Site (chair), UpToDate (section editor); Janice Lyons (Chair): ABR (board examiner), Primum (consultant); Icro Meattini: Accuray, Eli Lily, Ipsen, Novartis, Pfizer, Seagen (all advisory board); Elizabeth Nichols: ABR (board examiner), Applied Radiation Oncology (editorial board), Xcision (research, co-chair); Lori Pierce (American Society of Clinical Oncology [ASCO] representative): ASCO (board chair), Breast Cancer Research Foundation (advisory board and travel), BMS Foundation DCIDCP National Advisory Committee (advisory board and travel), Damon Runyon Cancer Research Foundation (board of directors and travel), Exact Sciences (consultant), Michigan Radiation Oncology Quality Consortium (director), PER Educational Symposium (speakers bureau and travel), UpToDate (editor); Matthew Poppe: Agency for Healthcare Research and Quality (technical expert), Alliance for Breast Clinical Trials in Oncology (vice chair), Alliance for Breast Clinical Trials Local Regional Working Group (chair), Mevion (honoraria and travel-ended 3/2022), NIH (research), NIH/NCI (research-PI), PEEL Therapeutics (stock), UpToDate (editor); Simona Shaitelman (Vice Chair): Alpha Tau Medical (research-ended 2022), Artios Pharma (research-ended 2022), Becton, Dickinson & Co (consultant), Brachytherapy Journal (editorial board), Elekta (MR-Linac Consortium, institutional representative), Emerson Collective Foundation (research), Exact Sciences (research), NIH (research-ended 8/2023), TAE Life Sciences (research); Patti Spears (patient representative): Pfizer (advocate advisory care committee member-ended 12/2022); Shaveta Vinayak (ASCO representative): OncoSec Biotech (research and consultant), Pfizer, Puma Biotech, Seattle Genetics (all research); Timothy Whelan: Exact Sciences (research). Lisa Bradfield and Madeera Kathpal (Guideline Subcommittee representative) reported no disclosures., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

The estrogen receptor (ER), a steroid hormone receptor important in female physiology, is a significant contributor to breast carcinogenesis and progression and, as such, is an important therapeutic target. Approximately 70% of breast cancers will express ER at presentation, and the determination of ER expression by tissue assay, usually by immunohistochemistry, is part of the standard of care for newly diagnosed breast cancer. ER expression is important in guiding the approach to treatment, especially with the increase in relevant systemic therapies. The ER-targeting imaging agent 16α-[ 18 F]fluoro-17β-estradiol ([ 18 F]FES) is approved for clinical use by regulatory agencies in France and the United States. Multiple studies suggest the advantages of [ 18 F]FES PET in assessing tumor ER expression, the ability of both qualitative and quantitative [ 18 F]FES PET measures to predict response to ER-targeted therapy, and the ability of [ 18 F]FES PET to clarify equivocal staging and restaging results in patients with ER-expressing cancers. [ 18 F]FES PET/CT may also be helpful in staging invasive lobular breast cancer and low-grade ER-expressing invasive ductal cancers and, in some cases, may be a substitute for biopsy. The Society of Nuclear Medicine and Molecular Imaging and the European Association of Nuclear Medicine in June 2023 released a procedure standard/practice guideline for [ 18 F]FES PET ER imaging of patients with breast cancer. The goal of the standard/guideline is to assist physicians in recommending, performing, interpreting, and reporting the results of [ 18 F]FES PET studies for patients with breast cancer and to provide clinicians with the best available evidence, inform them about areas where robust evidence is lacking, and help them deliver the best possible diagnostic efficacy and study quality for their patients. Also reviewed are standardized quality control, quality assurance, and imaging procedures for [ 18 F]FES PET. The authors emphasize the importance of precision, accuracy, repeatability, and reproducibility for both clinical management of patients and for use of [ 18 F]FES PET in multicenter trials. A standardized imaging procedure, in combination with already published appropriate-use criteria, will help promote the use of [ 18 F]FES PET and enhance subsequent research. This brief summary article reviews the content of the joint standard/guideline, which is available in its entirety at https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=6414&navItemNumbe=10790., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Importance: Breast cancer mortality in the US declined between 1975 and 2019. The association of changes in metastatic breast cancer treatment with improved breast cancer mortality is unclear., Objective: To simulate the relative associations of breast cancer screening, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer with improved breast cancer mortality., Design, Setting, and Participants: Using aggregated observational and clinical trial data on the dissemination and effects of screening and treatment, 4 Cancer Intervention and Surveillance Modeling Network (CISNET) models simulated US breast cancer mortality rates. Death due to breast cancer, overall and by estrogen receptor and ERBB2 (formerly HER2) status, among women aged 30 to 79 years in the US from 1975 to 2019 was simulated., Exposures: Screening mammography, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer., Main Outcomes and Measures: Model-estimated age-adjusted breast cancer mortality rate associated with screening, stage I to III treatment, and metastatic treatment relative to the absence of these exposures was assessed, as was model-estimated median survival after breast cancer metastatic recurrence., Results: The breast cancer mortality rate in the US (age adjusted) was 48/100 000 women in 1975 and 27/100 000 women in 2019. In 2019, the combination of screening, stage I to III treatment, and metastatic treatment was associated with a 58% reduction (model range, 55%-61%) in breast cancer mortality. Of this reduction, 29% (model range, 19%-33%) was associated with treatment of metastatic breast cancer, 47% (model range, 35%-60%) with treatment of stage I to III breast cancer, and 25% (model range, 21%-33%) with mammography screening. Based on simulations, the greatest change in survival after metastatic recurrence occurred between 2000 and 2019, from 1.9 years (model range, 1.0-2.7 years) to 3.2 years (model range, 2.0-4.9 years). Median survival for estrogen receptor (ER)-positive/ERBB2-positive breast cancer improved by 2.5 years (model range, 2.0-3.4 years), whereas median survival for ER-/ERBB2- breast cancer improved by 0.5 years (model range, 0.3-0.8 years)., Conclusions and Relevance: According to 4 simulation models, breast cancer screening and treatment in 2019 were associated with a 58% reduction in US breast cancer mortality compared with interventions in 1975. Simulations suggested that treatment for stage I to III breast cancer was associated with approximately 47% of the mortality reduction, whereas treatment for metastatic breast cancer was associated with 29% of the reduction and screening with 25% of the reduction.

Purpose: The assumption that patient-provider communication may mediate patients' sense of control over cancer to affect health outcomes has limited evidence. This study examines whether patient-perceived cancer care communication quality (PPCQ) mediates stress appraisal and coping behavior, affecting physical functioning across different racial groups., Methods: Two hundred and twenty Chinese American and 216 non-Hispanic White (NHW) women (ages 28-80) with stage 0-III breast cancer, 1-5 years post-diagnosis, and without recurrence, enrolled and completed a cross-sectional telephone survey. Physical functioning was measured by the NIH-PROMIS short form. Validated measures of PPCQ, patients' evaluation of their socioeconomic well-being, stress appraisal (perceived severity and control), use of coping strategies, treatment-related symptoms, and comorbidities were also assessed. Path analyses were used to examine the mediation for each racial group., Results: Regardless of race, treatment-related symptoms, comorbidities, and socioeconomic well-being were all directly related to physical functioning (p < 0.05). The impact of PPCQ on physical functioning was mediated by perceived control in the Chinese American group (p < 0.05), but not in the NHW group. Perceived severity and coping were not mediators of physical functioning in either group., Conclusions: The mediational pathway from PPCQ to perceived control to physical functioning in Chinese American survivors may be partially explained by their lower socioeconomic well-being and culturally valued conformity to physicians as a medical authority. These sociocultural dynamics reinforce the importance of cancer care communication. For NHW survivors, the impact of treatment-related symptoms and socioeconomic well-being on physical functioning outweighed their PPCQ and perceived control., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Obesity is a risk factor for breast cancer, and women with obesity that develop breast cancer have a worsened prognosis. Within the mammary gland, obesity causes chronic, macrophage-driven inflammation and adipose tissue fibrosis. Weight loss is a recommended intervention to resolve obesity, but the impact of weight loss on the mammary gland microenvironment and in tumors has not been well identified., Methods: To examine the effects of weight loss following obesity, mice were fed a high-fat diet for 16 weeks to induce obesity, then switched to a low-fat diet for 6 weeks. We examined changes in immune cells, including fibrocytes, which are myeloid lineage cells that have attributes of both macrophages and myofibroblasts, and collagen deposition within the mammary glands of non-tumor-bearing mice and within the tumors of mice that were transplanted with estrogen receptor alpha positive TC2 tumor cells., Results: In formerly obese mice, we observed reduced numbers of crown-like structures and fibrocytes in mammary glands, while collagen deposition was not resolved with weight loss. Following transplant of TC2 tumor cells into the mammary glands of lean, obese, and formerly obese mice, diminished collagen deposition and cancer-associated fibroblasts were observed in tumors from formerly obese mice compared to obese mice. Within tumors of obese mice, increased myeloid-derived suppressor cells and diminished CD8 + T cells were identified, while the microenvironment of tumors of formerly obese mice were more similar to tumors from lean mice. When TC2 tumor cells were mixed with CD11b + CD34 + myeloid progenitor cells, which are the cells of origin for fibrocytes, and transplanted into mammary glands of lean and obese mice, collagen deposition within the tumors of both lean and obese was significantly greater than when tumor cells were mixed with CD11b + CD34 - monocytes or total CD45 + immune cells., Conclusions: Overall, these studies demonstrate that weight loss resolved some of the microenvironmental conditions within the mammary gland that may contribute to tumor progression. Additionally, fibrocytes may contribute to early collagen deposition in mammary tumors of obese mice leading to the growth of desmoplastic tumors., (© 2023. The Author(s).)

Current breast cancer treatments involve aggressive and invasive methods, leaving room for new therapeutic approaches to emerge. In this work, we explore the possibility of using piezoelectric [P(VDF-TrFE)] microparticles (MPs) as a source of inducing irreversible electroporation (IRE) of 4T1 breast cancer cells. We detail the MP formation mechanism and size control and subsequent characterizations of the as-synthesized MPs which confirms the presence of piezoelectric β-phase. Production of the necessary piezoelectric output of the MPs is achieved by ultrasound agitation. We confirm the primary factor of the IRE effect on 4T1 breast cancer cells to be the local electric field produced from the MPs by using confocal imaging and an alamarBlue assay. The results show a 52.6% reduction in cell viability, indicating that the MP treatment can contribute to a reduction of live cancer cells. The proposed method of ultrasound-stimulated P(VDF-TrFE) MPs may offer a more benign cancer treatment approach.

Background: Populations of African American or Black women have persistently higher breast cancer mortality than the overall US population, despite having slightly lower age-adjusted incidence., Methods: Three Cancer Intervention and Surveillance Modeling Network simulation teams modeled cancer mortality disparities between Black female populations and the overall US population. Model inputs used racial group-specific data from clinical trials, national registries, nationally representative surveys, and observational studies. Analyses began with cancer mortality in the overall population and sequentially replaced parameters for Black populations to quantify the percentage of modeled breast cancer morality disparities attributable to differences in demographics, incidence, access to screening and treatment, and variation in tumor biology and response to therapy., Results: Results were similar across the 3 models. In 2019, racial differences in incidence and competing mortality accounted for a net ‒1% of mortality disparities, while tumor subtype and stage distributions accounted for a mean of 20% (range across models = 13%-24%), and screening accounted for a mean of 3% (range = 3%-4%) of the modeled mortality disparities. Treatment parameters accounted for the majority of modeled mortality disparities: mean = 17% (range = 16%-19%) for treatment initiation and mean = 61% (range = 57%-63%) for real-world effectiveness., Conclusion: Our model results suggest that changes in policies that target improvements in treatment access could increase breast cancer equity. The findings also highlight that efforts must extend beyond policies targeting equity in treatment initiation to include high-quality treatment completion. This research will facilitate future modeling to test the effects of different specific policy changes on mortality disparities., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Neuroendocrine neoplasms (NENs) of the breast are rare and not well-studied. NEN are subcategorized as well-differentiated neuroendocrine tumor (NET) and poorly differentiated neuroendocrine carcinoma (NEC). The objectives of the current study were to review the clinicopathologic features of NENs, therapeutic efficacy of current systemic therapy and clinical outcomes of NEN of the breast., Methods: Between 2004 and 2015, 420 NET, 205 NEC, 146 Adenocarcinoma with NE differentiation (ACNED) and 1,479,520 of invasive carcinoma, not otherwise specified (IC-NOS) of the breast were identified in the National Caner Database. Overall survival was compared among groups using Kaplan-Meier method and Log-rank test. Multivariate analyses were performed to identify prognostic factors., Results: After adjusting for other prognostic factors, both NET and NEC of the breast showed significantly worse OS than IC-NOS (HR (95% CI) = 1.41 (1.17, 1.72), p = 0.005 and HR (95% CI) = 2.11 (1.67, 2.67), p < 0.001, respectively). Both NET and NEC benefited from endocrine therapy if the tumors were hormonal receptor positive (median OS for treated with vs without: 125 vs 57 months in NET, not reached vs 29 months in NEC). NEC also benefited from chemotherapy (median OS for treated with vs without: 42 vs 34 months), but not NET., Conclusion: NEN is a unique pathologic and clinical entity, which has worse clinical outcome compared to IC-NOS of the breast. Current therapeutics used in the treatment of IC-NOS improve, but do not fully mitigate, the poorer prognosis of NEN patients. More effective therapy for patients with this unique tumor type are needed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: High mammographic density is among the strongest and most established predictors for breast cancer risk. Puberty, the period during which breasts undergo exponential mammary growth, is considered one of the critical stages of breast development for environmental exposures. Benzylbutyl phthalate (BBP) and perfluorooctanoic acid (PFOA) are pervasive endocrine disrupting chemicals that may increase hormone-sensitive cancers. Evaluating the potential impact of BBP and PFOA exposure on pubertal breast density is important to our understanding of early-life environmental influences on breast cancer etiology., Objective: To prospectively assess the effect of biomarker concentrations of monobenzyl phthalate (MBzP) and PFOA at specific pubertal window of susceptibility (WOS) on adolescent breast density., Method: This study included 376 Chilean girls from the Growth and Obesity Cohort Study with data collection at four timepoints: Tanner breast stages 1 (B1) and 4 (B4), 1- year post- menarche (1YPM) and 2-years post-menarche (2YPM). Dual-energy X-ray absorptiometry was used to assess the absolute fibroglandular volume (FGV) and percent breast density (%FGV) at 2YPM. We used concentrations of PFOA in serum and MBzP in urine as an index of exposure to PFOA and BBP, respectively. Parametric G-formula was used to estimate the time-specific effects of MBzP and PFOA on breast density. The models included body fat percentage as a time-varying confounder and age, birthweight, age at menarche, and maternal education as fixed covariates., Results: A doubling of serum PFOA concentration at B4 resulted in a non-significant increase in absolute FGV (β:11.25, 95% confidence interval (CI): -0.28, 23.49)), while a doubling of PFOA concentration at 1YPM resulted in a decrease in % FGV (β:-4.61, 95% CI: -7.45, -1.78). We observed no associations between urine MBzP and breast density measures., Conclusion: In this cohort of Latina girls, PFOA serum concentrations corresponded to a decrease in % FGV. No effect was observed between MBzP and breast density measures across pubertal WOS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Importance: Increased use of recommended screening could help achieve the Cancer Moonshot goal of reducing US cancer deaths., Objective: To estimate the number of cancer deaths that could be prevented with a 10-percentage point increase in the use of US Preventive Services Task Force (USPSTF)-recommended screening., Design, Setting, and Participants: This decision analytical model study is an extension of previous studies conducted for the USPSTF from 2018 to 2023. This study simulated contemporary cohorts of US adults eligible for lung, colorectal, breast, and cervical cancer screening., Exposures: Annual low-dose computed lung tomography among eligible adults aged 50 to 80 years; colonoscopy every 10 years among adults aged 45 to 75 years; biennial mammography among female adults aged 40 to 74 years; and triennial cervical cytology screening among female adults aged 21 to 29 years, followed by human papillomavirus testing every 5 years from ages 30 to 65 years., Main Outcomes and Measures: Estimated number of cancer deaths prevented with a 10-percentage point increase in screening use, assuming screening commences at the USPSTF-recommended starting age and continues throughout the lifetime. Outcomes were presented 2 ways: (1) per 100 000 and (2) among US adults in 2021; and they were expressed among the target population at the age of screening initiation. For lung cancer, estimates were among those who will also meet the smoking eligibility criteria during their lifetime. Harms from increased uptake were also reported., Results: A 10-percentage point increase in screening use at the age that USPSTF recommended screening commences was estimated to prevent 226 lung cancer deaths (range across models within the cancer site, 133-332 deaths), 283 (range, 263-313) colorectal cancer deaths, 82 (range, 61-106) breast cancer deaths, and 81 (1 model; no range available) cervical cancer deaths over the lifetimes of 100 000 persons eligible for screening. These rates corresponded with an estimated 1010 (range, 590-1480) lung cancer deaths prevented, 11 070 (range, 10 280-12 250) colorectal cancer deaths prevented, 1790 (range, 1330-2310) breast cancer deaths prevented, and 1710 (no range available) cervical cancer deaths prevented over the lifetimes of eligible US residents at the recommended age to initiate screening in 2021. Increased uptake was also estimated to generate harms, including 100 000 (range, 45 000-159 000) false-positive lung scans, 6000 (range, 6000-7000) colonoscopy complications, 300 000 (range, 295 000-302 000) false-positive mammograms, and 348 000 (no range available) colposcopies over the lifetime., Conclusions and Relevance: In this decision analytical model study, a 10-percentage point increase in uptake of USPSTF-recommended lung, colorectal, breast, and cervical cancer screening at the recommended starting age was estimated to yield important reductions in cancer deaths. Achieving these reductions is predicated on ensuring equitable access to screening.

Breast carcinomas classified based on traditional morphologic assessment provide useful prognostic information. Although morphology is still the gold standard of classification, recent advances in molecular technologies have enabled the classification of these tumors into four distinct subtypes based on its intrinsic molecular profile that provide both predictive and prognostic information. This article describes the association between the different molecular subtypes with the histologic subtypes of breast cancer and illustrates how these subtypes may affect the appearance of tumors on imaging studies., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To estimate the proportion of patients visiting urgent care centers or emergency departments or being hospitalized who were not up to date with recommended mammography screening to assess the potential impact of non-primary care-based cancer screening interventions., Methods: Adult participants from the 2019 National Health Interview Survey were included. Among participants not up to date with breast cancer screening guidelines based on ACR recommendations, the proportion of patients reporting an urgent care, emergency department visit, or hospitalization within the last year was estimated accounting for complex survey sampling design features. Multiple variable logistic regression analyses were then conducted to evaluate the association between sociodemographic characteristics and mammography screening adherence., Results: The study included 9,139 women between the ages of 40 and 74 years without history of breast cancer. Of these respondents, 44.9% did not report mammography screening within the last year. Among participants who did not report mammography screening, 29.2% reported visiting an urgent care center, 21.8% reported visiting an emergency room, and 9.6% reported being hospitalized within the last year. The majority of patients receiving non-primary care-based services, who were not up to date with mammography screening, were from historically underserved groups including Black and Hispanic patients., Conclusion: Nearly 10% to 30% of participants who have not obtained recommended breast cancer screening have visited non-primary care-based services including urgent care centers or emergency rooms or have been hospitalized within the last year., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Introduction: The "Going Flat" movement became widely publicized in 2016 and provides information and support to women who choose to forego post-mastectomy breast reconstruction (PMBR). The objectives of this study were to evaluate temporal trends in PMBR to ascertain the potential impact of this movement and assess which factors are associated with going flat., Methods: A retrospective cohort analysis was performed using the NCDB of women with non-metastatic breast cancer who underwent mastectomy between 2004 and 2019. Trends in going flat after mastectomy were examined and stratified by age (< 50, 50-69, ≥ 70). A multivariate logistic regression model was used to identify factors associated with going flat., Results: 650,983 patients met the inclusion criteria: 244,201 (37.5%) underwent PMBR and 406,782 (62.5%) went flat. Among women < 70, rates of going flat steadily decreased from 2004 to 2015 and then stabilized after 2015, coinciding with the rise of the "Going Flat" movement. In multivariate analysis, non-White race, older age, increasing comorbidities, government provided insurance, treatment at a community program, radiotherapy, and adjuvant chemotherapy were associated with a higher likelihood of going flat (p < 0.001)., Conclusion: In the first 2 years after the "Going Flat" movement, the number of women going flat after mastectomy has stabilized in women < 70 for the first time in over a decade. These trends suggest that the social and cultural impact of this movement may have contributed to the stabilization of PMBR rates., (© 2023. Society of Surgical Oncology.)

There is growing interest in application of functional imaging modalities for adjunct breast imaging due to their unique ability to evaluate molecular/pathophysiologic changes, not visible by standard anatomic breast imaging. This has led to increased use of nuclear medicine dedicated breast-specific single photon and coincidence imaging systems for multiple indications, such as supplemental screening, staging of newly diagnosed breast cancer, evaluation of response to neoadjuvant treatment, diagnosis of local disease recurrence in the breast, and problem solving. Studies show that these systems maybe especially useful for specific subsets of patients, not well served by available anatomic breast imaging modalities., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Breast cancer detection has a significant impact on population health. Although there are many breast imaging modalities, mammography is the predominant tool for breast cancer screening. The introduction of digital breast tomosynthesis to mammography has contributed to increased cancer detection rates and decreased recall rates. In average-risk women, starting annual screening mammography at age 40 years has demonstrated the highest mortality reduction. In intermediate- and high-risk women as well as in those with dense breasts, additional modalities, including MRI, ultrasound, and molecular breast imaging, can also be considered for adjunct screening to improve the detection of mammographically occult malignancy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To determine the prevalence of modifiable breast cancer risk factors among women engaged in screening mammography using nationally representative cross-sectional survey data and to inform potential opportunities for breast facilities to contribute to primary prevention., Methods: 2018 National Health Interview Survey respondents who were women ages 40-74 years without history of breast cancer were included and then categorized based on whether they reported screening mammography within the prior two years. Proportions of these women reporting evidence-based modifiable breast cancer risk factors, including elevated body mass index (BMI), lack of physical activity, or moderate or heavy alcohol consumption were calculated and stratified by demographics. Multivariable logistic regression was used to estimate the association between these risk factors and sociodemographic characteristics., Results: Among 4989 women meeting inclusion criteria and reporting screening mammography, 79% reported at least one modifiable risk factor. Elevated BMI was the most reported risk factor (67%), followed by lack of physical activity (24%) and alcohol consumption (16%). The majority of each race/ethnicity category reported at least one modifiable risk factor, with the highest proportion reported by Black respondents (90%). Asian, college educated, and higher-income participants were less likely to have at least one modifiable risk factor., Conclusion: Modifiable breast cancer risk factors are prevalent among women engaged in screening mammography. This provides potential opportunities for breast imaging facilities to contribute to the primary prevention of breast cancer by providing resources for lifestyle modification at the time of screening mammography., (© Society of Breast Imaging 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Racial disparities in breast cancer treatment contribute to Black women having the worst breast cancer survival rates in the U.S. We investigated whether differences in receipt of optimal locoregional treatment (OLT), defined as receipt of mastectomy, breast-conserving surgery, or no surgery when contraindicated, existed between Black and White women with early-stage breast cancer from 2008-2018., Methods: In this retrospective cohort study, data from the Surveillance, Epidemiology, and End Results (SEER) Program Incidence Database was utilized to identify tumor cases from Black and White women aged 20-64 years old with stage I-II breast cancer. Logistic regression analyses were used to evaluate the associations between race and receipt of OLT as well as potential effect modification by tumor characteristics, and year of diagnosis., Results: Among 177,234 women diagnosed with early-stage breast tumors, disparities in OLT between Black and White women were present from 2008-2010 (2008: 82.1% Black vs. 85.7% White, p<0.001; 2009: 82.1% Black vs. 85.8% White, p<0.001; 2010: 82.2% Black vs. 87.2% White, p<0.001). This disparity was eliminated between 2010-2011 (86.3% Black vs. 87.5% White, p = 0.15), and did not reoccur during the remainder of the study period. From 2010-2011, more Black women received radiation therapy following breast-conserving surgery (43.4% to 48.9%; p = 0.001), which accounted for an overall increased receipt of OLT., Conclusion: Increased receipt of radiation therapy with breast-conserving surgery appeared to drive a substantial increase in OLT for Black women from 2010-2011 that lasted throughout the study period. Further research on the underlying mechanisms that reduced this disparity is warranted., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nadeem et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT)., Experimental Design: We collected 460 CHEK2 missense VUS identified by the ENIGMA consortium in 15 countries. Their functional characterization was performed using CHEK2-complementation assays quantifying KAP1 phosphorylation and CHK2 autophosphorylation in human RPE1-CHEK2-knockout cells. Concordant results in both functional assays were used to categorize CHEK2 VUS from 12 ENIGMA case-control datasets, including 73,048 female patients with breast cancer and 88,658 ethnicity-matched controls., Results: A total of 430/460 VUS were successfully analyzed, of which 340 (79.1%) were concordant in both functional assays and categorized as functionally impaired (N = 102), functionally intermediate (N = 12), or functionally wild-type (WT)-like (N = 226). We then examined their association with breast cancer risk in the case-control analysis. The OR and 95% CI (confidence intervals) for carriers of functionally impaired, intermediate, and WT-like variants were 2.83 (95% CI, 2.35-3.41), 1.57 (95% CI, 1.41-1.75), and 1.19 (95% CI, 1.08-1.31), respectively. The meta-analysis of population-specific datasets showed similar results., Conclusions: We determined the functional consequences for the majority of CHEK2 missense VUS found in patients with breast cancer (3,660/4,436; 82.5%). Carriers of functionally impaired missense variants accounted for 0.5% of patients with breast cancer and were associated with a moderate risk similar to that of truncating CHEK2 variants. In contrast, 2.2% of all patients with breast cancer carried functionally wild-type/intermediate missense variants with no clinically relevant breast cancer risk in heterozygous carriers., (©2023 The Authors; Published by the American Association for Cancer Research.)

Arginine methylation catalyzed by protein arginine methyltransferases (PRMTs) is a prevalent post-translational modification (PTM) that regulates diverse cellular processes. Aberrant expression of type I PRMTs that catalyze asymmetric arginine dimethylation (ADMA) is often found in cancer, though little is known about the ADMA status of substrate proteins in tumors. Using LC-MS/MS along with pan-specific ADMA antibodies, we performed global mapping of ADMA in five patient-derived xenograft (PDX) tumors representing different subtypes of human breast cancer. In total, 403 methylated sites from 213 proteins were identified, including 322 novel sites when compared to the PhosphositesPlus database. Moreover, using peptide arrays in vitro , approximately 70% of the putative substrates were validated to be methylated by PRMT1, PRMT4, and PRMT6. Notably, when compared with our previously identified ADMA sites from breast cancer cell lines, only 75 ADMA sites overlapped between cell lines and PDX tumors. Collectively, this study provides a useful resource for both PRMT and breast cancer communities for further exploitation of the functions of PRMT dysregulation during breast cancer progression.

Pathogenic protein-truncating variants of RAD51C, which plays an integral role in promoting DNA damage repair, increase the risk of breast and ovarian cancer. A large number of RAD51C missense variants of uncertain significance (VUS) have been identified, but the effects of the majority of these variants on RAD51C function and cancer predisposition have not been established. Here, analysis of 173 missense variants by a homology-directed repair (HDR) assay in reconstituted RAD51C-/- cells identified 30 nonfunctional (deleterious) variants, including 18 in a hotspot within the ATP-binding region. The deleterious variants conferred sensitivity to cisplatin and olaparib and disrupted formation of RAD51C/XRCC3 and RAD51B/RAD51C/RAD51D/XRCC2 complexes. Computational analysis indicated the deleterious variant effects were consistent with structural effects on ATP-binding to RAD51C. A subset of the variants displayed similar effects on RAD51C activity in reconstituted human RAD51C-depleted cancer cells. Case-control association studies of deleterious variants in women with breast and ovarian cancer and noncancer controls showed associations with moderate breast cancer risk [OR, 3.92; 95% confidence interval (95% CI), 2.18-7.59] and high ovarian cancer risk (OR, 14.8; 95% CI, 7.71-30.36), similar to protein-truncating variants. This functional data supports the clinical classification of inactivating RAD51C missense variants as pathogenic or likely pathogenic, which may improve the clinical management of variant carriers., Significance: Functional analysis of the impact of a large number of missense variants on RAD51C function provides insight into RAD51C activity and information for classification of the cancer relevance of RAD51C variants., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Breast-conserving surgery (BCS) is an integral component of early-stage breast cancer treatment, but costly reexcision procedures are common due to the high prevalence of cancer-positive margins on primary resections. A need exists to develop and evaluate improved methods of margin assessment to detect positive margins intraoperatively., Methods: A prospective trial was conducted through which micro-computed tomography (micro-CT) with radiological interpretation by three independent readers was evaluated for BCS margin assessment. Results were compared to standard-of-care intraoperative margin assessment (i.e., specimen palpation and radiography [abbreviated SIA]) for detecting cancer-positive margins., Results: Six hundred margins from 100 patients were analyzed. Twenty-one margins in 14 patients were pathologically positive. On analysis at the specimen-level, SIA yielded a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 42.9%, 76.7%, 23.1%, and 89.2%, respectively. SIA correctly identified six of 14 margin-positive cases with a 23.5% false positive rate (FPR). Micro-CT readers achieved sensitivity, specificity, PPV, and NPV ranges of 35.7-50.0%, 55.8-68.6%, 15.6-15.8%, and 86.8-87.3%, respectively. Micro-CT readers correctly identified five to seven of 14 margin-positive cases with an FPR range of 31.4-44.2%. If micro-CT scanning had been combined with SIA, up to three additional margin-positive specimens would have been identified., Discussion: Micro-CT identified a similar proportion of margin-positive cases as standard specimen palpation and radiography, but due to difficulty distinguishing between radiodense fibroglandular tissue and cancer, resulted in a higher proportion of false positive margin assessments., (© 2023. Society of Surgical Oncology.)

Purpose: To evaluate geographic accessibility of ACR mammographic screening (MS), lung cancer screening (LCS), and CT colorectal cancer screening (CTCS) centers among US federally recognized American Indian and Alaskan Native (AI/AN) tribes., Methods: Distances from AI/AN tribes' ZIP codes to their closest ACR-accredited LCS and CTCS centers were recorded using tools from the ACR website. The FDA's database was used for MS. Persistent adult poverty (PPC-A), persistent child poverty (PPC-C), and rurality indexes (rural-urban continuum codes) were from the US Department of Agriculture. Logistic and linear regression analyses were used to assess distances to screening centers and relationships among rurality, PPC-A, and PPC-C., Results: Five hundred ninety-four federally recognized AI/AN tribes met the inclusion criteria. Among all closest MS, LCS, or CTCS center to AI/AN tribes, 77.8% (1,387 of 1,782) were located within 200 miles, with a mean distance of 53.6 ± 53.0 miles. Most tribes (93.6% [557 of 594]) had MS centers within 200 miles, 76.4% (454 of 594) had LCS centers within 200 miles, and 63.5% (376 of 594) had CTCS centers within 200 miles. Counties with PPC-A (odds ratio [OR], 0.47; P < .001) and PPC-C (OR, 0.19; P < .001) were significantly associated with decreased odds of having a cancer screening center within 200 miles. PPC-C was associated with decreased likelihood of having an LCS center (OR, 0.24; P < .001) and an CTCS center (OR, 0.52; P < .001) within the same state as the tribe's location. No significant association was found between PPC-A and PPC-C and MS centers., Conclusions: AI/AN tribes experience distance barriers to ACR-accredited screening centers, resulting in cancer screening deserts. Programs are needed to increase equity in screening access among AI/AN tribes., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: PAM50 profiling assigns each breast cancer to a single intrinsic subtype based on a bulk tissue sample. However, individual cancers may show evidence of admixture with an alternate subtype that could affect prognosis and treatment response. We developed a method to model subtype admixture using whole transcriptome data and associated it with tumor, molecular, and survival characteristics for Luminal A (LumA) samples., Methods: We combined TCGA and METABRIC cohorts and obtained transcriptome, molecular, and clinical data, which yielded 11,379 gene transcripts in common and 1,178 cases assigned to LumA. We used semi-supervised non-negative matrix factorization (ssNMF) to compute the subtype admixture proportions of the four major subtypes-pLumA, pLumB, pHER2, and pBasal-for each case and measured associations with tumor characteristics, molecular features, and survival., Results: Luminal A cases in the lowest versus highest quartile for pLumA transcriptomic proportion had a 27% higher prevalence of stage > 1, nearly a threefold higher prevalence of TP53 mutation, and a hazard ratio of 2.08 for overall mortality. We found positive associations between pHER2 and HER2 positivity by IHC or FISH; between pLumB and PR negativity; and between pBasal and younger age, node positivity, TP53 mutation, and EGFR expression. Predominant basal admixture, in contrast to predominant LumB or HER2 admixture, was not associated with shorter survival., Conclusion: Bulk sampling for genomic analyses provides an opportunity to expose intratumor heterogeneity, as reflected by subtype admixture. Our results elucidate the striking extent of diversity among LumA cancers and suggest that determining the extent and type of admixture holds promise for refining individualized therapy. LumA cancers with a high degree of basal admixture appear to have distinct biological characteristics that warrant further study., (© 2023. The Author(s).)

Purpose of Review: The study aims to review the literature regarding musculoskeletal complications of aromatase inhibitors and treatment options for these complications., Recent Findings: Aromatase inhibitors are common medications to treat hormone receptor-positive breast cancer in postmenopausal women and have been shown to improve survival and prevent disease recurrence. However, 20-60% patients stop treatment prematurely due to side effects. Side effects include joint stiffness and pain, tendonitis, tendon tears, muscle pain, and carpal tunnel syndrome known as aromatase inhibitor musculoskeletal syndrome (AIMSS) as well as bone loss. Proposed mechanisms of AIMSS include decreased estrogen levels, inflammation, and genetic factors. Switching aromatase inhibitors, exercise, non-steroidal anti-inflammatory medications, duloxetine, acupuncture, prednisone, and bisphosphonates are some treatment options for this syndrome and will be discussed in more detail in this review. Aromatase inhibitors are important in the treatment of hormone receptor-positive breast cancer in postmenopausal women. As we study the incidence of side effects of these medications including bone loss and AIMSS and determine the mechanisms of these symptoms and possible treatment options, we will decrease the incidence of patients discontinuing treatment prematurely and improve symptoms, quality of life, and survival in this patient population., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The aim of this study was to evaluate the presence or absence of accredited breast imaging facilities in ZIP codes with high or low neighborhood socioeconomic deprivation., Methods: A retrospective ecological study design was used. Neighborhood socioeconomic disadvantage rankings at the ZIP code level were defined by the University of Wisconsin Neighborhood Atlas Area Deprivation Index. Outcomes included the presence or absence of FDA- or ACR-accredited mammographic facilities, accredited stereotactic biopsy or breast ultrasound facilities, and ACR Breast Imaging Centers of Excellence. US Department of Agriculture rural-urban commuting area codes were used to define urban and rural status. Access to breast imaging facilities in high-disadvantage (≥97th percentile) and low-disadvantage (≤3rd percentile) ZIP codes was compared using χ 2 tests, stratified by urban or rural status., Results: Among 41,683 ZIP codes, 2,796 were classified as high disadvantage (1,160 rural, 1,636 urban) and 1,028 as low disadvantage (39 rural, 989 urban). High-disadvantage ZIP codes were more likely rural (P < .001) and less likely to have FDA-certified mammographic facilities (28% versus 35%, P < .001), ACR-accredited stereotactic biopsy (7% versus 15%, P < .001), breast ultrasound (9% versus 23%, P < .001), or Breast Imaging Centers of Excellence (7% versus 16%, P < .001). Among urban areas, high-disadvantage ZIP codes were less likely to have FDA-certified mammographic facilities (30% versus 36%, P = .002), ACR-accredited stereotactic biopsy (10% versus 16%, P < .001), breast ultrasound (13% versus 23%, P < .001), and Breast Imaging Centers of Excellence (10% versus 16%, P < .001)., Conclusions: People living in ZIP codes with high socioeconomic disadvantage are less likely to have accredited breast imaging facilities within their ZIP codes, which may contribute to disparities in access to breast cancer care experienced by underserved groups living in these areas., (Copyright © 2023 American College of Radiology. All rights reserved.)

Objective: While the American College of Radiology recommends annual screening mammography starting at age 40 years, the US Preventive Services Task Force (USPSTF) recommends that screening mammography in women younger than age 50 years should involve shared- decision making (SDM) between clinicians and patients, considering benefits and potential harms in younger women. Using a nationally representative cross-sectional survey, we aimed to evaluate patient-reported reasons and predictors of screening mammography utilization in this age group., Methods: Respondents aged 40-49 years from the 2018 National Health Interview Survey (NHIS) without a history of breast cancer were included (response rate 64%). Participants reported sociodemographic variables and reasons they did not engage in mammography screening within the last two years. Multiple variable logistic regression analyses were performed to evaluate the association between sociodemographic characteristics and patient-reported screening mammography use, accounting for complex survey sampling design elements., Results: 1,948 women between the ages of 40-49 years were included. Of this group, (758/1948) 46.6% reported receiving a screening mammogram within the last year, and 1196/1948 (61.4%) reported receiving a screening mammogram within the last two years. The most common reasons for not undergoing screening included: "No reason/never thought about it" 744/1948 (38.2%), "Put it off" 343/1948 (17.6%), "Didn't need it" 331/1948 (16.9%), "Doctor didn't order it" 162/1948 (8.3%), and "I'm too young" 63/1948 (5.3%). Multiple variable analyses demonstrated that lack of health insurance was the strongest predictor of mammography non-engagement (p< 0.001)., Conclusion: Deficits in shared- decision-making in women younger than 50 years related to mammography utilization exist. Radiologists may be key in addressing this issue among ambulatory care providers and patients, educating about the benefits and harms of screening younger women, particularly in racial/ethnic minorities and uninsured patients, who experience additional barriers to care and SDM discussions., (Copyright © 2022 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Introduction: The objective is to expand our understanding of the factors associated with receipt of breast reconstruction for socioeconomically disadvantaged women within Wisconsin., Methods: A purposeful sample of general/breast and plastic surgeons were identified. One-on-one interviews were conducted, audio-recorded, and transcribed in full (n = 15). Conventional content analysis was performed to identify themes., Results: Both general/breast and plastic surgeons perceived that general/breast surgeons served as gatekeepers to which patients are offered a referral for reconstruction. Given the additional recovery time, frequent clinic visits, and potential for complications associated with reconstruction, general/breast surgeons perceived that not all women prioritize it. Surgeons perceived this to be especially true for socioeconomically disadvantaged women. Surgeons identified time off work, travel for visits, and out-of-pocket costs as specific challenges to reconstruction experienced by socioeconomically disadvantaged women. Surgeons perceived that early education, incorporating financial considerations into discussions, and reducing travel burden may help to improve access to reconstruction., Conclusion: Wisconsin surgeons described factors they perceived contributed to lower rates of reconstruction for socioeconomically disadvantaged women and described ways to increase reconstruction access., (Copyright © 2023. Published by Elsevier Inc.)

Background: Diabetes mellitus has been associated with increased breast cancer (BC) risk; however, the magnitude of this effect is uncertain. This study focused on BC risk for women with type 2 diabetes mellitus (T2DM)., Methods: Two separate meta-analyses were conducted (1) to estimate the relative risk (RR) of BC for women with T2DM and (2) to evaluate the risk of BC for women with T2DM associated with the use of metformin, a common diabetes treatment. In addition, subgroup analyses adjusting for obesity as measured by body mass index (BMI) and menopausal status were also performed. Studies were identified via PubMed/Scopus database and manual search through April 2021., Results: A total of 30 and 15 studies were included in the first and second meta-analyses, respectively. The summary RR of BC for women with T2DM was 1.15 (95% confidence interval [CI], 1.09-1.21). The subgroup analyses adjusting BMI and adjusting BMI and menopause resulted in a summary RR of 1.22 (95% CI, 1.15-1.30) and 1.20 (95% CI, 1.05-1.36), respectively. For women with T2DM, the summary RR of BC was 0.82 (95% CI, 0.60-1.12) for metformin users compared with nonmetformin users., Conclusions: Women with T2DM were more likely to be diagnosed with BC and this association was strengthened by adjusting for BMI and menopausal status. No statistically significant reduction of BC risk was observed among metformin users., Impact: These two meta-analyses can inform decision-making for women with type 2 diabetes regarding their use of metformin and the use of screening mammography for early detection of breast cancer., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: We sought to evaluate local/regional recurrence rates after breast-conserving surgery in a cohort of patients enrolled in legacy trials of the Alliance for Clinical Trials in Oncology and to evaluate variation in recurrence rates by receptor subtype., Background: Multiple randomized controlled trials have demonstrated equivalent survival between breast conservation and mastectomy, albeit with higher local/regional recurrence rates after breast conservation. However, absolute rates of local/regional recurrence have been declining with multi-modality treatment., Methods: Data from 5 Alliance for Clinical Trials in Oncology legacy trials that enrolled women diagnosed with breast cancer between 1997 and 2010 were included. Women who underwent breast-conserving surgery and standard systemic therapies (n=4,404) were included. Five-year rates of local/regional recurrence were estimated from Kaplan-Meier curves. Patients were censored at the time of distant recurrence (if recorded as the first recurrence), death, or last follow-up. Multivariable Cox proportional hazards models were used to identify factors associated with time to local/regional recurrence, including patient age, tumor size, lymph node status, and receptor subtype., Results: Overall 5-year recurrence was 4.6% (95% CI=4.0-5.4%). Five-year recurrence rates were lowest in those with ER+ or PR+ tumors (Her2+ 3.4% [95% CI 2.0-5.7%], Her2- 4.0% [95% CI 3.2-4.9%]) and highest in the triple-negative subtype (7.1% [95% CI 5.4-9.3%]). On multivariable analysis, increasing nodal involvement and triple-negative subtype were positively associated with recurrence ( P <0.0001)., Conclusions: Rates of local/regional recurrence after breast conservation in women with breast cancer enrolled in legacy trials of the Alliance for Clinical Trials in Oncology are significantly lower than historic estimates. This data can better inform patient discussions and surgical decision-making., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Risk-stratified follow-up guidelines that account for the absolute risk and timing of recurrence may improve the quality and efficiency of breast cancer follow-up. The objective of this study was to assess the relationship of anatomic stage and receptor status with timing of the first recurrence for patients with local-regional breast cancer and generate risk-stratified follow-up recommendations., Methods: The authors conducted a secondary analysis of 8007 patients with stage I-III breast cancer who enrolled in nine Alliance legacy clinical trials from 1997 to 2013 (ClinicalTrials.gov identifier NCT02171078). Patients who received standard-of-care therapy were included. Patients who were missing stage or receptor status were excluded. The primary outcome was days from the earliest treatment start date to the date of first recurrence. The primary explanatory variable was anatomic stage. The analysis was stratified by receptor type. Cox proportional-hazards regression models produced cumulative probabilities of recurrence. A dynamic programming algorithm approach was used to optimize the timing of follow-up intervals based on the timing of recurrence events., Results: The time to first recurrence varied significantly between receptor types (p < .0001). Within each receptor type, stage influenced the time to recurrence (p < .0001). The risk of recurrence was highest and occurred earliest for estrogen receptor (ER)-negative/progesterone receptor (PR)-negative/Her2neu-negative tumors (stage III; 5-year probability of recurrence, 45.5%). The risk of recurrence was lower for ER-positive/PR-positive/Her2neu-positive tumors (stage III; 5-year probability of recurrence, 15.3%), with recurrences distributed over time. Model-generated follow-up recommendations by stage and receptor type were created., Conclusions: This study supports considering both anatomic stage and receptor status in follow-up recommendations. The implementation of risk-stratified guidelines based on these data has the potential to improve the quality and efficiency of follow-up., (© 2023 American Cancer Society.)

PET imaging with 16α- 18 F-fluoro-17β-fluoroestradiol ( 18 F-FES), a radiolabeled form of estradiol, allows whole-body, noninvasive evaluation of estrogen receptor (ER). 18 F-FES is approved by the U.S. Food and Drug Administration as a diagnostic agent "for the detection of ER-positive lesions as an adjunct to biopsy in patients with recurrent or metastatic breast cancer." The Society of Nuclear Medicine and Molecular Imaging (SNMMI) convened an expert work group to comprehensively review the published literature for 18 F-FES PET in patients with ER-positive breast cancer and to establish appropriate use criteria (AUC). The findings and discussions of the SNMMI 18 F-FES work group, including example clinical scenarios, were published in full in 2022 and are available at https://www.snmmi.org/auc Of the clinical scenarios evaluated, the work group concluded that the most appropriate uses of 18 F-FES PET are to assess ER functionality when endocrine therapy is considered either at initial diagnosis of metastatic breast cancer or after progression of disease on endocrine therapy, the ER status of lesions that are difficult or dangerous to biopsy, and the ER status of lesions when other tests are inconclusive. These AUC are intended to enable appropriate clinical use of 18 F-FES PET, more efficient approval of FES use by payers, and promotion of investigation into areas requiring further research. This summary includes the rationale, methodology, and main findings of the work group and refers the reader to the complete AUC document., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background and Objectives: Previous studies have identified racial-ethnic differences in the diagnostic patterns and recurrence outcomes of women with phyllodes tumors (PT). However, these studies are generally limited in size and generalizability. We therefore sought to explore racial-ethnic differences in age, tumor size, subtype, and recurrence in a large US cohort of women with PT., Methods: We performed an 11-institution retrospective review of women with PT from 2007 to 2017. Differences in age at diagnosis, tumor size and subtype, and recurrence-free survival according to race-ethnicity., Results: Women of non-White race or Hispanic ethnicity were younger at the time of diagnosis with phyllodes tumor. Non-Hispanic Other women had a larger proportion of malignant PT. There were no differences in recurrence-free survival in our cohort., Conclusions: Differences in age, tumor size, and subtype were small. Therefore, the workup of young women with breast masses and the treatment of women with PT should not differ according to race-ethnicity. These conclusions are supported by our finding that there were no differences in recurrence-free survival., (© 2022 Wiley Periodicals LLC.)