Mechanisms of Resistance and Synergy: The Role of Tumor Microenvironment in HER2-Low Breast Cancer Therapy.

Youssef Basem, Alamer Ata, Abanoub Sherif, Shaimaa Abdel-Ghany, Borros Arneth, Hussein Sabit

Abstract readReview

In one paragraph

Review in Pharmaceuticals (Basel, Switzerland), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it

0cells of the map it votes in

1citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

HER2-Targeted Antibody-Drug Conjugates in Advanced HER2-Low Breast Cancer: Mechanisms, Clinical Efficacy, and Resistance Strategies.Cancer management and research · 2026
Review

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Youssef BasemDepartment of Medical Biotechnology, College of Biotechnology, Misr University for Science and Technology, Giza P.O. Box 77, Egypt.ORCID 0009-0007-3529-4706

Alamer AtaDepartment of Medical Biotechnology, College of Biotechnology, Misr University for Science and Technology, Giza P.O. Box 77, Egypt.ORCID 0009-0001-4493-007X

Abanoub SherifDepartment of Medical Biotechnology, College of Biotechnology, Misr University for Science and Technology, Giza P.O. Box 77, Egypt.ORCID 0009-0005-2919-1271

Shaimaa Abdel-GhanyDepartment of Environmental Biotechnology, College of Biotechnology, Misr University for Science and Technology, Giza P.O. Box 77, Egypt.ORCID 0000-0002-3883-2000

Borros ArnethInstitute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Hospital of the Universities of Giessen and Marburg (UKGM), Philipps University Marburg, Baldingerstr 1, 35043 Marburg, Germany.ORCID 0000-0002-9793-0970

Hussein SabitDepartment of Medical Biotechnology, College of Biotechnology, Misr University for Science and Technology, Giza P.O. Box 77, Egypt.ORCID 0000-0001-9021-8334

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

HER2-low breast cancer, also known as IHC 1+ or IHC 2+ without ERBB2 amplification, is a new concept in the biology of breast cancer that has removed the binary classification of HER2-positive or HER2-negative breast cancer. The recent introduction of antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd), has improved therapeutic outcomes for HER2-low breast cancer by demonstrating high efficacy in HER2-low tumors through efficient payload delivery. However, differences in ADC efficacy exist among HER2-low breast cancer patients, with tumor cells showing resistance to ADCs. Recent research indicates that the tumor microenvironment (TME) plays a critical role in determining the efficacy of ADCs against tumor cells. TME creates a barrier to the delivery of ADCs to tumor cells that show resistance to ADCs. This review article aims to highlight the current understanding of the biology of HER2-low breast cancer and its response to ADCs with reference to the tumor microenvironment.

Indexed as

antibody–drug conjugatesdrug resistanceHER2-low breast cancertrastuzumab deruxtecantumor microenvironment

Identifiers

PMID42075798

DOI10.3390/ph19040541

PMCPMC13119038

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