Intratumoral Heterogeneity of HER-2/neu in Invasive Mammary Carcinomas Using Fluorescence In-Situ Hybridization and Tissue Microarray

Shin, Sandra J.; Hyjek, Elizabeth; Early, Erin; Knowles, Daniel M.

doi:10.1177/1066896906293055

Cited by 45 publications

(27 citation statements)

References 27 publications

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“…In every development stage of breast cancer, HER2 expression could keep stable. HER2 over-expression is detected in approximately range from 15% to 30% (Shin et al, 2006;Leong and Leong, 2006); in our study, HER2 over-expression is 26.6%.…”

Section: Comparison Of Response To Different Chemotherapy Regimens Inmentioning

confidence: 78%

HER2 over-expression and response to different chemotherapy regimens in breast cancer

Zhang¹,

Liu²

2008

J. Zhejiang Univ. Sci. B

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Abstract:Purpose: To exam the relationship between HER2 over-expression and different adjuvant chemotherapies in breast cancer. Patients and Methods: A total of 1625 primary breast cancer patients who received post-surgery adjuvant chemotherapy in Tianjin Cancer Hospital, China, from July 2002 to November 2005 were included in the study. Among them, 600 patients were given CMF (CTX+MTX+5-Fu) regimen, 600 given CEF (CTX+E-ADM+5-Fu) regimen, and 425 given anthracyclines plus taxanes regimen, with mean follow-up time of 42 months. Results: In CMF treatment group, the 3-year disease free survival (DFS) in HER2 over-expressed patients was lower than that of the HER2-negative ones (89.80% vs 91.24%, P=0.0348); in node-positive subgroup, the 3-year DFS was 84.72% in HER2 over-expressed patients, and 90.18% in the HER-2-negative ones (P=0.0271). Compared to CMF regimen, anthracyclines and anthracyclines plus taxanes regimens are more effective (P<0.05) in node-positive HER2 over-expression than those in the node-negative. Conclusion: HER2 over-expression is an independent index for predicting poor prognosis and short DFS for breast cancer patients. HER2 over-expressed patients are resistant to CMF regimen chemotherapy, but sensitive to anthracyclines-based or anthracyclines plus taxanes regimen. HER2 expression can be taken as a marker for therapies in breast cancer.

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Section: Comparison Of Response To Different Chemotherapy Regimens Inmentioning

confidence: 78%

HER2 over-expression and response to different chemotherapy regimens in breast cancer

Zhang¹,

Liu²

2008

J. Zhejiang Univ. Sci. B

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“…8,13,14 Intratumoral heterogeneity of HER2 gene amplification has been demonstrated in a subset of breast cancers. [15][16][17][18][19][20][21][22][23] However, as the previous studies targeted different sets of samples, the frequency of intratumoral HER2 heterogeneity was quite variable and was not comparable between the studies. Andersson et al 15 found HER2 heterogeneity within the invasive components of breast cancers in only 1 of 78 tumors.…”

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confidence: 93%

Intratumoral heterogeneity of HER2 gene amplification in breast cancer: its clinicopathological significance

et al. 2012

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Intratumoral heterogeneity of human epidermal growth factor receptor 2 (HER2) gene amplification has been reported to occur with variable frequencies in breast cancers. However, there have been few studies of its clinicopathological significance. We used tissue microarrays to evaluate two aspects of intratumoral heterogeneity of HER2 gene amplification: regional heterogeneity and genetic heterogeneity. We examined 96 invasive breast cancers in which HER2 amplification had been diagnosed in whole sections, and determined the clincopathological characteristics of those tumors. HER2 regional heterogeneity, defined as the existence of amplification/negative or amplification/equivocal patterns in different tissue microarray cores of a tumor, was present in 17 (18%) of the 96 cases. HER2 genetic heterogeneity, defined as the presence of tumor cells with a HER2/chromosome enumeration probe 17 ratio higher than 2.2 in 5-50% of the tumor cells, was found in 11 cases (11%), all of which showed HER2 regional heterogeneity. The cases with intratumoral heterogeneity of HER2 gene amplification were characterized by low grade or equivocal HER2 amplification and equivocal (2 þ ) HER2 expression in whole sections. The patients with intratumoral heterogeneity of HER2 gene amplification had significantly shorter disease-free survival times than those with homogeneous HER2 gene amplification, and this effect was also evident in subgroup analysis by hormone receptor status. In multivariate analysis, intratumoral HER2 heterogeneity retained its status as an independent prognostic factor for disease-free survival. In conclusion, intratumoral heterogeneity of HER2 gene amplification is present in a subset of HER2-amplified breast cancers, especially in cases with low-grade HER2 amplification and equivocal HER2 expression, indicating a need for HER2 testing on more representative, larger tumor samples for accurate assessment of HER2 status in such cases. The patients with this heterogeneity have decreased disease-free survival, suggesting that genetic instability, and hence aberrant HER2 amplification in subclones of such tumors, may be associated with breast cancer progression. Modern Pathology (2012) 25, 938-948;

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“…Meistens wird unter intratumoraler HER2-Heterogenität die regionale Variation des HER2-Status in Tumorzellen des gleichen Karzinoms verstanden [1,2,4,5,6,8,9,13,14,16]. Unterschiede hinsichtlich des Vorliegens oder des Grades einer HER2-Genamplifikation werden auch als genetische HER2-Heterogenität bezeichnet.…”

Section: Her2-heterogenitätunclassified

Intratumoral heterogeneity of HER2 status in breast carcinoma

et al. 2010

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Intratumoral Heterogeneity of HER-2/neu in Invasive Mammary Carcinomas Using Fluorescence In-Situ Hybridization and Tissue Microarray

Cited by 45 publications

References 27 publications

HER2 over-expression and response to different chemotherapy regimens in breast cancer

HER2 over-expression and response to different chemotherapy regimens in breast cancer

Intratumoral heterogeneity of HER2 gene amplification in breast cancer: its clinicopathological significance

Intratumoral heterogeneity of HER2 status in breast carcinoma

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