Expression of truncated HER2 and its prognostic value in HER2-positive breast cancer patients

Maria, Alaa; El-Shebiney, Mohamed; Elsaka, Ayman Mohamed; Zamzam, Yomna

doi:10.1016/j.jnci.2018.05.001

Cited by 11 publications

(8 citation statements)

References 25 publications

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“…D16HER-2 was sensitive to HER-2 TKIs, as lapatinib and neratinib, while p95HER-2 was sensitive to anti p95HER-2 antibodies. Some studies also indicated that truncated p95-HER2-expressing cells retain their kinase activity and are responsive to lapatinib therapy ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Effective Treatment With Pyrotinib and Capecitabine in a Heavily Pretreated Locally Advanced Breast Cancer Harboring Both HER2 Overexpression and Mutant

Gao

Wang

et al. 2021

Front. Oncol.

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The prognosis for female patients with locally advanced breast cancer (LABC) has improved with the emergence of novel drugs, especially for those who have HER2 overexpression or ERBB-2 amplification. Trastuzumab-based regimen has been the paradigm in guidelines as first-line therapy, whereas many patients got progressive disease after several cycles of treatment or rapidly progress because of primary resistance. Point mutations of ERBB2 gene occur in both HER2-amplication and non-amplification patients, with a 2% ratio in HER2 non-amplification cohort and 1.48% in HER2 amplication population. The acquired mutation ratio of ERBB2 substantially raised to 16.7%–17.7% in patients prior to trastuzumab treatment. ERBB2 mutation may be a critical reason of resistance and disease progression among the patients treated with anti-HER2 monoclonal trastuzumab or dual anti-HER2 antibodies with trastuzumab and pertuzumab, or tyrosine-kinase inhibitor. ERBB-2 mutation with L755S and V842I indicates resistance to trastuzumab, while that with L755S and K753I indicates resistance to lapatinib; these mutations maybe sensitive to pan-HER tyrosine-kinase inhibitors. A 48-year woman diagnosed with HER2-positive LABC developed trastuzumab resistance after three lines of trastuzumab cross-line treatment with partial response (PR) as the best response. The tissue was performed by next-generation sequencing (NGS), and the results discovered L755S in ERBB2 gene. Then, she received effective treatment with pyrotinib plus capecitabine and underwent mastectomy after six cycles of combined treatment with PR. Subsequently, breast mastectomy was performed, and she took pyrotinib plus capecitabine for 1 year and pyrotinib monotherapy for another 1 year as adjuvant therapy and achieved a long-term clinical benefit. In conclusion, pyrotinib is a potential neoadjuvant agent for patients who are heavily pretreated and harbor both ERBB2 amplification and ERBB2 mutant in locally advanced breast cancer.

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Section: Discussionmentioning

confidence: 99%

Case Report: Effective Treatment With Pyrotinib and Capecitabine in a Heavily Pretreated Locally Advanced Breast Cancer Harboring Both HER2 Overexpression and Mutant

Gao

Wang

et al. 2021

Front. Oncol.

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“…This HER2 lacks the extracellular domain to which trastuzumab binds and constitutively activates downstream signaling through its intracellular tyrosine kinase domains. The prevalence of p95 expression in HER2 + BC appears to be around 30% [ 37 ]. High levels of p95 expression correlate with increased nodal metastasis [ 38 ] and lower 5-year disease-free survival [ 39 ].…”

Section: Resistance To Anti-her2 Therapymentioning

confidence: 99%

Anti-HER2 therapy in metastatic breast cancer: many choices and future directions

Wynn

Tang

2022

Cancer Metastasis Rev

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Metastatic HER2 + breast cancer is an expanding area of drug development and research, with three new drugs approved in 2020 alone. While first-line therapy is well-established for metastatic HER2 + breast cancer, the standard of care for second-line therapy will likely be changing soon based on the results of the DESTINY-Breast03 trial. In the third-line setting, many options are available. Considerations in choosing between regimens in the third-line include resistance to trastuzumab, the presence of brain metastases, and tolerability. High rates of resistance exist in this setting particularly due to expression of p95, a truncated form of HER2 that constitutively activates downstream signaling pathways. We suggest a tyrosine kinase inhibitor (TKI)-based regimen because of the activity of TKIs in brain metastases and in p95-expressing tumors. Attempts to overcome resistance to anti-HER2 therapies with PI3K inhibitors, mTOR inhibitors, and CDK 4/6 inhibitors are an active area of research. In the future, biomarkers are needed to help predict which therapies patients may benefit from the most. We review the many new drugs in development, including those with novel mechanisms of action.

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“…52 High levels of p95HER2 expression have been significantly associated with poor clinical outcomes following trastuzumabbased therapy. 53 p95HER2 is expressed in 26.7-34.4% of breast cancer [54][55][56] and 77% of GC patients with HER2 amplification. 57 Activating mutations in PI3K/AKT, including PIK3CA mutation, influence the antitumor activity of HER2 inhibitors.…”

Section: Her2-targeted Therapymentioning

confidence: 99%

“…High levels of p95HER2 expression have been significantly associated with poor clinical outcomes following trastuzumab‐based therapy 53 . p95HER2 is expressed in 26.7–34.4% of breast cancer 54–56 and 77% of GC patients with HER2 amplification 57 …”

Section: Her2 and Ecmentioning

confidence: 99%

Selected updates in molecular and genomic pathology of esophageal cancer

Liu

Zhao

Xue

et al. 2020

Annals of the New York Academy of Sciences

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Recent years have seen rapid advances in the field of molecular and genomic pathology that have not only improved understanding of esophageal carcinogenesis and tumor immune environment in general but also have reshaped pathology practice and clinical management. In this article, we provide updates on three topics (1) human epidermal growth factor receptor 2, the first and most important biomarker in targeted therapy of esophageal cancer; (2) programmed death 1/programmed death ligand 1, recent biomarkers that have shown promise in treating both esophageal adenocarcinoma and esophageal squamous cell carcinoma; and (3) human papillomavirus involvement in esophageal carcinogenesis, one of the most debated topics in the field, discussed here with a renewed understanding from recent genomic and molecular data.

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Expression of truncated HER2 and its prognostic value in HER2-positive breast cancer patients

Cited by 11 publications

References 25 publications

Case Report: Effective Treatment With Pyrotinib and Capecitabine in a Heavily Pretreated Locally Advanced Breast Cancer Harboring Both HER2 Overexpression and Mutant

Case Report: Effective Treatment With Pyrotinib and Capecitabine in a Heavily Pretreated Locally Advanced Breast Cancer Harboring Both HER2 Overexpression and Mutant

Anti-HER2 therapy in metastatic breast cancer: many choices and future directions

Selected updates in molecular and genomic pathology of esophageal cancer

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