c-erbB-2 Positivity is a factor for poor prognosis in breast cancer and poor response to hormonal or chemotherapy treatment in advanced disease

Jukkola, Arja; Bloigu, Risto; Soini, Ylermi; Savolainen, Eeva‐Riitta; Holli, Kaija; Blanco, Guillermo

doi:10.1016/s0959-8049(00)00395-6

Cited by 54 publications

(49 citation statements)

References 21 publications

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“…HER-2 expression was evaluated with different methods: immunohistochemical detection of the p185 protein (13,18,19,22,24), evaluation of gene amplification by Southern blot (14,19) and ELISA (16,20,21,23,26), or chemoluminescent immunoassay (17) determination of circulating levels of HER-2 in the patient serum. Differences in the cutoff values chosen to distinguish between negative and positive HER-2 status complicate the picture even further, so that each study used its own particular methodology.…”

Section: Resultsmentioning

confidence: 99%

“…The study by Berns et al (14) did not report steroid receptor information for the 126 patients with HER-2 status evaluation; however, it was assumed that the proportion of ER-positive patients was approximately superimposable to that of the whole study population (ER positive: 193 of 259 = 59%). Two small studies (17,19) lacked clear information about steroid receptor status. However, given the selection criteria of these studies, it is reasonable to assume that ER-positive patients represent a vast proportion of subjects in this series.…”

Section: Resultsmentioning

confidence: 99%

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A Meta-Analysis on the Interaction between HER-2 Expression and Response to Endocrine Treatment in Advanced Breast Cancer

Laurentiis¹,

Arpino

Massarelli

et al. 2005

Clinical Cancer Research

310

195

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Purpose: Experimental data suggest a complex cross-talk between HER-2 and estrogen receptor, and it has been hypothesized that HER-2-positive tumors may be less responsive to certain endocrine treatments. Clinical data, however, have been conflicting. We have conducted a metaanalysis on the interaction between the response to endocrine treatment and the overexpression of HER-2 in metastatic breast cancer. Experimental Design: Studies have been identified by searching the Medline, Embase, and American Society of Clinical Oncology abstract databases. Selection criteria were (a) metastatic breast cancer, (b) endocrine therapy (any line of treatment), and (c) evaluation of HER-2 expression (any method). For each study, the relative risk for treatment failure for HER-2-positive over HER-2-negative patients with 95% confidence interval was calculated as an estimate of the predictive effect of HER-2. Pooled estimates of the relative risk were computed by the MantelHaenszel method. Results: Twelve studies (n = 2,379 patients) were included in the meta-analysis. The overall relative risk was 1.42 (95% confidence interval, 1.32-1.52; P < 0.00001; test for heterogeneity = 0.380). For studies involving tamoxifen, the pooled relative risk was 1.33 (95% confidence interval, 1.20-1.48; P < 0.00001; test for heterogeneity = 0.97); for studies involving other hormonal drugs, a pooled relative risk of 1.49 (95% confidence interval, 1.36-1.64; P < 0.00001; test for heterogeneity = 0.08) was estimated. A second meta-analysis limited to tumors that were either estrogen receptor positive, estrogen receptor unknown, or estrogen receptor negative/progesterone receptor positive yielded comparable results. Conclusions: HER-2-positive metastatic breast cancer is less responsive to any type of endocrine treatment. This effect holds in the subgroup of patients with positive or unknown steroid receptors.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A Meta-Analysis on the Interaction between HER-2 Expression and Response to Endocrine Treatment in Advanced Breast Cancer

Laurentiis¹,

Arpino

Massarelli

et al. 2005

Clinical Cancer Research

310

195

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“…In fact, when measured as continuous variables, the expression of HER-2/neu appears to be inversely related to the expression of ER and PR even in hormone receptor-positive tumors (190). In some studies, HER-2/ neu-positive tumors were specifically resistant to tamoxifen therapy (13,111,123,126,130,191). However, in other studies, HER-2/neu status failed to predict tamoxifen resistance in ERpositive cases (192).…”

Section: Her-2/neu Status and The Prediction Of Response Tomentioning

confidence: 99%

Targeted Therapy in Breast Cancer

Ross

Fletcher

Bloom³

et al. 2004

Molecular & Cellular Proteomics

259

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The HER-2/neu oncogene, a member of the epidermal growth factor receptor or erb gene family, encodes a transmembrane tyrosine kinase receptor that has been linked to prognosis and response to therapy with the anti-HER-2-humanized monoclonal antibody, trastuzumab (Herceptin, Genentech, South San Francisco, CA) in patients with advanced metastatic breast cancer. HER-2/neu status has also been tested for its ability to predict the response of breast cancer to other therapies including hormonal therapies, topoisomerase inhibitors, and anthracyclines. This review includes an analysis of 80 published studies encompassing more than 25,000 patients designed to consider the relative advantages and disadvantages of the various methods of measuring HER-2/neu in clinical breast cancer specimens. Southern blotting, PCR amplification detection, and fluorescence in situ hybridization assays designed to detect HER-2/neu gene amplification are compared with HER-2/neu protein overexpression assays performed by immunohistochemical techniques applied to frozen and paraffin-embedded tissues and enzyme immunoassays performed on tumor cytosols. The significance of HER-2/neu overexpression in ductal carcinoma in situ and the HER-2/neu status in uncommon female breast conditions and male breast cancer are also considered. The role of HER-2/neu testing for the prediction of response to trastuzumab therapy in breast cancer is reviewed along with the current studies designed to test whether HER-2/neu status can predict the response to standard and newer hormonal therapies, cytotoxic chemotherapy, and radiation. The review will also evaluate the status of serum-based testing for circulating HER-

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“…Among disease-related factors, HER2 status is associated with a poorer survival and lower sensitivity to tamoxifen and chemotherapy with CMF, [3][4][5][6][7][8][9][10] while it seems to improve sensitivity to anthracyclines and to taxanes. [11][12][13][14][15][16] Our study demonstrates that HER2 overexpression is associated with a higher sensitivity to HDCT (conversion rate 87.5% in HER2-positive patients vs 37% in HER2-negative patients).…”

Section: Discussionmentioning

confidence: 99%

“…This overexpression is associated with a poorer outcome and with resistance to conventional hormonal chemotherapy. [3][4][5][6][7][8][9][10] On the other hand, HER2 overexpression may correlate with a better response to doxorubicin and paclitaxel. [11][12][13][14][15][16] The efficacy of high-dose chemotherapy in metastatic breast cancer (MBC) is yet to be established.…”

Section: Metastatic Breast Cancermentioning

confidence: 99%

HER2 overexpression as a prognostic factor in metastatic breast cancer patients treated with high-dose chemotherapy and autologous stem cell support

Guarneri

Bengala²,

Orlandini³

et al. 2004

Bone Marrow Transplant

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Summary:We retrospectively evaluated the predictive and prognostic role of HER2 expression in 44 metastatic breast cancer (MBC) patients treated with high-dose consolidation chemotherapy (HDCT) and autologous stem cell support after induction chemotherapy (IC) with six courses of epirubicin þ paclitaxel (22 patients) or gemcitabine þ epirubicin þ paclitaxel (22 patients). HER2 expression was evaluated by an immunohistochemical method (Herceptest, Dako). A total of 13 patients (29.5%) showed a HER2 overexpression (score 3 þ ). After IC, nine patients were in complete response (CR), 30 in partial response (PR), and five in stable disease (SD); after HDCT, 20 (45.5%) obtained a CR, and 23 were in PR, for a conversion rate of 48.5%. Conversion rate for HER2-positive patients was 87.5 vs 37% for HER2-negative patients (P ¼ 0.018). The median progressionfree (PFS) and overall survivals (OS) were 17.6 (95% CI 13.2-22.0) and 44 (95% CI 25.9-62.3) months, respectively. Patients with HER2 overexpression experienced a significantly (P ¼ 0.0042) shorter median PFS (15.3 months, 95% CI 11.1-19.5) compared to HER2-negative patients (21.3 months,). The median OS was 27.6 months (95% CI 4.5-50.7) in HER2-positive patients and 50.3 months (95% CI 38.7-62.0) in HER2-negative patients (P ¼ 0.345). These results indicate that HER2 overexpression predicts a worse outcome for patients with MBC treated with HDCT, despite the high CR rate obtained in this subset of patients.

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c-erbB-2 Positivity is a factor for poor prognosis in breast cancer and poor response to hormonal or chemotherapy treatment in advanced disease

Cited by 54 publications

References 21 publications

A Meta-Analysis on the Interaction between HER-2 Expression and Response to Endocrine Treatment in Advanced Breast Cancer

A Meta-Analysis on the Interaction between HER-2 Expression and Response to Endocrine Treatment in Advanced Breast Cancer

Targeted Therapy in Breast Cancer

HER2 overexpression as a prognostic factor in metastatic breast cancer patients treated with high-dose chemotherapy and autologous stem cell support

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