Advertisement

Annals of Surgical Oncology

, Volume 23, Issue 10, pp 3093–3099 | Cite as

The Impact of Neoadjuvant Treatment on Surgical Options and Outcomes

  • Beyhan Ataseven
  • Gunter von MinckwitzEmail author
Breast Oncology

Abstract

Neoadjuvant systemic therapy (NST) has become a well-established treatment method for patients with breast cancer, not only for those with large tumors, but also for patients with early high-risk cancers. In earlier times, the clinical advantage of NST was seen in improvement of tumor shrinkage for better operability, conversion of mastectomy candidates to breast conservation, and optimization of cosmetic results. Over the decades, therapy regimens were optimized, resulting in significantly higher response rates. Rates for breast conservation and for conversion from mastectomy to breast conservation, especially for patients with advanced breast cancers, rose significantly for patients undergoing NST. A multidisciplinary approach with close and accurate diagnostic assessment of the breast, axillary tumor, or both during NST and individual-response-guided surgery is mandatory. To reduce unnecessary surgery and prevent mastectomies, more conclusive prediction models and minimally invasive methods for selection of patients with pathologic complete remission after NST are needed. Furthermore, prospective studies demonstrate that sentinel node biopsy for patients with initial clinically node-positive axillary nodes converting to clinically node-negative axillary nodes is oncologically safe and offers less morbidity, avoiding complete axillary node dissection. Initial concerns regarding surgical complications and morbidity due to potential immune frailty of patients with NST were not observed.

Keywords

Breast Cancer Sentinel Node Biopsy Axillary Lymph Node Dissection Inflammatory Breast Cancer Breast Conservation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Disclosures

Beyhan Ataseven declares no conflicts of interest regarding the contents of this manuscript. Gunter von Minckwitz declares that his institution received research funding from Pfizer, Sanofi, Amgen, Roche, Novartis, Celgene, Teva, AstraZeneca, and Myriad Genetics.

References

  1. 1.
    Hortobagyi GN, Blumenschein GR, Spanos W, et al. Multimodal treatment of locoregionally advanced breast cancer. Cancer. 1983;51:763–8.CrossRefPubMedGoogle Scholar
  2. 2.
    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;21:2600–8.CrossRefPubMedGoogle Scholar
  3. 3.
    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;15:2483–93.PubMedGoogle Scholar
  4. 4.
    Rastogi P, Anderson SJ, Bear HD, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;26:778–85.CrossRefPubMedGoogle Scholar
  5. 5.
    Gianni L, Baselga J, Eiermann W, et al. Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer. J Clin Oncol. 2009;27:2474–81.CrossRefPubMedGoogle Scholar
  6. 6.
    van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001;19:4224–37.PubMedGoogle Scholar
  7. 7.
    Bear HD, Anderson S, Brown A, et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003;21:4165–74.CrossRefPubMedGoogle Scholar
  8. 8.
    Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010;375:377–84.CrossRefPubMedGoogle Scholar
  9. 9.
    Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25–32.CrossRefPubMedGoogle Scholar
  10. 10.
    Untch M, Fasching PA, Konecny GE, et al. Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol. 2011;29:3351–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Untch M, Loibl S, Bischoff J, et al. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol. 2012;13:135–44.CrossRefPubMedGoogle Scholar
  12. 12.
    Untch M, Rezai M, Loibl S, et al. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010;28:2024–31.CrossRefPubMedGoogle Scholar
  13. 13.
    Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24:2278–84.CrossRefPubMedGoogle Scholar
  14. 14.
    Baselga J, Bradbury I, Eidtmann H, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012;379:633–40.CrossRefPubMedGoogle Scholar
  15. 15.
    Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26:1275–81.CrossRefPubMedGoogle Scholar
  16. 16.
    von Minckwitz G, Eidtmann H, Rezai M, et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012;366:299–309.CrossRefGoogle Scholar
  17. 17.
    von Minckwitz G, Schneeweiss A, Loibl S, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014;15:747–56.CrossRefGoogle Scholar
  18. 18.
    von Minckwitz G, Untch M, Nuesch E, et al. Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neoadjuvant chemotherapy trials. Breast Cancer Res Treat. 2011;125:145–56.CrossRefGoogle Scholar
  19. 19.
    Silver DP, Richardson AL, Eklund AC, et al. Efficacy of neoadjuvant cisplatin in triple-negative breast cancer. J Clin Oncol. 2010;28:1145–53.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Byrski T, Gronwald J, Huzarski T, et al. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol. 2010;28:375–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Chen XS, Nie XQ, Chen CM, et al. Weekly paclitaxel plus carboplatin is an effective nonanthracycline-containing regimen as neoadjuvant chemotherapy for breast cancer. Ann Oncol. 2010;21:961–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Chang HR, Glaspy J, Allison MA, et al. Differential response of triple-negative breast cancer to a docetaxel and carboplatin-based neoadjuvant treatment. Cancer. 2010;116:4227–37.CrossRefPubMedGoogle Scholar
  23. 23.
    Untch M, Jackisch C, Schneeweiss A, et al. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. 2016;17:345–56.CrossRefPubMedGoogle Scholar
  24. 24.
    Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164–72.CrossRefPubMedGoogle Scholar
  25. 25.
    Mieog JS, van der Hage JA, van de Velde CJ. Preoperative chemotherapy for women with operable breast cancer. Cochrane Database Systematic Rev. 2007;2:CD005002.Google Scholar
  26. 26.
    von Minckwitz G, Untch M, Blohmer JU, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804.CrossRefGoogle Scholar
  27. 27.
    Chagpar AB, Middleton LP, Sahin AA, et al. Accuracy of physical examination, ultrasonography, and mammography in predicting residual pathologic tumor size in patients treated with neoadjuvant chemotherapy. Ann Surg. 2006;243:257–64.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Fukuda T, Horii R, Gomi N, et al. Accuracy of magnetic resonance imaging for predicting pathological complete response of breast cancer after neoadjuvant chemotherapy: association with breast cancer subtype. SpringerPlus. 2016;5:152.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Straver ME, Loo CE, Rutgers EJ, et al. MRI-model to guide the surgical treatment in breast cancer patients after neoadjuvant chemotherapy. Ann Surg. 2010;251:701–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Schaefgen B, Mati M, Sinn HP, et al. Can routine imaging after neoadjuvant chemotherapy in breast cancer predict pathologic complete response? Ann Surg Oncol. 2016;23:789–95.CrossRefPubMedGoogle Scholar
  31. 31.
    Marinovich ML, Macaskill P, Irwig L, et al. Meta-analysis of agreement between MRI and pathologic breast tumour size after neoadjuvant chemotherapy. Br J Cancer. 2013;109:1528–36.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Heil J, Kummel S, Schaefgen B, et al. Diagnosis of pathological complete response to neoadjuvant chemotherapy in breast cancer by minimal invasive biopsy techniques. Br J Cancer. 2015;113:1565–70.CrossRefPubMedGoogle Scholar
  33. 33.
    Mittendorf EA, Buchholz TA, Tucker SL, et al. Impact of chemotherapy sequencing on local-regional failure risk in breast cancer patients undergoing breast-conserving therapy. Ann Surg. 2013;257:173–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Golshan M, Cirrincione CT, Sikov WM, et al. Impact of neoadjuvant chemotherapy in stage II-III triple negative breast cancer on eligibility for breast-conserving surgery and breast conservation rates: surgical results from CALGB 40603 (Alliance). Ann Surg. 2015;262:434–9; discussion 438–9.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    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;16:2672–85.PubMedGoogle Scholar
  36. 36.
    Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001; 30:96–102.CrossRefPubMedGoogle Scholar
  37. 37.
    Swisher SK, Vila J, Tucker SL, et al. Locoregional control according to breast cancer subtype and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast-conserving therapy. Ann Surg Oncol. 2016;23:749–56.CrossRefPubMedGoogle Scholar
  38. 38.
    Truin W, Vugts G, Roumen RM, et al. Differences in response and surgical management with neoadjuvant chemotherapy in invasive lobular versus ductal breast cancer. Ann Surg Oncol. 2016;23:51–7.CrossRefPubMedGoogle Scholar
  39. 39.
    Loibl S, von Minckwitz G, Raab G, et al. Surgical procedures after neoadjuvant chemotherapy in operable breast cancer: results of the GEPARDUO trial. Ann Surg Oncol. 2006;13:1434–42.CrossRefPubMedGoogle Scholar
  40. 40.
    Loibl S, Volz C, Mau C, et al. Response and prognosis after neoadjuvant chemotherapy in 1051 patients with infiltrating lobular breast carcinoma. Breast Cancer Res Treat. 2014;144:153–62.CrossRefPubMedGoogle Scholar
  41. 41.
    Petrelli F, Barni S. Response to neoadjuvant chemotherapy in ductal compared to lobular carcinoma of the breast: a meta-analysis of published trials including 1764 lobular breast cancer. Breast Cancer Res Treat. 2013;142:227–35.CrossRefPubMedGoogle Scholar
  42. 42.
    Ataseven B, Lederer B, Blohmer JU, et al. Impact of multifocal or multicentric disease on surgery and locoregional, distant and overall survival of 6134 breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol. 2014;22(4):1118–27.CrossRefPubMedGoogle Scholar
  43. 43.
    Oh JL, Dryden MJ, Woodward WA, et al. Locoregional control of clinically diagnosed multifocal or multicentric breast cancer after neoadjuvant chemotherapy and locoregional therapy. J Clin Oncol. 2006;24:4971–5.CrossRefPubMedGoogle Scholar
  44. 44.
    NCCN. NCCN Guidelines Version 1, 2016. http://www.nccn.org.
  45. 45.
    AGO. Empfehlungen gynäkologischen Onkologie Kommission Mamma. http://www.ago-online.de, 2016.
  46. 46.
    Kell MR, Morrow M. Surgical aspects of inflammatory breast cancer. Breast Dis. 2005;22:67–73.CrossRefPubMedGoogle Scholar
  47. 47.
    Monrigal E, Dauplat J, Gimbergues P, et al. Mastectomy with immediate breast reconstruction after neoadjuvant chemotherapy and radiation therapy: a new option for patients with operable invasive breast cancer: results of a 20 years single-institution study. Eur J Surg Oncol. 2011;37:864–70.CrossRefPubMedGoogle Scholar
  48. 48.
    Eriksen C, Frisell J, Wickman M, Lidbrink E, Krawiec K, Sandelin K. Immediate reconstruction with implants in women with invasive breast cancer does not affect oncological safety in a matched cohort study. Breast Cancer Res Treat. 2011;127:439–46.CrossRefPubMedGoogle Scholar
  49. 49.
    Schaverien MV, Munnoch DA. Effect of neoadjuvant chemotherapy on outcomes of immediate free autologous breast reconstruction. Eur J Surg Oncol. 2013;39:430–6.CrossRefPubMedGoogle Scholar
  50. 50.
    Zinzindohoue C, Bertrand P, Michel A, et al. A prospective study on skin-sparing mastectomy for immediate breast reconstruction with latissimus dorsi flap after neoadjuvant chemotherapy and radiotherapy in invasive breast carcinoma. Ann Surg Oncol. 2016;23(7):2350–6.CrossRefPubMedGoogle Scholar
  51. 51.
    Criscitiello C, Azim HA Jr, Agbor-tarh D, et al. Factors associated with surgical management following neoadjuvant therapy in patients with primary HER2-positive breast cancer: results from the NeoALTTO phase III trial. Ann Oncol. 2013;24:1980–5.CrossRefPubMedGoogle Scholar
  52. 52.
    Kummel S, Holtschmidt J, Loibl S. Surgical treatment of primary breast cancer in the neoadjuvant setting. Br J Surg. 2014;101:912–24.CrossRefPubMedGoogle Scholar
  53. 53.
    Killelea BK, Yang VQ, Mougalian S, et al. Neoadjuvant chemotherapy for breast cancer increases the rate of breast conservation: results from the National Cancer Database. J Am Coll Surg. 2015;220:1063–9.CrossRefPubMedGoogle Scholar
  54. 54.
    Graham PJ, Brar MS, Foster T, et al. Neoadjuvant chemotherapy for breast cancer, is practice changing? A population-based review of current surgical trends. Ann Surg Oncol. 2015;22:3376–82.CrossRefPubMedGoogle Scholar
  55. 55.
    Fisher CS, Martin-Dunlap T, Ruppel MB, Gao F, Atkins J, Margenthaler JA. Fear of recurrence and perceived survival benefit are primary motivators for choosing mastectomy over breast-conservation therapy regardless of age. Ann Surg Oncol. 2012;19:3246–50.CrossRefPubMedGoogle Scholar
  56. 56.
    Nold RJ, Beamer RL, Helmer SD, McBoyle MF. Factors influencing a woman’s choice to undergo breast-conserving surgery versus modified radical mastectomy. Am J Surg. 2000;180:413–8.CrossRefPubMedGoogle Scholar
  57. 57.
    Kuehn T, Bauerfeind I, Fehm T, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013;14:609–18.CrossRefPubMedGoogle Scholar
  58. 58.
    Bossuyt V, Provenzano E, Symmans WF, et al. Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration. Ann Oncol. 2015;26:1280–91.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Tan VK, Goh BK, Fook-Chong S, Khin LW, Wong WK, Yong WS. The feasibility and accuracy of sentinel lymph node biopsy in clinically node-negative patients after neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis. J Surg Oncol. 2011;104:97–103.CrossRefPubMedGoogle Scholar
  60. 60.
    Xing Y, Foy M, Cox DD, Kuerer HM, Hunt KK, Cormier JN. Meta-analysis of sentinel lymph node biopsy after preoperative chemotherapy in patients with breast cancer. Br J Surg. 2006;93:539–46.CrossRefPubMedGoogle Scholar
  61. 61.
    Kelly AM, Dwamena B, Cronin P, Carlos RC. Breast cancer sentinel node identification and classification after neoadjuvant chemotherapy-systematic review and meta analysis. Acad Radiol. 2009;16:551–63.CrossRefPubMedGoogle Scholar
  62. 62.
    van Deurzen CH, Vriens BE, Tjan-Heijnen VC, et al. Accuracy of sentinel node biopsy after neoadjuvant chemotherapy in breast cancer patients: a systematic review. Eur J Cancer. 2009;45:3124–30.CrossRefPubMedGoogle Scholar
  63. 63.
    Classe JM, Bordes V, Campion L, et al. Sentinel lymph node biopsy after neoadjuvant chemotherapy for advanced breast cancer: results of Ganglion Sentinelle et Chimiotherapie Neoadjuvante, a French prospective multicentric study. J Clin Oncol. 2009;27:726–32.CrossRefPubMedGoogle Scholar
  64. 64.
    Robidoux A, Tang G, Rastogi P, et al. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013;14:1183–92.CrossRefPubMedGoogle Scholar
  65. 65.
    Dominici LS, Negron Gonzalez VM, Buzdar AU, et al. Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2-positive breast cancer. Cancer. 2010;116:2884–9.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Hennessy BT, Hortobagyi GN, Rouzier R, et al. Outcome after pathologic complete eradication of cytologically proven breast cancer axillary node metastases following primary chemotherapy. J Clin Oncol. 2005;23:9304–11.CrossRefPubMedGoogle Scholar
  67. 67.
    Enokido K, Watanabe C, Nakamura S, et al. Sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with an initial diagnosis of cytology-proven lymph node-positive breast cancer. Clin Breast Cancer. 2016. doi: 10.1016/j.clbc.2016.02.009.PubMedGoogle Scholar
  68. 68.
    Boughey JC, Suman VJ, Mittendorf EA, et al. Factors affecting sentinel lymph node identification rate after neoadjuvant chemotherapy for breast cancer patients enrolled in ACOSOG Z1071 (Alliance). Ann Surg. 2015;261:547–52.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Boughey JC, Suman VJ, Mittendorf EA, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013;310:1455–61.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Boughey JC, Ballman KV, Hunt KK, et al. Axillary ultrasound after neoadjuvant chemotherapy and its impact on sentinel lymph node surgery: results from the American College of Surgeons Oncology Group Z1071 Trial (Alliance). J Clin Oncol. 2015;33:3386–93.CrossRefPubMedGoogle Scholar
  71. 71.
    Boughey JC, Ballman KV, Le-Petross HT, et al. Identification and resection of clipped node decreases the false-negative rate of sentinel lymph node surgery in patients presenting with node-positive breast cancer (T0–T4, N1–N2) who receive neoadjuvant chemotherapy: results from ACOSOG Z1071 (Alliance). Ann Surg. 2016;263:802–7.CrossRefPubMedGoogle Scholar
  72. 72.
    Caudle AS, Yang WT, Krishnamurthy S, et al. Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection. J Clin Oncol. 2016;34:1072–8.CrossRefPubMedGoogle Scholar
  73. 73.
    Broadwater JR, Edwards MJ, Kuglen C, Hortobagyi GN, Ames FC, Balch CM. Mastectomy following preoperative chemotherapy: strict operative criteria control operative morbidity. Ann Surg. 1991;213:126–9.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Decker MR, Greenblatt DY, Havlena J, Wilke LG, Greenberg CC, Neuman HB. Impact of neoadjuvant chemotherapy on wound complications after breast surgery. Surgery. 2012;152:382–8.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Bear HD, Tang G, Rastogi P, et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012;366:310–20.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Sikov WM, Berry DA, Perou CM, et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015;33:13–21.CrossRefPubMedGoogle Scholar
  77. 77.
    Earl HM, Hiller L, Dunn JA, et al. Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial. Lancet Oncol. 2015;16:656–66.CrossRefPubMedGoogle Scholar
  78. 78.
    Gerber B, von Minckwitz G, Eidtmann H, et al. Surgical outcome after neoadjuvant chemotherapy and bevacizumab: results from the GeparQuinto study (GBG 44). Ann Surg Oncol. 2014;21:2517–24.CrossRefPubMedGoogle Scholar
  79. 79.
    Bear H, Tang G, Rastogi P, et al. PD07-08: the effect on surgical complications of bevacizumab added to neoadjuvant chemotherapy: NSABP Protocol B-40. Cancer Res. 2011;71(24 Suppl):PD07-08.CrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2016

Authors and Affiliations

  1. 1.Department of Gynecology and Gynecologic OncologyKliniken Essen-MitteEssenGermany
  2. 2.German Breast Group c/o: GBG Forschungs GmbHNeu-IsenburgGermany

Personalised recommendations