The Impact of HER2-Low Expression on Oncologic Outcomes in Hormone Receptor-Positive Breast Cancer DOI Open Access
Woong Ki Park, Seok Jin Nam, Seok Won Kim

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(22), P. 5361 - 5361

Published: Nov. 10, 2023

Breast cancer is a prevalent malignancy with increasing incidence, particularly in Asian countries. Classification based on estrogen receptor (ER), progesterone (PR), and human epidermal growth factor 2 (HER2) status pivotal determining treatment. Recent advances have challenged the traditional dichotomy HER2 classification, prompting investigation into HER2-low subtype's characteristics outcomes. This retrospective study analyzed 10,186 non-metastatic hormone (HR)-positive, HER2-negative breast cases treated from 2008 to 2020. Data encompassed clinical, pathological, treatment information. Oncologic outcomes included disease-free survival (DFS), overall (OS), cancer-specific (BCSS). In total, 56.5% were cases. Differences patient noted, more BRCA1/2 mutations higher mastectomy rates group (p = 0.002, p < 0.001, respectively). Fewer received adjuvant chemotherapy or radiation therapy, fewer histologic nuclear grade 1 tumors identified (all 0.001). With median follow-up of 64 months (range: 13-174), exhibited better DFS, OS, BCSS than HER2-0 0.012, 0.013, Notably, prognosis differed between premenopausal postmenopausal subgroups, benefitting patients 0.047) DFS OS 0.004, 0.009, Multivariate analysis confirmed as an independent predictor these 0.010, 0.008, 0.014, extensive single-center elucidates favorable associated HR-positive cancer. However, this effect differs among patients, necessitating further research underlying tumor biology.

Language: Английский

Molecular characterization of HER2-negative breast cancers reveals a distinct patient subgroup with 17q12 deletion and heterozygous loss of ERBB2 DOI Creative Commons
Xintao Qiu,

P. Tarantino,

Rong Li

et al.

ESMO Open, Journal Year: 2025, Volume and Issue: 10(2), P. 104111 - 104111

Published: Jan. 18, 2025

Language: Английский

Citations

2
Standardized pathology report for HER2 testing in compliance with 2023 ASCO/CAP updates and 2023 ESMO consensus statements on HER2-low breast cancer DOI Creative Commons
Mariia Ivanova, Francesca Porta, Marianna D’Ercole

et al.

Virchows Archiv, Journal Year: 2023, Volume and Issue: 484(1), P. 3 - 14

Published: Sept. 28, 2023

Since the release of DESTINY-Breast04 (DB-04) trial findings in June 2022, field pathology has seen a renaissance HER2 as predictive biomarker breast cancer. The focused on patients with metastatic cancer who were classified "HER2-low," i.e., those immunohistochemistry (IHC) 1 + or 2 and negative situ hybridization (ISH) results. study revealed that treating these trastuzumab deruxtecan (T-DXd) instead oncologist's chosen chemotherapy led to outstanding improvements survival. This challenged existing binary pathological classification system, which categorized tumors either positive (overexpression/amplification) negative, per ASCO/CAP 2018 guideline reaffirmed by 2023 update. Given DB-04 excluded IHC score 0 status, results ongoing DB-06 may shed further light potential benefits T-DXd therapy for patients. Roughly half all cancers are estimated belong HER2-low category, does not represent distinct specific subtype Instead, it encompasses diverse group exhibit clinical, morphological, immunohistochemical, molecular variations. However, offers distinctive status identifies therapeutic regimen (i.e., T-DXd) linked favorable prognosis unique association emphasizes importance accurately identifying tumors. Differentiating between been clinically significant until now. To ensure accurate avoid misdiagnosis, is necessary adopt standardized procedures, guidelines, specialized training pathologists interpreting expression lower spectrum. Additionally, utilization artificial intelligence holds promise supporting this endeavor. Here, we address current state art unresolved issues assessing particular emphasis 0. We explore dilemma surrounding exclusion HER2-zero from potentially beneficial based traditional testing. examine clinical context, considering primarily involved heavily pretreated late-stage cancers. also delve into emerging evidence suggesting extrapolating original diagnosis lead misleading Finally, provide recommendations conducting high-quality testing propose report compliance updates ESMO consensus statements

Language: Английский

Citations

39
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
The effect of low HER2 expression on treatment outcomes in metastatic hormone receptor positive breast cancer patients treated with a combination of a CDK4/6 inhibitor and endocrine therapy: A multicentric retrospective study DOI Open Access
Eda Caliskan Yildirim, Elif Atağ,

Ezgi Çoban

et al.

The Breast, Journal Year: 2023, Volume and Issue: 70, P. 56 - 62

Published: June 15, 2023

BackgroundCDK4/6 inhibitors combined with endocrine therapy have significantly improved treatment outcomes for metastatic hormone receptor-positive (HR+) breast cancer patients. However, the impact of low HER2 expression on response and progression-free survival (PFS) remains unclear.MethodsThis multicenter retrospective study included 204 HR+ patients treated a combination CDK4/6 inhibitor therapy. HER2-zero disease was detected in 138 (68%) HER2-low 66 (32%) Treatment-related characteristics clinical were analyzed, median follow-up 22 months.ResultsThe objective rate (ORR) 72.7% group 66.6% zero (p = 0.54). Median PFS not different between groups (19 months vs.18 months, p 0.89), although there trend toward longer first-line (24 63% vs 49%). In recurrent disease, 25 12 0.08), while de novo 18 27 0.16). The order use presence visceral metastasis identified as independent variables affecting PFS.ConclusionLow did or Because conflicting results literature, further prospective studies are needed to evaluate significance cancer.

Language: Английский

Citations

12
Characterisation of luminal and triple-negative breast cancer with HER2 Low protein expression DOI Creative Commons
N Atallah,

Maria Haque,

Cecily Quinn

et al.

European Journal of Cancer, Journal Year: 2023, Volume and Issue: 195, P. 113371 - 113371

Published: Oct. 7, 2023

Breast cancer (BC) expressing low levels of human epidermal growth factor receptor 2 (HER2 Low) is an emerging category that needs further refining. This study aims to provide a comprehensive clinico-pathological and molecular profile HER2 Low BC including response therapy patient outcome in the adjuvant neoadjuvant settings.

Language: Английский

Citations

11
Clinical, Epidemiologic, and Pathologic Significance of ERBB2-Low Expression in Breast Cancer DOI Creative Commons
Thaer Khoury,

Lucas Mendicino,

Rochelle Payne Ondracek

et al.

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(3), P. e243345 - e243345

Published: March 22, 2024

Importance It is unclear whether breast cancer (BC) with low ERBB2 expression (ERBB2-low) a distinct clinical, pathological, and epidemiological entity from BC classified as no (ERBB2-negative). Objective To evaluate the epidemiologic features of ERBB2-low compared ERBB2-negative in large population study. Design, Setting, Participants This cohort study was conducted part Pathways Study, prospective, racially ethnically diverse women enrolled between 2006 2013 Kaiser Permanente Northern California (KPNC). The hematoxylin eosin slides underwent centralized pathology review, including percentage tumor infiltrating lymphocytes (TILs). Breast biomarker results were extracted reports, included if they had documented value that not ERBB2-positive. Data analyzed February 2023 through January 2024. Exposure Clinical characteristics associated or status. Main Outcome Measures defined immunohistochemistry score 1+ 2+ (negative by situ hybridization); 0+. Other data collected self-report extraction electronic health records, risk factors, characteristics, treatment modality, survival outcomes, recurrence-free (RFS) primary outcome overall (OS) BC-specific mortality (BCSM) secondary outcomes. variables BC. Results Of 2200 eligible patients (all female; mean [SD] age, 60.4 [11.9] years), 1295 (57.2%) tumors ERBB2-low. Hormone receptors positive 1956 (88.9%). sample 291 Asian (13.2%), 166 Black (7.5%), 253 Hispanic (11.5%), 1439 White (65.4%), 51 (2.3%) who identified other race ethnicity (eg, American Indian Alaska Native Pacific Islander). Within hormone receptor–negative group, whose staining, those tumors, better OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91; P = .02), RFS (HR, 0.53; 0.30-0.95; .03), BCSM 0.43; 0.22-0.84; .01). In multivariable analysis stratified receptor status adjusted for key covariates, lower 0.48; 0.27-0.83; .009), 0.45; 0.24-0.86; (subdistribution HR, 0.21; 0.10-0.46; &amp;lt; .001) tumors. subtype, high TILs across all 3 outcomes Additionally, 0.36; 0.14-0.92; .03). Conclusions Relevance These findings suggest there differences BC, raising possibility might be unique biologic entity.

Language: Английский

Citations

4
Clinicopathological characteristics of HER2-low breast cancer: a retrospective study DOI Creative Commons
Man Yang, Jiale Sun, Liqiong Liu

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: July 31, 2023

Abstract Human Epidermal Growth Factor Receptor-2 (HER2)-negative breast cancers (BCs) contain HER2-low and HER2-zero ones. cancer has been receiving wide-spread concerns as the marvelous effect of novel anti-HER2 antibody-drug conjugates, however, characteristic remains unknown. Our aim was to explore differences clinicopathological indicators survival outcomes between HER2-0 cancers. We retrospectively analyzed 501 invasive patients with complete data on HER2 status from 2017 2021 in our single center, whom 415 negative were included for subsequent analysis. Each cohort further divided into hormone receptor (HR) positive HR subgroup. Clinicopathological factors collected compared BCs BCs. obviously higher BCs, 277 (90.5%) patients, 29 (9.5%) 68 (62.4%) 41 (37.6%) ( P < 0.001). Significant Her2-0 observed lymph node ratio (LNR) (mean rank, 215 vs. 188 = 0.014), estrogen (ER)expression (90.5% 62.4% 0.001), progesterone (PR) expression (84.3% 56.9% Ki-67 (46.4% 61.5% androgen (AR) (68% 50.5% adjuvant chemotherapy (69% 79.8% 0.03). had lower histological grade than I–II (68.7% 43.1%) III (22.2% 0.01. No statistical detected two groups DFS DDFS. results demonstrated that AR closely related Further exploration about prognosis is badly needed.

Language: Английский

Citations

10
Investigating HER2‐Low in Early Breast Cancer: Prognostic Implications and Age‐Related Prognostic Stratification DOI Creative Commons
E Chen, Chen Chen, Yingying Chen

et al.

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(4)

Published: Feb. 1, 2025

ABSTRACT Background Recent studies about human epidermal growth factor receptor 2 (HER2)‐low values have garnered great interest among oncologists. We aimed to investigate whether HER2‐low impacts the prognosis of early‐stage breast cancer overall and in specific subgroups, explore differences clinicopathologic markers, examine role age prognostic stratification. Materials & Methods conducted a retrospective analysis 6920 HER2‐negative patients from First Affiliated Hospital Wenzhou Medical University (2010–2022). The study focused on impact status (immunohistochemistry +1 or +2, situ hybridization not amplified) survival (OS), considering at diagnosis. Results Generally, correlated with less aggressive indicators. No significant were observed between HER2‐0 entire cohort, HR‐positive, HR‐negative groups. However, TNBC aged ≥ 65, significantly better OS (HR = 0.45, 95% CI 0.24–0.83, p 0.011), finding consistent after multivariable adjustment 0.34, 0.14–0.80, 0.014). In other did correlate HER2 status. combination plays key stratification TNBC. Patients 65 had considerably poorer prognoses compared subgroups. Conclusion This extensive demonstrates that cannot serve as an independent nor HR‐positive groups individually. combined factors may indicate potential contribution

Language: Английский

Citations

0
Prognostic difference between early breast cancer patients with HER2 low and HER2 zero status DOI Creative Commons
Chihwan Cha, Kyung Eun Kim, Jungbin Kim

et al.

npj Breast Cancer, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 26, 2025

We aimed to investigate the differences in prognosis between patients with HER2-low and HER2-zero status. This retrospective cohort study conducted at multi-institution included 1627 diagnosed or breast cancer (stages I–III). Survival analysis after propensity score matching was used. In total, 445 707 status were included. The median follow-up 92.7 months. Locoregional distant recurrence-free survival comparable (p = 0.872, p 0.746, respectively). did not affect overall survival. However, subgroups lymph node metastases, showed better compared that of 0.033). conclusion, outcomes cancer. More studies are needed validate our findings examine biological mechanism underlying these prognostic differences.

Language: Английский

Citations

0
Clinical Impact and Genomic Features of Human Epidermal Growth Factor Receptor 2–Low Tumors in BRCA1/2 -Mutated Triple-Negative Breast Cancer DOI
Furong Kou,

Huimin Liu,

Yaxin Zhang

et al.

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

Published: March 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.

Language: Английский

Citations

0