title: Novel clinical trial designs for treatment of ductal carcinoma in situ of the breast with trastuzumab (herceptin).
abstract: Because ductal carcinoma in situ (DCIS) avidly expresses Her2/neu, the target of the monoclonal antibody trastuzumab, and because trastuzumab has been shown to be effective against invasive breast cancer, trastuzumab may be effective for reducing the tumor burden and abrogating or reversing the hypothesized transition from in situ to invasive disease in patients with DCIS. To test this hypothesis, a trial of neoadjuvant trastuzumab for DCIS has been opened at our institution. Because trastuzumab has been shown to act as a radiosensitizing agent for Her2/neu-overexpressing cancer and because there are currently no systemic treatments for estrogen-receptor-negative DCIS, it makes sense to investigate whether use of trastuzumab concurrently with postoperative radiation therapy improves local control of DCIS. The National Surgical Adjuvant Breast and Bowel Project (NSABP) is planning a trial to test this hypothesis. The risk of cardiac toxicity associated with the doses of trastuzumab planned for these trials (cumulative doses of 8 mg/kg for our trial and 14 mg/kg in the NSABP trial) is believed to be minimal, but the safety profile of these approaches will need to be closely monitored.
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Gonzalez
authors.forename: Aman U
authors.initials: AU
authors.lastname: Buzdar
authors.forename: W
authors.initials: W
authors.lastname: Fraser Symmans
authors.forename: Tina W
authors.initials: TW
authors.lastname: Yen
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Broglio
authors.forename: Anthony
authors.initials: A
authors.lastname: Lucci
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteva
authors.forename: Guosheng
authors.initials: G
authors.lastname: Yin
authors.forename: Henry M
authors.initials: HM
authors.lastname: Kuerer
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases; D012107:Research Design; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab