Unraveling the role of stromal disruption in aggressive breast cancer etiology and outcomes DOI
Mustapha Abubakar, Máire A. Duggan, Shaoqi Fan

et al.

JNCI Journal of the National Cancer Institute, Journal Year: 2025, Volume and Issue: unknown

Published: May 14, 2025

Abstract Background Aggressive (typically high-grade) breast cancers (BCs) remain major contributors to BC-related mortality globally. The tissue changes underpinning their etiology and outcomes, however, poorly characterized. Methods Spatially resolved machine-learning algorithms were used characterize “stromal disruption” as a morphological metric of reduced/altered extracellular matrix increased immune, inflammatory, and/or wound response-related processes in normal, benign disease (BBD), invasive hematoxylin eosin (H&E)-stained tissues. Associations stromal disruption with BC etiologic factors assessed among 4023 healthy donors, its impact on incidence was 974 BBD patients nested case–control study, while prognostic associations 4 patient cohorts (n = 4223). Results Epidemiologic risk for aggressive BC, including younger age, multiparity, Black race, obesity, family history, demonstrated strong increasing H&E sections prior tumor development. Substantial associated ∼4-fold (high-grade) ∼3 years shorter latency from diagnosis, independently histology. Across cohorts, (mostly phenotypes markedly poor prognosis ER-positive patients, irrespective immunobiology reflected heightened innate (CD68+), adaptive (CD3+CD4+, CD3+CD8+), immunoregulatory (CD3+CD4+FOXP3+), immune escape (PD1+PDL1+), endothelial (CD31+), myofibroblast (α-SMA+) marker expression. Conclusion Our findings highlight the active role opening possibilities readily identifying high-risk women across continuum that may benefit stroma-centric preventative or therapeutic strategies.

Language: Английский

BRCA1/2 and Other Predisposition Genes in High-Risk Hormone Receptor+/Human Epidermal Growth Factor Receptor 2– Breast Cancer Treated With Endocrine Therapy With or Without Palbociclib: A Secondary PENELOPE-B Study Analysis DOI
Eric Hahnen, Jan Hauke, Karen A. Gelmon

et al.

JCO Precision Oncology, Journal Year: 2025, Volume and Issue: 9

Published: April 1, 2025

PURPOSE The PENELOPE-B trial (ClinicalTrials.gov identifier: NCT01864746 ) recruited patients with hormone receptor+/human epidermal growth factor receptor 2– early breast cancer without a pathological complete response after taxane-containing neoadjuvant chemotherapy and at high risk of relapse. Patients were randomly assigned (1:1) to receive 13 cycles palbociclib once daily or placebo on days 1-21 in 28-day cycle addition endocrine therapy (ET). did not show improved invasive disease-free survival (iDFS) adding ET. This retrospective analysis investigated the impact germline pathogenic variant (PV) status BRCA1/2 non- predisposition genes outcomes patients. METHODS In total, 445 sampled following case-cohort design 442 analyzed for PVs. Statistical analyses performed time-to-event end points (iDFS, distant [DDFS], overall [OS]). RESULTS Of patients, 42 carried PVs any gene; 15 Irrespective treatment arms, PV was prognostic factor. Regarding arms carriers, numerically better 3-year observed arm 95%; DDFS, OS, 100%) than 72.8%; 87.5%; hazard ratios v 0.349 [iDFS] 0.562 calculated too few events). PVs, differences negligible. influence efficacy palbociclib, although gene-specific effects could be excluded. CONCLUSION had palbociclib. However, number carriers small. Larger randomized clinical trials should consider further evaluate whether benefit from cyclin-dependent kinase 4 6 inhibitor treatment.

Language: Английский

Citations

0
Chemotherapy receipt in affected BRCA1/2 and PALB2 carriers with operable breast cancer: the impact of early detection and pre-diagnostic awareness on clinical outcomes and treatment DOI Creative Commons
Stephanie M. Wong,

Carla Apostolova,

Amina Ferroum

et al.

Hereditary Cancer in Clinical Practice, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 24, 2025

Language: Английский

Citations

0
Clinicopathological Characteristics of Ovarian and Breast Cancer in PALB2, RAD51C, and RAD51D Germline Pathogenic Variant Carriers DOI Open Access

Jella-Rike J. A. H. Spijkervet,

Lieke Lanjouw, Lieke P.V. Berger

et al.

Genes, Journal Year: 2025, Volume and Issue: 16(5), P. 556 - 556

Published: May 2, 2025

Background/Objectives: Germline pathogenic variants (GPVs) in PALB2, RAD51C, and RAD51D increase breast cancer (BC) ovarian (OC) risk. Limited data on clinicopathological characteristics of BC OC women with these GPVs hamper guideline development. Therefore, this study aims to describe a consecutive series female GPV carriers. Methods: Women or determined before July 2023 at the University Medical Center Groningen were included. Cancer diagnoses obtained through linkage Dutch Nationwide Pathology Databank (Palga). Median onset age histopathological subtypes compared The Netherlands Registry (NCR). Results: Among 164 carriers (125 30 9 RAD51D), 54 6 cases identified. median was 52 (n = 50), 71 3), 43 years 1) for RAD51D, respectively, 62 NCR. No histological subtype differences observed PALB2 populations RAD51C too small compare NCR data. occurred 66 4) 56 2) carriers, versus 67 All had high-grade serous carcinoma, 51.5% Conclusions: Differences between national Further research is needed optimize counseling prevention women.

Language: Английский

Citations

0
Association of Polygenic-Based Breast Cancer Risk Prediction With Patient Management DOI

Katherine Johansen Taber,

Elisha Hughes, Alexander Gutin

et al.

JCO Precision Oncology, Journal Year: 2025, Volume and Issue: 9

Published: May 1, 2025

PURPOSE Breast cancer (BC) risk prediction is more accurate when clinical and polygenic factors are combined (combined score [CRS]), but little known about how CRS results affect real-world patient management. METHODS Deidentified medical pharmacy claims data were linked with Tyrer-Cuzick (TC) evaluated for BC Patients divided into subcohorts on the basis of lifetime predicted by TC (“+”: ≥20% risk, “–”: <20%): CRS+ TC+, TC–, CRS– TC–. Claims related to screening mammography (SM) in patients younger than 40 years, breast magnetic resonance imaging (MRI), genetic counseling (GC) compared 360 days before after testing. Differences pre- post-CRS management using McNemar tests, was multivariable logistic regression. RESULTS After testing, TC+ had 1.6-2.2-fold increases SM years (all P < .02) 4.7-5.6-fold MRI .001). The TC– 1.9-2.3-fold GC (both those MRI, did not increase subcohort. subcohort, significantly higher odds receiving age (odds ratio [OR], 3.80-5.19), (OR, 11.55-23.09), 2.03-2.91; all CONCLUSION either or likely receive enhanced who <20% suggesting that clinicians considered

Language: Английский

Citations

0
Unraveling the role of stromal disruption in aggressive breast cancer etiology and outcomes DOI
Mustapha Abubakar, Máire A. Duggan, Shaoqi Fan

et al.

JNCI Journal of the National Cancer Institute, Journal Year: 2025, Volume and Issue: unknown

Published: May 14, 2025

Abstract Background Aggressive (typically high-grade) breast cancers (BCs) remain major contributors to BC-related mortality globally. The tissue changes underpinning their etiology and outcomes, however, poorly characterized. Methods Spatially resolved machine-learning algorithms were used characterize “stromal disruption” as a morphological metric of reduced/altered extracellular matrix increased immune, inflammatory, and/or wound response-related processes in normal, benign disease (BBD), invasive hematoxylin eosin (H&E)-stained tissues. Associations stromal disruption with BC etiologic factors assessed among 4023 healthy donors, its impact on incidence was 974 BBD patients nested case–control study, while prognostic associations 4 patient cohorts (n = 4223). Results Epidemiologic risk for aggressive BC, including younger age, multiparity, Black race, obesity, family history, demonstrated strong increasing H&E sections prior tumor development. Substantial associated ∼4-fold (high-grade) ∼3 years shorter latency from diagnosis, independently histology. Across cohorts, (mostly phenotypes markedly poor prognosis ER-positive patients, irrespective immunobiology reflected heightened innate (CD68+), adaptive (CD3+CD4+, CD3+CD8+), immunoregulatory (CD3+CD4+FOXP3+), immune escape (PD1+PDL1+), endothelial (CD31+), myofibroblast (α-SMA+) marker expression. Conclusion Our findings highlight the active role opening possibilities readily identifying high-risk women across continuum that may benefit stroma-centric preventative or therapeutic strategies.

Language: Английский

Citations

0