title: Hypothesis: primary antiangiogenic method proposed to treat early stage breast cancer.
abstract: BACKGROUND
  Women with Down syndrome very rarely develop breast cancer even though they now live to an age when it normally occurs. This may be related to the fact that Down syndrome persons have an additional copy of chromosome 21 where the gene that codes for the antiangiogenic protein Endostatin is located. Can this information lead to a primary antiangiogenic therapy for early stage breast cancer that indefinitely prolongs remission? A key question that arises is when is the initial angiogenic switch thrown in micrometastases? We have conjectured that avascular micrometastases are dormant and relatively stable if undisturbed but that for some patients angiogenesis is precipitated by surgery. We also proposed that angiogenesis of micrometastases very rarely occurs before surgical removal of the primary tumor. If that is so, it seems possible that we could suggest a primary antiangiogenic therapy but the problem then arises that starting a therapy before surgery would interfere with wound healing.
  
  
  RESULTS
  The therapy must be initiated at least one day prior to surgical removal of the primary tumor and kept at a Down syndrome level perhaps indefinitely. That means the drug must have virtually no toxicity and not interfere meaningfully with wound healing. This specifically excludes drugs that significantly inhibit the VEGF pathway since that is important for wound healing and because these agents have some toxicity. Endostatin is apparently non-toxic and does not significantly interfere with wound healing since Down syndrome patients have no abnormal wound healing problems.
  
  
  CONCLUSIONS
  We propose a therapy for early stage breast cancer consisting of Endostatin at or above Down syndrome levels starting at least one day before surgery and continuing at that level. This should prevent micrometastatic angiogenesis resulting from surgery or at any time later. Adjuvant chemotherapy or hormone therapy should not be necessary. This can be continued indefinitely since there is no acquired resistance that develops, as happens in most cancer therapies.
authors.affiliation: Department of Vascular Biology, Children's Hospital and Harvard Medical School, Boston 02115, MA, USA. michael.retsky@childrens.harvard.edu
authors.forename: Michael W
authors.initials: MW
authors.lastname: Retsky
authors.forename: William J M
authors.initials: WJ
authors.lastname: Hrushesky
authors.forename: Isaac D
authors.initials: ID
authors.lastname: Gukas
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D003198:Computer Simulation; D004314:Down Syndrome / Q000235:genetics; D043169:Endostatins / Q000008:administration & dosage* / Q000235:genetics; D005260:Female; D006801:Humans; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000517:prevention & control*; D011292:Premedication; D014945:Wound Healing / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D043169:Endostatins