The Predictive Value of HER2 in Breast Cancer

Piccart, Martine; Lohrisch, Caroline; Leo, Angelo Di; Larsimont, Denis

doi:10.1159/000055405

Cited by 121 publications

(87 citation statements)

References 29 publications

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“…5,6 Response to some types of chemotherapy and hormonal therapy also appears to be dependent on HER2 status. [9][10][11][12][13][14] Results of this study show CISH to be a practical and reliable alternative to FISH for the assessment of HER2 gene amplification in breast cancer specimens. A very high level of concordance was seen between CISH and FISH in each of the tumor sample groups tested.…”

Section: Discussionmentioning

confidence: 99%

Chromogenic in-situ hybridization: a viable alternative to fluorescence in-situ hybridization in the HER2 testing algorithm

Hanna

Kwok

2006

Modern Pathology

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Assessment of human epidermal growth factor receptor-2 status is standard practice in women with breast cancer. Most laboratories use immunohistochemistry as a screening test, with equivocal results confirmed by fluorescence in-situ hybridization (FISH). Chromogenic in-situ hybridization (CISH) is a relatively new method for detection of gene amplification using a peroxidase reaction, which can be viewed using a standard light microscope. This study was undertaken to validate CISH as a method for assessing human epidermal growth factor receptor-2 gene amplification. The gene amplification status of human epidermal growth factor receptor-2 immunohistochemistry negative (0/1 þ , n ¼ 69; Group 1), immunohistochemistry positive (3 þ , n ¼ 50; Group 2) and equivocal tumor samples (2 þ , n ¼ 135; Group 3) was evaluated by FISH and CISH, and the concordance between FISH and CISH results calculated. In Group 1, 67/69 cases did not show amplification by CISH and 69/ 69 showed no amplification by FISH. Two cases were discordant; therefore, fluorescence/CISH concordance was 97%. In Group 2, 46/50 cases were amplified by FISH and 47/50 cases were amplified by CISH; three cases were not amplified by either method (immunohistochemistry false-positives). Only one case showed discordant FISH and CISH results, making the fluorescence/CISH concordance 98%. In Group 3, 89/135 cases were not amplified and 37/135 were amplified by both methods. Nine cases were discordant, giving a fluorescence/CISH concordance of 93%. The discordant cases were those with very low or borderline amplification with FISH. The high level of concordance between FISH and CISH seen in this study suggests that CISH may be a viable alternative to FISH for use in the human epidermal growth factor receptor-2 testing algorithm.

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Section: Discussionmentioning

confidence: 99%

Chromogenic in-situ hybridization: a viable alternative to fluorescence in-situ hybridization in the HER2 testing algorithm

Hanna

Kwok

2006

Modern Pathology

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“…Meme karsinomu hastasında HeR-2 gen amplifikasyonu, kemoterapi ve hormonoterapiye yanıtın tahmininde kullanılır (5,10,11). Meme karsinomunda, HeR-2 gen amplifikasyon durumunun bilinmesi, HeR-2 pozitif olan ileri evre metastatik meme CA tedavisinde, bu reseptörü hedef alan monoklonal antikor (MAb) olan "transtuzumab"ın (Herceptin: Genentech, San Francisco, CA, USA) geliştirilmesi ile daha da önem kazanmıştır (10)(11)(12).…”

Section: Introductionunclassified

Comparison of immunohistochemistry and fluorescence in situ hybridization for the analysis of her2/neu and topoisomerase ii-alpha status in human breast cancer

Pala¹,

Zekioğlu²,

Özdemir³

et al. 2010

TJPATH

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Objective: The aim of the study is to evaluate HeR-2 gene amplification ratio in c-erbB-2 score 2 breast carcinoma cases which have been controversial for targeted terapy and determinate its correlation with pathologic prognostic factors. Material and Method:We analyzed 80 infiltrating breast carcinomas, which were immunohistochemically score 2 with silver in situ hybridization (SISH) assay to determine Her-2 gene amplification. Afterwards cases have been grouped as amplification positive (AP) and amplification negative (AN). These groups have been compared with each other to reveal their relationship with pathologic prognostic factors.Results: 30% of the cases showed HeR-2 gene amplification with SISH. Median age of patients in AP group was 50.3 (±11.4). Median age of AN group was 56.7 (±13.0). We found that tumors in AP group had much higher mitotic rate (p= 0.044). Mean metastatic lenf node number in AP group was 10, while it was only 1 in AN group. Lenfovascular invasion was the other striking parameter which showed statisticaly significant correlation with HeR-2 amplification. We didn't find any statisticaly significant correlation between HeR-2 amplification and tumor size, histologic grade, nuclear grade, diameter of the largest metastatic lenf node, steroid receptor expression and tumor necrosis. Conclusion:Tumors that show HeR-2 gene amplification have much higher mitotic rate, increased metastatic lenf node number and increased lenfovascular invasion rate. Unignorable part of controversial immunohistochemically c-erbB-2 score 2 cases show HeR-2 gene amplification and we need to confirm these cases with genetic tests. SISH is a cheap, easy and cantitative alternative.

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“…ERBB2, more commonly referred to as HER-2/neu, is the other most significantly studied member of this family and is discussed later (Piccart et al, 2001). Signaling through EGFR stimulates the cell cycle pathways that control cell proliferation (Wells, 1999).…”

Section: Epidermal Growth Factor Receptormentioning

confidence: 99%

“…A substantial amount of research efforts have been devoted to identifying molecular markers as prognostic factors and as potential targets for therapeutic intervention (Zatterstrom et al, 1991;Silvestrini and Daidone, 1993;Smith and Haffty, 1999;Bartelink and Horiot, 2000;Bartelink, 2001;Piccart et al, 2001;Rockwell et al, 2001;Esteva et al, 2002;Haffty, 2002). While a majority of these efforts have been focused on metastatic disease and survival, there is a rapidly growing body of literature focused on molecular factors associated with radiation resistance and locoregional failure (Walter et al, 1991;Haffty, 2002;Harari and Huang, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…This strategy is already being evaluated in clinical trials with the use of antibodies directed at epidermal growth factor in combination with radiation therapy for head and neck cancers (Harari and Huang, 2001b). The potential utility of such strategies is evidenced by the recent emergence of data demonstrating improved outcomes in patients with metastatic breast cancer treated with antibodies to the HER-2/neu oncoprotein, in combination with chemotherapy (Pietras et al, 1999;Slamon, 1999;Piccart et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Molecular markers in clinical radiation oncology

Haffty¹,

Glazer²

2003

Oncogene

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Radiation therapy plays a critical role in the management of a majority of patients diagnosed with cancer. Identification of factors that help predict which patients are at risk for relapse within the irradiated field remains an active area of investigation. Although conventional clinical and pathologic factors have been helpful in identifying risk and guiding clinical decision-making for both local and systemic management, there is clearly a need to identify additional prognostic markers, which can aid in refining our treatment strategies and improving outcomes. A substantial amount of research efforts have been devoted to identifying molecular markers for prognostic and therapeutic strategies. The recent emergence of a powerful armamentarium of molecular tools has resulted in rapid expansion of our fund of knowledge and understanding of the molecular biology underlying tumor behavior and response. While a majority of these efforts have been focused on risk factors for metastatic disease and survival, there is a rapidly growing body of literature focused on molecular factors associated with radiation resistance and locoregional failure. In this review, we summarize recent advances and the available literature evaluating molecular markers as they relate to radiation sensitivity of solid tumors. Literature regarding the potential application of expression of genes related to apoptosis, angiogenesis, cell cycle, DNA repair and growth factors will be reviewed. Some of the basic biology and laboratory evidence demonstrating how the marker relates to radiation response and available correlative clinical studies employing these markers as prognostic tools are presented. The majority of molecular markers that have potential clinical significance with respect to radiation sensitivity and local control will be highlighted.

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The Predictive Value of HER2 in Breast Cancer

Cited by 121 publications

References 29 publications

Chromogenic in-situ hybridization: a viable alternative to fluorescence in-situ hybridization in the HER2 testing algorithm

Chromogenic in-situ hybridization: a viable alternative to fluorescence in-situ hybridization in the HER2 testing algorithm

Comparison of immunohistochemistry and fluorescence in situ hybridization for the analysis of her2/neu and topoisomerase ii-alpha status in human breast cancer

Molecular markers in clinical radiation oncology

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