Serum HER2 extracellular domain in metastatic breast cancer patients treated with weekly trastuzumab and paclitaxel: association with HER2 status by immunohistochemistry and fluorescence in situ hybridization and with response rate

Fornier, Monica; Seidman, Andrew D.; Schwartz, Morton K.; Ghani, Farooq; Thiel, Robert; Norton, Larry; Hudis, Clifford A.

doi:10.1093/annonc/mdi059

Cited by 113 publications

(85 citation statements)

References 19 publications

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“…Circulating ECD-HER2 basal levels were significantly associated with IHC score in agreement with the study by Fornier et al [32], but they did not retain predictive value. Similarly both circulating EGFR and CA15.3 were not predictive for response.…”

Section: Discussionsupporting

confidence: 89%

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer

Gasparini

Gion²,

Mariani³

et al. 2006

Breast Cancer Res Treat

128

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Background A randomized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2. Patients and methods Among 124 patients randomized, 123 are assessable for toxicity and 118 for response. Patients received weekly paclitaxel single agent (80 mg/m 2 ) or combined with trastuzumab (4 mg/kg loading dose, then weekly 2 mg/kg). HER-2 overexpression was determined by immunohistochemistry (IHC). Patients with 2+/3+ IHC scores were eligible. IHC was compared with HER-2 serum extracellular domain (ECD). Results Patient characteristics were similar in the two arms. Both treatments were feasible and well tolerated with no grade 4 hematologic toxicity. No patient developed cardiac toxicity. The combined treatment was statistically significant superior for overall response rate (ORR) (75% vs. 56.9%; P = 0.037), particularly in the subset of IHC 3+ patients (84.5% vs. 47.5%; P = 0.00050). A statistically significant better median time to progression was seen in the subgroup with IHC 3+ (369 vs. 272 days; P = 0.030) and visceral disease (301 vs. 183 days; P = 0.0080) treated with combination. Multivariable analysis of predictive factors showed that only IHC score retained statistically significant value for ORR (P = 0.0035). Conclusion Weekly paclitaxel plus trastuzumab is highly active and safe and it is superior to paclitaxel alone in patients with IHC score of 3+.

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Section: Discussionsupporting

confidence: 89%

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer

Gasparini

Gion²,

Mariani³

et al. 2006

Breast Cancer Res Treat

128

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“…This assay has been approved by the FDA for the monitoring of HER-2-positive breast cancers, including the identification of disease relapse and on- going response to HER-2-targeted therapies [227]. Attempts to use this serum-based test as the sole classifier of HER-2 status for newly diagnosed cases have not been widely accepted, although fairly good correlation exists between serum HER-2 ECD levels and the results of IHC and FISH assessments on primary tumor tissues [228]. It has been recommended that a 37 g/l serum HER-2 ECD cutoff be used, which can achieve 95% specificity but low sensitivity for HER-2-positive status determined on primary tumors [229].…”

Section: Tissue and Serum Enzyme-linked Immunosorbentmentioning

confidence: 99%

The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

et al. 2009

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1. Contrast the current strengths and limitations of the three main slide-based techniques (IHC, FISH, and CISH) currently in clinical use for testing breast cancer tissues for HER-2 status.2. Compare the efficacy of trastuzumab-and lapatinib-based regimens in the adjuvant and metastatic settings as reported in published clinical trials and regulatory approval databases.3. Contrast the list of biomarkers that have been associated with clinical resistance to trastuzumab and lapatinib and describe their current level of validation.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTThe human epidermal growth factor receptor (HER-2) oncogene encodes a transmembrane tyrosine kinase receptor that has evolved as a major classifier of invasive breast cancer and target of therapy for the disease. The validation of the general prognostic significance of HER-2 gene amplification and protein overexpression in the absence of anti-HER-2 targeted therapy is discussed in a study of 107 published studies involving 39,730 patients, which produced an overall HER-2-positive rate of 22.2% and a mean relative risk for overall survival (OS) of 2.74. The issue of HER-2 status in primary versus metastatic breast cancer is considered along with a section on the features of metastatic HER-2-positive disease. The major marketed slide-based HER-2 testing approaches, immunohistochemistry, fluorescence in situ hybridization, and chromogenic in situ

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“…Other stages on the way have been the benefits achieved by increasing the doses of cyclophosphamide, doxorubicin, and 5-fluorouracil used in CAF, and the advent of the taxanes. Further improvements may stem from current research aimed at: A) reducing the interval between cycles from 14 days to 10 or 11 days; B) extending the period for which anthracyclines and taxanes can be given; C) adding noncytotoxic agents such as the humanized anti-HER2 antibody trastuzumab (Herceptin ® ; Genentech, Inc., South San Francisco, CA, http://www.gene.com) to chemotherapy in HER2-positive cases [7,[19][20][21][22][23][24]; and D) adding antiangiogenesis agents, e.g. bevacizumab (Avastin ® ; Genentech, Inc.).…”

Section: Lessons Learnedmentioning

confidence: 99%

Conceptual and Practical Implications of Breast Tissue Geometry: Toward a More Effective, Less Toxic Therapy

2005

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Mathematics provides greater understanding of the complex process of tumorigenesis.Based on the Gompertzian phenomenon and the Norton-Simon hypothesis, enhanced cell kill can be obtained through a greater chemotherapy dose rate. Results from the 1995 Bonadonna et al. study and the CALGB/Intergroup C9741 study demonstrated that patients in the dose-dense arms had significantly longer disease-free survival and overall survival.Because of the demonstrated applicability of Gompertzian kinetics, attention has been turned to the etiology of the Gompertzian curve. Breast tumor dimensions, as with all tissue dimensions in biology, can be calculated by fractals. A less cell-dense tissue usually has a lower fractal dimension than a tissue with more cells (i.e., a higher cell density is usually due to a higher fractal dimension). Density is the number of cells divided by the tissue volume. When allowed to grow, the density of a tissue with a lower fractal dimension drops quickly. However, a tumor, since it has a higher fractal mass dimension, maintains a high density as it grows bigger, resulting in a more rapid growth rate and a larger final size. Fractal dimensions of infiltrating ductal adenocarcinomas of the breast are high (i.e., 2.98), which results in a very dense tissue compared with normal breast tissue (with a fractal dimension of about 2.25). As expected, the higher fractal dimension results in a high rate of growth.

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Serum HER2 extracellular domain in metastatic breast cancer patients treated with weekly trastuzumab and paclitaxel: association with HER2 status by immunohistochemistry and fluorescence in situ hybridization and with response rate

Abstract: A statistically significant association was observed between pretreatment serum HER2 ECD and tissue HER2 status as assessed by IHC and FISH. A decrease in serum HER2 ECD level was a significant predictor of response to trastuzumab-based therapy.

Cited by 113 publications

References 19 publications

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer

The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine

Conceptual and Practical Implications of Breast Tissue Geometry: Toward a More Effective, Less Toxic Therapy

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