☆ 4.7 Review

Low and Ultra-Low HER2 in Human Breast Cancer: An Effort to Define New Neoplastic Subtypes

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

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Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial

Sara A. Hurvitz et al.

Summary: In the DESTINY-Breast03 trial, trastuzumab deruxtecan showed superior progression-free survival compared to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer. The study aimed to compare the efficacy and safety of trastuzumab deruxtecan versus trastuzumab emtansine. The results demonstrated that trastuzumab deruxtecan had the longest reported median progression-free survival and improved overall survival, reaffirming its role as the standard of care in the second-line setting.

LANCET (2023)

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Current Biological, Pathological and Clinical Landscape of HER2-Low Breast Cancer

Huina Zhang et al.

Summary: The breakthrough in developing novel HER2-targeting antibody drug conjugates and identifying their clinical benefits in HER2-low breast cancer will revolutionize the clinical treatment landscape of HER2 negative breast cancers and the pathologic evaluation of HER2 status. This review updates the current biological, pathological and clinical landscape of HER2-low breast cancer and proposes future directions on clinical management, pathology practice, and translational research in this subset of breast cancer.

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Article Oncology

Distribution, dynamic evolution, and clinical outcomes of patients with advanced breast cancer according to HER2 expression

Qin Shi et al.

Summary: This study aimed to evaluate the distribution and dynamic change in HER2 expression in patients with disease recurrence and their clinical outcome. Nearly half of the advanced breast cancer patients had HER2-low disease, which had a poorer prognosis than HER2-positive disease but marginally better outcomes than HER2-zero disease. About one-fifth of tumors converted to HER2-low entities during disease progression, and corresponding patients may benefit from ADC treatment.

BMC CANCER (2023)

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Article Oncology

HER2 overexpression/amplification status in colorectal cancer: a comparison between immunohistochemistry and fluorescence in situ hybridization using five different immunohistochemical scoring criteria

Qi Sun et al.

Summary: In this study, the HER2 scoring system in colorectal cancer (CRC) was evaluated using five immunohistochemical (IHC) scoring criteria and two fluorescence in situ hybridization (FISH) criteria. The study found that the IRS-p criterion was more suitable for assessing the HER2 status in CRC patients, while the FISH scoring system could identify subgroups with unique clinicopathological characteristics.

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Review Biochemistry & Molecular Biology

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

Marina Popovic et al.

Summary: Despite advances in understanding the biology of invasive breast cancer, there is no single classification that accurately predicts the clinical course of different subtypes. The classification of breast cancer as HER2-positive or HER2-negative has been challenged by the discovery of new treatment options for HER2-low breast cancer. More robust testing methods are needed to accurately assess HER2 heterogeneity. It is unclear if low HER2 will continue to be targeted with specific treatments or if distinct subgroups within HER2-low tumors will be identified.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

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HER2-Low Breast Cancer-Diagnostic Challenges and Opportunities for Insights from Ongoing Studies: A Podcast

Aditya Bardia et al.

Summary: Breast cancer is traditionally classified as HER2-positive or HER2-negative based on immunohistochemistry (IHC) scoring and/or gene amplification. Recently, the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd) was approved for HER2-low breast cancer. Current methodologies may not identify all patients with HER2-low breast cancer expected to benefit from HER2-targeted therapy, but ongoing studies may improve the identification of these patients.

TARGETED ONCOLOGY (2023)

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Article Pathology

Quantitative Image Analysis as an Adjunct to Manual Scoring of ER, PgR, and HER2 in Invasive Breast Carcinoma

Mustafa Yousif et al.

Summary: This study compared the concordance between quantitative image analysis (QIA) and pathologists' scoring in evaluating the expression of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) in breast cancer. The results showed that QIA had excellent concordance with pathologists' scores for ER, PgR, and HER2. Pathologist oversight of representative region selection is recommended to avoid errors.

AMERICAN JOURNAL OF CLINICAL PATHOLOGY (2022)

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Discordance Between Immunohistochemistry and In Situ Hybridization to Detect HER2 Overexpression/Gene Amplification in Breast Cancer in the Modern Age: A Single Institution Experience and Pooled Literature Review Study

Raima Memon et al.

Summary: Accurate detection of HER2 is critical in predicting response to HER2-targeted therapy. Immunohistochemistry and in situ hybridization are FDA-approved methods for detecting HER2 status, but there is a high level of discordance between these methods.

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Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue

Aileen Fernandez et al.

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JAMA ONCOLOGY (2022)

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Prediction of HER2-positive breast cancer recurrence and metastasis risk from histopathological images and clinical information via multimodal deep learning

Jialiang Yang et al.

Summary: By integrating deep learning models with H&E images and clinical information, accurate prediction of relapse and metastasis risk in HER2-positive breast cancer patients can be achieved.

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Primary analysis from DS8201-A-U105: A 2-part, open label, phase Ib trial assessing trastuzumab deruxtecan (T-DXd) with nivolumab (nivo) in patients (pts) with HER2-expressing advanced breast cancer

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Deep learning trained on hematoxylin and eosin tumor region of Interest predicts HER2 status and trastuzumab treatment response in HER2+breast cancer

Saman Farahmand et al.

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MODERN PATHOLOGY (2022)

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Article Medicine, General & Internal

Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer

J. Cortes et al.

Summary: Among patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane, trastuzumab deruxtecan was associated with a lower risk of disease progression or death compared to trastuzumab emtansine. However, treatment with trastuzumab deruxtecan was associated with interstitial lung disease and pneumonitis.

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Antibody-Drug Conjugates for the Treatment of HER2-Positive Breast Cancer

Mariana K. Najjar et al.

Summary: HER2 overexpression is associated with poor prognosis in breast cancer, with HER2-targeted therapies, such as antibody-drug conjugates (ADCs), showing promising results in treating HER2-positive breast cancer. The development of ADCs leveraging the high specificity of HER2-targeted monoclonal antibodies with cytotoxic small molecules represents a significant advancement in the management of the disease.

GENES (2022)

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Article Medicine, General & Internal

Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer

Shanu Modi et al.

Summary: Trastuzumab deruxtecan demonstrated significantly longer progression-free and overall survival compared to physician's choice chemotherapy in patients with HER2-low metastatic breast cancer.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Lapatinib and lapatinib plus trastuzumab therapy versus trastuzumab therapy for HER2 positive breast cancer patients: an updated systematic review and meta-analysis

Ye Yuan et al.

Summary: This study compared the efficacy of trastuzumab plus lapatinib therapy versus standard trastuzumab therapy in HER2-positive breast cancer patients. The results showed that trastuzumab combined with lapatinib therapy was superior in overall survival, disease-free survival, and pathologic complete response, but had more non-cardiac grade III/IV toxicities. Lapatinib therapy was inferior to standard trastuzumab therapy in terms of efficacy.

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Comparison of HercepTest™ mAb pharmDx (Dako Omnis, GE001) with Ventana PATHWAY anti-HER-2/neu (4B5) in breast cancer: correlation with HER2 amplification and HER2 low status

Josef Rueschoff et al.

Summary: This study compared the performance of two different HER2 detection assays in breast cancer samples and found a high concordance between the results. The HercepTest (mAb) assay showed a tendency to overscore HER2 status in some cases, but demonstrated higher sensitivity for tumors with gene amplification and HER2-low expression. Further research will explore whether this assay can improve patient selection, particularly for new HER2-directed therapies.

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Heng-Zhou Lai et al.

Summary: HER2-low breast cancer is a subtype that accounts for more than half of breast cancer patients. Currently, anti-HER2 therapy is ineffective for HER2-low BC, and palliative chemotherapy is the main treatment modality. However, a new antibody-drug conjugate called T-Dxd has shown promise in clinical trials, which may redefine the treatment for HER2-low BC. This review summarizes the detection technologies and novel agents for HER2-low BC, and explores their potential role in future clinics, providing new ideas for the diagnosis and treatment of this subtype of breast cancer.

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Long-term follow-up of early stage HER2-positive breast cancer patients treated with trastuzumab: A population-based real world multicenter cohort study

Sander Ellegard et al.

Summary: The study assessed the real-world outcomes of HER2-positive breast cancer patients treated with trastuzumab, finding that their survival, prognostic factors, and relapse patterns were similar to those reported in long-term follow up of prospective clinical trials. ER status, nodal status, and trastuzumab treatment were identified as independent prognostic factors for breast cancer specific mortality rate, distant recurrence rate, and locoregional recurrence rate in HER2-positive patients in the trastuzumab era.

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Enrico Berrino et al.

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GENOME MEDICINE (2022)

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Event-Free Survival in Patients with Early HER2-Positive Breast Cancer with a Pathological Complete Response after HER2-Targeted Therapy: A Pooled Analysis

Sandra M. Swain et al.

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New treatment options for metastatic HER2-low breast cancer Consequences for histopathological diagnosis

Carsten Denkert et al.

Summary: The overexpression of HER2 in breast cancer is a classic example of molecular targeted therapy, and recent clinical trials have shown that ADCs are effective against both HER2 overexpressing and HER2-low tumors, leading to a paradigm shift in treatment and new diagnostic requirements.

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Elham Sajjadi et al.

Summary: HER2 is an important biomarker in breast cancer, and novel HER2-directed antibody-drug conjugates have shown significant antitumor activity in breast cancers with low levels of HER2 expression. However, primary and acquired resistance to anti-HER2 therapies remain challenging. Therefore, precise discrimination of different levels of HER2 expression is crucial for better treatment opportunities.

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Evolving concepts in HER2 evaluation in breast cancer: Heterogeneity, HER2-low carcinomas and beyond

Caterina Marchio et al.

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Elham Sajjadi et al.

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BMC CANCER (2021)

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Review Oncology

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JAMA ONCOLOGY (2021)

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Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung et al.

Summary: The global cancer burden in 2020 saw an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths. Female breast cancer surpassed lung cancer as the most commonly diagnosed cancer, while lung cancer remained the leading cause of cancer death. These trends are expected to rise in 2040, with transitioning countries experiencing a larger increase compared to transitioned countries due to demographic changes and risk factors associated with globalization and a growing economy. Efforts to improve cancer prevention measures and provision of cancer care in transitioning countries will be crucial for global cancer control.

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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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NPJ BREAST CANCER (2021)

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NATURE COMMUNICATIONS (2021)

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ESMO OPEN (2020)

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PLOS ONE (2019)

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