Prognostic and predictive value of c-erbB-2 overexpression in primary breast cancer, alone and in combination with other prognostic markers.

Sjögren, S.; Inganäs, M.; Lindgren, Anders; Holmberg, Lars; Bergh, Jonas

doi:10.1200/jco.1998.16.2.462

Cited by 300 publications

(172 citation statements)

References 29 publications

Supporting

Mentioning

162

Contrasting

Unclassified

Order By: Relevance

“…Other groups have also found that overexpression of the HER-2 receptor by patients with breast carcinoma also was predictive of a poor disease prognosis. 13,22,23 Multiple investigators have also found HER-1 overexpression to represent a negative prognosticator for patients with breast carcinoma. 24,25 However, to our knowledge, few groups to date have evaluated the expression of the entire T1GFR family in human breast carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Coexpression of the type 1 growth factor receptor family members HER‐1, HER‐2, and HER‐3 has a synergistic negative prognostic effect on breast carcinoma survival

Wiseman¹,

Makretsov²,

Nielsen³

et al. 2005

Cancer

View full text Add to dashboard Cite

BACKGROUNDThe clinical significance of coexpression of type 1 growth factor receptor (T1GFR) family members remains largely unknown. The objective of the current study was to determine the frequency and the possible prognostic effect of coexpression of HER‐1, HER‐2, HER‐3, and HER‐4 by breast carcinoma.METHODSTissue microarrays were constructed using clinically annotated formalin‐fixed, paraffin‐embedded tumor samples from 242 patients with invasive breast carcinomas with a median 15‐year follow‐up. The levels of TIGFR family members (HER‐1–HER‐4) were measured by immunohistochemistry. K‐means clustering algorithm, as well as univariate (Kaplan–Meier, log‐rank test) and multivariate (Cox regression) survival analyses were applied to the data set.RESULTSUsing univariate analysis, expression of HER‐1, HER‐2, and HER‐3, but not HER‐4, was significantly associated with decreased patient disease‐specific survival (P < 0.05). Kaplan–Meier survival analysis showed that coexpression of ≥ 2 of HER‐1, HER‐2, and HER‐3 in any combination was associated with reduced patient disease‐specific survival compared with single marker expression or no expression (35% vs. 65% vs. 78% 10‐year survival rates, P = 0.001). Using multivariate analysis, expression of ≥ 2 of HER‐1, HER‐2, and HER‐3 was independent of lymph node status and tumor size.CONCLUSIONSIn a cohort of patients with breast carcinoma, the authors observed T1GFR family member coexpression (HER‐1, HER‐2, and HER‐3) to have a negative synergistic effect on patient outcome, independent of tumor size or lymph node status. Thus, coexpression of T1GFR family members identified a subset of patients with a poor disease prognosis who may potentially benefit from therapy simultaneously targeting several T1GFR family members. Cancer 2005. © 2005 American Cancer Society.

show abstract

Section: Discussionmentioning

confidence: 99%

Coexpression of the type 1 growth factor receptor family members HER‐1, HER‐2, and HER‐3 has a synergistic negative prognostic effect on breast carcinoma survival

Wiseman¹,

Makretsov²,

Nielsen³

et al. 2005

Cancer

View full text Add to dashboard Cite

show abstract

“…4,5 Furthermore, amplification of HER2 has also been shown to correlate with resistance to conventional adjuvant chemotherapy and tamoxifen. [6][7][8][9][10] Topoisomerase IIa (TOP2A) gene amplification seems to be predictive of response to a class of cytostatic agents called TopoII inhibitors, which include the anthracyclines. [11][12][13][14][15][16] Recently, estrogen receptor alpha (ESR1) gene amplification has been implicated in response to tamoxifen therapy, 17 but its significance was doubted by others.…”

mentioning

confidence: 99%

Molecular profiling of invasive breast cancer by multiplex ligation-dependent probe amplification-based copy number analysis of tumor suppressor and oncogenes

et al. 2010

View full text Add to dashboard Cite

Several oncogenes and tumor-suppressor genes have been shown to be implicated in the development, progression and response to therapy of invasive breast cancer. The phenotypic uniqueness (and thus the heterogeneity of clinical behavior) among patients' tumors may be traceable to the underlying variation in gene copy number of these genes. To obtain a more complete view of gene copy number changes and their relation to phenotype, we analyzed 20 breast cancer-related genes in 104 invasive breast cancers with the use of multiplex ligation-dependent probe amplification (MLPA). We identified MYC gene amplification in 48% of patients, PRDM14 in 34%, topoisomerase IIa (TOP2A) in 32%, ADAM9 in 32%, HER2 in 28%, cyclin D1 (CCND1) in 26%, EMSY in 25%, IKBKB in 21%, AURKA in 17%, FGFR1 in 17%, estrogen receptor alpha (ESR1) in 16%, CCNE1 in 12% and EGFR in 9% of patients. There was a significant correlation between the number of amplified genes and the histological grade and mitotic index of the tumor. Gene amplifications of EGFR, CCNE1 and HER2 were negatively associated with estrogen receptor status whereas FGFR1, ADAM9, IKBKB and TOP2A revealed a positive association. Amplifications of ESR1, PRDM14, MYC and HER2 were associated with a high mitotic index, and PRDM14 and HER2 amplifications with high histological grade. MYC amplification was detected more frequently in ductal tumors and high-level MYC amplifications were significantly associated with large tumor size. HER2/MYC, HER2/CCNE1 and EGFR/MYC co-amplified tumors were significantly larger than tumors with either of these amplifications. Gene loss occurred most frequently in E-cadherin (CDH1) (20%) and FGFR1 (10%). In conclusion, MLPA analysis with this 'breast cancer kit' allowed to simultaneously assess copy numbers of 20 important breast cancer genes, providing an overview of the most frequent (co)amplifications as well as interesting phenotypic correlations, and thereby data on the potential importance of these genes in breast cancer.

show abstract

“…[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.…”

mentioning

confidence: 99%

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

Chang

2010

Cancer

View full text Add to dashboard Cite

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...

show abstract

Prognostic and predictive value of c-erbB-2 overexpression in primary breast cancer, alone and in combination with other prognostic markers.

Cited by 300 publications

References 29 publications

Coexpression of the type 1 growth factor receptor family members HER‐1, HER‐2, and HER‐3 has a synergistic negative prognostic effect on breast carcinoma survival

Coexpression of the type 1 growth factor receptor family members HER‐1, HER‐2, and HER‐3 has a synergistic negative prognostic effect on breast carcinoma survival

Molecular profiling of invasive breast cancer by multiplex ligation-dependent probe amplification-based copy number analysis of tumor suppressor and oncogenes

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

Contact Info

Product

Resources

About