title: Preliminary results of centralized HER2 testing in ductal carcinoma in situ (DCIS): NSABP B-43.
abstract: NSABP B-43 is the first prospective, randomized phase III multi-institution clinical trial targeting high-risk, HER2-positive DCIS. It compares whole breast irradiation alone with WBI given concurrently with trastuzumab in women with HER2-positive DCIS treated by lumpectomy. The primary aim is to determine if trastuzumab plus radiation will reduce in-breast tumor recurrence. HER2-positive DCIS was previously estimated at >50 %, occurring primarily in ER-negative, comedo-type DCIS of high nuclear grade. There has been no documented centralized multi-institutional HER2 analysis of DCIS. NSABP B-43 provides a unique opportunity to evaluate this in a large cohort of DCIS patients. Patients undergoing lumpectomy for DCIS without evidence of an invasive component are eligible. A central review of each patient's pure DCIS lesion is carried out by immunohistochemistry analysis. If the lesion is 2+, FISH analysis is performed. Patients whose tumors are HER2 3+ or FISH-positive are randomly assigned to receive two doses of trastuzumab during WBI or WBI alone. NSABP B-43 opened 11/9/08. As of 7/31/2013, 5,861 patients have had specimens received centrally, and 5,645 of those had analyzable blocks; 1,969 (34.9 %) were HER2 positive. A total of 1,428 patients have been accrued, 1,137 (79.6 %) of whom have follow-up information. The average follow-up time for the 1,137 patients is 23.3 months. No grade 4 or 5 toxicity has been observed. In NSABP B-43 the HER2-positive rate for pure DCIS among patients undergoing breast-preserving surgery is 34.9 %, lower than the previously reported rate. No trastuzumab-related safety signals have been observed. Interest in this trial has been robust.
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA.
authors.forename: Kalliopi P
authors.initials: KP
authors.lastname: Siziopikou
authors.forename: Stewart J
authors.initials: SJ
authors.lastname: Anderson
authors.forename: Melody A
authors.initials: MA
authors.lastname: Cobleigh
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Julian
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Arthur
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Mamounas
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Pajon
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Behrens
authors.forename: Janice F
authors.initials: JF
authors.lastname: Eakle
authors.forename: Nick C
authors.initials: NC
authors.lastname: Leasure
authors.forename: James N
authors.initials: JN
authors.lastname: Atkins
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Polikoff
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Seay
authors.forename: Worta J
authors.initials: WJ
authors.lastname: McCaskill-Stevens
authors.forename: Rachel
authors.initials: R
authors.lastname: Rabinovitch
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Costantino
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000532:radiotherapy* / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy* / Q000378:metabolism* / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human