Clinicopathological significance of HER2/neu genetic heterogeneity in HER2/neu non-amplified invasive breast carcinomas and its concurrent axillary metastasis

Shafi, Hedyeh; Astvatsaturyan, Kristine; Chung, Fai; Mirocha, James; Schmidt, Michael; Bose, Shikha

doi:10.1136/jclinpath-2012-201403

Cited by 23 publications

(22 citation statements)

References 28 publications

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“…48 HER2 FISH negative cases with HER2 gene amplified tumor cells exhibited an aggressive characteristic of breast cancer. 49 HER2 negative cases containing obvious HER2 gene amplified tumor cells are not eligible for HER2-targeted therapy by the current criteria regardless of HER2 positive tumor cell populations. A model study for intratumoral heterogeneity in HER2 positive xenograft tumors demonstrated the correlation between the efficacy of anti-HER2 antibody therapy and the degree of HER2 tumor heterogeneity.…”

Section: Her2 Tumor Heterogeneitymentioning

confidence: 96%

“…HER2 genetic heterogeneity is frequently detected among HER2 equivocal (HER2 IHC 2+) cases. 43,48,49 Individual breast tumor cells with HER2 gene amplification are also often found in HER2 negative breast cancer cases classified by the current HER2 testing guidelines. 48 HER2 FISH negative cases with HER2 gene amplified tumor cells exhibited an aggressive characteristic of breast cancer.…”

Section: Her2 Tumor Heterogeneitymentioning

confidence: 99%

“…Individual breast tumor cells with HER2 gene amplification are also often found in HER2 negative breast cancer cases classified by the current HER2 testing guidelines . HER2 FISH negative cases with HER2 gene amplified tumor cells exhibited an aggressive characteristic of breast cancer . HER2 negative cases containing obvious HER2 gene amplified tumor cells are not eligible for HER2‐targeted therapy by the current criteria regardless of HER2 positive tumor cell populations.…”

Section: Introductionmentioning

confidence: 98%

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The assessment of HER2 status in breast cancer: the past, the present, and the future

Nitta

Kelly

Allred

et al. 2016

Pathology International

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Humanized monoclonal anti-human growth factor receptor 2 (HER2) antibody trastuzumab was approved for HER2 positive breast cancer patient treatment 11 years after the demonstration of HER2 gene amplification associated with the HER2 protein overexpression in breast cancer in 1987. HER2 positive status of breast cancer patients is assessed by HER2 gene amplification with in situ hybridization (ISH) and/or HER2 protein overexpression with immunohistochemistry (IHC). Because the discordance between quantitative HER2 ISH and subjective, semiquantitative HER2 IHC assay results is a well-recognized issue of HER2 testing, we developed an assay combining HER2 ISH and HER2 IHC assays (HER2 gene-protein assay; HER2 GPA) as one test on the same tissue section. HER2 GPA allows pathologists to score the HER2 gene and HER2 protein status simultaneously at the individual cell level. The possibility that HER2 GPA may become the next generation of HER2 testing is discussed, particularly for cases in which it is difficult to assess the HER2 status of breast cancer patients due to the HER2 heterogeneity.

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Section: Her2 Tumor Heterogeneitymentioning

confidence: 96%

Section: Her2 Tumor Heterogeneitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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The assessment of HER2 status in breast cancer: the past, the present, and the future

Nitta

Kelly

Allred

et al. 2016

Pathology International

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“…HER2 tumor heterogeneity is more often observed with HER2 IHC 2+/equivocal cases, mainly in HER2 gene negative status assessed cases containing individual amplified HER2 gene tumor cells [ 22 ]. Furthermore, breast cancer with HER2 heterogeneity presented an aggressive phenotype [ 23 ]. However, the significance of HER2 heterogeneity evaluation has not been established for a long-term breast cancer patient outcome after the surgical procedure yet.…”

Section: Introductionmentioning

confidence: 99%

HER2 intratumoral heterogeneity analyses by concurrent HER2 gene and protein assessment for the prognosis of HER2 negative invasive breast cancer patients

Kurozumi

Padilla

Kurosumi

et al. 2016

Breast Cancer Res Treat

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HER2 gene-protein assay (GPA) is a new method for the simultaneous evaluation of HER2 immunohistochemistry (IHC) and HER2 dual in situ hybridization (DISH) on single tissue sections of breast cancer. We investigated the presence of HER2 gene and protein discrepancy and HER2-heterogeneity using HER2-GPA. HER2 status was analyzed for the correlation between the presence of HER2-heterogeneity and patient prognosis. Consecutive 280 invasive breast cancer were examined. Statuses of HER2 protein and gene were evaluated in whole tumor sections of HER2 GPA slides. HER2 protein and gene combination patterns were classified to six phenotypic and genotypic types for each case, as well as at individual cell levels: (A) IHC and DISH positive; (B) IHC positive and DISH negative; (C) IHC equivocal and DISH positive; (D) IHC equivocal and DISH negative; (E) IHC negative and DISH positive; and (F) IHC and DISH negative. The presence of HER2-heterogeneity was determined by the existence of at least two of six types within one tumor. HER2-IHC positive patients had significantly worse survival than IHC negative patients and HER2-DISH positive patients had significantly worse survival than DISH negative patients. HER2 IHC negative and DISH positive patients had significantly worse recurrence-free survival than IHC and DISH negative patients. In the HER2 IHC and DISH negative group, the HER2 heterogeneous group had significantly worse survival than the nonheterogeneous group. Notably, among triple negative breast cancer (TNBC), the HER2 heterogeneous group had significantly worse survival than the nonheterogeneous group. Our study suggests that the presence of HER2-heterogeneity might be a prognostic factor in HER2 negative breast cancer patients, especially in TNBC.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-016-3856-2) contains supplementary material, which is available to authorized users.

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“…However, this can be intricate as HER2 expression may vary through progression from primary to secondary disease with locoregional and distant recurrences often not being amenable to biopsy (11). Furthermore, recent studies have highlighted spatial heterogeneity as a potential source of incorrect assessment (12). The vast majority of U.S. Food and Drug Administration (FDA)-approved diagnostics are based on immunohistochemistry (IHC) and FISH.…”

Section: Introductionmentioning

confidence: 99%

Positron Emission Tomography Imaging with 18F-Labeled ZHER2:2891 Affibody for Detection of HER2 Expression and Pharmacodynamic Response to HER2-Modulating Therapies

Trousil

Hoppmann

Nguyen

et al. 2014

Clinical Cancer Research

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Clinicopathological significance of HER2/neu genetic heterogeneity in HER2/neu non-amplified invasive breast carcinomas and its concurrent axillary metastasis

Abstract: HER2 GH is present in 27% of breast carcinomas, portends an aggressive phenotype and contributes to the equivocal HER2 status. Evaluation of the HER2 status in nodal metastasis of select primary carcinomas with GH may be beneficial before treatment selection.

Cited by 23 publications

References 28 publications

The assessment of HER2 status in breast cancer: the past, the present, and the future

The assessment of HER2 status in breast cancer: the past, the present, and the future

HER2 intratumoral heterogeneity analyses by concurrent HER2 gene and protein assessment for the prognosis of HER2 negative invasive breast cancer patients

Positron Emission Tomography Imaging with 18F-Labeled ZHER2:2891 Affibody for Detection of HER2 Expression and Pharmacodynamic Response to HER2-Modulating Therapies

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