Human Epidermal Growth Factor Receptor 2–Low Breast Cancer Brain Metastases: An Opportunity for Targeted Systemic Therapies in a High-Need Patient Population DOI
Rania Chehade,

Sharon Nofech‐Mozes,

Anna Plotkin

et al.

JCO Precision Oncology, Journal Year: 2024, Volume and Issue: 8

Published: March 1, 2024

PURPOSE Trastuzumab deruxtecan is a new treatment option for patients with advanced human epidermal growth factor receptor 2 (HER2)–low breast cancer (BC). Although HER2-low status has been characterized in early and BC, it yet to be fully brain metastases (BrM). METHODS Patients who underwent surgery BC BrM at Sunnybrook Health Sciences Centre whom HER2 was available on resected were studied. Estrogen receptor, progesterone assessed the basis of ASCO/College American Pathologists (CAP) guidelines. HER2-zero defined as immunohistochemistry (IHC) 0; IHC 1+ or 2+ fluorescence situ hybridization (FISH)–negative status. HER2-positive (HER2+) 3+ positive FISH. Clinicopathologic features recorded. We also prognostic association between extent expression (1) brain-specific progression-free survival (bsPFS), well (2) overall (OS). RESULTS In this retrospective cohort 102 BrM, 53% (n = 54) HER2+, 29.4% 30) HER2-low, 17.6% 18) had Among that triple-negative ASCO/CAP guidelines, 63.6% 14/22) reclassified being HER2-low. Sixty percent 15/25) hormone receptor–positive/HER2-negative (HR+/HER2–) total, 51 matched primary tissue available; results when categorized HER2-zero, HER2+ concordant 82.3% 42/51) cases (Cohen's kappa, 0.58; P .07). There no significant either bsPFS OS. CONCLUSION surgically high proportion those metastatic HR+/HER2– disease have potential benefit from HER2-targeted therapy.

Language: Английский

Discrimination between HER2-overexpressing, -low-expressing, and -zero-expressing statuses in breast cancer using multiparametric MRI-based radiomics DOI

Shaoyan Zheng,

Zehong Yang,

Guangzhou Du

et al.

European Radiology, Journal Year: 2024, Volume and Issue: 34(9), P. 6132 - 6144

Published: Feb. 16, 2024

Language: Английский

Citations

17
Evolution of HER2 expression between pre-treatment biopsy and residual disease after neoadjuvant therapy for breast cancer DOI
Paolo Tarantino, Ogheneochuko Ajari, Noah Graham

et al.

European Journal of Cancer, Journal Year: 2024, Volume and Issue: 201, P. 113920 - 113920

Published: Feb. 10, 2024

Language: Английский

Citations

10
Unraveling the clinicopathological and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-low and HER2-0 breast cancer DOI Creative Commons
Francesco Schettini,

S. Nucera,

F. Brasó-Maristany

et al.

ESMO Open, Journal Year: 2024, Volume and Issue: 9(7), P. 103619 - 103619

Published: June 28, 2024

The characterization and comparison of gene expression intrinsic subtype (IS) changes induced by neoadjuvant chemotherapy (NACT) endocrine therapy in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-low versus HR+/HER2-0 breast cancer (BC) has not been conducted so far. Most evidence on the association HER2 status with pathologic responses prognosis HR+/HER2-negative BC is controversial restricted to NACT-treated disease. Similarly, a temporal heterogeneity described only NACT.

Language: Английский

Citations

9
Molecular Basis of Breast Tumor Heterogeneity DOI
Esra Dikoglu, Fresia Pareja

Advances in experimental medicine and biology, Journal Year: 2025, Volume and Issue: unknown, P. 237 - 257

Published: Jan. 1, 2025

Language: Английский

Citations

1
HER2-low breast cancers: Current insights and future directions DOI
Huina Zhang, Cansu Karakaş,

Haley Tyburski

et al.

Seminars in Diagnostic Pathology, Journal Year: 2022, Volume and Issue: 39(5), P. 305 - 312

Published: July 9, 2022

Language: Английский

Citations

30
Discordance of HER2-Low between Primary Tumors and Matched Distant Metastases in Breast Cancer DOI Open Access
Katrin Almstedt, Lisa Krauthauser, Franziska Kappenberg

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(5), P. 1413 - 1413

Published: Feb. 23, 2023

We examined differences in HER2 expression between primary tumors and distant metastases, particularly within the HER2-negative breast cancer cohort (HER2-low HER2-zero). The retrospective study included 191 consecutive paired samples of metastases diagnosed 1995 2019. were divided into HER2-zero (immunohistochemistry [IHC] score 0) HER2-low (IHC 1+ or 2+/in situ hybridization [ISH]-negative). main objective was to analyze discordance rate matched metastatic samples, focusing on site metastasis, molecular subtype, de novo cancer. relationship determined by cross-tabulation calculation Cohen's Kappa coefficient. final 148 samples. largest proportion [primary tumor 61.4% (n = 78), 73.5% 86)]. status corresponding 49.6% 63) (Kappa -0.003, 95%CI -0.15-0.15). Development a phenotype occurred most frequently 52, 40.9%), mostly with switch from 34, 26.8%). Relevant rates observed different sites subtypes. Primary had significantly lower than secondary [30.2% 0.48, 0.27-0.69) versus 50.5% 0.14, 95% CI -0.03-0.32)]. This highlights importance evaluating potentially therapy-relevant metastases.

Language: Английский

Citations

20
Peptides Targeting HER2-Positive Breast Cancer Cells and Applications in Tumor Imaging and Delivery of Chemotherapeutics DOI Creative Commons

Palmira Alessia Cavallaro,

Marzia De Santo,

Emilia Lucia Belsito

et al.

Nanomaterials, Journal Year: 2023, Volume and Issue: 13(17), P. 2476 - 2476

Published: Sept. 1, 2023

Breast cancer represents the most common type and one of major leading causes death in female worldwide population. Overexpression HER2, a transmembrane glycoprotein related to epidermal growth factor receptor, results biologically clinically aggressive breast subtype. It is also primary driver for tumor detection progression and, addition being an important prognostic women diagnosed with cancer, HER2 widely known therapeutic target drug development. The aim this review provide updated overview main approaches diagnosis treatment HER2-positive proposed literature over past decade. We focused on different targeting strategies involving antibodies peptides that have been explored their relative outcomes current limitations need be improved. encompasses discussion targeted acting as probes molecular imaging. By using types HER2-targeting strategies, nanotechnology promises overcome some clinical challenges by developing novel HER2-guided nanosystems suitable powerful tools imaging, targeting, therapy.

Language: Английский

Citations

20
Pathological complete response, category change, and prognostic significance of HER2-low breast cancer receiving neoadjuvant treatment: a multicenter analysis of 2489 cases DOI Creative Commons
Siji Zhu, Yujie Lu, Xiaochun Fei

et al.

British Journal of Cancer, Journal Year: 2023, Volume and Issue: 129(8), P. 1274 - 1283

Published: Aug. 21, 2023

HER2-low breast cancers (BC) show a good response to novel anti-HER2 antibody-drug conjugates (ADCs) in advanced setting. Nevertheless, little is known about the response, category change, and prognosis of BC receiving neoadjuvant treatment (NAT).Consecutive invasive patients who underwent ≥ 4 cycles NAT surgery from January 2009 December 2020 were retrospectively reviewed. was defined as IHC 1+ or 2+ FISH negative. Concordance rates HER2 other biomarkers analyzed by Kappa test. Kaplan-Meier analysis Cox regression used assess recurrence-free interval (RFI) overall survival (OS).A total 2489 included, whom 1023 (41.1%) had tumors. higher ER positivity rate than HER2-0 (78.5% vs. 63.6%, P < 0.001), similar pathological complete (pCR) (20.6% 21.8%, = 0.617). Among non-pCR cases, 39.5% tumors changed HER2-low, 14.3% after NAT. Low concordance status found both ER-positive (Kappa 0.368) ER-negative 0.444) patients. Primary significantly better RFI (P 0.014), especially among subset 0.016). Moreover, change associated with (adjusted 0.043).Compared patients, high proportion tumor pCR rate, which related prognosis, residual cases A remarkable instability between primary tumor, indicating re-testing new era ADCs therapy.

Language: Английский

Citations

18
Characterization of HER2‐low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study DOI Creative Commons
Francesco Schettini, Eva Blondeaux, Chiara Molinelli

et al.

Cancer, Journal Year: 2024, Volume and Issue: 130(16), P. 2746 - 2762

Published: May 16, 2024

Abstract Background Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)‐low‐expressing BC has recently emerged as a novel therapeutic target not been characterized this rare patient subset. Methods Women newly diagnosed early‐stage HER2‐negative (HER2‐0 and HER2‐low) PVs from 78 health care centers worldwide were retrospectively included. Chi‐square test Student t ‐test used to describe variable distribution between HER2‐0 HER2‐low. Associations HER2‐low status assessed logistic regression. Kaplan–Meier method Cox regression analysis assess disease‐free survival (DFS) overall survival. Statistical significance was considered for p ≤ .05. Results Of 3547 included patients, 32.3% had BC, representing 46.3% of hormone receptor–positive 21.3% triple‐negative (TN) tumors. vs. more grade 1/2 ( < .001), node‐positive = .003). BRCA2 than BRCA1 .001). versus showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76–0.97) the population favorable (HR, 0.78; 0.64–0.95) 0.65; 0.46–0.93) TN subgroup. Luminal A–like tumors .014) luminal A‐like .019) worst DFS. Conclusions In young patients PVs, disease less frequent expected frequently linked luminal‐like disease. modestly improved prognosis.

Language: Английский

Citations

9
Quantitative comparison of immunohistochemical HER2‐low detection in an interlaboratory study DOI Creative Commons
Maaike Anna Hempenius,

Maran A Eenkhoorn,

Henrik Høeg

et al.

Histopathology, Journal Year: 2024, Volume and Issue: 85(6), P. 920 - 928

Published: July 29, 2024

Aims Recently, human epidermal growth factor 2 (HER2)‐low (i.e. HER2 score 1+ or 2+ without amplification) breast cancer patients became eligible for trastuzumab–deruxtecan treatment. To improve assay standardisation and detection of HER2‐low in a quantitative manner, we conducted an external quality assessment‐like study the Netherlands. Dynamic range cell lines immunohistochemistry (IHC) calibrators were used to quantify expression assess interlaboratory variability. Methods results Three blank slides with dynamic line IHC calibrator stained routine assays by 35 laboratories. Four different antibody clones used: 19 (54.3%) 4B5, six (17.1%) A0485, five (14.3%) DG44 (HercepTest) SP3. Laboratories two kits 4B5 assays: 14 (73.7%) ultraView (26.3%) OptiView. Variability lines, measured artificial intelligence software, was median (min–max) = negative core 0.5% (0.0–57.0), 4.3% (1.6–71.3), 42.8% (30.4–92.6) 3+ 96.2% (91.8–98.8). The OptiView had highest analytical sensitivity, closely followed ultraView. SP3 least sensitive. Calibrators A0485 not analysable due background staining. Conclusions As validated detecting HER2‐amplified tumours, all antibodies proved suitable detection. Some tests showed distinct line. controls analysis using demonstrated more variability than commonly appreciated. Revalidation laboratories is needed ensure clinical applicable assays.

Language: Английский

Citations

7