Citations

Critically ill patients frequently require intrahospital transport (IHT) to diagnostic exams or procedures and must remain connected to life-sustaining medical lines. During IHT, the risk of tangled medical lines is unavoidable. The idea for a novel medical line securement device was inspired by a patient transport nurse due to frustrations and workflow inefficiencies managing tangled medical lines. The study aim was to explore the correlation between the utilization of a single-use securement device to manual or accidental disconnections of medical lines during IHT, and nurses’ perception of efficiency, compared to the current practice of no utilization of a securement device. In 2019, a randomized, descriptive, correlational study was conducted on 142 progressive and intensive care hospitalized patients. Study coordinators measured the number of times either IV lines or monitor cords were accidentally or manually disconnected to detangle during or after transportation and the perception of transport efficiency. Results revealed fewer manual disconnections among intervention group compared to the control. Nurses’ perception regarding the efficiency between the intervention and control group was statistically significant when the device was utilized to secure the lines and cords during transport. Nurses reported much higher satisfaction rates of transport efficiency when the device was used. This finding showed the device’s utility for improving nurse satisfaction during IHT of critically ill patients. Utilization of the medical line securement device may be generalizable across other healthcare settings and disciplines where the complexity of medical lines may exist.

Abstract Background: Up to 50% of patients with breast cancer experience chemotherapy-inducednausea (CIN) and 95% experience fatigue. A comprehensive understanding of biological mechanisms remains elusive. Herein, we evaluated the association of CIN and fatigue with clinical and multi-omics features, including serum and stool metabolites before (T1) to after chemotherapy (T2). Methods: Patients with breast cancer (n=36) who were to receive chemotherapy, provided symptom assessment using the Memorial Symptom Assessment Scale, stool and blood samples at T1 and T2. Patients provided dietary intake data using a Dietary Screener Questionnaire at T1. Descriptive and univariate analyses evaluated associations of co-occurringsymptoms and diet with CIN and fatigue at T2. Gut microbiome was sequenced using shotgun metagenomics. Targeted metabolomics was performed on stool and serum. Shift in the abundance of taxonomic groups and metabolite levels from T1 to T2 were evaluated in association with CIN and fatigue. Results: Approximately 64% of the patients experienced CIN and 94% experienced fatigue atT2. Three gastrointestinal symptoms co-occurred with CIN and fatigue. Higher daily average intake of calcium (p=0.013) and dairy (p=0.035) were associated with CIN. Levels of hexosylceramides, ceramide, phosphatidylcholine and sphingomyelins were significantly perturbed in association with CIN and fatigue (p<0.05). Conclusion: CIN and fatigue are associated with perturbation in the sphingolipid turnover pathway, which negatively impacts functions in the gut-liver axis that include apoptosis activity and change in bile acid levels. Confirmatory studies are warranted to support the development of interventions to alleviate CIN and fatigue in patients with breast cancer receiving chemotherapy.Keywords: breast cancer; chemotherapy-induced nausea; fatigue; metabolites; sphingolipids Citation Format: Komal Preet Singh, Brenda J. Ernst, Jun Chen, Surendra Dasari, Felipe Batalini, Cindy Tofthagen, Kathryn J. Ruddy, Keenan Pituch, Linda Chlan. Perturbations in gut liver axis functions are associated with chemotherapy induced nausea and fatigue in patients with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6309.

Abstract Background: Patients with residual invasive disease after neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer remain at high risk for recurrence even with standard adjuvant trastuzumab emtansine (T-DM1). H2NVAC, a multi-epitope HER2 peptide vaccine, has previously demonstrated the ability to elicit robust and durable immune responses. Here, we assessed the safety and early immunogenicity of H2NVAC in combination with T-DM1 in this high-risk population. Methods: Patients with stage II-III HER2-positive breast cancer and residual invasive disease following NAC and HER2-directed therapy received standard adjuvant T-DM1 alongside six priming doses of H2NVAC administered every 3 weeks. The primary endpoint was the occurrence of dose-limiting toxicity (DLT) within 21 days of the first vaccination, with adverse events graded per CTCAE v5.0. Immunogenicity assessments included HER2-specific T-cell responses measured by IFNγ ELISpot and HER-specific serum antibodies measured by ELISA at baseline and 30 days after the sixth priming dose. Results: 20 patients were enrolled. H2NVAC plus T-DM1 was well tolerated with no DLTs observed. All treatment-emergent AEs were grade 1-2, with fatigue (grade 1 60%, grade 2 5%), peripheral sensory neuropathy (grade 1 35%, grade 2 10%), elevated alkaline phosphatase (grade 1 40%), nausea (grade 1 35%, grade 2 5%), arthralgia (grade 1 30%), and injection-site reactions (grade 1 50%) being most common. Robust vaccine-specific T-cell responses by ELISpot were observed in 94% of evaluable patients, who mounted HER2-specific T-cell responses at 30 days after the sixth priming dose, with a mean 197-fold increase over baseline. Further CYTOF analysis showed a significant decrease in exhausted T-cell phenotypes, with reduced LAG3 and TIM3 expression on both CD4+ and CD8+ T cells. For antibody responses by ELISA, 26% of patients developed HER2 protein-specific antibody responses at this time point. There was no significant increase in antibodies to H2NVAC peptides or to unrelated tumor antigens (p53, IGFBP2, TERT, myoglobin) at 30 days after the sixth vaccine. Ongoing correlative analyses will assess the evolution of immune responses at later time points following completion of T-DM1 therapy. Conclusions: Concurrent administration of H2NVAC with T-DM1 was safe and did not increase toxicity beyond single-agent T-DM1. To our knowledge, this is the first study to demonstrate that a cancer vaccine can be delivered concurrently with an antibody-drug conjugate without increasing adverse effects while still eliciting robust T-cell responses. Ongoing analyses will further define the kinetics and durability of vaccine-induced antibody and T-cell responses at later time points, as well as evaluate the efficacy of H2NVAC in reducing recurrence risk in the randomized phase 2 trial. Citation Format: Saranya Chumsri, Sharmila Giri, Andy J. Ness, David W. Hillman, Nadine Norton, Davitte Cogen, Brian M. Necela, Aziza Nassar, Donald W. Northfelt, Pooja Advani, Rohit Rao, Alvaro Mareno-Aspitia, Brenda Ernst, Kathryn J. Ruddy, Matthew P. Goetz, Keith L. Knutson. Safety, tolerability, and early immune responses in the safety run-in of an HER2 multi-epitope vaccine combined with T-DM1 in residual HER2-positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6715.

Abstract Background: Accurate staging is essential for treatment selection, prognosis assessment, and trial eligibility. While prior studies attempted automating pathological (p) staging, few address clinical (c) staging and no studies have compared LLM-derived staging with clinician staging during clinical visit and retrospective cancer registry staging. Methods: We developed a multi-agent framework using Gemini-2.0-Flash-001 and GPT-5 to (1) identify reports (2) extract key data, and (3) apply AJCC 8th edition staging criteria. LLM staging was compared with clinician documentation and registry staging in breast cancer patients. Clinician-registry agreement served as the reference standard. Two independent breast oncologists reviewed discordant cases. Results: We analyzed 122 randomly selected breast cancer patients across all three Mayo Clinic sites from 2018 - 2023. LLM performance matched or exceeded human inter-rater agreement for pathological staging (95-99.2% vs. 95-98.4%). Clinical staging was more challenging, with LLM concordance of 73-77.9% for cT and 87-89.3% for cN versus 87.8% and 91.0% clinician-registry agreement. Among 89 patients with clinician-registry concordance, LLM concordance was 98.9% for pT/pN, 79.8% for cT, and 91.0% for cN. Experts favored LLM staging in 27.8% (5/18) of cT and 25.0% (2/8) of cN discordances. Error analysis revealed LLM challenges in handling non-mass enhancements (6 cases), selecting radiologic measurements (2 cases), identifying discrete masses (2 cases), and miscellaneous (3 cases). Conclusion: LLMs achieved human-level performance for pathological staging (98%), supporting human-in-the-loop deployment. For clinical staging (79.8% cT, 91.0% cN), future work must enhance multimodal reasoning and integrate physical examination data. Prospective validation is needed to assess real-world impact. With targeted refinements and oversight, automated staging can transform registry workflows while augmenting clinical decision-making. Citation Format: Arshad Mohammed, Umair Ayub, Pooja Advani, Shakeela W. Bahadur, Amye J. Tevaarwerk, Tufia C. Haddad, Elisabeth I. Heath, Brenda J. Ernst, Ben Zhou, Cui Tao, Sara J. Holton, Karthik V. Giridhar, Irbaz B. Riaz. Automating clinical and pathological staging for breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2744.

Abstract Myocardial infarction (MI) triggers a systemic neutrophil response, yet the roles of distinct neutrophil subsets in cardiac remodeling remain unclear. Studying this requires murine models that accurately mirror human neutrophil dynamics. Here, we show that a minimally invasive intact-chest MI model is more pathophysiologically relevant than the standard open-chest approach for investigating post-MI immune responses. In the open-chest model, surgical trauma disrupts bone marrow homeostasis, releases large numbers of immature neutrophils, and masks MI-specific immune mechanisms. In contrast, the intact-chest model preserves bone marrow integrity and induces only a modest rise in circulating immature neutrophils, closely reflecting MI patient profiles. We further demonstrate that accumulation of immature neutrophils in the infarcted heart exacerbates cardiac dysfunction. Beyond neutrophils, the overall cardiac immune landscape differs markedly between both models. Collectively, our findings establish the intact-chest model as superior for studying post-MI inflammation and reveal immature neutrophils as mediators of adverse cardiac remodeling.

ABSTRACT Background Sunlight has profound impacts on physical and mental health, beyond vision, including effects on circadian rhythms, alertness, mood, and sleep. A family history of any mood disorders is strongly associated with psychiatric disorders including bipolar disorder. The purpose of this study was to evaluate the association between a family history of any mood disorder in patients with bipolar I disorder and solar insolation at varied international onset locations. Methods Data for this analysis were available from 5842 patients with a diagnosis of bipolar I disorder obtained at 83 collection sites in both hemispheres. This included 4752 patients from 71 collection sites in the northern hemisphere and 1090 patients from 12 collection sites in the southern hemisphere. Patient data variables were obtained from records or interviews. Solar insolation data were obtained from The National Aeronautics and Space Administration (NASA) Power database for each onset location, and the ratio of the mean monthly minimum/mean monthly maximum solar insolation was calculated. Typically, the ratio is largest near the equator (little yearly change in solar insolation) and smallest near the poles (large yearly change in solar insolation). Results A significant relationship was found between a family history of any mood disorder, the ratio of the mean monthly minimum/mean monthly maximum solar insolation, and gender. The odds of a family history of mood disorder increased as patient location nears the poles and decreased near the equator. Female gender also increased the odds of having a family history of a mood disorder. Conclusions This study highlighted the association between family history, solar insolation, and gender in international patients with bipolar I disorder. Given the profound effects of sunlight on human health, the family of patients with bipolar disorder who live in the same location with the same solar insolation, and especially females, may be at increased risk for a mood disorder.

46 Background: Primary results from the randomized, multicenter, open-label, phase 3 TRITON3 (NCT02975934) study demonstrated that rucaparib significantly improved radiographic progression-free survival (rPFS) vs physician’s choice of DTX or an ARPI. ECOG PS is used as a predictor of prostate cancer survival. In this post hoc analysis, we report results from the BRCA1/2 subgroup of pts stratified by ECOG PS. Methods: Pts with disease progression after 1 prior second-generation ARPI in any setting were randomized 2:1 to rucaparib 600 mg BID or physician’s choice of DTX or ARPI (abiraterone acetate or enzalutamide). Primary endpoint was rPFS by independent radiology review (IRR). Objective response rate (ORR) for pts with measurable disease and overall survival (OS) were key secondary endpoints. Crossover from physician’s choice to rucaparib was allowed after radiographic progression was confirmed by IRR. Data cutoff was August 25, 2022. Results: Of 302 pts in the BRCA1/2 population, 147 had an ECOG status of 0 (97 rucaparib; 50 physician’s choice) and 155 had ECOG 1 (104 rucaparib; 51 physician’s choice). Baseline characteristics and demographics were generally similar between arms for pts in the ECOG 0 and ECOG 1 groups. Median rPFS favored rucaparib vs physician’s choice for pts with ECOG 0 (11.4 vs 8.2 months; HR, 0.48 [95% CI, 0.30-0.76]) and ECOG 1 (10.9 vs 6.1 months; HR, 0.48 [95% CI, 0.31-0.74]) (Table). Additionally, rPFS favored rucaparib for ECOG 0 and ECOG 1 including those whose prespecified physician’s choice was ARPI or docetaxel (Table). The confirmed ORR (95% CI) of rucaparib vs physician’s choice for ECOG 0 was 54% (37%–69%) vs 16% (3%–40%); the ORR for ECOG 1 was 37% (22%–53%) vs 18% (5%–40%), respectively. Median OS was similar between arms for rucaparib or physician’s choice; median OS was 23.7 vs 21.7 months (HR, 0.91 [95% CI, 0.61–1.37]) for ECOG 0 and 21.8 vs 20.4 months (HR, 0.85 [95% CI, 0.58–1.24]) for ECOG 1. Conclusions: Rucaparib improved rPFS and ORR in pts with BRCA-mutated prostate cancer with an ECOG PS of 0 or 1. OS was similar for these groups in both arms. These data support rucaparib as a treatment option for pts with BRCA-mutated mCRPC, whether ECOG 0 or 1. Clinical trial information: NCT02975934 . Median rPFS in patients in the ECOG 0 and ECOG 1 groups. Rucaparib, n Physician’s choice, n rPFS Rucaparib, median months rPFS Physician’s choice, median months HR (95% CI) rPFS, ECOG 0 97 50 11.4 8.2 0.48 (0.30–0.76) rPFS, ECOG 1 104 51 10.9 6.1 0.48 (0.31–0.74) rPFS, physician’s choice ARPI, ECOG 0 51 24 11.2 5.6 0.42 (0.22–0.78) rPFS, physician’s choice docetaxel, ECOG 0 46 26 11.5 8.8 0.49 (0.24–0.98) rPFS, physician’s choice ARPI, ECOG 1 52 17 11.2 4.5 0.33 (0.16–0.68) rPFS, physician’s choice docetaxel, ECOG 1 52 34 10.7 7.1 0.59 (0.34–1.01)

Abstract Background: Fatty Acid Synthase (FASN) is a key lipogenic enzyme co-regulated with HER2 and highly expressed in ER+ and HER2+ BC. Its targeting downregulates HER2 expression. Our preclinical studies revealed that FASN inhibition can sensitize or restore sensitivity to trastuzumab, paclitaxel and ET in HER2+ BC models. Denifanstat (deni, formerly TVB-2640) is a novel FASN inhibitor that demonstrated promising clinical activity and safety in a prior phase I trial as either monotherapy or in combination with paclitaxel. The primary objective of this study was to evaluate the objective tumor response rate (ORR) of deni plus trastuzumab (H) in combination with paclitaxel (T) or ET. Methods: Two independent, phase II clinical trials were initiated to assess the efficacy and safety of deni plus H in combination with T (Cohort A) or ET (Cohort B). Key inclusion criteria included HER2+ MBC resistant to HER2-directed therapy, measurable disease, unlimited ET, ≤6 prior chemotherapy or antibody drug conjugate regimens, and confirmation of HER2+ MBC on a pre-registration biopsy. Deni was administered 100 mg/m2 orally once daily. HP or H plus ET (fulvestrant or aromatase inhibitor) was administered at standard dose and schedule. Blood was collected on Cycle 1 Day 1 (C1D1), C1D8 and C2D1 for serum FASN analysis. An additional MBC tumor biopsy was collected on C2D1 for correlative studies. A 2-stage Simon design with a safety-run in was used to test the null hypothesis that the true ORR is at most 5% against the alternative it is at least 20%. With a sample size of 32 patients (pts) per cohort, if ≥4 responses are seen, this design has a 90% chance of rejecting the true ORR is <5% when the true ORR is ≥20% at a 0.10 level of significance. The decision to close both trials to enrollment early was multifactorial. Results: From August 2017 - February 2024, 33 pts with HER2+ MBC pre-registered, among which 17 were eligible and 16 were evaluable (15 pts in Cohort A and 1 pt in Cohort B). The most common reason for ineligibility was HER2-negative status on central review of the pre-registration biopsy. Median age was 57 years (range 35-80). All pts were non-Hispanic and 13 (81.3%) were White. Median prior lines of therapy was 5 (range 0 - 11). In Cohort A, there were 5 partial responses; thus, the primary endpoint was met with the ORR estimated to be 33.3% (90% CI: 14.2-57.7%). The median PFS time was 7.0 months (95 %CI: 3.7 - 11.3), and median OS was 25.7 months (95%CI: 10.2 - NE). No dose limiting toxicities were observed during the C1 safety run-in (6 pts). In Cohort A, 7 (46.7%) developed a grade 3 or 4 adverse event (AE) attributed to combination therapy. Grade ≥2 AEs regardless of attribution occurring in ≥20% of all pts included anemia, fatigue, neutropenia, palmar plantar erythrodysesthesia (PPE), and peripheral neuropathy. Treatment was discontinued due to progression (12; 80%) or AE (3; 20% - pneumonitis; neuropathy; PPE). In Cohort B, the pt maintained stable disease through 8 cycles with grade 3 ALT increase, and she remained alive 31.2 months post-registration. Median C1D1 FASN level was 32.7 ng/mL (IQR: 18.7 - 49.6 ng/mL). There was minimal association between C1D8 and C2D1 FASN levels and time to disease progression (C1D8 n=9, Spearman rank correlation coefficient (r s) = 0.040; C2D1 n=13, r s = -0.019). Analyses of changes in MBC tumor expression of FASN, phospho-AKT, and phospho-S6 are in progress. Conclusion: Deni combined with HP provided clinical antitumor activity in pts with HER2+ MBC resistant to trastuzumab. Expected paclitaxel-associated AEs were observed. Nearly half of pts experienced a grade 3 or 4 AE attributed to the combination therapy, and 20% stopped treatment due to AE. Further study of deni, H plus ET is necessary to draw safety and efficacy conclusions. Citation Format: T. C. Haddad, V. J. Suman, R. R. Roa, B. J. Ernst, R. Lupu, T. Vander Steen, M. H. Solanki, M. Keeney, D. W. Northfelt, K. S. Anderson, T. J. Hobday, S. Chumsri, J. E. Hoppenworth, J. L. Carroll, K. V. Giridhar, C. C. O’Sullivan, R. A. Leon-Ferre, M. P. Goetz. Phase II Trial of the FASN Inhibitor, Denifanstat (TVB-2640), Plus Trastuzumab in Combination with Paclitaxel or Endocrine Therapy (ET) in Patients with HER2+ Metastatic Breast Cancer (MBC) Resistant to Trastuzumab [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-01-16.

Abstract Introduction: An Our Practice Advisory (OPA), formerly known as Best Practice Advisory (BPA), is an electronic health record (EHR) tool. OPAs identify key parameters to alert providers of potential interventions that could enhance quality of care. Such functionality is increasingly relevant given the rapid pace of new drug approvals. Within the Mayo Clinic system, we previously identified that amongst Mayo Clinic patients (pts) meeting the MonarchE criteria, 28% of pts did not undergo a documented discussion with their provider regarding the role of adjuvant abemaciclib (Premji, SABCS 2024). Further, a Flatiron study identified that only 40% of eligible pts received abemaciclib (Sandoval, Miami Breast 2025). To address this practice gap, in 2024 we began to implement EHR clinical decision support by creating an OPA trigger for pts eligible for an adjuvant CDK 4/6 inhibitor (CDK 4/6i). Here we report on ‘action taken’ versus not for the OPA and the most common reasons for re-prompts. Methods: The Mayo Breast Disease Group designed an OPA including pts who are within 14 months of a clinical or pathologic diagnosis of high-risk early-stage breast cancer. We leveraged structured data captured in the Epic staging forms (Epic Systems) to identify pts with clinical or pathologic T-stage, N-stage, grade, ± Ki-67/ multigene signature to identify ER+/HER2- pts eligible for adjuvant ribociclib or abemaciclib based on FDA approvals. The OPA was triggered by a patient encounter in oncology when endocrine therapy (but not CDK4/6i) was on the active medication list resulting in a hard stop. The OPA gathered limited details about whether adjuvant CDK4/6 inhibitors were discussed and whether the provider followed a link that resulted in prescribing one—considered an indicator of action taken. In this IRB-exempt quality improvement project, we describe the responses captured in the OPA trigger utilizing Epic tools. Results: The OPA went live on 1/10/2025. Over a 5-month period post OPA initiation, we identified 517 OPA alerts among 332 unique pts. Their median age was 62.5 years, and the majority were female (97%). The median time to resolve the OPA was 17.5 seconds (range 2-567 seconds). 12.6% (65/517) of the time there was ‘action taken’ by selecting the hyperlink to potentially start a treatment plan. Providers selected the following OPA pre-set responses: ‘re-prompt in one month’ 248 (48%), ‘patient not a candidate for therapy’ 48 (9%), ‘patient declines’ 69 (13%), ‘outside oncologist will prescribe’ 36 (7%), ‘not discussed’ 44 (9%), and unknown 72 (14%). The most common free text comments among the 517 OPA alerts (summarized) included: ‘revisit in future’ 108 (21%), ‘too early’ 65 (13%), ‘patient declines’ 66 (13%), ‘outside oncologist will start’ 31 (6%), ‘not a candidate’ 26 (5%), and ‘co-morbidities’ 18 (3%). Erroneous OPA prompting occurred in 14 (3%) who previously failed a CDK4/6i due to toxicity and in 18 (3%) for pts currently on a CDK4/6i. 30 (6%) OPA comments noted that they discussed or started therapy that day. Conclusion: The OPA offered clinical decision support and ensured that clinicians considered prescribing CDK 4/6i in all pts identified as eligible, and captured deferrals. Refinements are needed to ensure appropriate timing of OPA and minimize erroneous firing. The OPA remains active and captures the reason for deferral of adjuvant CDK 4/6i prescription. This data pairs real world decision making to better understand clinically meaningful application of improved invasive disease-free survival (iDFS). Citation Format: S. Premji, P. Advani, S. Chumsri, L. Mina, J. Taraba, J. Carroll, J. Hoppenworth, E. Cathcart-Rake, T. Haddad, B. Rudder, G. Choong, D. Idossa, C. O’Sullivan, S. Yadav, K. Ruddy, P. Peethambaram, T. Hobday, M. Goetz, R. Rao, B. Ernst, F. Batalini, R. Leon-Ferre, A. Tevaarwerk, K. Giridhar. Implementing an Our Practice Advisory (OPA) to provide clinical decision support for adjuvant CDK4/6 inhibitors in early-stage hormone receptor positive breast cancer: The Mayo Clinic Experience [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-11-10.

Abstract INTRODUCTION Associations of short‐term use of menopausal hormone therapy (mHT) with Alzheimer's disease (AD) and structural magnetic resonance imaging (MRI) biomarkers were investigated 10 years after an mHT trial. METHODS Recently menopausal women with good cardiovascular health were randomized to oral conjugated equine estrogens (oCEE) or transdermal 17β‐estradiol (tE2) and micronized progesterone, or placebo for 4 years. Amyloid beta (Aβ) on positron emission tomography, hippocampal atrophy, and dorsolateral prefrontal cortex thickness on MRI were assessed 10 years after completion of the mHT trial ( n = 266). RESULTS Aβ and structural MRI biomarkers were not different in the oCEE and tE2 groups compared to placebo. Apolipoprotein E ε4 status did not modify the findings. DISCUSSION There was no evidence of adverse effects or benefits associated with 4 years of use of oral or transdermal mHT on Aβ and structural MRI biomarkers in relatively healthy women, 10 years after mHT. Findings support the long‐term safety of short‐term use of mHT on brain health. CLINICAL TRIALS REGISTRATION NCT00154180 Kronos Early Estrogen Prevention Study (KEEPS) Highlights There were no menopausal hormone therapy–related adverse effects or benefits on amyloid beta and magnetic resonance imaging biomarkers in the long term. Apolipoprotein E ε4 carrier status did not modify these findings. Findings align with neutral cognitive and cerebrovascular outcomes in this cohort.