European Journal of Cancer, Год журнала: 2023, Номер 195, С. 113371 - 113371
Опубликована: Окт. 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.
Язык: Английский
The Breast, Год журнала: 2023, Номер 67, С. 116 - 123
Опубликована: Янв. 12, 2023
Highlights•HER2-low is defined as a HER2 immunohistochemical expression of 1+ or 2+ without amplification by in-situ hybridization.•HER2-low not distinct breast cancer subtype, but rather target for potent, novel HER2-directed agents.•Trastuzumab-deruxtecan (TDX-d) approved the treatment pretreated, advanced HER2-low cancer.•Education about risk interstitial lung disease and cardiac toxicity needed prior to initiation TDX-d.AbstractIntroductionTargeting low levels human receptor epidermal growth factor 2 (HER2) has reshaped paradigm half patients with cancer. currently hybridization. Until recently, HER2-targeted agents were ineffective in treating disease.Areas coveredIn this narrative review, we summarize current management We highlight findings DESTINY-Breast 04 phase 3 trial, which confirmed efficacy trastuzumab-deruxtecan (T-DXd) advanced, pretreated also discuss how implement new option algorithms hormone (HR)-positive triple-negative tumors, well optimally manage selected toxicities T-DXd.Expert opinionT-DXd standard care Based on design DESTINY-Breast04 optimal place after first line chemotherapy, both HR-positive Up 10–15% receiving T-DXd are expected develop disease, 1–2% cases can be fatal. Adequate monitoring prompt required minimize impact ILD safely clinical practice.
Язык: Английский
Процитировано
28
Modern Pathology, Год журнала: 2023, Номер 36(4), С. 100087 - 100087
Опубликована: Янв. 10, 2023
Язык: Английский
Процитировано
24
Breast Cancer Targets and Therapy, Год журнала: 2023, Номер Volume 15, С. 605 - 616
Опубликована: Авг. 1, 2023
Abstract: More than 50% of breast cancers are currently defined as "Human epidermal growth factor receptor 2 (HER2) low cancer (BC)", with HER2 immunohistochemistry (IHC) scores +1 or +2 a negative fluorescence in situ hybridization (FISH) test. In most studies that compared the clinical and biological characteristics HER2-low BC HER2-negative BC, was not associated unique molecular characteristics, it seems importance these tumors is being docking site for antibody portion drug conjugates (ADCs). Current pathological methods may underestimate proportion BCs express levels due to analytical limitations tumor heterogeneity. this review we summarize contextualize recent literature on cancers, including translational We also challenges assessing expression discuss current future therapeutic landscape tumors. Keywords: HER2-low, ERBB2 low, cancer, targeted therapy, trastuzumab, trastuzumab-deruxtecan, T-DXd
Язык: Английский
Процитировано
24
Pathology, Год журнала: 2024, Номер 56(3), С. 334 - 342
Опубликована: Янв. 21, 2024
Язык: Английский
Процитировано
10
The Breast, Год журнала: 2022, Номер 67, С. 1 - 7
Опубликована: Дек. 14, 2022
Novel anti-HER2 antibody-drug conjugates trastuzumab deruxtecan (DS-8201a) showed its effect in previously-treated HER2-low metastatic breast cancer, suggesting a promising future cancer. We retrospectively reviewed the clinicopathological data of 325 patients with stage I-III HER2 negative cancer who received neoadjuvant chemotherapy First Affiliated Hospital Sun Yat-sen University from January 2016 to June 2021. In general, 91 (28.0%) were HER2-zero, and 234 (72.0%) HER2-low. The pathological complete response (pCR) rate entire cohort was 17.3%. pCR 16.7% group, 18.9% HER2-zero showing no significant difference. Patients tumors had significantly longer overall survival (OS) than tumors. ER status affecting factor OS both univariate multivariate analysis. conclusion, evidence for BC as distinct entity is insufficient, more efforts are needed standardize scoring
Язык: Английский
Процитировано
34
Seminars in Diagnostic Pathology, Год журнала: 2022, Номер 39(5), С. 305 - 312
Опубликована: Июль 9, 2022
Язык: Английский
Процитировано
30
Cancers, Год журнала: 2023, Номер 15(5), С. 1413 - 1413
Опубликована: Фев. 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.
Язык: Английский
Процитировано
20
Cancer, Год журнала: 2024, Номер 130(16), С. 2746 - 2762
Опубликована: Май 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.
Язык: Английский
Процитировано
9
ESMO Open, Год журнала: 2024, Номер 9(4), С. 102989 - 102989
Опубликована: Апрель 1, 2024
•The DESTINY-Breast04 trial established HER2-low metastatic breast cancer (IHC 1+ or IHC 2+/ISH−) as a targetable disease.•Treating patients without traditional HER2+ tumors with HER2-directed antibody–drug conjugates represents paradigm shift.•Appropriate identification of eligible for T-DXd is paramount.•Novel biopsy to reassess HER2 expression in cases 0 encouraged. Approximately 60% traditionally defined human epidermal growth factor receptor 2 (HER2)-negative cancers express low levels [HER2-low; immunohistochemistry (IHC) 2+/in situ hybridization (ISH)−]. encompass large percentage both hormone receptor-positive (up 85%) and triple-negative 63%) cancers. The that are targetable, leading the approval trastuzumab deruxtecan (T-DXd) first therapy treatment United States Europe. This change clinical landscape results number questions challenges—including those related assessment patient identification—and highlights need careful identify T-DXd. review provides context understanding how respect sample types, scoring reporting status, testing methods assays. It also discusses management important T-DXd-related adverse events. Available evidence supports efficacy any history 2+/ISH− scores; however, future research may further refine population who could benefit from other therapies novel identification. Because can disease progression treatment, variability exists interpretation re-evaluation certain scenarios help more
Язык: Английский
Процитировано
7
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 8206 - 8206
Опубликована: Май 4, 2023
Despite the great progress made in understanding of biological behavior certain types invasive breast cancer, there is still no single histological or molecular classification that encompasses such diversity and accurately predicts clinical course distinct cancer subtypes. The long-lasting as HER2-positive vs. HER2-negative has recently come into question with discovery new antibody drug conjugates (ADC), which are proven to be remarkably efficient treating HER2-low cancer. paradigm challenged traditional HER2 overexpression emphasized need for more robust testing order encompass intratumoral heterogeneity spatial distribution accurately. It yet seen if low will remain merely a marker HER2-equipped tumors targetable ADCs distinctive phenotypic groups within eventually discerned.
Язык: Английский
Процитировано
17