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

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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.

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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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Authors and Affiliations

  1. National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA

    Kalliopi P. Siziopikou, Stewart J. Anderson, Melody A. Cobleigh, Thomas B. Julian, Douglas W. Arthur, 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

  2. Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Kalliopi P. Siziopikou

  3. Department of Biostatistics, NSABP Biostatistical Center, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA

    Stewart J. Anderson, Ping Zheng & Joseph P. Costantino

  4. Rush University Medical Center, Chicago, IL, USA

    Melody A. Cobleigh

  5. Allegheny Cancer Center, Allegheny General Hospital, 320 East North Ave, Pittsburgh, PA, 15212, USA

    Thomas B. Julian & Norman Wolmark

  6. Virginia Commonwealth University, Richmond, VA, USA

    Douglas W. Arthur

  7. Aultman Hospital, Canton, OH, USA

    Eleftherios P. Mamounas

  8. Colorado Cancer Research Program, Denver, CO, USA

    Eduardo R. Pajon

  9. Iowa Oncology Research Association, Des Moines, IA, USA

    Robert J. Behrens

  10. Florida Cancer Specialists, Sarasota, FL, USA

    Janice F. Eakle

  11. McGlinn Family Cancer Center at Reading Regional Hospital, West Reading, PA, USA

    Nick C. Leasure

  12. Southeast Cancer Control Consortium-CCOP, Winston-Salem, NC, USA

    James N. Atkins

  13. Kaiser Permanente Southern California, San Diego, CA, USA

    Jonathan A. Polikoff

  14. Atlanta Regional Community Clinical Oncology Program, Atlanta, GA, USA

    Thomas E. Seay

  15. Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA

    Worta J. McCaskill-Stevens

  16. University of Colorado, Aurora, CO, USA

    Rachel Rabinovitch

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  1. Kalliopi P. Siziopikou
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Correspondence to Thomas B. Julian.

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Siziopikou, K.P., Anderson, S.J., Cobleigh, M.A. et al. Preliminary results of centralized HER2 testing in ductal carcinoma in situ (DCIS): NSABP B-43. Breast Cancer Res Treat 142, 415–421 (2013). https://doi.org/10.1007/s10549-013-2755-z

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