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537 citation(s) found for "Walker, A".

The Baseline Molecular Profile of Late Relapse: Identifying Drivers of Delayed Recurrence in DLBCL
Masar, Michal , Walker, Janek S. , Vodicka, Prokop , Dropik, Abigail R , Xianyu, Zilin , Maurer, Matthew , Habermann, Thomas , Mou, Eric , Witzig, T.E. , Ansell, Stephen M , Klener, Pavel , Cerhan, James R , Trnĕný, Marek , Wang, Yucai , Novak, Anne J

Hematological Oncology | October 12, 2026 | Volume: 44 | Issue: 6 | Pages: No page available

10.1002/hon.70275 | PMID 42861738 Get It

Multimorbidity, Polypharmacy, and Neighborhood Disadvantage as Determinants of Cognitive Performance in the ARCHES Cohort
Gebremichael, Dagem , Bekena, Semere , Singh, Ramkrishna K. , Walker, Alexis I. B., Millsap, Mario , Banks, Christian F., Bekele, Bisrat, Zhu, Yiqi, Trani, Jean-Francois, Babulal, Ganesh M.

Journal of Applied Gerontology | October 7, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1177/07334648261491344 | PMID 42842789 Get It

Background African American adults experience a disproportionate burden of dementia, shaped by structural and clinical factors that remain unclear. Objective To quantify associations between multimorbidity, polypharmacy, and cognition in the context of neighborhood disadvantage. Methods This study is a cross-sectional analysis of 348 African American adults aged 45–92 years (mean 64.3 years; 73.6% female) from the Aging Research Characterizing Health Exposome via Social drivers (ARCHES) cohort. Comorbidity burden was assessed using a modified Charlson Comorbidity Index (CCI), polypharmacy as ≥5 medications, and neighborhood disadvantage using the Area Deprivation Index (ADI). Linear regression estimated associations with a Preclinical Alzheimer’s Cognitive Composite (PACC). The polypharmacy model included modified CCI as a covariate, and effect modification by ADI was assessed using an interaction term between polypharmacy and ADI. Results Higher modified CCI was associated with lower cognitive performance (B = −0.071; 95% CI: −0.130, −0.012). Polypharmacy was not independently associated with cognition after modified CCI adjustment (B = −0.081; β = −0.057; p = 0.257). No significant ADI interaction was found (p = 0.064).
Hidradenitis Suppurativa: Part of a Tetrad of Follicular Occlusion Disorders
Sie, Shannon P., Sibbald, R. Gary, Akpala, Christeebella, Miller, Jonathan, Coutts, Patricia, Alavi, A., Walker, David , Akpala, Christeebella O.

Advances in Skin & Wound Care | September 18, 2026 | Volume: 39 | Issue: 9 | Pages: 462-475

10.1097/asw.0000000000000523 | PMID 42759045 Get It

Follicular occlusion disorders (FOD) represent a tetrad of chronic, recurrent inflammatory conditions united by a common pathophysiologic mechanism: follicular hyperkeratosis leading to occlusion, rupture, and subsequent abscess or sinus tract formation. First conceptualized as a triad in the 1950s and later expanded to a tetrad in the 1970s, this grouping includes hidradenitis suppurativa (HS), acne conglobata (AC), dissecting cellulitis of the scalp (DCS), and pilonidal sinus (PS). Despite their shared pathogenesis, each condition carries distinct clinical features, epidemiological profiles, and management considerations. This article aims to provide a comprehensive review of FOD, with a primary emphasis on HS (the most prevalent of the disorders). Hidradenitis suppurativa is a debilitating disease affecting ∼1% of the global population, predominantly in females, and the diagnosis is often delayed by 7 or more years. Multiple genes are linked to FOD patients with a positive familial history in 35% to 40%, along with lifestyle factors (smoking, alcohol consumption, and obesity). Key inflammatory mediators, including TNF-α, IL-1β, and IL-17, drive the chronic tissue destruction characteristic of FOD, frequently resulting in scarring, lymphedema, and significant psychosocial impairment. Wound care is critical and often underemphasized in disease management. This article outlines evidence-informed wound care strategies for both nonsurgical and postsurgical presentations, including dressing selection, exudate and odor management, pain and itch control, infection management, and the emerging role of intravenous ertapenem as rescue therapy. An interprofessional approach, integrating dermatology, surgery, wound care nursing, and psychosocial support, is emphasized throughout as essential to improving patient outcomes and quality of life. GENERAL PURPOSE: To increase clinicians’ understanding of follicular occlusion disorders including the associated risk factors, clinical manifestations, and evidence-based approaches for management. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will: Assess clinical characteristics of each follicular occlusion disorder Evaluate the basic disease mechanisms for follicular occlusion disorders Describe principal disease burdens that require wound care attention Identify the unique wound care strategies and follicular occlusion disorder challenges JOURNAL/aswca/04.03/00129334-202610000-00004/figure1/v/2026-09-18T181327Z/r/image-jpeg
Upper Extremity Symptoms After A Fall In A Recreational Walker: A Multisystem Puzzle
Tran, Apollo, Phrathep, David, Wong, Alyssa, Nunez, Rigoberto, Pujalte, George, Phrathep, Davong David , Phrathep, Davong D

Medicine & Science in Sports & Exercise | September 18, 2026 | Volume: 58 | Issue: 10S | Pages: No page available

10.1249/01.mss.0001262832.08066.80 Get It

Longitudinal single-cell and spatial transcriptomics reveals intratumor heterogeneity, therapeutic response, and comparative value of canine marginal zone lymphoma
Walker, Grace E., Macchietto, Marissa, Reid, Kelly, Burt, Lauren E., Winter, Amber, Pracht, Sara, Buettner, Michelle, Penza, Velia , Yung, Caitlin, Dicovitsky, Rose, Kuzmik, Alana, Vallera, Daniel A. , Demos-Davies, Kimberly, Seelig, Davis , Borgatti, Antonella , Henson, Mike, Feiock, Caitlin, Modiano, Jaime F. , Naik, Shruthi, Sarver, Aaron L. , Treeful, Amy E. , Macchietto, Marissa , Pracht, Sara, Dicovitsky, Rose, Kuzmik, Alana R., Demos-Davies, Kimberly , Naik, Shruthi

No container title available | September 14, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.64898/2026.09.10.750253 | PMID 42779884 Get It

Diffuse B-cell lymphomas are the most prevalent canine hematologic malignancies, and their clinical presentation resembles that of human B-cell non-Hodgkin lymphomas (NHLs). However, a lack of a clear subtyping framework perpetuates imprecise treatment approaches that fail to address mechanisms of therapy resistance. Here, we employed deep phenotyping via serial sampling and longitudinal transcriptomics to evaluate intratumoral composition and therapy response in a 6-year-old neutered male goldendoodle with stage 5A marginal zone lymphoma (MZL). Following sequential treatment consisting of a single IV dose of oncolytic vesicular stomatitis virotherapy (VSV) and standard CHOP chemotherapy 30 days later, we performed scRNAseq on seven serial lymph node biopsies and spatial sequencing on a resection taken 10 days post-VSV treatment. B cells (>90%) comprised three transcriptionally distinct and temporally stable subpopulations, with specific copy number profiles and robust spatial organization despite disrupted lymph node architecture. Analysis across subpopulations revealed downregulation of the quiescence program including KLF2, suggesting similarity to KLF2-deficient human MZL. While VSV successfully reached target B cells, downstream transcriptional responses were predominantly localized to the T-cell compartment. T cells (≤6%) showed increased proliferation and upregulation of cytotoxicity markers post-VSV administration, enriching for leukocyte-mediated cytotoxicity pathways consistent with an anti-viral immune response. Ultimately, these results provide an in vivo proof-of-concept for the treatment paradigm in canine lymphoma, while emphasizing the need for improved subtyping frameworks and multidimensional treatment strategies targeting intratumoral heterogeneity.
From Housing to Hotspots: Integrating a Housing-Based Measure of Individual Socioeconomic Status with Geospatial Analysis to Target Colorectal Cancer Screening in Rural Communities
Yao, Rebecca , Beenken, Madison, Watson, Dave , Wheeler, Philip H., Finch, Mike, Kelleher, Dan , Anil, Gokhan , Anderson, Trent, Madden, Kathy A., Okuno, Scott H. , Odedina, Folakemi T., Park, Eunice , Dugani, Sagar B., Sosso, Jessica , Sabarish, Shivani , Singh, Gurpreet, Lugo-Fagundo, Nahyr, Kim, W. Ray, Walker-Mcgill, Cheryl L., Juhn, Young J. , Lynch, Brian , Wi, Chung‐Il , Madden, Kathy A., Westfall, Erin , Sharma, Pravesh , Dugani, Sagar B. , Foss, Randy , Hidaka, Brandon H. , Singh, Gurpreet, Howick V, James F , Calvin, Andrew D. , Walker-McGill, Cheryl Lynn, Rennert, Lior , Cerhan, James R.

No container title available | September 3, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.64898/2026.08.28.26361444 Get It

ABSTRACT Purpose This study assesses the association between colorectal cancer (CRC) screening and a validated, housing-based measure of individual-level socioeconomic status (SES, called HOUSES hereafter) within rural communities and determines whether HOUSES-integrated geospatial analysis can be used to tailor interventions. Methods We used CRC screening data from a subset of Mayo Clinic Midwest patients living in cities without ready access to routine care in the Mayo Clinic Health System in 2019 to represent rural communities. At the individual level, we assessed the association between CRC screening rates and the HOUSES index, adjusting for age, sex, race/ethnicity, comorbidity, distance from home address to clinic, and area deprivation index, using a multilevel mixed-effects logistic regression model. Additionally, we conducted geospatial analysis to examine the correlation between hotspots of 1) lower CRC screening rates and 2) lower SES of the subject population (HOUSES quartile 1). Findings Among 34,489 individuals (median age 64.0 years, 52.4% female), those with the lowest SES (HOUSES Q1) had 37% lower odds of being CRC screening adherent than those with the highest SES (HOUSES Q4) (adj. OR [95% CI]: 0.63 [0.58-0.69]). In the 14 identified HOUSES Q1 hotspots, there was a significant correlation in counts of HOUSES Q1 and low CRC screening (correlation coefficient=0.81). Conclusion Lower SES was significantly associated with lower CRC screening among rural populations. HOUSES-enabled geospatial analysis identified geographic hotspots with lower CRC screening rates for targeted interventions to address disparities in CRC screening in rural communities. HOUSES may be a useful digital tool for cancer preventive care and research.
Incidence of Chronic Rhinosinusitis in Patients Who Receive Rituximab
Walker, Kendra, Valencia‐Sanchez, Bastien A., Wilson, Penny , Najmi, Natasha, Donaldson, Angela M. , Donaldson, Angela M , Wilson, Prishae , Valencia‐Sanchez, Bastien A. , Najmi, Natasha N.

Otolaryngology–Head and Neck Surgery | August 17, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1002/ohn.70390 | PMID 42605935 Get It

Abstract Objective Rituximab causes B‐cell depletion and hypogammaglobulinemia, increasing risk for infections. This study aims to determine the incidence of chronic rhinosinusitis (CRS) in patients following rituximab therapy. Study Design Retrospective cohort study using chart review of patients prescribed rituximab between January 2019 and January 2025. Setting Multisite study across Mayo Clinic Enterprise locations in Arizona, Florida, Minnesota, and Wisconsin. Methods Patients with documented rituximab use were included; those with pre‐existing CRS were excluded. Demographic and clinical data—including timing and duration of rituximab therapy, CRS diagnosis, comorbidities (asthma, allergic rhinitis, GERD), and need for sinus surgery—were collected. Descriptive statistics summarized patient characteristics. Group comparisons were performed using t ‐tests, Mann‐Whitney U , and chi‐square tests. Analyses were conducted using SPSS v28. Results Among 17,851 patients prescribed rituximab (median age 64.0 years, M:F ratio 1.1:1), 1105 (6.2%) developed CRS, with an annual incidence of 1.03% (1032 cases per 100,000 person‐years). The median duration of rituximab therapy for those diagnosed with CRS was 5.9 months (IQR, 0.5‐42.6). Most CRS cases occurred after rituximab discontinuation (62.7%, n = 693) compared to during active treatment (37.3%, n = 412). The median delay between rituximab discontinuation and CRS diagnosis was 17.0 months (IQR, 4.3‐41.7). Conclusions This study demonstrates an annual incidence of 1.03% for CRS diagnoses following rituximab. While prior studies report varying CRS incidences in the general population (0.25%‐0.73%), our findings suggest increased risk among rituximab users. Most CRS diagnoses occurred after rituximab discontinuation, emphasizing the need for a comprehensive medication history review during CRS evaluation.
Pharmacoexposomics: The Environmental Complement to Pharmacogenomics to Advance Precision Medicine
Reho, Paolo, Athreya, Arjun P. , Hripcsak, George, Kim, Soon-Mi, Li, Shuzhao, Walker, Douglas I., Patel, Chirag J., Miller, Gary W., Reho, Paolo , Thaker, Vidhu , Cremers, Serge , Go, Young‐Mi , Hripcsak, George , Hu, Xin , Jones, Dean P. , Lazaridis, Konstantinos N. , Li, Shuzhao, Pennell, Kurt D. , Singh, Randolph R. , Walker, Douglas Ian , Patel, Chirag J.

Annual Review of Pharmacology and Toxicology | August 13, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1146/annurev-pharmtox-062624-113658 | PMID 42594291 Get It

Despite advances in pharmacogenomics that have led to innovative therapeutic strategies, substantial interindividual variability in drug efficacy and toxicity persists. Both endogenous and exogenous factors contribute to this unexplained variation, resulting in suboptimal treatment effectiveness, unnecessary healthcare costs, preventable mortality, and significant human suffering. The emerging field of exposomics is aimed at addressing the complex exposures that impact human health and offers an opportunity to interrogate how these exposures influence drug actions and outcomes. Here, we introduce pharmacoexposomics as a complementary framework that systematically quantifies the body's metabolic response to drug and environmental exposures using high-resolution mass spectrometry. We then present IndiPHARM (Individualized Pharmacology), a multi-institution, Advanced Research Projects Agency for Health–supported platform designed to integrate population-scale pharmacoexposomics with pharmacogenomics and clinical data to elucidate interindividual variability in drug response, identify adverse reactions, and inform tailored, effective treatment strategies that advance precision medicine.
Characteristics of Gender-Diverse Patients With Breast Cancer
Cortina, Chandler S., Brazauskas, Ruta , Flanagan, Meghan R., Dill, Ellen D., Joseph, Kathe-Ann P., Trifonov, Alexandr , Kim, Esther A. , Kantor, Olga, Barmettler, Gabi , Rosenberger, Laura H., Jordan, Sumanas W., Perez, Megan M. , Jimenez, Rachel B., Smart, Alicia , Walker, J C, Lautner, Meeghan A., Siegel, Emily L., Brabender, Danielle , Al-Hilli, Zahraa, Cassidy, Michael R., Weiss, Anna, McCaffrey, Rachel L., Lee, M Catherine, Kaoutzanis, Christodoulos, Nguyen, Khoa N., Son, Jennifer D., Williams, Austin D., Madrigrano, Andrea, McLaughlin, Sarah A., Stolley, Melinda, Cortina, Chandler S. , Flanagan, Meghan R. , Mukhtar, Rita A. , Kantor, Olga , Rezak, Kristen M. , Rosenberger, Laura H. , Jimenez, Rachel , Kopkash, Katherine A. , Hughes, Tasha M. , Walker, Jasmine C. , Lautner, Meeghan Ann, Siegel, Emily , Al‐Hilli, Zahraa , Cassidy, Michael Ryan , Weiss, Anna, McCaffrey, Rachel Louise , Kaoutzanis, Christodoulos , Son, Jennifer D. , Williams, Austin David , Petroll, Andrew E. , Stolley, Melinda R.

JAMA Network Open | July 23, 2026 | Volume: 9 | Issue: 7 | Pages: e2624824

10.1001/jamanetworkopen.2026.24824 | PMID 42490110 Get It

Importance Limited granular data exist on breast cancer in transgender, nonbinary, and/or gender-diverse (TGD) individuals. Objective To describe patient demographic and tumor clinicopathological variables, clinically relevant risk factors, method of breast cancer detection, treatment characteristics, and locoregional outcomes and to estimate a 5-year breast cancer–specific survival (BCSS). Design, Setting, and Participants This cohort study obtained data on patients treated from 1990 to 2023 from 22 US academic medical centers using institutional databases, electronic medical records, and tumor registries. Included participants were TGD individuals 18 years or older with stage 0 to IV breast cancer. A comparative breast cancer cohort was selected from the 2016 to 2021 Surveillance, Epidemiology, and End Results Program (SEER) breast cancer dataset. Data were analyzed from January to October 2025. Exposure Breast cancer. Main Outcomes and Measures Estimated 5-year BCSS and locoregional recurrence rates. Wilcoxon rank sum and χ 2 tests were used to compare continuous and categorical variables. Kaplan-Meier analysis was used to estimate 5-year BCSS. Results A total of 112 TGD persons (median [IQR] age at diagnosis, 42.5 [36.5-51.0] years; 104 individuals [92.9%] were assigned female at birth) with breast cancer and 1 with bilateral disease were included in the analysis. Forty-three patients (38.4%) used gender-affirming hormone therapy before diagnosis. Among the entire cohort, 58 patients (51.8%) detected their own breast cancer, 68 (60.7%) had a familial breast cancer history, and 16 (14.3%) had a pathogenic germline variant. Tumors were predominantly hormone receptor positive (96 [85.7%]) and early stage (29 [25.7%] ductal carcinoma in situ [DCIS]; 51 [45.1%] stage I). The TGD cohort, compared with patients with breast cancer in the SEER dataset (N = 480 915), was younger (median [IQR] age, 42.5 [36.5-51.0] years vs 62.0 [52.0-72.0] years), had a higher proportion of persons assigned male at birth (8 [7.1%] vs 3522 [0.7%]), more often had progesterone receptor–positive disease (89 [79.5%] vs 335 491 [69.8%]), and presented with earlier-stage disease (eg, DCIS: 29 [25.9%] vs 79 604 [16.6%]). With a median (IQR) follow-up time for the TGD cohort of 38 (24-74) months, 5-year BCSS was favorable at 96.2% (95% CI, 85.3%-99.0%). Conclusions and Relevance This cohort study of TGD patients with breast cancer found that this population was young and often detected their own tumors via self-examination, suggesting opportunities to improve early detection through screening for individuals at elevated risk. Although short-term BCSS appeared favorable, prospective research is essential to define evidence-based guidelines and elucidate long-term outcomes.
Clarifying risk-factor associations with quantitative breast tumor features: a pooled analysis of 24 studies
Adams, Daniel , Hurson, Amber N. , Ahearn, Thomas U, Andrulis, Irene L, Antoniou, Antonis C, Auvinen, Päivi, Bane, Anita, González, Amy Berrington de , Bodelon, Clara, Bolla, Manjeet K. , Borrero, Maria , Brenner, Hermann, Brock, Ian W., Camp, Nicola J. , Cessna, Melissa H., Chanock, Stephen J, Chenevix-Trench, G, Copson, ER, Fh, Couch, Devilee, P, Easton, Douglas F, Eccles, Diana, Figueroa, Jonine D, Glendon, Gord, Hamann, U, Hartman, Mikael, Heemskerk-Gerritsen, Bernadette A M, Hodge, James M, Holleczek, Bernd, Hollestelle, A M, Mj, Hooning, Investigators, kConFab, Amor, David, Andrews, Lesley , Antill, Y , Rl, Balleine, Beesley, Jonathan, Bennett, Ian, Bogwitz, Michael, Bodek, Simon, Botes, Leon, Brennan, Meagan, Brown, Melissa, Buckley, Michael, Caldon, Liz, Campbell, Ian, Chakrabarti, Anannya , Chauhan, Deepa, Chauhan, Manisha, Christian, Alice, Cohen, Paul, Colley, Alison, Cui, James, Courtney, Eliza, Cummings, Margaret, Delatycki, Martin, Dickson, Rebecca, Dixon, Joanne, Duijf, Pascal, Edwards, Stacey, Farshid, Gelareh , Fellows, AM, Fenton, Georgina, Field, Michael, Flanagan, James, Fong, Peter, Forrest, Laura, Fox, Stephen, French, Juliet , Friedlander, Michael, Gattas, Mike, George, Peter, Greening, Sian, Harris, Marion, Harraka, Philip, Hayward, Nick, Hoskins, Cass , Hunt, Clare, James, Paul, Jenkins, Mark, Kidd, Alexa, Koehler, Jessica, Kollias, J, Lakhani, Sunil, Lawrence, Mitchell, Lee, Jason , Li, Shuai, Lindeman, Geoff, Lippey, Jocelyn, Lipton, Lara, Loi, Sherene, Mann, Graham, Marsh, Deborah, McLachlan, Sue Anne, Reed, Amy McCart, Milne, Roger, Nightingale, Sophie , O’Connell, Shona, O’Sullivan, Sarah, Reilly, Robert O', Ortega, David Gallego, Pachter, Nick, Pang, Jia-Min, Pathak, Gargi, Patterson, Briony, Phillips, Kelly, Pieper, Ellen, Ramus, Susan, Rickard, Edwina, Ragunathan, Abi, Robinson, Bridget, Skandarajah, Anita, Salisbury, Elizabeth, Saunders, Christobel, Saunus, Jodi, Scott, Rodney, Scott, Clare, Sexton, Adrienne, Shaw, Joanne, Shelling, Andrew, Srinivasa, Shweta , Simpson, Peter, Mc, Southey, Spurdle, Amanda, Taylor, Jessica, Taylor, Renea, Thorne, Heather, Trainer, A H, Tucker, Kathy , Visvader, Jane, Walker, Logan, Williams, Rachael, Winship, I, Young, Mary Ann, Zaheed, Milita , Investigators, S On Behalf Of The Chlovis Study, Tan, Veronique Kiak Mien , Lim, Geok Hoon, Tan, Ern Yu , Tan, Su-Ming, Iau, Philip Tsau Choong , Jakubowska, A, Jones, Michael E. , Jones, Louise , Jones, Brandt, Jung, Audrey, Kaaks, Rudolf, Keeman, Renske , Lawrence, Scott, Li, J M, Lubiński, J, Mannermaa, Arto, Manoochehri, Mehdi, Martens, John W M, Mesker, Wilma E, Muhammad, Noor , Obi, Nadia, Olson, Janet E, Patel, Alpa V, Prajzendanc, Karolina , Ruddy, Kathryn J, Safizadeh, Fatemeh , Schöttker, Ben, Tengström, Maria , Le, Teras, Timmermans, M, Tollenaar, RA, Vachon, Celine M, Wang, Q, Yang, Xiaohong R, Zamora, M Pilar, Chang-Claude, Jenny, Schmidt, M K, Pharoah, Paul D P, Abubakar, Mustapha, Eccles, Diana , Ahearn, Thomas U. , Eccles, Diana , Jones, Michael E , Jones, J. Louise , Berrington de Gonzalez, Amy , Antoniou, Antonis C. , Bane, Anita, Behrens, Sabine , Białkowska, Katarzyna , Bodelón, Clara , Brenner, Hermann , Broeks, Annegien , Chanock, Stephen Jacob , Chenevix‐Trench, Georgia , Copson, Ellen , Couch, Fergus J, Cox, Angela , Cross, Simon S. , Devilee, Peter , Dunning, Alison M. , Easton, Douglas F. , Figueroa, Jonine D. , Glendon, Gord, González‐Neira, Anna , Hartikainen, Jaana M. , Hartman, Mikael , Heemskerk‐Gerritsen, Bernadette A. M. , Ho, Peh Joo , Hodge, James M. , Holleczek, Bernd , Hollestelle, Antoinette , Hooning, Maartje J. , Investigators, kConFab, Balleine, Rosemary L. , Bennett, Ian, Bogwitz, Michael R. , Bodek, Simon , Botes, Leon P., Buckley, Michael , Cohen, Paul A. , Crook, Ashley , Courtney, Eliza , Dawson, Sarah‐Jane , DeFazio, Anna , Delatycki, Martin B. , Duijf, Pascal H. G. , Fellows, Andrew, Fenton, Georgina L. , Flanagan, James M. , Forrest, Laura Elenor , Friedländer, Michael , Harraka, Philip A. , Kidd, Alexa, Kollias, James, Lakhani, Sunil R. , Lawrence, Mitchell, Lindeman, Geoffrey J. , Lippey, Jocelyn , Loi, Sherene , Reed, Amy E. McCart , Milne, Roger L , Gallego‐Ortega, David , Pathak, Gargi, Pearn, Amy , Robinson, Bridget A. , Skandarajah, Anita Rohini , Salisbury, Elizabeth, Saunders, Christobel , Saunus, Jodi M. , Savas, Peter Stephen , Sexton, Adrienne , Shelling, Andrew Neil , Simpson, Peter, Spurdle, Amanda B. , Visvader, Jane E. , Williams, Rachael, Tan, Bien‐Keem , Lim, Geok Hoon , Kaaks, Rudolf , Lawrence, Scott M. , Lissowska, Jolanta , Mannermaa, Arto , Manoochehri, Mehdi, Mesker, Wilma E. , Mulligan, Anna Marie , Obi, Nadia , Olson, Janet E. , Osório, Ana , Ottewell, Penelope Dawn , Patel, Alpa V , Pita, Guillermo , Rashid, Muhammad Usman , Ruddy, Kathryn J. , Schöttker, Ben , Seibold, Petra , Tapper, William , Teras, Lauren R , Timmermans, Mieke, Vachon, Celine M. , Wesseling, Jelle , Yadav, Siddhartha , Chang‐Claude, Jenny , Schmidt, Marjanka K. , Abubakar, Mustapha , García‐Closas, Montserrat

JNCI: Journal of the National Cancer Institute | July 18, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1093/jnci/djag244 | PMID 42498670 Get It

Abstract Background Breast cancer is etiologically heterogeneous, but which risk factors differ in their associations across tumor subtypes remains unclear. We conducted a large, pooled analysis to evaluate independent, dose-response associations between breast cancer risk factors and quantitative tumor features. Methods Analyses of 15,731 invasive breast cancers from 24 studies evaluated associations (p-trend) between reproductive and hormonal factors, body mass index (BMI), alcohol, smoking, and family history in relation to quantitative immunohistochemistry measures on tissue microarrays (ER, PR, HER2, KI67, TP53) and tumor grade. Analyses in a subset of 10 population-based studies estimated subtype-specific odds ratios (ORs) comparing cases to controls. A Bayesian False Discovery Probability (BFDP) <0.2 was used to identify associations with strong statistical evidence. Results Nulliparity and later age at menopause were associated with higher ER-positivity (p-trend=0.021 and 0.001, respectively), with corresponding OR[ER+] (95% CI) = 1.49 (1.16-1.90) for nulliparous vs. parous and 1.07 (1.03-1.11) per 5 years. Current combined menopausal hormone therapy (MHT) use was associated with lower grade (p-trend<0.001), with OR [grade1] = 3.37 (2.69-4.21) for current vs. never users. Higher BMI was associated with lower ER-positivity and higher grade in premenopausal women (p-trend<0.001 and <0.001), with OR[ER+] = 0.80 (0.74-0.87) and OR[grade1] = 0.75 (0.63-0.88) per 5 units, and with higher PR-positivity and higher grade in postmenopausal women (p-trend<0.001 and <0.001), with OR[PR+] = 1.08 (1.03-1.14) and OR[grade 3] = 1.10 (1.04-1.17) per 5 units. Conclusion This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity. Associations with HER2, KI67 and TP53, or other risk factors did not meet our threshold for strong evidence.