Evaluation of the prognostic value of HER-2 and VEGF in breast cancer patients participating in a randomized study with dose–dense sequential adjuvant chemotherapy

Kostopoulos, Ioannis; Arapantoni-Dadioti, Petroula; Gogas, Helen; Papadopoulos, Savvas; Malamou-Mitsi, Vasiliki; Scopa, Chrisoula D.; S, Markaki; Karagianni, Evangelia; Kyriakou, V.; Margariti, Apostolia; Kyrkou, Elisavet; Pavlakis, Kitty; Zaramboukas, Thomas; Skordalaki, A.; Bourli, Antonia; Markopoulos, Christos; Pectasides, Dimitrios; Dimopoulos, Meletios Α.; Skarlos, Dimosthenis; Fountzilas, George

doi:10.1007/s10549-005-9062-2

Cited by 39 publications

(37 citation statements)

References 33 publications

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“…In another randomised study comparing docetaxel-based (TAC) with non-docetaxel-containing adjuvant chemotherapy, the observed reduction in the risk for relapse in patients treated with TAC, did not seem to be driven by HER2 status (Martin et al, 2005). A recent study, investigating the predictive power of HER2 protein overexpression assessed by IHC in patients who were part of the HE10/97 trial, did not find predictive ability of HER2 for treatment with paclitaxel (Kostopoulos et al, 2006). However, a meta-analysis (Dhesy-Thind et al, 2008) including the above three trials (Martin et al, 2005;Kostopoulos et al, 2006;Hayes et al, 2007) demonstrated a significant interaction in terms of DFS.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study, investigating the predictive power of HER2 protein overexpression assessed by IHC in patients who were part of the HE10/97 trial, did not find predictive ability of HER2 for treatment with paclitaxel (Kostopoulos et al, 2006). However, a meta-analysis (Dhesy-Thind et al, 2008) including the above three trials (Martin et al, 2005;Kostopoulos et al, 2006;Hayes et al, 2007) demonstrated a significant interaction in terms of DFS. Patients with HER2-positive tumours derived greater benefit from the taxane, but there was a significant benefit for both groups.…”

Section: Discussionmentioning

confidence: 99%

“…EGFR was assessed at the Department of Pathology of the Metaxas Cancer Hospital, Athens, as described earlier (Tzaida et al, 2007). HER2 was determined at the Department of Pathology of the Hygeia Hospital, Athens, with additional analysis of cases with an IHC score of 2 þ by FISH, as described earlier (Kostopoulos et al, 2006).…”

Section: Molecular and Immunohistochemical Studiesmentioning

confidence: 99%

“…Although some trials have supported an interaction between HER2 overexpression and taxane activity (Konecny et al, 2004;Hayes et al, 2007), others have failed to demonstrate such an association (Gonzalez-Angulo et al, 2004). Only a limited number of studies have evaluated the effect of taxane-containing regimens with respect to HER2 status in the adjuvant setting (Martin et al, 2005;Kostopoulos et al, 2006;Hayes et al, 2007).…”

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confidence: 99%

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Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: A Hellenic Cooperative Oncology Group (HeCOG) study

et al. 2008

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The aim of the study was to evaluate the prognostic ability of the transcriptional profiling of the HER family genes in early breast cancer, as well as to investigate the predictive value of HER2 mRNA expression for adjuvant treatment with paclitaxel. RNA was extracted from 268 formalin-fixed paraffin-embedded (FFPE) tumour tissue samples of high-risk breast cancer patients enrolled in the randomised HE10/97 trial, evaluating the effect of dose-dense anthracycline-based sequential adjuvant chemotherapy with or without paclitaxel. The mRNA expression of all four HER family members was assessed by kinetic reverse transcription-polymerase chain reaction (kRT -PCR). The overall concordance between kRT -PCR and IHC/FISH for HER2 status determination was 74%. At a median follow-up of 8 years, multivariate analysis showed that EGFR and HER2 mRNA expression was associated with reduced overall survival (OS). HER3 and HER4 mRNA level had a favourable prognostic value in terms of OS and disease-free survival (DFS), respectively. Adjusting for HER2 mRNA expression, OS and DFS did not differ between treatment groups. These data indicate that EGFR as well as HER2 are prognostic factors of worse clinical outcomes, whereas HER3 and HER4 gene transcription is associated with better prognosis in high-risk early breast cancer. However, HER2 mRNA expression did not predict clinical benefit from paclitaxel. Kinetic RT -PCR represents an alternative method for evaluating the expression of HER family members in FFPE breast carcinomas.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Molecular and Immunohistochemical Studiesmentioning

confidence: 99%

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confidence: 99%

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Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: A Hellenic Cooperative Oncology Group (HeCOG) study

et al. 2008

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“…A molecular target of interest in this respect is vascular endothelial growth factor (VEGF)-A. VEGF-A is involved in the development and maintenance of tumor angiogenesis and is involved early during tumorigenesis. Various studies have reported overexpression of VEGF-A in the breast cancer microenvironment, compared with normal breast tissue (2)(3)(4)(5). All VEGF-A splice variants are bound by the clinically used monoclonal antibody bevacizumab.…”

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⁸⁹Zr-Bevacizumab PET Imaging in Primary Breast Cancer

et al. 2013

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Vascular endothelial growth factor (VEGF)-A is overexpressed in most malignant and premalignant breast lesions. VEGF-A can be visualized noninvasively with PET imaging and using the tracer 89 Zr-labeled bevacizumab. In this clinical feasibility study, we assessed whether VEGF-A in primary breast cancer can be visualized by 89 Zr-bevacizumab PET. Methods: Before surgery, breast cancer patients underwent a PET/CT scan of the breasts and axillary regions 4 d after intravenous administration of 37 MBq of 89 Zr-bevacizumab per 5 mg. PET images were compared with standard imaging modalities. 89 Zr-bevacizumab uptake was quantified as the maximum standardized uptake value (SUV max ). VEGF-A levels in tumor and normal breast tissues were assessed with enzyme-linked immunosorbent assay. Data are presented as mean 6 SD. Results: Twenty-five of 26 breast tumors (mean size 6 SD, 25.1 6 19.8 mm; range, 4-80 mm) in 23 patients were visualized. SUV max was higher in tumors (1.85 6 1.22; range, 0.52-5.64) than in normal breasts (0.59 6 0.37; range, 0.27-1.69; P , 0.001). The only tumor not detected on PET was 10 mm in diameter. Lymph node metastases were present in 10 axillary regions; 4 could be detected with PET (SUV max , 2.66 6 2.03; range, 1.32-5.68). VEGF-A levels in the 17 assessable tumors were higher than in normal breast tissue in all cases (VEGF-A/mg protein, 184 6 169 pg vs. 10 6 21 pg; P 5 0.001), whereas 89 Zr-bevacizumab tumor uptake correlated with VEGF-A tumor levels (r 5 0.49). Conclusion: VEGF-A in primary breast cancer can be visualized by means of 89 Zr-bevacizumab PET.

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Update on Clinical Trials: Genetic Targets in Breast Cancer

Cream

Harvey

2012

Advances in Experimental Medicine and Biology

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Breast cancer is the most commonly diagnosed cancer in women in United States. From data of American Cancer Society from 2007 reported total of 178,480 women diagnosed with breast cancer. The death rate from breast cancer has decreased in North America over time, but still accounts for second highest cancer death, following lung cancer. Breast cancer is staged based on tumor size, nodal involvement, and distant metastasis like any other solid tumors. However clinical staging is not the only important factor in management of breast cancer. Various molecular features divides breast cancer into many subgroups - that act differently, and respond differently from therapy. Thus the focus of breast cancer treatment has evolved focusing on specific targets. The most important biologic markers in subtyping of breast cancer so far are hormone receptor positivity and HER2/neu protein expression. Five molecular subtypes using intrinsic gene set include Basal mRNA, HER2 + mRNA, Luminal AmRNA, Luminal B mRNA, and Normal-like mRNA. In addition, better understanding of genetic target of breast cancer has given us arsenal of personalized, and more effective treatment approach.This review will focus on examples that highlight several mechanism of tumorigenesis, giving us not just understanding of gene pathways and the molecular biology, that could lead us to therapeutic target. Several important molecular targets have been investigated in preclinical and clinical trials, others are yet to be explored. We will also describe genetic mechanisms discovery related to overcoming resistance to current targeted therapies in breast cancer, including hormone receptor expression and HER 2- neu amplification. We will also review other exciting developments in understanding of breast cancer, the tumor microenvironment and cancer stem cells, and targeting agents in that area.

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Evaluation of the prognostic value of HER-2 and VEGF in breast cancer patients participating in a randomized study with dose–dense sequential adjuvant chemotherapy

Abstract: For both treatments, HER-2 overexpression was a significant negative prognostic factor for DFS but not for OS, while high expression of VEGF was not significantly associated to either DFS or OS. No predictive ability of HER-2 status or VEGF overexpression for T treatment was evident.

Cited by 39 publications

References 33 publications

Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: A Hellenic Cooperative Oncology Group (HeCOG) study

Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: A Hellenic Cooperative Oncology Group (HeCOG) study

⁸⁹Zr-Bevacizumab PET Imaging in Primary Breast Cancer

Update on Clinical Trials: Genetic Targets in Breast Cancer

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Evaluation of the prognostic value of HER-2 and VEGF in breast cancer patients participating in a randomized study with dose–dense sequential adjuvant chemotherapy

Abstract: For both treatments, HER-2 overexpression was a significant negative prognostic factor for DFS but not for OS, while high expression of VEGF was not significantly associated to either DFS or OS. No predictive ability of HER-2 status or VEGF overexpression for T treatment was evident.

Cited by 39 publications

References 33 publications

Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: A Hellenic Cooperative Oncology Group (HeCOG) study

Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: A Hellenic Cooperative Oncology Group (HeCOG) study

89Zr-Bevacizumab PET Imaging in Primary Breast Cancer

Update on Clinical Trials: Genetic Targets in Breast Cancer

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⁸⁹Zr-Bevacizumab PET Imaging in Primary Breast Cancer