Special Issue "Breast Cancer"
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A special issue of Cancers (ISSN 2072-6694).
Deadline for manuscript submissions: closed (28 February 2010)
Special Issue Editor
Guest Editor
Dr. Tomoharu Sugie
Breast Surgery, Kyoto University Hospital, 54 Shogoin Kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan
E-Mail: sugie@kuhp.kyoto-u.ac.jp
Phone: +81 75 751 3660
Fax: +81 75 751 3616
Interests: breast surgery; cancer immunology
Special Issue Information
Dear Colleagues,
Current topics in breast cancer include the novel imaging in cancer, the minimal invasive operation, and tailoring therapeutic approach on the basis of cancer biology. Regarding the imaging, possible topics of interest may include the functional imaging on PET, molecular imaging on targeting molecules. Regarding surgery, possible topics of interest may include sentinel lymph node biopsy, the minimal surgery after chemotherapy and/or endocrine therapy, the plastic surgery. Regarding of cancer biology, possible topics of interest may include cancer stem cell, EMT, circulating tumor cell, and disseminated tumor cell. In clinical practice, we may interest in biomarkers predicting prognosis and therapeutic effect, chemotherapy and endocrine therapy on the basis of the intrinstic subtype, and immunotherapy (i.e. cancer vaccine, transferring CTL).
Tomoharu Sugie, MD
Guest Editor
Submission Information
All manuscripts should be submitted to cancers@mdpi.com with a copy to the Guest Editor. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed Open Access monthly journal published by MDPI.
For the first two issues, to be published in 2009 and 2010, the Article Processing Charges (APC) will be waived for well-prepared manuscripts. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.
Keywords
- cancer imaging
- minimal breast surgery
- cancer biology
- biomarker
- intrinstic subtype
- chemotherapy
- endocrine therapy
- immunotherapy
Published Papers (10 papers)
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Received: 13 October 2009; in revised form: 23 November 2009 / Accepted: 25 November 2009 / Published: 4 December 2009
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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 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.
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Received: 17 November 2009; in revised form: 29 December 2009 / Accepted: 5 January 2010 / Published: 14 January 2010
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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 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.
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Received: 18 December 2009; in revised form: 5 January 2010 / Accepted: 3 February 2010 / Published: 4 February 2010
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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 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.
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Received: 25 January 2010; in revised form: 23 February 2010 / Accepted: 5 March 2010 / Published: 12 March 2010
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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 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.
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Received: 23 February 2010 / Accepted: 19 March 2010 / Published: 25 March 2010
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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 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.
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Received: 1 March 2010; in revised form: 3 April 2010 / Accepted: 12 April 2010 / Published: 13 April 2010
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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 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.
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Received: 20 February 2010; in revised form: 14 April 2010 / Accepted: 22 April 2010 / Published: 27 April 2010
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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 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.
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Received: 1 February 2010; in revised form: 19 April 2010 / Accepted: 26 April 2010 / Published: 28 April 2010
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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 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.
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Received: 8 March 2010; in revised form: 7 April 2010 / Accepted: 26 April 2010 / Published: 30 April 2010
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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 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.
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Received: 8 March 2010; in revised form: 13 May 2010 / Accepted: 15 May 2010 / Published: 26 May 2010
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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 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.
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Last update: 25 September 2012
