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Breast Cancer Research and Treatment

, Volume 142, Issue 2, pp 415–421 | Cite as

Preliminary results of centralized HER2 testing in ductal carcinoma in situ (DCIS): NSABP B-43

  • Kalliopi P. Siziopikou
  • Stewart J. Anderson
  • Melody A. Cobleigh
  • Thomas B. Julian
  • Douglas W. Arthur
  • Ping Zheng
  • Eleftherios P. Mamounas
  • Eduardo R. Pajon
  • Robert J. Behrens
  • Janice F. Eakle
  • Nick C. Leasure
  • James N. Atkins
  • Jonathan A. Polikoff
  • Thomas E. Seay
  • Worta J. McCaskill-Stevens
  • Rachel Rabinovitch
  • Joseph P. Costantino
  • Norman Wolmark
Clinical trial

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.

Keywords

DCIS Non-invasive breast cancer HER2 Clinical trials 

Notes

Acknowledgments

This work was supported by NCI-U10-CA-12027, U10-CA-37377, U10-CA-69974, U10-CA-69651, U10-CA-21661, and Genentech, Inc., a member of the Roche Group. The authors wish to acknowledge Dr. Luis Chu, and the following pathologists for interpreting HER2 tests: Drs. Pincas Bitterman, Paolo Gattuso, and Ritu Ghai, Rush University Medical Center.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Kalliopi P. Siziopikou
    • 1
    • 2
  • Stewart J. Anderson
    • 1
    • 3
  • Melody A. Cobleigh
    • 1
    • 4
  • Thomas B. Julian
    • 1
    • 5
  • Douglas W. Arthur
    • 1
    • 6
  • Ping Zheng
    • 3
  • Eleftherios P. Mamounas
    • 1
    • 7
  • Eduardo R. Pajon
    • 1
    • 8
  • Robert J. Behrens
    • 1
    • 9
  • Janice F. Eakle
    • 1
    • 10
  • Nick C. Leasure
    • 1
    • 11
  • James N. Atkins
    • 1
    • 12
  • Jonathan A. Polikoff
    • 1
    • 13
  • Thomas E. Seay
    • 1
    • 14
  • Worta J. McCaskill-Stevens
    • 1
    • 15
  • Rachel Rabinovitch
    • 1
    • 16
  • Joseph P. Costantino
    • 1
    • 3
  • Norman Wolmark
    • 1
    • 5
  1. 1.National Surgical Adjuvant Breast and Bowel Project (NSABP)PittsburghUSA
  2. 2.Northwestern University Feinberg School of MedicineChicagoUSA
  3. 3.Department of BiostatisticsNSABP Biostatistical Center, University of Pittsburgh Graduate School of Public HealthPittsburghUSA
  4. 4.Rush University Medical CenterChicagoUSA
  5. 5.Allegheny Cancer Center, Allegheny General HospitalPittsburghUSA
  6. 6.Virginia Commonwealth UniversityRichmondUSA
  7. 7.Aultman HospitalCantonUSA
  8. 8.Colorado Cancer Research ProgramDenverUSA
  9. 9.Iowa Oncology Research AssociationDes MoinesUSA
  10. 10.Florida Cancer SpecialistsSarasotaUSA
  11. 11.McGlinn Family Cancer Center at Reading Regional HospitalWest ReadingUSA
  12. 12.Southeast Cancer Control Consortium-CCOPWinston-SalemUSA
  13. 13.Kaiser Permanente Southern CaliforniaSan DiegoUSA
  14. 14.Atlanta Regional Community Clinical Oncology ProgramAtlantaUSA
  15. 15.Division of Cancer PreventionNational Cancer InstituteBethesdaUSA
  16. 16.University of ColoradoAuroraUSA

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