HER2 in well differentiated breast cancer: is testing necessary?

BackgroundOncoprotein HCCR-1 functions as a negative regulator of the p53 and contributes breast tumorigenesis. The serum HCCR-1 assay is useful in diagnosing breast cancer and mice transgenic for HCCR developed breast cancers. But it is unknown how HCCR-1 contributes to human breast tumorigenesis.MethodsOncogene HCCR-1 expression levels were determined in normal breast tissues, breast cancer tissues and cancer cell lines. We examined whether HCCR-1 protein expression in breast cancer is related to different biological characteristics, including ER, PR, p53 genotype, and HER2 status in 104 primary breast cancer tissues using immunohistochemical analyses.ResultsHCCR-1 was upregulated in breast cancer cells and tissues compared with normal breast tissues. In this study, overexpression of HCCR-1 was well correlated with known breast cancer prognostic markers including the presence of steroid receptors (ER and PR), p53 mutation and high HER2 overexpression. HCCR-1 was not detected in the ER-negative, PR-negative, p53 negative and low HER2 breast cancer tissues. These data indicate that the level of HCCR-1 in breast cancer tissues is relatively well correlated with known breast cancer factors, including the HER2 overexpression, p53 mutation, and ER/PR status.ConclusionDetermination of HCCR-1 levels as options for HER2 testing is promising although it needs further evaluation.

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“…Development of a rational approach to selecting cases for HER2 testing would promote cost effectiveness in the health care system [25]. …”

Section: Introductionmentioning

confidence: 99%

Oncoprotein HCCR-1 expression in breast cancer is well correlated with known breast cancer prognostic factors including the HER2 overexpression, p53 mutation, and ER/PR status

Lee

Shin

et al. 2009

BMC Cancer

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“…All cases had been reported as nuclear grade 1 and/or modified Scarf–Bloom Richardson (SBR) grade 1. The grading systems utilized were not standardized among the study sites, and review of slides was not performed to confirm tumour grade or HER2 IHC status . The authors concluded that as the rate of HER2 positivity in well‐differentiated breast cancer is extremely low, elimination of routine HER2 testing for this subset should be considered …”

Section: Discussionmentioning

confidence: 99%

“…This is particularly true of Nottingham grade 3 tumours, as HER2 amplification is more likely to be demonstrated in this group. In the setting of well‐differentiated carcinomas, however, interpretation of the HER2 IHC as equivocal can be more challenging, given the necessity of an expensive reflex test coupled with the knowledge that such tumours are rarely HER2 amplified . Adding to the interpretive difficulty is the fact that many of these cases have ‘weak’ or ‘borderline’ equivocal features, some of which might be categorized differently depending on the definition of 2+ HER2 IHC used and because of interobserver variability .…”

Section: Introductionmentioning

confidence: 99%

Well‐differentiated invasive breast cancers with equivocal HER2 immunohistochemistry: what is the yield of routine reflex in‐situ hybridization testing?

et al. 2017

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“…This process occurs through the binding of the Par6 and atypical protein kinase C (Par6-aPKC) components of the Par complex upon HER2 activation [ 37 ]. Thus, HER2(+) tumours are poorly differentiated [ 36 , 39 ]. Amplification of the HER2 gene, located on chromosome 17 (17q12q21), leads to the overexpression of HER2 receptors and is highly associated with increased cell proliferation, tumorigenesis and invasion, resulting in distant metastases [ 33 , 40 ].…”

Section: Her2 Breast Cancermentioning

confidence: 99%

Diagnostics and Therapeutics in Targeting HER2 Breast Cancer: A Novel Approach

Mandarano

Shigdar

2021

IJMS

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Breast cancer is one of the most commonly occurring cancers in women globally and is the primary cause of cancer mortality in females. BC is highly heterogeneous with various phenotypic expressions. The overexpression of HER2 is responsible for 15–30% of all invasive BC and is strongly associated with malignant behaviours, poor prognosis and decline in overall survival. Molecular imaging offers advantages over conventional imaging modalities, as it provides more sensitive and specific detection of tumours, as these techniques measure the biological and physiological processes at the cellular level to visualise the disease. Early detection and diagnosis of BC is crucial to improving clinical outcomes and prognosis. While HER2-specific antibodies and nanobodies may improve the sensitivity and specificity of molecular imaging, the radioisotope conjugation process may interfere with and may compromise their binding functionalities. Aptamers are single-stranded oligonucleotides capable of targeting biomarkers with remarkable binding specificity and affinity. Aptamers can be functionalised with radioisotopes without compromising target specificity. The attachment of different radioisotopes can determine the aptamer’s functionality in the treatment of HER2(+) BC. Several HER2 aptamers and investigations of them have been described and evaluated in this paper. We also provide recommendations for future studies with HER2 aptamers to target HER2(+) BC.

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HER2 in well differentiated breast cancer: is testing necessary?

Cited by 15 publications

References 29 publications

Oncoprotein HCCR-1 expression in breast cancer is well correlated with known breast cancer prognostic factors including the HER2 overexpression, p53 mutation, and ER/PR status

Oncoprotein HCCR-1 expression in breast cancer is well correlated with known breast cancer prognostic factors including the HER2 overexpression, p53 mutation, and ER/PR status

Well‐differentiated invasive breast cancers with equivocal HER2 immunohistochemistry: what is the yield of routine reflex in‐situ hybridization testing?

Diagnostics and Therapeutics in Targeting HER2 Breast Cancer: A Novel Approach

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