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304 KiB

Open AccessArticle

A Novel Method for Sentinel Lymph Node Biopsy by Indocyanine Green Fluorescence Technique in Breast Cancer

by Tomoharu Sugie, Kassim Abdelazeem Kassim, Megumi Takeuchi, Takashi Hashimoto, Kazuhiko Yamagami, Yoshikazu Masai and Masakazu Toi

Cancers 2010, 2(2), 713-720; https://doi.org/10.3390/cancers2020713 - 27 Apr 2010

Cited by 65 | Viewed by 15377

Abstract

We investigated the feasibility of sentinel lymph node (SLN) biopsy using indocyanine green (ICG) technique in 411 patients with early breast cancer at three institutes. ICG, a fluorescence source, and blue dye were injected into the subareolar area to enable real-time image-guided surgery [...] Read more.

We investigated the feasibility of sentinel lymph node (SLN) biopsy using indocyanine green (ICG) technique in 411 patients with early breast cancer at three institutes. ICG, a fluorescence source, and blue dye were injected into the subareolar area to enable real-time image-guided surgery and identification of SLN fluorescence after meticulous dissection. The subcutaneous lymphatic channels were precisely detected in all cases. SLN identification rate was 99% (408/411) with a mean of 2.3 nodes identified per patient. Thirty-nine cases (9.5%) had SLNs involved and all of them were ICG positive. Thus, the ICG technique has a high SLN identification rate comparable with that of the radioisotope method. Full article

(This article belongs to the Special Issue Breast Cancer)

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527 KiB

Open AccessArticle

Identification of Insulin-Like Growth Factor-I Receptor (IGF-IR) Gene Promoter-Binding Proteins in Estrogen Receptor (ER)-Positive and ER-Depleted Breast Cancer Cells

by Rive Sarfstein, Antonino Belfiore and Haim Werner

Cancers 2010, 2(2), 233-261; https://doi.org/10.3390/cancers2020233 - 25 Mar 2010

Cited by 29 | Viewed by 13752 | Correction

Abstract

The insulin-like growth factor I receptor (IGF-IR) has been implicated in the etiology of breast cancer. Overexpression of the IGF-IR gene is a typical feature of most primary breast cancers, whereas low IGF-IR levels are seen at advanced stages. Hence, evaluation of IGF-IR [...] Read more.

The insulin-like growth factor I receptor (IGF-IR) has been implicated in the etiology of breast cancer. Overexpression of the IGF-IR gene is a typical feature of most primary breast cancers, whereas low IGF-IR levels are seen at advanced stages. Hence, evaluation of IGF-IR levels might be important for assessing prognosis. In the present study, we employed a proteomic approach based on DNA affinity chromatography followed either by mass spectroscopy (MS) or Western blot analysis to identify transcription factors that may associate with the IGF-IR promoter in estrogen receptor (ER)-positive and ER-depleted breast cancer cells. A biotinylated IGF-IR promoter fragment was bound to streptavidin magnetic beads and incubated with nuclear extracts of breast cancer cells. IGF-IR promoter-binding proteins were eluted with high salt and analyzed by MS and Western blots. Among the proteins that were found to bind to the IGF-IR promoter we identified zinc finger transcription factors Sp1 and KLF6, ER-, p53, c-jun, and poly (ADP-ribosylation) polymerase. Furthermore, chromatin immune-precipitation (ChIP) analysis confirmed the direct in vivo binding of some of these transcription factors to IGF-IR promoter DNA. The functional relevance of binding data was assessed by cotransfection experiments with specific expression vectors along with an IGF-IR promoter reporter. In summary, we identified nuclear proteins that are potentially responsible for the differential expression of the IGF-IR gene in ER-positive and ER-depleted breast cancer cells. Full article

(This article belongs to the Special Issue Breast Cancer)

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171 KiB

Open AccessArticle

Increased Level of Phosphorylated ShcA Measured by Chemiluminescence-Linked Immunoassay Is a Predictor of Good Prognosis in Primary Breast Cancer Expressing Low Levels of Estrogen Receptor

by Jonas Cicenas, Willy Küng, Urs Eppenberger and Serenella Eppenberger-Castori

Cancers 2010, 2(1), 153-164; https://doi.org/10.3390/cancers2010153 - 12 Mar 2010

Cited by 6 | Viewed by 12276

Abstract

The SH2 domain-containing adaptor protein ShcA is a proto-oncogene involved in growth factor receptor signaling. The role of phosphorylated ShcA is to link receptor tyrosine kinases with the SH2-containing adaptor protein Grb2, thus facilitating signal transduction from receptor tyrosine kinases to Ras, leading [...] Read more.

The SH2 domain-containing adaptor protein ShcA is a proto-oncogene involved in growth factor receptor signaling. The role of phosphorylated ShcA is to link receptor tyrosine kinases with the SH2-containing adaptor protein Grb2, thus facilitating signal transduction from receptor tyrosine kinases to Ras, leading to MAPK activation. The present study was designed to investigate the prognostic significance of phosphorylated ShcA in primary breast cancer and its association in the interactions between the ER and ErbB2 pathways. Using a two-site chemiluminescence-linked immunosorbent assay, we detected the quantitative expression levels of total tyrosine- and threonine-phosphorylated ShcA in cytosol fractions obtained from fresh frozen tissue samples of 153 selected primary breast cancer patients. ShcA phosphorylation was not associated with nodal status, estrogen receptor (ER) status or grading. High levels of both tyrosine (pYShcA) and serine (pSShcA) phosphorylated ShcA correlated with good prognosis (p < 0.01), with respect to both disease-free (DFS) and overall survival (OS). In addition, pShcA levels were found to correlate with threonine-phosphorylated ErbB2 and inversely with phosphorylated Akt (pAkt), as well as ErbB2 and ER expression levels. Our findings demonstrate that ShcA activation in primary breast cancer patients correlates with low levels of ER, and is associated with good prognosis. Full article

(This article belongs to the Special Issue Breast Cancer)

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366 KiB

Open AccessArticle

Number of Axillary Lymph Node Metastases Determined by Preoperative Ultrasound is Related to Prognosis in Patients with Breast Cancer

by Yuko Kijima, Heiji Yoshinaka, Munetsugu Hirata, Tadao Mizoguchi, Sumiya Ishigami, Akihiro Nakajo, Hideo Arima, Shinichi Ueno and Shoji Natsugoe

Cancers 2010, 2(1), 20-31; https://doi.org/10.3390/cancers2010020 - 4 Feb 2010

Cited by 10 | Viewed by 12741

Abstract

Objective: To analyze the impact on prognosis of the number of axillary lymph node metastases (LNM) detected by ultrasound (US) in patients with breast cancer. Methods: One-to-one comparison of LNM was performed between the ultrasound and histologic diagnosis in 380 patients. Results: The [...] Read more.

Objective: To analyze the impact on prognosis of the number of axillary lymph node metastases (LNM) detected by ultrasound (US) in patients with breast cancer. Methods: One-to-one comparison of LNM was performed between the ultrasound and histologic diagnosis in 380 patients. Results: The accuracy of preoperative ultrasound diagnosis was 79.7%. According to the subdivision of number of LNM (0, 1–3, 4–9, 10+), the accuracy rates associated with LNM were 82%, 49%, 34%, and 86%, respectively. The disease-free-survival curves according to the number of LNM were similar in them. Conclusion: Preoperative ultrasound can determine axillary involvement and may be useful for predicting prognosis. Full article

(This article belongs to the Special Issue Breast Cancer)

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Open AccessArticle

Comparison of Locoregional Recurrence with Mastectomy vs. Breast Conserving Surgery in Pregnancy Associated Breast Cancer (PABC)

by Sushil Beriwal, Bunja Rungruang, Atilla Soran, Darcy Thull, Joseph L. Kelley, Rohit Bhargava, Chyongchiou J. Lin and Paniti Sukumvanich

Cancers 2009, 1(1), 12-20; https://doi.org/10.3390/cancers1010012 - 4 Dec 2009

Cited by 2 | Viewed by 10918

Abstract

We have compared outcomes, including the locoregional recurrence, between mastectomy and breast conserving therapy in PABC. Patients were divided into those who were treated with mastectomies (group 1) and those with breast conserving surgery (group 2). The groups were comparable except for lower [...] Read more.

We have compared outcomes, including the locoregional recurrence, between mastectomy and breast conserving therapy in PABC. Patients were divided into those who were treated with mastectomies (group 1) and those with breast conserving surgery (group 2). The groups were comparable except for lower mean age in group 2 and more patients with stage III disease and higher number of nodes positive in the group 1. Five-year actuarial LRR, distant metastases free survival and overall survival in group 1 vs. 2 were 10% vs. 37%, 73% vs. 81% and 57% vs. 59% respectively. The patients with PABC treated with breast conserving therapy, despite having lower stage disease, have a higher risk of local regional recurrence in comparison with those treated with mastectomy. Full article

(This article belongs to the Special Issue Breast Cancer)

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Review

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605 KiB

Open AccessReview

VEGF and Pleiotrophin Modulate the Immune Profile of Breast Cancer

by Kristi D. Lynn, Christina L. Roland and Rolf A. Brekken

Cancers 2010, 2(2), 970-988; https://doi.org/10.3390/cancers2020970 - 26 May 2010

Cited by 20 | Viewed by 10010

Abstract

Angiogenesis, the sprouting of the existing vascular network to form new vessels, is required for the growth of solid tumors. For this reason, the primary stimulant of angiogenesis, vascular endothelial growth factor-A (VEGF), is an attractive target for tumor therapy. In fact, there [...] Read more.

Angiogenesis, the sprouting of the existing vascular network to form new vessels, is required for the growth of solid tumors. For this reason, the primary stimulant of angiogenesis, vascular endothelial growth factor-A (VEGF), is an attractive target for tumor therapy. In fact, there are currently numerous anti-VEGF therapies in clinical development for the treatment of various cancers, including breast cancer. VEGF signals through two primary VEGF receptors, VEGFR1 and VEGFR2. VEGFR2 is the primary angiogenic receptor, and VEGFR1 has been implicated in macrophage chemotaxis and tumor cell survival and invasion. It has only been appreciated recently that the VEGFRs are expressed not only on endothelial cells and tumor cells but also on many host immune cells. Therefore, to better understand the effects of anti-VEGF therapy it is important to consider the effects of VEGF on all cells in the tumor microenvironment, including immune cells. Bevacizumab (Avastin^®, Genetech), which binds VEGF and inhibits interaction with VEGFR1 and VEGFR2, was approved for the treatment of metastatic HER2/NEU-negative breast cancer in 2008, however, the majority of human mammary tumors are either innately resistant or will acquire resistance to anti-VEGF therapy. This suggests that these tumors activate alternate angiogenesis pathways. Pleiotrophin (PTN) is an important angiogenic cytokine in breast cancer and is expressed at high levels in approximately 60% of human breast tumors. PTN functions as an angiogenic factor and promotes remodeling of the tumor microenvironment as well as epithelial-mesenchymal transition (EMT). In addition, PTN can have profound effects on macrophage phenotype. The present review focuses on the functions of VEGF and PTN on immune cell infiltration and function in breast cancer. Furthermore, we will discuss how anti-VEGF therapy modulates the immune cell profile. Full article

(This article belongs to the Special Issue Breast Cancer)

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332 KiB

Open AccessReview

Viruses and Breast Cancer

by James S. Lawson and Benjamin Heng

Cancers 2010, 2(2), 752-772; https://doi.org/10.3390/cancers2020752 - 30 Apr 2010

Cited by 44 | Viewed by 17156

Abstract

Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify [...] Read more.

Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix. Full article

(This article belongs to the Special Issue Breast Cancer)

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328 KiB

Open AccessReview

Do All Patients Require Radiotherapy after Breast-Conserving Surgery?

by Anita R. Skandarajah and G. Bruce Mann

Cancers 2010, 2(2), 740-751; https://doi.org/10.3390/cancers2020740 - 28 Apr 2010

Cited by 7 | Viewed by 10769

Abstract

Radiotherapy following breast conservation is routine in the treatment of breast cancer. This creates a large demand for radiotherapy services with implicit cost effects and potential morbidity to patients. Radiotherapy is administered to decrease local recurrence, but is radiotherapy required for all breast [...] Read more.

Radiotherapy following breast conservation is routine in the treatment of breast cancer. This creates a large demand for radiotherapy services with implicit cost effects and potential morbidity to patients. Radiotherapy is administered to decrease local recurrence, but is radiotherapy required for all breast cancers? A literature search using the Medline and Ovid databases was conducted between 1965 and 2010 using the terms ‘role of radiotherapy’, ‘early breast cancer’, and omission of radiotherapy’. Papers with clinical trials published in English in adult humans were included. Fourteen randomized controlled trials were included. Local recurrence rates range from 0.8–35% in patients in whom radiotherapy was omitted. Low risk characteristics include older age, small tumor size, no lymphovascular invasion and low to moderate grade. At present, there is no clearly defined low risk group of patients in whom radiotherapy can be omitted. Full article

(This article belongs to the Special Issue Breast Cancer)

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Open AccessReview

Possible DNA Viral Factors of Human Breast Cancer

by Chun-Ru Hsu, Tsong-Ming Lu, Lengsu William Chin and Chi-Chiang Yang

Cancers 2010, 2(2), 498-512; https://doi.org/10.3390/cancers2020498 - 13 Apr 2010

Cited by 30 | Viewed by 12173

Abstract

Viruses are considered to be one of the high-risk factors closely related to human breast cancer. However, different studies of viruses in breast cancer present conflicting results and some of these works remain in dispute. DNA viruses, such as specific types of human [...] Read more.

Viruses are considered to be one of the high-risk factors closely related to human breast cancer. However, different studies of viruses in breast cancer present conflicting results and some of these works remain in dispute. DNA viruses, such as specific types of human papillomaviruses (HPV), Epstein–Barr virus (EBV), human cytomegalovirus (HCMV), herpes simplex virus (HSV), and human herpes virus type 8 (HHV-8), have emerged as causal factors of some human cancers. These respective exogenous viruses and the possibility of multiple viral factors are discussed in this review. Full article

(This article belongs to the Special Issue Breast Cancer)

526 KiB

Open AccessReview

Novel Combinations for the Treatment of Metastatic Breast Cancer

by Linda T. Vahdat

Cancers 2010, 2(1), 1-19; https://doi.org/10.3390/cancers2010001 - 14 Jan 2010

Cited by 5 | Viewed by 10015

Abstract

Anthracyclines and taxanes represent the mainstay of first-line cytotoxic therapy for metastatic breast cancer (MBC), but most patients eventually develop resistance to these agents. Consequently, alternative combinations for MBC therapy are the subject of much ongoing research. Capecitabine and ixabepilone is the only [...] Read more.

Anthracyclines and taxanes represent the mainstay of first-line cytotoxic therapy for metastatic breast cancer (MBC), but most patients eventually develop resistance to these agents. Consequently, alternative combinations for MBC therapy are the subject of much ongoing research. Capecitabine and ixabepilone is the only chemotherapy combination specifically approved for MBC after failure of anthracyclines and taxanes. Other options have limited data to support their use in this setting but are commonly used in practice. Future MBC therapies will likely combine alternative chemotherapies and novel biologic agents, and numerous ongoing trials should help to further define the proper use of these regimens. Full article

(This article belongs to the Special Issue Breast Cancer)

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