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6593 citation(s) found for "Ha, Richard".

Risk Factors for Surgical Revision Following Ventricular Shunt Placement for Idiopathic Normal Pressure Hydrocephalus
Hamouda, Abdelrahman, Kumar, Rahul , Pennington, Zach, Naylor, Ryan M. , McQuinn, Michelle W., Potes, Maria Astudillo , Jusué-Torres, Ignacio, Loomis, Erica, Kim, Brian D. , Heller, Stephanie F. , Ballinger, Beth A. , Graff-Radford, Jonathan, Jones, D. Richard, Cutsforth-Gregory, Jeremy K., Cogswell, Petrice M., Rinaldo, Lorenzo , Meyer, Frederic B., Elder, Benjamin D., Pennington, Zach , Astudillo Potes, Maria D, Loomis, Erica A, Pennington, Zach , Kumar, Rahul , Hamouda, Abdelrahman M. , Jusué-Torres, Ignacio , Graff‐Radford, Jonathan , Jones, David T. , Cutsforth‐Gregory, Jeremy K. , Cogswell, Petrice M. , Elder, Benjamin D.

Operative Neurosurgery | February 18, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1227/ons.0000000000001964 | PMID 41705955 Get It

BACKGROUND AND OBJECTIVES: Ventriculoperitoneal shunt (VPS) placement is a common treatment for idiopathic normal pressure hydrocephalus (iNPH), but patients may require VPS revision. This study aims to evaluate the effectiveness of a standardized VPS placement protocol by comparing indications and rates of shunt revision compared with a historical institutional cohort. METHODS: All patients treated with VPS for “suspected” iNPH at a tertiary care center between January 2000 and January 2023 were retrospectively reviewed and divided into temporally distinct historical (before 2017) and standardized (after 2017) cohorts. Cumulative incidence and timing of VPS revision were compared using competing risks analyses. RESULTS: A total of 561 patients (median age 75.0 years) were identified with 324 (57.8%) in the historical and 237 (42.2%) in the standardized cohorts. Significant variations in surgical technique and shunt hardware were noted between the cohorts. With a median follow-up of 11.4 months for historical and 12.4 months for standardized cohort, shunt revisions occurred in 19.4% and 8.4% of patients in the historical and standardized cohorts, respectively ( P < .001). Revision indications also varied significantly with lower rates of overdrainage ( P < .001), infection ( P < .001), and proximal malfunction ( P = .042) but higher rate of distal malfunction ( P = .03) in the standardized cohort. Notably, no infections were noted in the standardized cohort. CONCLUSION: Risk of shunt revision among iNPH patients may be associated with modifiable factors related to surgical technique and shunt hardware selection. Importantly, no short-term complications such as hemorrhage, infection, or catheter malposition were observed with the standardized protocol. Development and refinement of standardized shunt protocols for iNPH patients should be commonplace to facilitate tracking, identification, and modification of modifiable technical risk factors.
Conflation of Covariate Adjustments With Causal Effects—The Table 2 Fallacy in Surgical Literature
Mah, Alexis , Miller, Richard M., Hallet, Julie H., Ven Fong, Zhi, Hallet, Julie , Fong, Zhi Ven

Annals of Surgery | February 18, 2026 | Volume: 284 | Issue: 2 | Pages: 445-447

10.1097/sla.0000000000007034 | PMID 41703678 Get It

Deriving wisdom from data: The value and continued rationale for structured data in the era of artificial intelligence–driven oncology care
Emamekhoo, Hamid, Riaz, Irbaz, Martin, Daniel B., Gabriel, Peter E. , Bruckner, Lauren B. , Arafat, Waddah, Fu, Penelope, Liebovitz, David , Stillman, Robert C. , Stapp, Robert T, Perkins, Randa M., Sugalski, Jessica , Heinrichs, Tricia , Tevaarwerk, Amye J., Gabriel, Peter , Emamekhoo, Hamid , Emamekhoo, Hamid , Stillman, Robert C , Heinrichs, Tricia , Tevaarwerk, Amye J , Shah, Neil J , Arafat, Waddah , Freimuth, Robert R. , Stapp, Robert , Perkins, Randa, Tevaarwerk, Amyé

Cancer | February 17, 2026 | Volume: 132 | Issue: 4 | Pages: No page available

10.1002/cncr.70307 | PMID 41701629 Get It

Abstract The adoption of electronic health records (EHRs) has transformed health care, improving efficiency and chart accessibility. However, the widespread reliance on unstructured data entry and the lack of standardized documentation frameworks have resulted in significant data fragmentation across health care systems. The prevalence of unstructured data in EHRs limits their potential for clinical decision support, trial matching, real‐world evidence (RWE) generation, and quality measurement. Data fragmentation in health care triggers a cascade of challenges that ultimately compromise patient care. Clinicians face an excessive documentation burden and struggle to locate critical information buried in unstructured notes. Researchers encounter difficulties in extracting reliable clinical data. EHR vendors grapple with standardizing unstructured information for interoperability, and payers are unable to process unstructured clinical data efficiently to support value‐based care models. These challenges are particularly acute in oncology, where complex clinical elements like cancer staging, disease status, and treatment changes require precise, structured documentation. Emerging artificial intelligence (AI) technologies, such as large language models (LLMs) and ambient listening, offer a path to automate structured data generation while reducing the workload on providers. Here, the authors propose LLM‐based workflows that balance automation with clinician verification, streamlining data entry without compromising accuracy. Realizing these benefits requires coordinated efforts among clinicians, researchers, EHR vendors, payers, and policymakers to align regulatory frameworks with AI‐driven innovations. This article outlines a strategy to enhance structured data capture within EHRs, ultimately improving patient care, research, and health care efficiency.
Abstract PS5-08-20: A phase III trial evaluating De-escalation of Breast Radiation (DEBRA) following breast-conserving surgery of stage 1, HR+, HER2-, RS ≤18 breast cancer: NRG-BR007
White, J. R., Cecchini, R. S., Harris, E. E., Mamounas, E. P., Bazan, J. G., Stover, D. G., Ganz, P. A., Jagsi, R., Anderson, S. J., Théberge, Valérie, El-Tamer, M. B., Zellars, R. C., Shumway, D. A., Chen, G., Julian, T. B., Wolmark, N., Cecchini, Reena S. , Bazan, J.G., Ganz, PA, Anderson, SJ, Bergom, Carmen , El-Tamer, Mahmoud Bahij , Zellars, Richard C. , Shumway, D., Julian, TB

Clinical Cancer Research | February 17, 2026 | Volume: 32 | Issue: 4_Supplement | Pages: PS5-08-20-PS5-08-20

10.1158/1557-3265.sabcs25-ps5-08-20 Get It

Abstract Background: Approximately 50% of newly diagnosed invasive breast cancers are stage 1, with the majority being ER/PR-positive, HER2-negative. Genomic assays such as the Oncotype DX® have identified patients (pts) with reduced risk of distant metastasis and without benefit from chemotherapy added to endocrine therapy (ET), freeing them from excess toxicity. Genomic assays are also recognized as prognostic for in-breast recurrence (IBR) after breast-conserving surgery (BCS) and could similarly allow de-escalation of adjuvant radiotherapy (RT). Reducing overtreatment is of interest to pts, providers, and payers. Methods: We hypothesize that BCS alone is non-inferior to BCS plus RT for IBR and breast preservation in women intending ET for stage 1 invasive breast cancer (ER and/or PR-positive, HER2-negative with an Oncotype DX Recurrence Score [RS] of ≤18). Stratification is by age (&lt;60; ≥60), tumor size (≤1 cm; &gt;1-2cm), and RS (≤11, &gt;11-18/MammaPrint Low). Pts are randomized post-BCS to Arm 1 with breast RT using standard methods (moderate or ultra hypo- or conventional-fractionated whole breast RT with/without boost, or APBI) with ≥5 yrs of ET (tamoxifen or AI) or Arm 2 with ≥5 yrs of ET (tamoxifen or AI) alone. The specific regimen of ET in both arms is at the treating physician’s discretion. Eligible pts are stage 1: pT1 (≤2 cm), pN0, age ≥50 to &lt;70 yrs, s/p BCS with negative margins (no ink on tumor), s/p axillary nodal staging (SNB or ALND), ER and/or PR-positive (ASCO/CAP), HER2-negative (ASCO/CAP), and Oncotype DX RS ≤18 (diagnostic core biopsy or resected specimen). A “low risk” MammaPrint is permissible if completed as part of usual care prior to screening. Primary endpoint is IBR (invasive breast cancer or DCIS). Secondary endpoints are breast conservation rate, invasive in-breast recurrence, relapse-free interval, distant disease-free survival, overall survival, patient-reported breast pain, patient-reported worry about recurrence, and adherence to ET. We assume a clinically acceptable difference in IBR of 4% at 10 yrs to judge omission of RT as non-inferior (10-yr event-free survival for RT group is 95.6% v 91.6% for the omission-of-RT group). BR007 is powered to detect non-inferiority with 80% power and a one-sided α=0.025, assuming that there would be a ramp-up in accrual in the first two years (leveling off in Yrs 3-5); 1,670 pts (835 per arm) are required for randomization. Conservative loss to follow-up is 1%/yr. Some T1a pts screened may have Oncotype DX scores &gt;18, making them ineligible for the study. In the accrual process, 1,714 pts will be required to register to ensure that our final randomized cohort is 1,670 pts. As of July 9, 2025, 1,490 pts have been screened and 1,349 randomly assigned. NCT #: NCT04852887 Support: U10 CA180868, -180822, U24 CA196067, UG1 CA189867 Citation Format: J. R. White, R. S. Cecchini, E. E. Harris, E. P. Mamounas, J. G. Bazan, D. G. Stover, P. A. Ganz, R. Jagsi, S. J. Anderson, C. Bergom, V. Théberge, M. B. El-Tamer, R. C. Zellars, D. A. Shumway, G. Chen, T. B. Julian, N. Wolmark. A phase III trial evaluating De-escalation of Breast Radiation (DEBRA) following breast-conserving surgery of stage 1, HR+, HER2-, RS ≤18 breast cancer: NRG-BR007 [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 PS5-08-20.
Abstract PS3-01-15: Making informed choices on incorporating chemoprevention into care (MiCHOICE): Cluster randomized controlled trial of decision support for breast cancer chemoprevention, SWOG 1904
Crew, K. D., Anderson, G. L., Arnold, K. B., Michel, Alissa , DeLucie, M. T., Law, C. W., Pruthi, Sandhya, Leon, A. C. Sandoval, Shirley, Rachel, Perdekamp, M. T. Grosse, Colonna, S. V., Krisher, S. L., King, T. A., Yee, L. D., Ballinger, T. J., Braun‐Inglis, Christa , Mangino, D. A., Wisinski, K. B., DeYoung, C. A., Ross, M., Floyd, J. D., Kaster, Andrea, VanderWalde, Lindi, Saphner, Thomas J. , Zarwan, Corrine, Lo, S., Graham, C., Conlin, A. K., Yost, K. J., Agnese, D. M., Jernigan, C., Hershman, D. L., Neuhouser, M. L., Zell, J. A., Arun, B. K., Sandoval-Leon, Ana Cristina , Colonna, Sarah V. , Krisher, Stacy, Ballinger, T.J., Mangino, D., DeYoung, Claudia A, Conlin, Alison, KJ, Yost, Jernigan, Cheryl, Hershman, Dawn L. , Zell, Jason A. , Arun, Banu , Kukafka, Rita

Clinical Cancer Research | February 17, 2026 | Volume: 32 | Issue: 4_Supplement | Pages: PS3-01-15-PS3-01-15

10.1158/1557-3265.sabcs25-ps3-01-15 Get It

Abstract Background: Breast cancer (BC) chemoprevention with selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) remains underutilized among high-risk women. Improving knowledge about BC risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this BC risk reduction strategy. Methods: We conducted a cluster randomized controlled trial to evaluate the effectiveness of web-based patient and provider decision support, RealRisks and BNAV, to improve chemoprevention informed choice among women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS). Thirty-one sites, including academic and community practices across the U.S., were randomized to standard patient educational materials alone or combined with RealRisks and BNAV. A total of 412 patients and 210 healthcare providers were enrolled. Patient surveys were administered at baseline, 6 and 12 months. The primary outcome at 6 months was chemoprevention informed choice, defined as adequate chemoprevention knowledge and attitudes congruent with decision. Secondary endpoints included BC risk perceptions, worry, chemoprevention knowledge, decision conflict and chemoprevention decision. Assuming 10% loss to follow up (LTFU), roughly equal accrual across sites, and an intraclass coefficient (ICC) of 0.02, we had 90% power to detect a 15% absolute difference in informed choice if the event rate in the control arm was 10%. Results: Among 24 evaluable sites, 14 were randomized to the intervention arm and 10 to the control arm. Among 210 enrolled providers, median age was 46 (range, 28-83) and 78% were female; 75% physicians and 25% advanced practice providers/nurses; 53% medical oncologists, 29% surgeons, and 10% gynecologists/family practitioners/internists; and 83% had previously prescribed chemoprevention. Among 412 enrolled patients, median age was 53 (range, 35-74), including 77% White, 8% Black, and 10% Asian race, and 14% Hispanic ethnicity. In terms of BC risk factors, 77% had AH and 23% LCIS, 34% had a first-degree family history of BC, and 65% had heterogeneously or extremely dense breasts on mammography. Thirty percent were unevaluable for the primary endpoint (1% ineligible, 26% LTFU, 3% missing data). Among 288 evaluable patients (148 at intervention sites, 140 at control sites), the proportion of patients exercising informed choice at 6 months in the intervention and control arms was 35% vs. 27%, respectively (odds ratio [OR]=1.44, 95% confidence interval [CI]=0.84-2.46, p=0.19; observed ICC=0.006). Compared to patients in the control arm at 6 months, those in the intervention arm were more likely to have accurate BC risk perceptions (OR=1.80, 95% CI=1.11-2.91) and adequate chemoprevention knowledge (OR=1.62, 95% CI=1.00-2.61). We observed no significant differences in BC worry, decision conflict, or chemoprevention decision between study arms. At 6 months, 49% of women in the control arm and 51% in the intervention arm decided to take a SERM or AI for BC chemoprevention (p=0.58), a rate higher than anticipated. Conclusions: We did not observe a significant increase in informed choice among patients and providers assigned to chemoprevention decision support compared to standard educational materials alone. Among women with AH or LCIS seen mainly by breast specialists who prescribed chemoprevention, about half decided to take a SERM or AI. Therefore, relatively high chemoprevention uptake may be achieved among women with high-risk breast lesions managed by breast specialists. Chemoprevention decision support may improve decision antecedents, such as accurate BC risk perceptions and chemoprevention knowledge, but may have a limited role in changing health behaviors. Citation Format: K. D. Crew, G. L. Anderson, K. B. Arnold, A. Michel, M. T. DeLucie, C. W. Law, S. Pruthi, A. C. Sandoval Leon, R. Shirley, M. T. Grosse Perdekamp, S. V. Colonna, S. L. Krisher, T. King, L. D. Yee, T. J. Ballinger, C. Braun-Inglis, D. A. Mangino, K. B. Wisinski, C. A. DeYoung, M. Ross, J. D. Floyd, A. Kaster, L. VanderWalde, T. Saphner, C. Zarwan, S. Lo, C. Graham, A. K. Conlin, K. J. Yost, D. M. Agnese, C. Jernigan, D. L. Hershman, M. L. Neuhouser, J. A. Zell, B. Arun, R. Kukafka. Making informed choices on incorporating chemoprevention into care (MiCHOICE): Cluster randomized controlled trial of decision support for breast cancer chemoprevention, SWOG 1904 [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 PS3-01-15.
Abstract PS2-11-03: Fish-positive circulating tumor cells persist after effective therapy in estrogen receptor positive breast cancer: insights into genomic mechanisms of endocrine resistance
Baldwin, K., Maltzan, Kristine von , Zulli, Adam, Richard, Madeleine, Abdulsattar, J., Maroni, Dulce, Greipp, P. T., Knudson, R., Core, Mayo Cytogenetics, Thayer, S. P., Abdulsattar, Jehan, Thayer, SP

Clinical Cancer Research | February 17, 2026 | Volume: 32 | Issue: 4_Supplement | Pages: PS2-11-03-PS2-11-03

10.1158/1557-3265.sabcs25-ps2-11-03 Get It

Abstract Background: Estrogen receptor (ER) positive breast cancer is commonly treated with endocrine therapy, yet resistance to estrogen deprivation remains a significant clinical challenge. Using custom FISH probes designed to detect tumor-specific genomic alterations, we identified circulating tumor cells (CTCs) of true tumor origin in early-stage luminal breast cancer patients. Longitudinal analysis revealed that 80% of patients had FISH-positive CTCs after completing therapy and while on antiestrogen treatment, despite no clinical evidence of disease. This finding suggests that standard endocrine therapy is insufficient to eradicate all malignant clones, indicating the persistence of therapy-resistant tumor cells. Methods: Primary tumor DNA was analyzed using the Oncoscan microarray platform to identify somatic copy-number alterations (SCNAs). Custom FISH probes targeting these alterations were applied to peripheral blood samples before and after therapy. Immunofluorescence characterization of CTCs was performed to assess epithelial and mesenchymal phenotypes as well as ER expression status. Genomic profiling focused on identifying drivers of proliferation, known ER resistance genes, and ER transcriptional regulators. Results: Immunofluorescence revealed that CTCs were highly heterogeneous, displaying both epithelial and mesenchymal phenotypes. ER expression among CTCs was variable: while some CTCs were ER-positive, a significant proportion showed reduced or absent ER staining. This heterogeneity suggests that loss or downregulation of ER is a key mechanism of resistance, allowing tumor cells to persist despite antiestrogen therapy. Genomic profiling of parent tumors demonstrated multiple, overlapping mechanisms supporting both proliferation and endocrine resistance. All tumors harbored several genomic alterations known to drive proliferation, most commonly involving MCL1, NTRK1, SDHC, SDHD, CHEK1, ATM, and BCL6. Every tumor exhibited at least one established mechanism of ER resistance, with frequent alterations in ATM and PIK3CA, and additional recurrent changes in AKT3, MTOR, and ARID1A. Several tumors also had alterations in genes directly involved in ER transcriptional regulation, notably ARID1A and SPEN. Conclusions: The persistence of FISH-positive CTCs in the majority of patients after therapy—despite no clinical evidence of disease—highlights the insufficiency of current endocrine regimens. The underlying genomic complexity, characterized by multiple drivers of proliferation, redundant ER resistance mechanisms, and disruption of ER regulatory pathways, underpins the survival and persistence of CTCs. These findings underscore the need for therapeutic strategies that address the multifaceted and overlapping nature of endocrine resistance in luminal breast cancer. Citation Format: K. Baldwin, K. von Maltzan, A. Zulli, M. Richard, J. Abdulsattar, D. Maroni, P. T. Greipp, R. Knudson, Mayo Cytogenetics Core, S. P. Thayer. Fish-positive circulating tumor cells persist after effective therapy in estrogen receptor positive breast cancer: insights into genomic mechanisms of endocrine resistance [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 PS2-11-03.
Abstract PD4-11: Contralateral Breast Cancer Risk in Women with PALB2-Associated Breast Cancer
Metcalfe, Kelly , Stachowski, A , Couch, F. J., Marabelli, Monica , Wong, S. M., Domchek, S. M., Kim, R., Cajal, T. Ramon y, Fruscio, R, Yadav, S., Hoey, C., Karamali, S., Sun, P., Lubinski, J., Narod, S., Pal, T., Eisen, Andrea , Kim, Raymond H. , Metcalfe, Kelly A , Eisen, Andrea , Kim, Raymond H , Couch, F.J., Aeilts, Amber M. , Eisen, Andrew , Hoey, Christianne, Lubiński, Jan

Clinical Cancer Research | February 17, 2026 | Volume: 32 | Issue: 4_Supplement | Pages: PD4-11-PD4-11

10.1158/1557-3265.sabcs25-pd4-11 Get It

Abstract Introduction: Women with a germline pathogenic variant (PV) in PALB2 face a lifetime risk of breast cancer, generally exceeding 40%. We have initiated an international clinical follow up study of women with stage 0 to stage 4 breast cancer and a PALB2 PV to evaluate clinical characteristics and to determine optimal treatments. The objective of the current study was to estimate and to identify factors predictive of contralateral breast cancer (CBC) risk. Methods: Clinical data, including diagnostic, treatment, and follow-up data, were collected by medical record review for eligible women with breast cancer and a germline PV in PALB2. PV carriers were followed every two years to collect information about recurrences, new cancers, and vital status. Data was summarized using descriptive statistics. The risk of CBC was estimated by following women from the date of breast cancer diagnosis until the date of: 1) contralateral breast cancer, 2) contralateral mastectomy, 3) death from any cause, or 4) last follow-up. The cumulative incidence of CBC was calculated with the Kaplan-Meier method. Cox proportional hazards regression was used to identify factors associated with contralateral breast cancer risk. Covariates included age at diagnosis, ER status, grade, nodal status, chemotherapy, radiation therapy, tamoxifen, and bilateral salpingo-oophorectomy (time-dependent). Results: Among 888 PALB2 carriers, the mean age at diagnosis of breast cancer was 49.3 years (range 22 to 83 years). Overall, 36 women (4.1%) were diagnosed with synchronous bilateral breast cancer. 73.6% of the breast cancers were ER-positive, and 29% were lymph node-positive. Patients were followed for a mean of 5.6 years (range 0.3 to 22 years) from date of diagnosis. During the follow-up period, 53 patients were diagnosed with a metachronous CBC. The 15-year risk of metachronous CBC was 26.4% overall; 19.5% for those diagnosed younger than 50 years, and 34.8% for those diagnosed at 50 years or older. In a multivariate analysis, ER status was not significantly associated with CBC risk (RR 1.15, 95%CI 0.45-2.93, p=0.77). Bilateral salpingo-oophorectomy (BSO) was associated with a significant reduction in the risk of CBC (RR 0.17, 95%CI 0.04-0.70, p=0.02). In the follow-up period, 47 women were diagnosed with another incident cancer, including seven with pancreatic cancer and three with ovarian cancer Conclusion: The high 15-year risk of contralateral breast cancer suggests that bilateral mastectomy should be considered for primary surgical intervention. Moreover, bilateral salpingo-oophorectomy (BSO) significantly reduces the risk of CBC and should be considered post-treatment. Citation Format: K. Metcalfe, A. Stachowski, F. Couch, M. Marabelli, S. Wong, S. Domchek, A. Aeilts, A. Eisen, R. Kim, T. Ramon y Cajal, R. Fruscio, S. Yadav, C. Hoey, S. Karamali, P. Sun, J. Lubinski, S. Narod, T. Pal. Contralateral Breast Cancer Risk in Women with PALB2-Associated Breast Cancer [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 PD4-11.
Abstract GS3-01: Menopausal Hormone Therapy and the Risk of Breast Cancer in Women with a Pathogenic Variant in BRCA1 or BRCA2
Kotsopoulos, J., Seca, M., Jacek, G., Huzarski, T., Møller, P., Kim, R. H., Singer, C. F., Karlan, B., Cajal, T. Ramon y, Pal, Tuya, Bordeleau, Louise , Foulkes, W., Tung, N. M., Couch, F. J., Neuhausen, S., Zakalik, Dana , Cybulski, C., Olopade, O. I., Metcalfe, K., Fruscio, R, Sun, P., Lubinski, J., Narod, S., Eisen, Andrea , Metcalfe, Kelly , Kim, Raymond H. , Metcalfe, Kelly A , Eisen, Andrea , Bordeleau, Louise , Kim, Raymond H , Kotsopoulos, Joanne , Seca, Marta , Huzarski, T., Møller, Pål , Kim, R.H., Singer, Christian F. , Karlan, Beth Y. , Aeilts, Amber M. , Pal, Tuya , Eisen, Andrew , Foulkes, William D. , Couch, F.J., Neuhausen, Susan L. , Cybulski, Cezary , Lubiński, Jan

Clinical Cancer Research | February 17, 2026 | Volume: 32 | Issue: 4_Supplement | Pages: GS3-01-GS3-01

10.1158/1557-3265.sabcs25-gs3-01 Get It

Abstract Background: Women with a pathogenic variant in the BRCA1 or BRCA2 gene (carriers) are at a high risk of developing ovarian cancer and recommended to undergo bilateral salpingo-oophorectomy at an early age resulting in surgical menopause. Menopausal hormone therapy (MHT) is the most effective way to mitigate the adverse outcomes of early menopause; however, the safety of MHT on breast cancer risk in this population has not been established. Methods: We conducted a prospective matched analysis of MHT use following menopause (predominantly surgical) and breast cancer risk in BRCA carriers using a matched prospective analysis to emulate a randomized clinical trial. Women without a history of any cancer or bilateral mastectomy and who were enrolled in a longitudinal study with detailed data collection were eligible for inclusion. Women who initiated MHT (exposed) after menopause were matched one-to-one to women who had not initiated MHT (unexposed) by gene, year of birth, and age at menopause, resulting in 676 matched pairs. Cox proportional hazards regression to estimate the hazard ratios (HR) and 95%CIs (CI) of incident breast cancer associated with MHT use. Results: After a mean follow-up of 5.6 years from the date of first MHT use in the exposed woman, there were 87 incident breast cancer cases in the exposed group (12·9%) and 128 cases in the unexposed group (18·9%) (P = 0·002). Compared to their unexposed match, women who used estrogen (E) experienced a significant decrease in the risk of breast cancer (HR = 0·37; 95%: CI 0·24-0·57). There was no protective (or adverse) effect associated with the use of E plus progestogen (E+P) (HR = 0·94; 95%CI 0·54-1·63), with progestogen alone (P) (HR = 1·14; 95%CI: 0·21-6·22) or with tibolone (HR = 0·57; 95%CI: 0·19-1·69). There were no diagnoses of breast cancer in the 43 women who used a CEE + bazedoxifene. Findings were similar for carriers of either gene mutation. Conclusion: To our knowledge, this represents the largest prospective report of MHT use and breast cancer risk in BRCA1 and BRCA2 carriers. Our findings showed no increase in the risk of breast cancer with the use of MHT, irrespective of gene mutation or formulation. These findings provide an evidence-based approach for the management of women at high-risk of breast cancer who are facing the acute and chronic effects of early surgical menopause. The safe use of MHT by BRCA carriers will continue to be an important research topic as formulations continue to evolve. Citation Format: J. Kotsopoulos, M. Seca, G. Jacek, T. Huzarski, P. Møller, R. H. Kim, C. Singer, B. Karlan, A. Aeilts, T. Ramon y Cajal, T. Pal, A. Eisen, L. Bordeleau, W. Foulkes, N. Tung, F. Couch, S. Neuhausen, D. Zakalik, C. Cybulski, O. Olopade, K. Metcalfe, R. Fruscio, P. Sun, J. Lubinski, S. Narod, Hereditary Breast Cancer Clinical Study Group. Menopausal Hormone Therapy and the Risk of Breast Cancer in Women with a Pathogenic Variant in BRCA1 or BRCA2 [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 GS3-01.
Abstract GS1-04: Tumor infiltrating lymphocytes (TILs) and pathologic complete response (pCR) in stage II/III HER2+ breast cancer treated with taxane, trastuzumab, and pertuzumab (THP): secondary results from the ECOG-ACRIN EA1181/CompassHER2 pCR trial
Badve, S. S., Zhao, F., Tung, NM, O'Sullivan, C. C., Prat, A., Winer, E. P., Wright, J. L., Recht, A., Weiss, A. C., Tjoe, J. A., Feldman, S. M., Rocque, G. B., Smith, M., Unni, N., Sardesai, S., Modi, S., Irvin, W. J., Villagrassa, P., Battelli, Chiara, Krie, A. K., Bagegni, N. A., George, M. A., Telli, M. L., Borges, V. F., D’Abreo, Nina , Shah, P. D., Miller, K. D., Partridge, A. H., Carey, L. A., DeMichele, A. M., Wolff, A. C., ECOG-ACRIN, Badve, Sunil , Tung, Nadine , Gökmen‐Polar, Yesim , O’Sullivan, Ciara C. , Prat, Aleix , Wright, J. L., Recht, A., Weiss, A. C., Rocque, Gabrielle B. , Unni, N., Sardesai, Sagar , Tang, Shou-Ching , Irvin, William , Bagegni, Nusayba , Telli, M.L., Partridge, Ann H. , Carey, L., DeMichele, Angela , Wolff, Antonio C

Clinical Cancer Research | February 17, 2026 | Volume: 32 | Issue: 4_Supplement | Pages: GS1-04-GS1-04

10.1158/1557-3265.sabcs25-gs1-04 Get It

Abstract Background: The association of TILs with pathologic complete response (pCR) and survival in HER2+ breast cancer is not well established with several prior studies showing inconsistent results. In this secondary analysis of EA1181, we evaluated the association between stromal TILs (sTILs) and pCR rates. Methods: EA1181 (NCT04266249) enrolled patients (pts) with anatomic clinical stage II/III HER2+ breast cancer who preoperatively received 4 cycles of trastuzumab and pertuzumab with 12 weeks of paclitaxel or docetaxel q3w x 4 (THP), followed by surgery. sTILs density was assessed on full-face hematoxylin and eosin (H&E)-stained tumor biopsy sections. sTILs scores were analyzed per protocol as a continuous variable (every 10% increment) and as a categorical variable (&lt;10% vs 10-60% vs &gt;60% as per Denkert et al, 2018), and also with an exploratory 30% cutoff commonly used in TNBC. Cox proportional hazards models were used to examine the association between sTILs and pCR, adjusting for available baseline factors. The associations between sTILs (by category) and clinicopathologic characteristics were examined using Fishers’ exact test. Results: Among 2141 pts with HER2+ BC treated on EA1181, H&E slides were available for 1328 (62%). The study population evaluated for sTILs was comparable to the overall population. pCR rates were 44.5% overall, 64% for HER2+/ER- and 33% for HER2+/ER+ disease. sTILs distribution was: 623 (47%) &lt;10%, 698 (52%) 10-60%, and 7 (0.5%) &gt;60%, which led us to merge the latter two groups (705 [53%] had ≥10% sTILs). In univariable and multivariable analyses, increasing sTILs (as a continuous variable) were associated with increasing pCR rates in both HER2+/ER+ and HER2+/ER- disease (p&lt;0.001; Table). sTILs analyzed as a categorical variable (&lt;10% vs ≥10%) were significantly associated with pCR for all patients (combined) and for those with HER2+/ER+ disease. In exploratory analysis using a cutoff of &lt;30% vs ≥30% sTILs, an association with pCR was also seen in univariable analysis for both HER2+/ER+ disease (p&lt;0.001) and HER2+/ER- disease (p=0.045), though in multivariable analysis with clinical factors, sTILs &gt;30% remained a significant predictor for pCR only in HER2+/ER+ disease. Additional exploratory analysis with other molecular biomarkers, intrinsic subtypes, and immune signatures will be presented. Conclusion: sTILs were associated with pCR after THP, further supporting the important role of immune mechanisms in HER2+ breast cancer, and highlighting a potentially robust predictive tool to assess pathologic response. Baseline sTILs could potentially inform the preoperative design of future trials of therapy optimalization. Association of baseline sTILs with recurrence free survival in EA1181 will be reported in the future. Citation Format: S. S. Badve, F. Zhao, N. Tung, Y. Gokmen-Polar, C. C. O'Sullivan, A. Prat, E. P. Winer, J. L. Wright, A. Recht, A. C. Weiss, J. A. Tjoe, S. M. Feldman, G. B. Rocque, M. Smith, N. Unni, S. Sardesai, S. Tang, S. Modi, W. J. Irvin, P. Villagrassa, C. Battelli, A. K. Krie, N. Bagegni, M. A. George, M. L. Telli, V. F. Borges, N. D’Abreo, P. Shah, K. D. Miller, A. H. Partridge, L. A. Carey, A. M. DeMichele, A. C. Wolff, ECOG-ACRIN.Tumor infiltrating lymphocytes (TILs) and pathologic complete response (pCR) in stage II/III HER2+ breast cancer treated with taxane, trastuzumab, and pertuzumab (THP): secondary results from the ECOG-ACRIN EA1181/CompassHER2 pCR trial [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 GS1-04.
A precise atlas of the human subcortex
Friedrich, Helen, Sahin, Ilkem Aysu , Alho, Eduardo Joaquim Lopes , Holanda, Vanessa Milanese, Brammerloh, Malte , Matthies, Cordula , Volkmann, Jens, Meyer, Garance M. , Kirilina, E. ; https://orcid.org/0000-0003-1304-4363, Pijar, Julianna , Garimella, Arun , Fox, Michael D, Friedrich, Maximilian, Edlow, Brian L., Neudorfer, Clemens, Horn, Andreas, Li, Ningfei , Edlow, Brian L , Horn, Andreas , Rajamani, Nanditha , Oxenford, Simón , Mustin, Maike, Zvarova, Patricia , Krüger, Lara, Demann, Richard, Goede, Lukas L. , Kirilina, Evgeniya P. , Volkmann, Jens , Horisawa, Shiro , Howard, Calvin, Fox, Michael , Friedrich, Maximilian, Bochtler, Anja, Edlow, Brian L. , Neudorfer, Clemens , Horn, Andreas

No container title available | February 15, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.64898/2026.02.13.705755 | PMID 41726876 Get It

Abstract Clinical interventions and neuroimaging in the subcortex require anatomical definitions that exceed the resolution and anatomical detail of currently available deformable brain atlases. Here, we introduce a high-resolution human brain atlas comprising 95 manually segmented grey and white matter structures as well as 82 white matter tracts compiled from a multitude of resources including ex-vivo MRI, histology, fibre dissections, and neuroanatomy textbooks. The atlas is defined at an isotropic resolution of 100 μm and can be precisely deformed to individual subject brain anatomy. By providing precise definitions of both grey and white matter structures within and around the basal ganglia, thalamus, subthalamus, midbrain and cerebellum, the atlas provides a foundational resource for stereotactic surgery and subcortical brain imaging research, as well as for development of next-generation neuromodulation strategies.