Background: Epidermal Growth Factor Receptor (EGFR) is a transmembrane cell-surface glycoprotein with intrinsic tyrosine kinase activity. EGFR has been shown to stimulate cell proliferation and to enhance the migration and invasiveness of breast cancer. EGFR is expressed in epidermal cell lines and have been implicated in the pathogenesis of many different types of cancer. Objective: To evaluate the level of EGFR transcript in breast cancer and normal tissues; comparison the EGFR transcript level at different development stages and cancer cell types. Subject and methods: Total RNA from 62 tissue samples including 47 breast cancer and 15 normal tissues were extracted; cDNA synthesis by reverse transcript polymerase chain reaction, EGFR transcript level were determined using semi-quantitative RT-PCR. Result and conclusions: EGFR transcript level was highly expressed in breast cancer tissues compared to the normal tissues. Especially, its expression was related to the different status and cancer cell types of breast cancer. There was a difference of EGFR transcript level between histological pathology\u2019s forms of breast cancer in the same stage.
breast cancer ; Epidermal growth factor receptor

TGF-beta pathway is being extensively evaluated as a potential therapeutic target. The transforming growth factor-beta (TGF-beta) signaling pathway has the dual role in both tumor suppression and tumor promotion. To design cancer therapeutics successfully, it is important to understand TGF-beta related functional contexts. This review discusses the molecular mechanism of the TGF-beta pathway and describes the different ways of tumor suppression and promotion by TGF-beta. In the last part of the review, the data on targeting TGF-beta pathway for cancer treatment is assessed. The TGF-beta inhibitors in pre-clinical studies, and Phase I and II clinical trials are updated.
Breast Neoplasms ; Neoplasm Metastasis ; Transforming Growth Factor beta

BACKGROUND: Metaplastic carcinoma of the breast is a rare subtype of breast cancer, which is characterized by estrogen receptor/progesterone receptor and HER2 negativity. METHODS: Tissue specimens from 60 metaplastic breast cancer and 60 triple-negative breast cancer patients diagnosed at a single institution between 1995 and 2009 were analyzed. Immunohistochemistry for caveolin-1 (CAV-1), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), c-kit, p53, Ki-67, breast cancer type 1 susceptibility protein (BRCA1), cytokeratin (CK)14, and CK17 were performed on both retained tissue sets. RESULTS: Of the 60 metaplastic carcinomas, 15 tumors (25%) exhibited spindle cell component, 27 (45%) exhibited chondroid differentiation, and 18 (30%) exhibited squamous areas. Compared to triple-negative carcinomas, metaplastic carcinomas significantly more frequently expressed CK14 (p < 0.0001), CK17 (p = 0.002), EGFR (p < 0.0001), CAV-1 (p < 0.0001), and VEGF (p = 0.029). However, expressions of BRCA1, p53, c-kit, and Ki-67 were not significantly different between both groups. CONCLUSIONS: The expression profile of metaplastic carcinoma of the breast is more homogeneous than that of other triple-negative tumors and frequently over-expresses basal markers, CAV-1, and VEGF. A typical "basal-like" phenotype and frequent expressions of CAV-1 and VEGF may justify specific therapeutic approaches.
Breast ; Breast Neoplasms ; Caveolin 1 ; Cellular Structures ; Estrogens ; Humans ; Immunohistochemistry ; Keratins ; Phenotype ; Receptor, Epidermal Growth Factor ; Vascular Endothelial Growth Factor A

PURPOSE: The objective of this study was to ascertain the relationship between epidermal growth factor receptor(EGFR) status and estrogen receptor(ER) and other prognostic factors in primary human breast cancer patients. We tried to evaluate the value of EGFR as a prognostic factor. MATERIALS AND METHODS: EGFR and ER were measured by immunohistochemical staining. It was performed on section from paraffin blocks of 60 primary breast cancer patients who underwent mastectomy at Chung-Ang University Hospital. And we evaluate the relationship between EGFR and ER and other prognostic factors. RESULTS: In 20 of 60 patients(33.3%), the staining was positive for the expression of EGFR. Of the 60 patients, 6 were both positive for EGFR and ER, 25 were both negative, 14 were EGFR positive and ER negative, 15 were EGFR negative and ER positive. Between EGFR and estrogen receptor(ER) status, previously known clear inverse relationship was not observed in our study. The EGFR status was not correlated with axillary lymph node involvement, histologic type, and histologic grading. But it was correlated with tumor size(p=0.049), and there was a high tendency of recurrence rate of patients with EGFR-positive tumors as compared with those with EGFR-negative tumors(p=0.078). CONCLUSION: EGFR status may be valuable as a prognostic factor in determining the prognosis of breast cancer. However, the study of more cases will be needed for the significance of the information about the EGFR as an independent prognostic factor.
Breast Neoplasms* ; Breast* ; Epidermal Growth Factor* ; Estrogens ; Humans ; Lymph Nodes ; Mastectomy ; Paraffin ; Prognosis ; Receptor, Epidermal Growth Factor* ; Recurrence

PURPOSE: We investigated the relationships between metastasis-free interval (MFI) and tumor characteristics, and assessed the prognostic value of MFI for survival after metastasis in patients with metastatic breast cancer. Furthermore, we compared MFI among the subtypes. METHODS: We identified 335 patients with postoperative tumor recurrence at distant site(s). All patients underwent curative resection and had a MFI of at least 6 months. MFI was categorized as short (<2 years), intermediate (> or =2 years and <5 years), or long (> or =5 years). Overall survival after metastasis (OSM) was estimated. RESULTS: Patients with a shorter MFI were younger, more likely to have initial metastasis to visceral organs, and had a larger tumor with a higher stage and grade as well as a higher rate of nodal involvement at initial diagnosis. Among 136 patients with known disease subtypes, shorter MFI was associated with the triple-negative subtype while longer MFI was associated with the hormone receptor-positive/human epidermal growth factor receptor 2 negative subtype. Mortality after metastasis declined sharply with increasing MFI up to approximately 2 years, and continued gradually declining between 2 and 5 years. An MFI longer than 5 years did not add any survival benefit. MFI was a significant prognostic factor for OSM independent of nodal status, stage, metastatic site, and hormone receptor status of the metastasized cancer. CONCLUSION: MFI is closely related to biological characteristics of both primary tumors and their metastases, and has a prognostic value for survival after metastasis. We therefore suggest investigation into treatments targeting improvement of MFI as a potential novel strategy.
Breast Neoplasms* ; Breast* ; Diagnosis ; Humans ; Mortality ; Neoplasm Metastasis ; Population Characteristics ; Receptor, Epidermal Growth Factor ; Recurrence*

Leptomeningeal carcinomatosis is a fatal manifestation of metastatic breast cancer. Investigation of intrathecal (IT) trastuzumab for leptomeningeal carcinomatosis is currently underway; however, there has been no consensus. We report on two cases of human epidermal growth factor receptor 2 positive (HER2+) breast cancer following IT trastuzumab for leptomeningeal carcinomatosis. The first patient was treated with weekly IT 15 mg methotrexate plus IT 50 mg trastuzumab for 7 months, followed by IT trastuzumab (50 mg > 25 mg) for 18 months. The other patient received IT trastuzumab with systemic chemotherapy (trastuzumab and/or paclitaxel) for 13 months. Good control of leptomeningeal disease was achieved with IT trastuzumab in both patients, with survival durations of 20 and 29 months, respectively. We suggest that IT trastuzumab is a promising treatment for patients with HER2+ breast cancer and leptomeningeal carcinomatosis.
Breast Neoplasms* ; Breast* ; Consensus ; Drug Therapy ; Humans ; Injections, Spinal ; Meningeal Carcinomatosis* ; Methotrexate ; Receptor, Epidermal Growth Factor

Leptomeningeal carcinomatosis is a fatal manifestation of metastatic breast cancer. Investigation of intrathecal (IT) trastuzumab for leptomeningeal carcinomatosis is currently underway; however, there has been no consensus. We report on two cases of human epidermal growth factor receptor 2 positive (HER2+) breast cancer following IT trastuzumab for leptomeningeal carcinomatosis. The first patient was treated with weekly IT 15 mg methotrexate plus IT 50 mg trastuzumab for 7 months, followed by IT trastuzumab (50 mg > 25 mg) for 18 months. The other patient received IT trastuzumab with systemic chemotherapy (trastuzumab and/or paclitaxel) for 13 months. Good control of leptomeningeal disease was achieved with IT trastuzumab in both patients, with survival durations of 20 and 29 months, respectively. We suggest that IT trastuzumab is a promising treatment for patients with HER2+ breast cancer and leptomeningeal carcinomatosis.
Breast Neoplasms* ; Breast* ; Consensus ; Drug Therapy ; Humans ; Injections, Spinal ; Meningeal Carcinomatosis* ; Methotrexate ; Receptor, Epidermal Growth Factor

Angiogenesis is essential for tumor growth and metastasis, however, the prognostic value of neovascularization is undetermined. The aim of this study is to evaluate the prognostic significance of microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in breast carcinomas. An immunohistochemical stains for CD 31 (DAKO) to estimate MVD and VEGF (Santa Cruz) were done on 40 cases of invasive breast carcinoma. MVD was calculated as an average count of vessels per 200 power field in the most vascularized areas. VEGF expression was interpreted according to staining intensity and number of positive cells. Mean MVD was 35, and MVD was not correlated with lymph node metastasis or histologic grade, but high MVD (mean MVD>35) showed an increasing tendency in cases with larger size, negative ER/PR, and positive cathepsin D. All of the cases showed VEGF expression, but VEGF expression was not correlated with tumor size, histologic grade, lymph node metastasis, ER/PR status, and cathepsin D expression. These results suggest that MVD and VEGF expressions are not reliable prognostic factors.
Breast Neoplasms* ; Breast* ; Cathepsin D ; Coloring Agents ; Lymph Nodes ; Microvessels* ; Neoplasm Metastasis ; Vascular Endothelial Growth Factor A*

PURPOSE: We analyzed the responses of patients with locally advanced breast cancer to neoadjuvant chemotherapy (NAC) and NAC combined with neoadjuvant human epidermal growth factor receptor-2 (HER2) targeted therapy (NCHTT). METHODS: We retrospectively reviewed 59 patients with HER2 amplified locally advanced breast cancer among patients who were treated surgically after neoadjuvant therapy at Samsung Medical Center between 2005 and 2009. Thirty-one patients received conventional NAC and 28 patients received NCHTT. Pathologic responses were assessed according to response evaluation criteria in solid tumors (RECIST) guidelines. RESULTS: Pathologic complete response (pCR) was achieved in 13 out of 28 patients treated with NCHTT and in 6 out of 31 patients treated with NAC alone (46.4% vs. 19.4%, respectively, P = 0.049). Breast conserving surgery (BCS) was more frequently performed in the NCHTT group than in the NAC only group (71.4% vs. 19.4%, P < 0.001). The 3-year recurrence-free survival (RFS) rate was 100% in the NCHTT group and 76.4% in the NAC group (P = 0.014). Together, NCHTT, type of operation (BCS vs. mastectomy) and pathologic nodal status were significant prognostic factors for RFS in univariate analysis. CONCLUSION: We found that NCHTT produced higher pCR rates than NAC alone in locally advanced breast cancer.
Breast ; Breast Neoplasms ; Epidermal Growth Factor ; Humans ; Mastectomy, Segmental ; Neoadjuvant Therapy ; Polymerase Chain Reaction ; Retrospective Studies

PURPOSE: The aim of this study was to examine molecular subtype conversions in patients who underwent neoadjuvant chemotherapy (NAC) and analyze their clinical implications. MATERIALS AND METHODS: We included consecutive breast cancer patients who received NAC at the National Cancer Center, Korea, between August 2002 and June 2011, and had available data on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) receptor status prior to NAC. Molecular subtypes, hormone receptor (HR) status, and ER and PR Allred scores before and after NAC were compared, and the long-term outcomes were analyzed. RESULTS: Of 322 patients, 32 (9.9%) achieved a pathologic complete response after NAC. HR+/HER2- tumors tended to convert into triple negative (TN) tumors (10.3%), whereas 34.6% of TN tumors gained HR positivity to become HR+/HER2- tumors. Clinical outcomes of molecular subtype conversion groups were compared against patients who remained as HR+/HER2- throughout. The HR+/HER2- to TN group had significantly poorer recurrence-free survival (RFS) (hazard ratio, 3.54; 95% confidence interval [CI], 1.60 to 7.85) and overall survival (OS) (hazard ratio, 3.73; 95% CI, 1.34 to 10.38). Patients who remained TN throughout had the worst outcomes (for RFS: hazard ratio, 3.70; 95% CI, 1.86 to 7.36; for OS: hazard ratio, 5.85; 95% CI, 2.53 to 13.51), while those who converted from TN to HR+/HER2-showed improved comparable survival outcomes. CONCLUSION: Molecular subtypes of breast cancers changed frequently after NAC, resulting in different tumor prognostication. Tumor subtyping should be repeated after NAC in patients with breast cancer.
Breast Neoplasms ; Breast* ; Drug Therapy* ; Epidermal Growth Factor ; Estrogens ; Humans ; Korea ; Receptors, Progesterone