Annals of Surgical Oncology

, Volume 13, Issue 11, pp 1434–1442 | Cite as

Surgical Procedures After Neoadjuvant Chemotherapy in Operable Breast Cancer: Results of the GEPARDUO Trial

  • Sibylle LoiblEmail author
  • Gunter von Minckwitz
  • Günther Raab
  • Jens-Uwe Blohmer
  • Serban Dan Costa
  • Bernd Gerber
  • Holger Eidtmann
  • Simone Petrich
  • Jörn Hilfrich
  • Christian Jackisch
  • Andreas du Bois
  • Manfred Kaufmann



Neoadjuvant chemotherapy can increase the rate of breast-conserving surgery in patients with operable breast cancer. However, uncertainty remains regarding surgical procedures and predictors for successful breast-conserving surgery.


This study was an analysis of surgical data of a representative data subset of 607 patients enrolled in the GEPARDUO study. This prospective, multicenter, phase III study randomly assigned patients with operable breast cancer (≥ 2 cm) to neoadjuvant 8-week dose-dense doxorubicin plus docetaxel or a 24-week schedule of doxorubicin plus cyclophosphamide followed by docetaxel (AC-DOC).


Breast conservation was attempted in 493 (81.2%) patients, but 43 patients eventually required mastectomy, thus resulting in a breast-conserving surgery rate of 74.1%. Breast-conserving re-excision was performed in 61 patients (12.4%). Factors associated with a significantly higher breast-conserving surgery rate were a prechemotherapy tumor size ≤ 40 mm, nonlobular histological characteristics, treatment with AC-DOC, clinical response, postchemotherapy tumor size ≤ 20 mm, and treatment in a larger center (>10 enrolled patients). Nonlobular histological characteristics and intraoperative frozen-section analysis for margin evaluation were associated with significantly lower reoperation rates (P = .015).


Breast conservation after neoadjuvant chemotherapy is feasible in most patients with operable breast cancer. For surgical planning, tumor characteristics and response to neoadjuvant chemotherapy should be taken into account. Improved breast-imaging modalities are necessary to improve detection of residual disease after neoadjuvant chemotherapy, especially when breast cancer is of lobular invasive histology. Margin assessment by intraoperative frozen-section analysis is helpful to avoid reoperation. To achieve an optimal result, an interdisciplinary surgical approach is important.


Neoadjuvant therapy Breast cancer Breast conservation Surgery Re-excision 



The authors thank Michaela Kandel, MD, who provided medical writing services on behalf of the German Breast Group.


  1. 1.
    Kaufmann M, Hortobagyi GN, Goldhirsch A, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol 2006;24:1940–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Hortobagyi GN, Singletary E, Strom EA. (2000) Treatment of locally advanced and inflammatory breast cancer. In: Harris J, ed. Diseases of the Breast. 2nd ed. Lippincott Williams & Wilkins, Philadelphia, pp 645–60Google Scholar
  3. 3.
    Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 1998;16:2483–93Google Scholar
  4. 4.
    van der Hage JA, van de Velde CJ, Julien JP, et al. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol 2001;19:4224–37PubMedGoogle Scholar
  5. 5.
    Scholl SM, Fourquet A, Asselain B, et al. Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: preliminary results of a randomised trial—S6. Eur J Cancer 1994;30A:645–52CrossRefPubMedGoogle Scholar
  6. 6.
    Broet P, Scholl SM, De la Rochefordiere A, et al. Short and long term effects on survival in breast cancer patients treated by primary chemotherapy: an updated analysis of a randomised trial. Breast Cancer Res Treat 1999;58:151–6CrossRefPubMedGoogle Scholar
  7. 7.
    Scholl SM, Pierga J, Asselain B, et al. Breast tumor response to primary chemotherapy predicts local and distant control as well as survival. Eur J Cancer 1995;31:1969–75CrossRefGoogle Scholar
  8. 8.
    Kuerer HM, Newman LA, Smith TL, et al. Clinical course of breast cancer patients with complete pathologic primary and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 1999;17:460–9PubMedGoogle Scholar
  9. 9.
    Chollet P, Amat S, Cure H, et al. Prognostic significance of a complete pathological response after induction chemotherapy in operable breast cancer. Br J Cancer 2002;86:1041–106CrossRefPubMedGoogle Scholar
  10. 10.
    Thomas E, Holmes FA, Smith TL, et al. The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial. J Clin Oncol 2004;22:2294–302CrossRefPubMedGoogle Scholar
  11. 11.
    Bonnadonna G, Veronesi U, Brambilla C, et al. Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimeters or more. J Natl Cancer Inst 1990;82:1539–45Google Scholar
  12. 12.
    Makris A, Powles TJ, Ashley SE, et al. A reduction of requirements for mastectomy in a randomised trial of neoadjuvant chemoendocrine therapy in primary breast cancer. Ann Oncol 1998;9:1179–84CrossRefPubMedGoogle Scholar
  13. 13.
    Fisher B, Brown A, Mamounas E, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 1997;15:2483–93PubMedGoogle Scholar
  14. 14.
    Shen J, Valero V, Buchholz TA, et al. Effective local control and long-term survival in patients with T4 locally advanced breast cancer treated with breast conservation therapy. Ann Surg Oncol 2004;11:854–60CrossRefPubMedGoogle Scholar
  15. 15.
    Kaufmann M, von Minckwitz G, Smith R, et al. International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations. J Clin Oncol 2003;21:2600–8CrossRefPubMedGoogle Scholar
  16. 16.
    Mauri D, Pavlidis N, Ioannidis JPA. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a metaanalysis. J Natl Cancer Inst 2005;97:188–94PubMedCrossRefGoogle Scholar
  17. 17.
    Chen AM, Meric-Bernstam F, Hunt KK, et al. Breast conservation after neoadjuvant chemotherapy. Cancer 2005;103:689–95CrossRefPubMedGoogle Scholar
  18. 18.
    Sadetzki S, Oberman B, Zipple D, et al. Breast conservation after neoadjuvant chemotherapy. Ann Surg Oncol 2005;12:1–8CrossRefGoogle Scholar
  19. 19.
    von Minckwitz G, Raab G, Caputo A, et al. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol 2005;23:2676–85CrossRefGoogle Scholar
  20. 20.
    Papa M, Zippel D, Koller M, et al. Positive margins of breast biopsy: is reexcision always necessary? Surg Oncol 1999;70:167–71CrossRefGoogle Scholar
  21. 21.
    Cellini C, Hollenbeck ST, Christis P, et al. Factors associated with residual breast cancer after re-excision for close or positive margins. Ann Surg Oncol 2004;11:915–20CrossRefPubMedGoogle Scholar
  22. 22.
    Fisher B, Brown E, Mamounas E, et al. The effect of preoperative chemotherapy on loco-regional disease in women with operable breast cancer: findings from NSABP B-18. J Clin Oncol 1997;15:2483–93PubMedGoogle Scholar
  23. 23.
    Dieras V, Fumoleau P, Romieu G, et al. Randomized parallel study of doxorubicin plus paclitaxel and doxorubicin plus cyclophosphamide as neoadjuvant treatment of patients with breast cancer. J Clin Oncol 2004;22:4958–65CrossRefPubMedGoogle Scholar
  24. 24.
    Untch M, Konency G, Ditsch N, et al. Dose-dense sequential epirubicin-paclitaxel as preoperative treatment of breast cancer: results of a randomised AGO study (abstract 133). Proc Am Soc Clin Oncol 2002;21:34aGoogle Scholar
  25. 25.
    Noh WC, Paik NS, Kim MS, et al. Ipsilateral breast tumor recurrence after breast-conserving therapy: a comparison of quadrantectomy versus lumpectomy at a single institution. World J Surg 2005;29:1001–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Veronesi U, Volterrani F, Luini A, et al. Quadrantectomy versus lumpectomy for small size breast cancer. Eur J Cancer 1990;26:671–3PubMedCrossRefGoogle Scholar
  27. 27.
    Fleming FJ, Hill AD, McDermott EW, O’Doherty A, O’Higgins NJ, Quinn CM. Intraoperative margin assessment and re-excision rate in breast conserving surgery. Eur J Surg Oncol 2004;30:233–7CrossRefPubMedGoogle Scholar
  28. 28.
    Weber S, Storm FK, Stitt J, Mahvi DM. The role of frozen section analysis of margins during breast conservation surgery. Cancer J Sci Am 1997;3:273–7PubMedGoogle Scholar
  29. 29.
    von Minckwitz G, Blohmer JU, Raab G, et al. In vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer: the GEPARTRIO pilot study. Ann Oncol 2005;16:56–63CrossRefGoogle Scholar
  30. 30.
    Cocquyt VF, Blondeel PN, Depypere HT, et al. Different responses to preoperative chemotherapy for invasive lobular and invasive ductal breast carcinoma. Eur J Surg Oncol 2003;29:361–7CrossRefPubMedGoogle Scholar
  31. 31.
    Mathieu MC, Rouzier R, Llombart-Cussac A, et al. The poor responsiveness of infiltrating lobular breast carcinomas to neoadjuvant chemotherapy can be explained by their biological profile. Eur J Cancer 2004;40:342–51CrossRefPubMedGoogle Scholar
  32. 32.
    Newman LA, Buzdar AU, Singletary SE, et al. A prospective trial of preoperative chemotherapy in resectable breast cancer: predictors of breast-conservation therapy feasibility. Ann Surg Oncol 2002;9:228–34CrossRefPubMedGoogle Scholar
  33. 33.
    du Bois A, Misselwitz B, Wagner U, et al. Disease Management Programm (DMP) Brustkrebs und Versorgungsstruktur bei der operativen Therapie des Mammakarzinoms in Hessen 2002. Geburtshilfe Frauenheilkd 2004;64:261–70CrossRefGoogle Scholar
  34. 34.
    Hiotis K, Ye W, Sposto R, Skinner KA. Predictors of breast conservation therapy. Size is not all that matters. Cancer 2005;103:892–9PubMedGoogle Scholar
  35. 35.
    Morrow M, Bucci C, Rademaker A. Medical contraindications are not a major factor in the underutilization of breast conserving therapy. J Am Coll Surg 1998;186:269–74CrossRefPubMedGoogle Scholar
  36. 36.
    Kuerer HM, Singletary SE, Buzdar AU, et al. Surgical conservation planning after neoadjuvant chemotherapy for stage II and operable stage III breast carcinoma. Am J Surg 2001;182:601–8CrossRefPubMedGoogle Scholar
  37. 37.
    Yeh E, Slanetz P, Kopans DB, et al. Prospective comparison of mammography, sonography, and MRI in patients undergoing neoadjuvant chemotherapy for palpable breast cancer. AJR Am J Roentgenol 2005;184:868–77PubMedGoogle Scholar
  38. 38.
    Rosen EL, Blackwell KL, Baker JA, et al. Accuracy of MRI in the detection of residual breast cancer after neoadjuvant chemotherapy. AJR Am J Roentgenol 2003;181:1275–82PubMedGoogle Scholar
  39. 39.
    Veronesi U, Bonnadonna G, Zurrida S, et al. Conservation surgery after primary chemotherapy in large carcinomas of the breast. Ann Surg 1995;222:612–8CrossRefPubMedGoogle Scholar
  40. 40.
    Margolese RG. Surgical considerations in preoperative chemotherapy of breast cancer. Recent Results Cancer Res 1998;152:193–201PubMedGoogle Scholar
  41. 41.
    Chen AM, Meric-Bernstam F, Hunt KK, et al. Breast conservation after neoadjuvant chemotherapy. A prognostic index for clinical decision-making. Cancer 2005;103:689–95CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2006

Authors and Affiliations

  • Sibylle Loibl
    • 1
    • 2
    Email author
  • Gunter von Minckwitz
    • 1
    • 2
  • Günther Raab
    • 3
    • 11
  • Jens-Uwe Blohmer
    • 4
  • Serban Dan Costa
    • 5
  • Bernd Gerber
    • 6
  • Holger Eidtmann
    • 7
  • Simone Petrich
    • 1
  • Jörn Hilfrich
    • 8
  • Christian Jackisch
    • 9
  • Andreas du Bois
    • 10
  • Manfred Kaufmann
    • 1
  1. 1.Department of Obstetrics and GynecologyJ. W. Goethe UniversityFrankfurt am MainGermany
  2. 2.German Breast GroupNeu-IsenburgGermany
  3. 3.PraxisMünchenGermany
  4. 4.St. Gertrauden KrankenhausBerlinGermany
  5. 5.Department of Obstetrics and GynecologyOtto-von-Guericke-UniversityMagdeburgGermany
  6. 6.Department of Obstetrics and GynecologyKlinikum SüdRostockGermany
  7. 7.Department of Obstetrics and GynecologyChristian-Albrecht-UniversityKielGermany
  8. 8.HenriettenstiftungHannoverGermany
  9. 9.Klinikum OffenbachOffenbachGermany
  10. 10.HSK, Dr. Horst Schmidt KlinikWiesbadenGermany
  11. 11.WolfartklinikGräfelfingGermany

Personalised recommendations