HER2 Amplification Ratios by Fluorescence In Situ Hybridization and Correlation with Immunohistochemistry in a Cohort of 6556 Breast Cancer Tissues

Owens, Marilyn A.; Horten, Bruce; Silva, Moacyr M. Da

doi:10.3816/cbc.2004.n.011

Cited by 571 publications

(372 citation statements)

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“…HER2 is overexpressed in 20-30% of malignant breast tumors as a result of amplification of the coding gene [1,2]. HER2-positive status is associated with poor prognosis and is a strong predictor of response to trastuzumab therapy [1,3]. Assessment of HER2 status has become standard practice to identify breast cancer patients most likely to benefit from trastuzumab therapy [3].…”

Section: Introductionmentioning

confidence: 99%

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

et al. 2008

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Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with colorectal carcinoma. However, these therapies are effective only in a subset of patients. Activating mutations in the KRAS gene are found in 30-40% of colorectal tumors and are associated with poor response to anti-EGFR therapies. Thus, KRAS mutation status can predict which patient may or may not benefit from anti-EGFR therapy. Although many diagnostic tools have been developed for KRAS mutation analysis, validated methods and standardized testing procedures are lacking. This poses a challenge for the optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Here we review the molecular basis of EGFR-targeted therapies and the resistance to treatment conferred by KRAS mutations. We also present guideline recommendations and a proposal for a European quality assurance program to help ensure accuracy and proficiency in KRAS mutation testing across the European Union.

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Section: Introductionmentioning

confidence: 99%

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

et al. 2008

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“…Two of them revealed a borderline FISH result (ratior3.0; maximal HER-2 gene copy number 10) which may have resulted in a low level of expression not detectable by IHC. 20 Four cases with a high level (43.0) HER-2 amplification but negative IHC result (score 0) are most likely explained by false negative IHC. Examples of tumors Figure 1 Relationship between immunohistochemical overexpression and amplification of HER2 in breast and non-breast cancers.…”

Section: Ihc and Fishmentioning

confidence: 99%

Close association between HER-2 amplification and overexpression in human tumors of non-breast origin

et al. 2007

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“…[2][3][4] Of the total number of patients diagnosed with BC in the United States, 20% to 25% will have tumors that exhibit HER2 gene amplification or protein overexpression. 2,5,6 Trastuzumab (Herceptin), a humanized, monoclonal antibody that blocks the activity of HER2, is the only anti-HER2 agent that is approved for adjuvant therapy in patients who have HER2-positive disease with either positive or negative lymph node status, estrogen receptor (ER)/progesterone receptor (PR)-negative disease, or a high-risk feature, either in combination with chemotherapy or as a single agent after chemotherapy. Adjuvant trastuzumab significantly improves disease-free survival (DFS) and overall survival (OS) compared with chemotherapy or observation alone.…”

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confidence: 99%

Trastuzumab‐based neoadjuvant therapy in patients with HER2‐positive breast cancer

Chang

2010

Cancer

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Overexpression, or gene amplification, of the human epidermal growth factor receptor 2 (HER2) is evident in 20% to 25% of breast cancers. The biologic agent trastuzumab is an HER2-targeted monoclonal antibody that inhibits the proliferation of tumor cells and induces tumor cell death through multiple mechanisms of action. Currently, trastuzumab is approved for use in the adjuvant and metastatic settings. Trials combining trastuzumab with neoadjuvant chemotherapy suggest that patients with HER2-positive breast cancer also may benefit from preoperative trastuzumab. For this article, the author reviewed efficacy and safety data from key studies of patients who received neoadjuvant trastuzumab-based therapy. Studies were identified from literature searches of publication and congress databases. The results of 3 large phase 3 trials (the M. D. Anderson Cancer Center neoadjuvant trastuzumab trial, the Neoadjuvant Herceptin [NOAH] trial, and the German Breast Group/Gynecologic Oncology Study Group ''GeparQuattro'' trial) demonstrated that, compared with chemotherapy alone, neoadjuvant trastuzumab plus chemotherapy significantly increased pathologic complete response rates to as high as 65%. Improvements in disease-free, overall, and event-free survival also were reported in the NOAH trial. In addition to demonstrated efficacy, a low incidence of cardiac dysfunction suggests that neoadjuvant trastuzumab is both effective and well tolerated. Similar results have been reported in a range of phase 2 studies using different trastuzumab-based regimens. These encouraging data led the National Comprehensive Cancer Network to recommend treating patients who have operable, locally advanced, HER2-positive breast cancer with neoadjuvant paclitaxel plus trastuzumab followed by 5-fluorouracil, epirubicin, and cyclophosphamide plus trastuzumab. Cancer 2010;116:2856-67. V C 2010 American Cancer Society.KEYWORDS: neoadjuvant, trastuzumab, HER-2, chemotherapy, biologic, breast cancer, breast conservation surgery, lymph node management.Breast cancer (BC) is the most frequently diagnosed form of cancer among women in the United States. 1 Of the various subtypes of BC, tumors that have gene amplification or protein overexpression of human epidermal growth factor receptor 2 (HER2) are among the most aggressive and are associated with poor clinical outcomes compared with tumors that do not have HER2 overexpression. 2-4 Of the total number of patients diagnosed with BC in the United States, 20% to 25% will have tumors that exhibit HER2 gene amplification or protein overexpression. 2,5,6 Trastuzumab (Herceptin), a humanized, monoclonal antibody that blocks the activity of HER2, is the only anti-HER2 agent that is approved for adjuvant therapy in patients who have HER2-positive disease with either positive or negative lymph node status, estrogen receptor (ER)/progesterone receptor (PR)-negative disease, or a high-risk feature, either in combination with chemotherapy or as a single agent after chemotherapy. Adjuvant trastuzumab significantly imp...

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HER2 Amplification Ratios by Fluorescence In Situ Hybridization and Correlation with Immunohistochemistry in a Cohort of 6556 Breast Cancer Tissues

Cited by 571 publications

References 35 publications

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

Close association between HER-2 amplification and overexpression in human tumors of non-breast origin

Trastuzumab‐based neoadjuvant therapy in patients with HER2‐positive breast cancer

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