Prognostic significance of c-erbB-2 expression in node negative breast cancer

Bianchi, Simonetta; Paglierani, Milena; Zampi, G; Cardona, G; Cataliotti, Luigi; Bonardi, R; Ciatto, Stefano

doi:10.1038/bjc.1993.114

Cited by 73 publications

(16 citation statements)

References 17 publications

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“…On the other hand, some investigators found a prognostic value of c-erbB2 in the node negative breast cancer [8,10,17,19±22], whereas others failed to ®nd a statistical signi®cance of the c-erbB2 expression in node negative breast cancer [2,7,9,13,18,19,23,24]. Some studies have failed to observe the prognostic signi®cance of the c-erbB2 expression because of a small sample size or a short observation period [4,8,17,19,21,23,24]. Since the risk of recurrence and death in node negative breast cancer is low, many cases are required to achieve a statistically signi®cant association, which is found in node positive breast cancer.…”

Section: Discussionmentioning

confidence: 98%

Prognostic value of c‐erbB2 expression in breast cancer

Tsutsui

Ohno

Murakami

et al. 2002

Journal of Surgical Oncology

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The c-erbB2 expression is an independent significant factor for breast cancer and the prognostic significance remains in the node negative as well as node positive breast cancer, while the same effect was also found in all subgroups stratified according to the adjuvant therapies. In addition, the combination of c-erbB2 and ER made it possible to identify the subgroup with the worst clinical outcome.

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Section: Discussionmentioning

confidence: 98%

Prognostic value of c‐erbB2 expression in breast cancer

Tsutsui

Ohno

Murakami

et al. 2002

Journal of Surgical Oncology

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“…In addition to Southern and slot-blotting techniques to evaluate HER2 status in breast cancer, polymerase chain reaction (PCR) methods, and more recently, in situ hybridization (Ross and Fletcher, 1999) have been used. Qualitative and quantitative HER2 protein measurements have been obtained using immunohistochemistry (Allred et al, 1992;Battifora et al, 1991;Berger et al, 1988;Bianchi et al, 1993;Charpin et al, 1997;Dykens et al, 1991;Fernandez et al, 1997;Gusterson et al, 1992;Hartmann et al, 1994;Hieken et al, 1996;Jacquemier et al, 1994;Kallioniemi et al, 1991;Lovekin et al, 1991;Marks et al, 1994;McCann et al, 1991;Molina et al, 1992;Muss et al, 1994;Noguchi et al, 1992;O'Malley et al, 1996;O'Reilly et al, 1991;Paik et al, 1990;Press et al, 1993;Quenel et al, 1995;Rilke et al, 1991;Rosen et al, 1995;Sundblad et al, 1996;Tetu and Brisson 1994;Van de Vijver et al, 1988;Winstanley et al, 1991) on frozen and archival tissues, and Western blotting (Giai et al, 1994;Molina et al, 1992), and enzyme immunoassays Eissa et al, 1997;Hieken et al, 1996) on solubilized tumor extracts. Northern blot has been used to measure the level of specific mRNA (Gia...…”

Section: Her2 Amplification and Overexpression: Prognostic Valuementioning

confidence: 99%

Role of HER2 gene overexpression in breast carcinoma

et al. 2000

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The HER2 proto-oncogene encodes a transmembrane glycoprotein of 185 kDa (p185(HER2)) with intrinsic tyrosine kinase activity. Amplification of the HER2 gene and overexpression of its product induce cell transformation. Numerous studies have demonstrated the prognostic relevance of p185(HER2), which is overexpressed in 10% to 40% of human breast tumors. Recent data suggest that p185(HER2) is a ligand orphan receptor that amplifies the signal provided by other receptors of the HER family by heterodimerizing with them. Ligand-dependent activation of HER1, HER3, and HER4 by EGF or heregulin results in heterodimerization and, thereby, HER2 activation. HER2 overexpression is associated with breast cancer patient responsiveness to doxorubicin, to cyclophosphamide, methotrexate, and fluorouracil (CMF), and to paclitaxel, whereas tamoxifen was found to be ineffective and even detrimental in patients with HER2-positive tumors. In vitro analyses have shown that the role of HER2 overexpression in determining the sensitivity of cancer cells to drugs is complex, and molecules involved in its signaling pathway are probably the actual protagonists of the sensitivity to drugs. The association of HER2 overexpression with human tumors, its extracellular accessibility, as well as its involvement in tumor aggressiveness are all factors that make this receptor an appropriate target for tumor-specific therapies. A number of approaches are being investigated as possible therapeutic strategies that target HER2: (1) growth inhibitory antibodies, which can be used alone or in combination with standard chemotherapeutics; (2) tyrosine kinase inhibitors (TKI), which have been developed in an effort to block receptor activity because phosphorylation is the key event leading to activation and initiation of the signaling pathway; and (3) active immunotherapy, because the HER2 oncoprotein is immunogenic in some breast carcinoma patients.

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“…However, when analyzed in this manner, the relationship b e t w e e n m e m b r a n e positivity and relapse-free survival loses statistical significance; this latter phenomenon has been noted by previous investigators. 17,22,23 The fact that cytoplasmic positivity retains its significant association with relapsefree survival when other prognostic variables are included in the analysis makes the significance of cytoplasmic positivity even more intriguing.…”

Section: Ajcp • October 1997mentioning

confidence: 99%

erbB-2 Oncoprotein Expression in Breast Carcinoma:Poor Prognosis Associated With High Degree of Cytoplasmic Positivity Using CB-11 Antibody

Keshgegian

Cnaan

1997

Am J Clin Pathol

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e r b B -2 O n c o p r o t e i n E x p r e s s i o n i n B r e a s t C a r c i n o m aThe relationship between immunohistochemically measured membranous expression of erbB-2 oncoprotein and prognosis in breast cancer is controversial, and the relationship between cytoplasmic positivity and prognosis has been minimally investigated.The clinical course of 300 women with infiltrating breast carcinoma, whose tumors were stained for erbB-2 oncoprotein with CB-11 monoclonal antibody, was followed for 5 to 79 months (median, 41 months). Higher numbers of cancer-related deaths were observed in patients with moderate-to-strong cytoplasmic positivity (15/60, 25%) and strong membranous positivity (9/29, 31%) than in patients with negatively stained tumors (8/53, 15%) or tumors with weaker degrees of cytoplasmic or membranous positivity (rate similar to or less than negative tumors). Relapsefree survival was also significantly shorter in patients with Because of the variable clinical course of breast cancer, identification of prognostic factors is of great interest.1,2 One of the proposed prognostic factors is the erbB-2 (HER-2/neu) oncogene, 3 which encodes a 185-kd glycoprotein on the cell surface that has tyrosine kinase activity and shows structural similarities to the epidermal growth factor receptor. 3,4 There is amplification of the erbB-2 oncogene or overexpression of the protein product in approxim a t e l y 15% to 30% of b r e a s t c a r c i n o m a s .

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Prognostic significance of c-erbB-2 expression in node negative breast cancer

Cited by 73 publications

References 17 publications

Prognostic value of c‐erbB2 expression in breast cancer

Prognostic value of c‐erbB2 expression in breast cancer

Role of HER2 gene overexpression in breast carcinoma

erbB-2 Oncoprotein Expression in Breast Carcinoma:Poor Prognosis Associated With High Degree of Cytoplasmic Positivity Using CB-11 Antibody

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