How I treat HER2-low advanced breast cancer

The Breast, Journal Year: 2023, Volume and Issue: 67, P. 116 - 123

Published: Jan. 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.

Language: Английский

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HER2-Low Breast Cancer: Incidence, Clinicopathologic Features, and Survival Outcomes From Real-World Data of a Large Nationwide Cohort

Modern Pathology, Journal Year: 2023, Volume and Issue: 36(4), P. 100087 - 100087

Published: Jan. 10, 2023

Language: Английский

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HER2-Low Breast Cancer: Current Landscape and Future Prospects

Breast Cancer Targets and Therapy, Journal Year: 2023, Volume and Issue: Volume 15, P. 605 - 616

Published: Aug. 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

Language: Английский

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HER2-low breast cancer and response to neoadjuvant chemotherapy: a population-based cohort study

Pathology, Journal Year: 2024, Volume and Issue: 56(3), P. 334 - 342

Published: Jan. 21, 2024

Language: Английский

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Characterization of HER2‐low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study

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

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Comparison of clinicopathological characteristics and response to neoadjuvant chemotherapy between HER2-low and HER2-zero breast cancer

The Breast, Journal Year: 2022, Volume and Issue: 67, P. 1 - 7

Published: Dec. 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

Language: Английский

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HER2-low breast cancers: Current insights and future directions

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

Published: July 9, 2022

Language: Английский

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Discordance of HER2-Low between Primary Tumors and Matched Distant Metastases in Breast Cancer

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

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HER2 Low Breast Cancer: A New Subtype or a Trojan for Cytotoxic Drug Delivery?

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8206 - 8206

Published: May 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.

Language: Английский

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HER2-Low Breast Cancer: Where Are We?

Breast Care, Journal Year: 2022, Volume and Issue: 17(6), P. 533 - 545

Published: Jan. 1, 2022

Breast cancer is traditionally classified into three clinical subtypes based on hormone receptor and HER2 status (i.e., luminal-like, HER2-positive, triple negative). Each subtype has distinct clinical-pathological molecular characteristics requires tailored treatments. Recent research efforts have been focusing a new classification, identifying the so-called "HER2-low" category, including tumors characterized by low level of expression (immunohistochemistry score 1+ or 2+ without in situ hybridization amplification). Emerging evidence shows that patients with HER2-low can derive benefit from selected anti-HER2 therapies. This represents major advancement field breast oncology, where broader proportion ultimately effective targeted treatment strategies.The antibody-drug conjugate trastuzumab deruxtecan proven impressive efficacy cancer, several other drugs are currently under investigation this subset patients. Additional needed to address open issues exist field, appropriate pathological assessment status, clarification its prognostic implications, global access newly approved drugs.Our review aims summarize available regarding illustrating current challenges being addressed future perspectives exciting field.

Language: Английский

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