Serum <i>HER-2/neu</i> and Response to the Aromatase Inhibitor Letrozole Versus Tamoxifen

Lipton, Allan; Ali, Suhail M.; Leitzel, Kim; Demers, Laurence M.; Harvey, Harold A.; Chaudri-Ross, Hilary A.; Brady, C.; Wyld, Peter; Carney, Walter P.

doi:10.1200/jco.2003.09.098

Cited by 115 publications

(70 citation statements)

References 12 publications

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“…38 We reported that patients who had elevated serum HER-2 had significantly decreased ORR, CBR, TTP, TTF, and overall survival compared with patients who had normal serum HER-2.…”

Section: Resultsmentioning

confidence: 85%

“…38 Combined analysis of pretreatment serum EGFR and HER-2 levels yielded no additional predictive information compared with serum HER-2 levels alone for clinical response to first-line hormone therapy as measured by ORR, CBR, TTF, and TTP (Fig. 1).…”

Section: Serum Egfr/her-2 Combined Analysismentioning

confidence: 97%

“…[34][35][36][37] We previously reported that patients with metastatic breast cancer who had elevated pretreatment serum HER-2 levels had a decreased response to firstline hormone therapy and decreased survival. 38 The objective of the current study was to determine the predictive and prognostic significance of serum EGFR levels in 535 women with advanced breast cancer who were enrolled in a Phase III, first-line, hormone therapy trial in patients with metastatic breast cancer.…”

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confidence: 99%

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Serum epidermal growth factor receptor/HER‐2 predicts poor survival in patients with metastatic breast cancer

Souder

Leitzel

Ali

et al. 2006

Cancer

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BACKGROUND.Epidermal growth factor receptor (EGFR, HER‐1, and erbB1) is overexpressed in primary breast cancer and had been identified as a poor prognostic factor.METHODS.Pretreatment serum EGFR levels were quantified by using an enzyme‐linked immunoadsorbent assay in a Phase III first‐line trial of letrozole and tamoxifen and were correlated with patient outcomes.RESULTS.Serum EGFR levels in a control group of 117 healthy, postmenopausal women measured 64.1 ± 13.3 ng/mL (mean ± standard deviation). Using a cutoff EGFR level of 44.1 ng/mL from the control group (5% nonparametric method), 53 of 535 patients (10%) had decreased serum levels of EGFR. Patients with decreased serum EGFR had no significant difference in objective response rate (ORR), clinical benefit rate (CBR), time to progression (TTP), or time to treatment failure (TTF); however, they did have significantly reduced survival compared with patients who had normal serum EGFR levels (median survival, 23.3 months vs. 30.9 months; P = .007). A combined analysis of pretreatment serum EGFR and HER‐2 yielded no additional predictive information for ORR, CBR, TTP, or TTF compared to serum HER‐2 alone. However, in the current analysis, a subgroup of patients who had decreased serum EGFR and normal serum HER‐2 was identified (n = 39 of 535 patients; 7.3%) that had significantly reduced survival compared with patients who had normal serum levels of both EGFR and HER‐2 (median survival, 23.5 months vs. 37.1 months; P = .005). In multivariate analysis, a decreased serum EGFR level remained a significant independent prognostic factor for decreased survival (hazards ratio, 1.58; P = .007).CONCLUSIONS.In patients who had metastatic breast cancer, decreased serum EGFR/normal serum HER‐2 predicted shorter survival compared with patients who had normal levels of serum EGFR/HER‐2. This patient subgroup deserves further study to assess their response to and selection for anti‐EGFR‐directed therapies. Cancer 2006. © 2006 American Cancer Society.

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“…38 We reported that patients who had elevated serum HER-2 had significantly decreased ORR, CBR, TTP, TTF, and overall survival compared with patients who had normal serum HER-2.…”

Section: Resultsmentioning

confidence: 85%

Section: Serum Egfr/her-2 Combined Analysismentioning

confidence: 97%

mentioning

confidence: 99%

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Serum epidermal growth factor receptor/HER‐2 predicts poor survival in patients with metastatic breast cancer

Souder

Leitzel

Ali

et al. 2006

Cancer

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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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“…Some of the more convincing studies concerned the outcome of patients with an elevated baseline serum biomarker for the extracellular domain of ErbB-2 (ECD). These patients do poorly when compared with patients with low levels of serum ECD regardless of whether they receive an aromatase inhibitor or tamoxifen [28].…”

Section: Clinical Studies Of Erbb-2 and Er Interactions In The Advancmentioning

confidence: 98%

Overcoming Endocrine Therapy Resistance by Signal Transduction Inhibition

Ellis

2004

The Oncologist

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Endocrine therapy is the most effective systemic treatment for patients with hormone-receptor-positive (HR + ) breast cancer. Unfortunately, efficacy is often limited by the onset of resistance, which is almost inevitable for patients with advanced disease. Several patterns of endocrine resistance are recognizable clinically, including: A) tumors that are inherently insensitive to all attempts at estrogen receptor (ER) targeting despite expression of ER (pan-endocrine therapy resistance); B) tumors that are estrogen dependent but resistant to one or more specific endocrine therapies (agent-selective resistance); and C) tumors that initially respond but subsequently progress (acquired resistance). Current insights into the molecular basis for these resistance patterns are rudimentary, but are most clearly illuminated by investigations that focus on the crosstalk between the ErbB or HER peptide growth factor family and the ER. The data are sufficiently compelling to be addressed by ongoing clinical trials that examine combinations of endocrine agents and either trastuzumab Medicine, 660 South Euclid Avenue, Campus Box 8056, Division of Oncology, St. Louis, Missouri 63110, USA. Telephone: 314-362-8866; Fax: 314-362-7086; e-mail: mellis@im.wustl.edu Received March 26, 2004; accepted for publication April 15, 2004. ©AlphaMed Press 1083-7159/2004 The Oncologist ® LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Discuss patterns of resistance to endocrine therapy for breast cancer.2. Relate differences in resistance patterns in early and advanced disease settings.3. Identify potential treatment strategies to overcome resistance and/or restore endocrine therapy efficacy.Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com CME CME This material is protected by U.S.

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Serum HER-2/neu and Response to the Aromatase Inhibitor Letrozole Versus Tamoxifen

Cited by 115 publications

References 12 publications

Serum epidermal growth factor receptor/HER‐2 predicts poor survival in patients with metastatic breast cancer

Serum epidermal growth factor receptor/HER‐2 predicts poor survival in patients with metastatic breast cancer

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

Overcoming Endocrine Therapy Resistance by Signal Transduction Inhibition

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