c-erb B2 overexpression decreases the benefit of adjuvant tamoxifen in early-stage breast cancer without axillary lymph node metastases.

Carlomagno, Chiara; Perrone, Francesco; Gallo, Ciro; Laurentiis, Michelino De; Lauria, Rossella; Morabito, Alessandro; Pettinato, Guido; Panico, Luigi; D’Antonio, Antonio; Bianco, A. R.; Placido, Sabino De

doi:10.1200/jco.1996.14.10.2702

Cited by 359 publications

(175 citation statements)

References 22 publications

Supporting

Mentioning

154

Contrasting

Unclassified

Order By: Relevance

“…Consistent with the results of a large number of studies, our study findings showed that nuclear grade played a prognostic role in node negative patients (Yuan et al, 1992;Gasparini et al, 1994;Carlmagno et al, 1996;Andrulis et al, 1998;Carol et al, 2002;Bekir et al, 2003;Polednak, 2003;Sebastian et al, 2004a;2004b;Gurleyik et al, 2007;Lee et al, 2009;Nimeus-Malmstrom et al, 2010;Song et al, 2011;Clayton et al, 2012). In the current study, the survival rate was obtained as 74.8% in grade three compared to 87.1% in grade one (Table 1), which is in contrast with the study by Ashwini et al (2008).…”

Section: Discussionsupporting

confidence: 90%

“…These findings are in line with the results of a large number of studies (Yuan et al, 1992;Gasparini et al, 1994;Carlmagno et al, 1996;Carol et al, 2002;Gurleyik et al, 2007;Florence et al, 2010), while in contrast with those of Androlis' study (Andrulis et al, 1998). Moreover, Herceptin protein had only a significant effect on survival in lymph node positive patients, which is in agreement with the results of the study by Flourence et al (2010).…”

Section: Discussionsupporting

confidence: 89%

See 1 more Smart Citation

Vascular Invasion as an Independent Prognostic Factor in Lymph Node Negative Invasive Breast Cancer

Rezaianzadeh¹,

Talei²,

Rajaeefard³

et al. 2012

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Introduction: Identification of simple and measurable prognostic factors is an important issue in treatment evaluation of breast cancer. The present study was conducted to evaluate the prognostic role of vascular invasion in lymph node negative breast cancer patients. Methods: in a retrospective design, we analyzed the recorded profiles of the 1,640 patients treated in the breast cancer department of Motahari clinic affiliated to Shiraz University of Medical Sciences, Shiraz, Iran, from January 1999 to December 2012. Overall and adjusted survivals were evaluated by the Cox proportional hazard model. All the hypotheses were considered two-sided and a p-value of 0.05 or less was considered as statistically significant. Results: Mean age in lymph node negative and positive patients was 50.0 and 49.8 respectively. In lymph node negative patients, the number of nodes, tumor size, lymphatic invasion, vascular invasion, progesterone receptor, and nuclear grade were significant predictors. In lymph node and lymphatic negative patients, vascular invasion also played a significant prognostic role in the survival which was not evident in lymph node negative patients with lymphatic invasion. Discussion: The results of our large cohort study, with long term follow up and using multivariate Cox proportional model and comparative design showed a significant prognostic role of vascular invasion in early breast cancer patients. Vascular invasion as an independent prognostic factor in lymph node negative invasive breast cancer

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 89%

Vascular Invasion as an Independent Prognostic Factor in Lymph Node Negative Invasive Breast Cancer

Rezaianzadeh¹,

Talei²,

Rajaeefard³

et al. 2012

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…39 Because 40 -50% of Her2/neu overexpressing breast cancers are also ER-positive, 40 treatment designed to block estrogen's effects remains one of the most challenging areas of study. 41 This is the first report demonstrating that the combination of PB and RA enhances the antiproliferative effects of TAM in ER-positive, Her2/neu overexpressing breast cancer by modulating simultaneously the interactions between Her2/neu and cell membrane ER and between RAR and nuclear ER. Our study also provides evidence that Her2/neu may directly interfere with the TAM effect on the cell membrane ER.…”

Section: Discussionmentioning

confidence: 83%

Resistance to tamoxifen‐induced apoptosis is associated with direct interaction between Her2/neu and cell membrane estrogen receptor in breast cancer

Chung

Sheu

Yang

et al. 2001

Intl Journal of Cancer

124

View full text Add to dashboard Cite

Overexpression of Her2/neu is implicated in the development of resistance to the antiestrogen tamoxifen (TAM) that exerts its inhibitory effect through interaction with estrogen receptor (ER). Whereas Her2/neu and ER are believed to be important cell survival/death factors in human breast cancer cells, if and how they interact to confer resistance to hormone therapy is not known. This prompted us to investigate whether modulation of the effect of TAM occurs via the Her2/neu pathway and whether targeting the interaction between the Her2/neu pathway and the ER pathway is beneficial. There are 2 forms of ER that are localized to the cell membrane and to the nucleus. For the first time, we found that Her2/neu directly interacts with ER at the cell membrane. We then investigated the role of Her2/neu overexpression in the regulation of the cell membrane ER pathway in TAM-resistant breast cancer cells and the nature of this interaction in apoptotic signaling. Relief of TAM resistance was associated with Her2/neu downregulation and ER upregulation. TAM-induced apoptosis occurred immediately after dissociation of Her2/neu from cell membrane ER. These results demonstrate a novel mechanism by which Her2/neu regulates the cell membrane ER-coupled apoptosis and the possible involvement of the Her2/neu in TAM resistance of breast cancer cells. Moreover, the antiproliferative activity of TAM should rely on the integration between the signal transduction from the cell membrane ER and the gene regulation by the nuclear ER. Coordinated modulation on the cell membrane ER/Her2/neu pathway and the nuclear ER/RAR pathway may provide a new approach for treatment of ER-positive, Her2/neu overexpressing breast cancer.

show abstract

“…The clinical association of c-erbB-2 with poor prognosis in cancer patients may depend on alterations in the physiological hormonal signaling pathway, and the decrease survival of c-erbB-2-positive tumor patients treated with tamoxifene as compared to untreated patients (Carlomagno et al, 1996) might depend in part of the inhibition of the cross-talk between the two receptors.…”

Section: Discussionmentioning

confidence: 99%

Increased expression of c-erbB-2 in hormone-dependent breast cancer cells inhibits cell growth and induces differentiation

et al. 1998

View full text Add to dashboard Cite

c-erbB-2, a member of the tyrosine kinase oncogene family, is overexpressed in about 30% of human breast tumors where it correlates with poor prognosis. In vitro studies have suggested that increased expression of the receptor plays an important role in malignant progression. To better understand the direct e ects of p185 HER2 overexpression, a human c-erbB-2 expression vector was transfected into the hormone-dependent MCF-7 human breast carcinoma cell line and cell growth was analysed. Unexpectedly, colony formation assay revealed a reduction in the number and size of colonies as compared with mock-transfected cells. In hormone-deprived medium, c-erbB-2 transfected cells acquired growth capability, consistent with previous reports. By contrast, two c-erbB-2-transfected clones grown in complete medium showed a reduced proliferation rate despite the activation of a fully functional oncoprotein capable of autophosphorylation and induction of the MAPK pathway. The number of c-erbB-2-overexpressing cells in the S phase of the cell cycle was about one-half the number of control and mock-transfected cells. Also, overexpression of c-erbB-2 induced overexpression of p21 WAF1 , pRB hypophosphorylation and a mature di erentiated cell phenotype with production of lipid droplets. Functional inactivation of p185 HER2 by means of a speci®c single chain antibody indicated the c-erbB-2-dependence of the observed alterations. These data show that the exogenous overexpression of the c-erbB-2 gene in hormonedependent breast cancer cells inhibits proliferation and induces di erentiation.

show abstract

c-erb B2 overexpression decreases the benefit of adjuvant tamoxifen in early-stage breast cancer without axillary lymph node metastases.

Abstract: In early-stage breast cancer patients, overexpression of c-erbB2 is a marker of lack of efficacy of adjuvant tamoxifen.

Cited by 359 publications

References 22 publications

Vascular Invasion as an Independent Prognostic Factor in Lymph Node Negative Invasive Breast Cancer

Vascular Invasion as an Independent Prognostic Factor in Lymph Node Negative Invasive Breast Cancer

Resistance to tamoxifen‐induced apoptosis is associated with direct interaction between Her2/neu and cell membrane estrogen receptor in breast cancer

Increased expression of c-erbB-2 in hormone-dependent breast cancer cells inhibits cell growth and induces differentiation

Contact Info

Product

Resources

About