Elevated Serum HER-2/neu Level Predicts Decreased Response to Hormone Therapy in Metastatic Breast Cancer

Lipton, Allan; Ali, Suhail M.; Leitzel, Kim; Demers, Laurence M.; Chinchilli, Vernon M.; Engle, Linda; Harvey, Harold A.; Brady, C.; Nalin, Carlo M.; Dugan, Margaret; Carney, Walter P.; Allard, Jeffrey

doi:10.1200/jco.20.6.1467

Cited by 178 publications

(103 citation statements)

References 17 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%

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

307

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%

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

307

195

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“…[4][5][6] Other studies have shown that patients with high levels of HER-2 have significantly poorer progression-free and overall survival using either high-dose chemotherapy, 7,8 or standard chemotherapy. 6 These results suggest that it is important to evaluate HER-2 levels in treatment trials for breast cancer to determine appropriate therapy.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] Overexpression of the HER-2 proto-oncogene in patients with node-positive and nodenegative breast cancer correlates with a poorer response and a reduced overall and progression-free survival in patients treated with hormone therapy, adjuvant radiotherapy, adjuvant and high-dose chemotherapy treatment regimens. [4][5][6][7][8] In general, HER-2 overexpression predicts for poor prognosis in breast cancer.…”

mentioning

confidence: 99%

HER-2 expression is a prognostic factor in patients with metastatic breast cancer treated with a combination of high-dose cyclophosphamide, mitoxantrone, paclitaxel and autologous blood stem cell support

Bewick

Conlon

Gerard

et al. 2001

Bone Marrow Transplant

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Summary:The expression levels of a circulating extracellular domain of HER-2 can be detected in the plasma and serum of patients with metastatic breast cancer using an enzyme immunoassay (ELISA) method. In this study, we evaluated the clinical significance of high and low levels of HER-2 in the plasma of 46 patients with metastatic breast cancer enrolled in a clinical trial of high-dose chemotherapy (HDCT) using cyclophosphamide, mitoxantrone, and paclitaxel with autologous stem cell transplantation (ASCT). Using 2500 U/ml as the cut-point, 20 patients (46%) had elevated HER-2 levels (HER-2 positive). Our results suggest that patients with metastatic breast cancer and high soluble plasma HER-2 have a significantly poorer overall (OS) and progression-free survival (PFS) following high-dose chemotherapy with paclitaxel and ASCT. The median OS of patients with low levels of HER-2 was significantly longer (P Ͻ 0.01) than the median OS of patients with high levels of HER-2 (29.8 months vs 15.9 months). PFS was also significantly longer (P Ͻ 0.01) for patients who were HER-2-negative, than for patients who were HER-2-positive (13.0 vs 8.6 months). Univariate analysis showed that patients with liver or lung metastases had significantly reduced OS and PFS. Patients with metastases to two or more sites also had a significantly reduced time to disease progression, but not OS. In multivariable analysis, lung metastases contributed along with HER-2-positive status to determine a group of patients with significantly poorer OS. However, HER-2-positive status remained the only independent predictor of PFS. Bone Marrow Transplantation (2001) 27, 847-853.

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“…Of the 11 studies in which serum HER-2/neu protein levels were tested for their ability to predict response to therapy, 8 (73%) of the studies found that elevated serum HER-2/neu protein levels predicted therapy resistance (8, 16 -18, 21), whereas three additional studies did not demonstrate this association (15,23,25). Serum HER-2/neu levels have correlated with decreased survival and absence of clinical response to hormonal therapy in estrogen receptor (ER)-positive tumors in some studies (13,21), but not in others (23). Serum HER-2/neu protein measurements have successfully predicted resistance to high-dose chemotherapy (16 -18), bone marrow transplantation (17), and response to trastuzumab single agent and combination treatment for metastatic HER-2/neu-positive disease (26 -29).…”

Section: Serum Her-2/neu Antigen Levels As a Tumor Marker-mentioning

confidence: 99%

Targeted Therapy in Breast Cancer

Ross

Fletcher

Bloom³

et al. 2004

Molecular & Cellular Proteomics

257

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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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Elevated Serum HER-2/neu Level Predicts Decreased Response to Hormone Therapy in Metastatic Breast Cancer

Abstract: Patients with ER(+) and serum HER-2/neu-positive metastatic breast cancer are less likely to respond to hormone treatment and have a shorter duration of response than ER(+) and serum HER-2/neu-negative patients. Their survival duration is also shorter.

Cited by 178 publications

References 17 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

HER-2 expression is a prognostic factor in patients with metastatic breast cancer treated with a combination of high-dose cyclophosphamide, mitoxantrone, paclitaxel and autologous blood stem cell support

Targeted Therapy in Breast Cancer

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