Special Issue "Surgery Induced Tumorigenesis in Breast and Other Cancers: An Inconvenient Truth?"
QuicklinksA special issue of Cancers (ISSN 2072-6694).
Deadline for manuscript submissions: closed (30 November 2010)
Special Issue Editor
Guest Editor
Dr. Michael W. Retsky
1 Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
2 Adjoint Professor, Universidad Autonoma de Nuevo Leon (UANL) Center for Research and Health Science Development in Monterrey, Mexico
Website: http://connects.catalyst.harvard.edu/PROFILES/ProfileDetails.aspx?Person=MWR2
E-Mail:
Phone: +1 203 675 0017
Interests: cancer research; electron beam technology
Published Papers
Special Issue Information
Dear Colleagues,
Bimodal relapse patterns in early stage breast cancer are observed in multiple databases. This is unexplainable with the long-accepted continuous growth model. In order to explain these data, it was proposed with the aid of computer simulations that micrometastatic tumor growth includes periods of temporary dormancy and furthermore, surgery to remove primary tumors kick-starts growth of dormant distant disease. Apparently over half of all relapses are accelerated by such means. Two previously unreported modes of relapse were proposed as the dominant paths leading to treatment failure in early stage breast cancer. Single dormant cells are induced into division by surgery, an effect that increases with primary size. Also angiogenesis is induced in dormant avascular micrometastases mainly for premenopausal patients with positive lymph nodes. This theory may provide new explanations for a wide variety of clinical breast cancer features that were previously thought to be unconnected. In addition to the relapse patterns, this is proposed to at least partly explain paradoxical mammography data for women age 40-49, that the benefit of adjuvant chemotherapy is most effective by far for premenopausal node positive patients, breast cancer in young women is often labeled “aggressive”, the overall heterogeneous nature of breast cancer, and the racial disparity in outcome. To present a forum for focused discussion, this special issue of Cancers will be devoted to papers that argue for and against this new theory.
Dr. Michael W. Retsky
Guest Editor
Submission
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. 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 quarterly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 500 CHF (Swiss Francs). 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
- breast cancer
- dormancy
- angiogenesis
- distant relapse
- mammography
- adjuvant chemotherapy
- racial disparities in outcome
- heterogeneity
- aggressiveness
- bimodal relapse pattern
- surgery
Planned Papers
Authors: Fabio Grizzi 1 and Pier Carlo Muzzio 2,3
Affiliations: 1 IRCCS Istituto Clinico Humanitas, Via Manzoni 56 – 20089 Rozzano, Milan, Italy; E-mail: fabio.grizzi@humanitasresearch.it;
2 Department of Medical-Diagnostic Sciences and Special Therapies, University of Padua, Via 8 Febbraio 1848, 2 – 35121 Padua, Italy; E-mail: pcmuzzio@unipd.it;
3 I.O.V. – Istituto Oncologico Veneto IRCCS - Via Gattamelata 64 – 35128 Padua, Italy
Abstract: Breast cancer is the most common malignancy among women, accounting for nearly one in three cancers diagnosed among women in the United States. It is widely accepted that molecular subtypes in breast cancer determine differences in prognosis and chemotherapy response. It is also known that most breast cancer patients die from metastasis, and that early surgery and radiation therapy remain often the only cure. Expansion of the blood supply is required for the growth of metastasis beyond the limits of diffusion, and provide oxygen, growth factors, nutrients and metabolites. Although it is now recognized that the term “angiogenesis” refers to the formation of a new blood vessels from pre-existing vasculature and that it is stimulated by an angiogenic “switch” that occurs when the ratio of inducers to inhibitors tips in favour of inducer, there are currently no truthful biomarkers of the net angiogenic activity of a tumour that can help investigators to design more effective and less toxic anti-angiogenic treatment strategies. One often-quantified parameter of breast tumour vasculature in two-dimensional histological sections is microvessel density (MVD). However, MVD has substantial limitations that are due to the complex biology of tumour vasculature and the irregular geometry of the vascular system. The non-linear, temporal and spatial advance of the promotion, progression, mediation and inhibition of angiogenesis generates a complex ramified network that irregularly fills the surrounding environment. The main histomorphological feature of the newly generated vasculature is the diversity of the vessel sizes, shapes and connecting patterns, which inevitably gives rise to highly variable vessel densities and vascular surface configurations in two-dimensional histological sections. These geometrical characteristics are the main sources of errors in visual interpretations of the same tumour, and contradictory laboratory assessments. The aim of the present review is to discuss breast cancer neovascularity as a dynamical process using the basic principles of the mathematics of non-linear systems and chaos theory. Additionally, some of the critical concepts necessary to give meaning to its underlying physical complexity are introduced. Viewing breast cancer neovascularity as a system that is dynamically complex in time and space may reveal more about its underlying behavioural characteristics. This way of thinking may further help to clarify concepts, indicate alternative experiments and categorize the actual knowledge.
Last update: 2 March 2011