Clinical Behavior of Breast Cancer in Young BRCA Carriers and Prediagnostic Awareness of Germline BRCA Status

Journal of Clinical Oncology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

PURPOSE To investigate the clinical behavior of breast cancer in young BRCA carriers according to specific gene ( BRCA1 v BRCA2 ) and association timing genetic testing (before at diagnosis) with prognosis. METHODS This was an international, multicenter, hospital-based, retrospective cohort study that included 4,752 patients harboring germline pathogenic/likely pathogenic variants (PVs) or , who were diagnosed stage I-III invasive 40 years younger between January 2000 December 2020 78 centers worldwide (ClinicalTrials.gov identifier: NCT03673306 ). RESULTS Compared (n = 1,683), 3,069) had more frequently hormone receptor–negative (74.4% 15.5%) high-grade (77.5% 49.1%) tumors. Similar outcomes observed but a different pattern risk disease-free survival events over time. tested for diagnosis (ie, 2 months before up 6 after diagnosis; n 1,671), those any time 411) smaller tumors (T1: 61.3% 32.4%), less nodal involvement (N0: 65.9% 50.8%), received chemotherapy (84.4% 92.9%), axillary dissection (37.5% 47.4%). Patients better overall (OS; unadjusted hazard ratio [HR], 0.61 [95% CI, 0.40 0.92]); however, this result lost statistical significance adjustment potential confounders including tumor (adjusted HR, 0.74 0.47 1.15]). CONCLUSION global provides evidence on carriers. Identifying PV healthy individuals associated earlier-stage lower treatment burden, as well OS.

Язык: Английский

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SLC7A5/E2F1/PTBP1/PKM2 axis mediates progression and therapy effect of triple-negative breast cancer through the crosstalk of amino acid metabolism and glycolysis pathway

Cancer Letters, Год журнала: 2025, Номер unknown, С. 217612 - 217612

Опубликована: Март 1, 2025

Triple-negative breast cancer (TNBC) is one of the most challenging malignancies with highest mortality rates among women. TNBC relies on both amino acid metabolism and glycolysis to fuel its bioenergetic biosynthetic demand. However, potential crosstalk between these two metabolic pathways impact progression remains largely unexplored. In this study, we observed that SLC7A5, a key transporter, was upregulated in strongly associated poor patient prognosis. We demonstrated elevated SLC7A5 expression activated pathway promoted cell proliferation, tumor growth, therapeutic resistance by inducing switch from PKM1 PKM2 expression, thereby mediating glycolysis. further identified upregulation resulted miR-152 suppression, which regulates cellular function growth. addition, miR-152/SLC7A5 axis mediated PTBP1, maintains balance PKM2, linking signaling pathway. To understand mechanism PTBP1 upregulation, E2F1 transcriptionally through direct binding at seed site, while also induced TNBC. This novel SLC7A5/ E2F1/PTBP1 plays crucial role regulating essential for effectiveness. Our findings offer valuable insights into molecular mechanisms underlying reprogramming highlight targets future interventions.

Язык: Английский

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Hormone receptor-positive early breast cancer in young women: A comprehensive review

Cancer Treatment Reviews, Год журнала: 2024, Номер 129, С. 102804 - 102804

Опубликована: Июль 14, 2024

Язык: Английский

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Risk of second primary cancer in young breast cancer survivors: an important yet overlooked issue

Therapeutic Advances in Medical Oncology, Год журнала: 2025, Номер 17

Опубликована: Янв. 1, 2025

Currently, female breast cancer (BC) represents the highest incidence of globally. This trend has raised significant attention regarding young women (BCYW). With advancements in treatment technology, BCYW survivors are living longer; however, risk developing or succumbing to a second primary (SPC) greatly increased. In addition, several factors, including age, menstrual cycle, hormonal changes, obesity, pregnancy, and breastfeeding, interact influence development SPC make its more difficult. study investigates relationship between SPC, focusing on morbidity trends, pathological genomics, recurrence rates, survival times, modalities, physiological fertility. Most involve BRCA pathogenic variants fall under triple-negative human epidermal growth factor receptor 2-overexpressing subtypes, increasing SPC. While there regional variations time following diagnosis an long-term outcomes remain unfavorable. choice for prolonged cumulative toxic effect. The combination endocrine therapy chemotherapy is effective treating BC, but it simultaneously increases specifically endometrial cancer. Furthermore, radiotherapy associated with heightened contralateral BC lung We aim address existing gaps literature enhance awareness risks BCYW, thereby offering valuable insights clinical treatment.

Язык: Английский

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Clinical Impact and Genomic Features of Human Epidermal Growth Factor Receptor 2–Low Tumors in BRCA1/2 -Mutated Triple-Negative Breast Cancer

JCO Precision Oncology, Год журнала: 2025, Номер 9

Опубликована: Март 1, 2025

PURPOSE Data about the clinical impact of human epidermal growth factor receptor 2 (HER2)–low expression in BRCA1/2 -mutated breast cancer (BC) are limited. This study aimed to clarify relevance HER2-low operable BC. MATERIALS AND METHODS A total 495 HER2-negative BC with germline pathogenic variants treated at our institute between October 2003 and September 2020 were included. was defined as immunohistochemistry (IHC) 1+ or 2+/fluorescence situ hybridization–negative, while HER2-zero IHC 0. Tumor DNA from 25 triple-negative BCs (TNBCs) subjected whole-exome sequencing. RESULTS Among 186 BRCA1 carriers, 38.8% TNBC (n = 121) 52.3% hormone receptor–positive/HER2-negative 65) exhibited tumors subgroup; among 309 BRCA2 44.9% 49) 68.1% 260) subgroup. After a median follow-up 10.9 years (range, 1.23-19.8 years), TNBC, significantly associated better recurrence-free survival (RFS; 10-year RFS: 90.3% v 75.1%; P .015), distant (DRFS; DRFS: 92.4% 76.5%; .010), overall (OS; OS: 94.6% 77.4%; .007) than tumors. However, not observed either BRCA1- Notably, mutated showed higher homologous recombination deficiency scores those CONCLUSION patients have favorable survival, highlighting possibility stratifying these into two subgroups on basis status.

Язык: Английский

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Key decision factors in second-line therapy: Expert insights on HR+/HER2-metastatic breast cancer post-CDK4/6 inhibitor progression

Cancer Treatment Reviews, Год журнала: 2025, Номер 138, С. 102972 - 102972

Опубликована: Май 27, 2025

Язык: Английский

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High-altitude hypoxia exacerbates chemotherapy-induced myelosuppression by lowering serum G-CSF/GM-CSF and regulating apoptosis and proliferation

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Май 28, 2025

Язык: Английский

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Age and Late Recurrence in Young Patients With ER–Positive, ERBB2-Negative Breast Cancer

JAMA Network Open, Год журнала: 2024, Номер 7(11), С. e2442663 - e2442663

Опубликована: Ноя. 7, 2024

Young patients with breast cancer estrogen receptor (ER)-positive, ERBB2-negative tumors have a poor prognosis. Understanding factors influencing late recurrence is crucial for improving management and outcomes.

Язык: Английский

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