Skip to main content

Advertisement

SpringerLink
Log in

Eliminating Surgery in Early-Stage Breast Cancer: Pipe-Dream or Worthy Consideration in Selected Patients?

  • Local-Regional Evaluation and Therapy (EP Mamounas, Section Editor)
  • Published:
Current Breast Cancer Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Neoadjuvant systemic therapy (NST) has become a valuable treatment approach for women with large operable and locally advanced breast cancers by lessening the extent of surgery required to adequately resect the primary tumour. As molecular subtyping has evolved, the development of highly efficient systemic and targeted therapies has resulted in a marked improvement in pathologic complete response (pCR) rates in specific breast cancer subtypes. As a result, breast surgeons are often performing surgery on the breasts that contain no tumour cells. Thus, the notion of de-escalating or avoiding surgery after neoadjuvant treatment has re-emerged.

Recent Findings

Retrospective series evaluating omission of surgery in women who demonstrate complete clinical response to NST suggest a trend towards increased rates of locoregional recurrence but predate the use of modern, targeted regimens. To be able to avoid surgery, it is critical to have the tools to accurately detect residual tumour disease and predict pCR after NST. Breast imaging including the recent addition of breast MRI has not sufficiently accurately predicted which patients will demonstrate pathologic complete response following NST. The combination of modern radiologic evaluation with image-guided tumour bed biopsies represents a potentially novel method towards selecting patients who could safely avoid surgical resection.

Summary

This article reviews the current evidence supporting the elimination of surgery in selected patients, and discusses ongoing and future trials that address the possibility of a non-operative approach in women with early-stage breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. • Mamounas EP. Impact of neoadjuvant chemotherapy on locoregional surgical treatment of breast cancer. Ann Surg Oncol. 2015;22:1425–33. This article provides a comprehensive review of surgical and axillary management in patients receiving modern-era neoadjuvant chemotherapy, summarizing evidence from recent clinical trials and highlighting the potential benefits of preoperative systemic therapy on reducing extent of local treatment.

    Article  PubMed  Google Scholar 

  2. Bear HD, Anderson S, Smith RE, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006;24:2019–27.

    Article  CAS  PubMed  Google Scholar 

  3. 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.

    Article  CAS  PubMed  Google Scholar 

  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;19:4224–37.

    Article  PubMed  Google Scholar 

  5. Wolmark N, Wang J, Mamounas E, et al. 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. 2001:96–102.

  6. 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.

    Article  PubMed  Google Scholar 

  7. 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.

    Article  PubMed  Google Scholar 

  8. Houssami N, Macaskill P, von Minckwitz G, et al. Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy. Eur J Cancer. 2012;48:3342–54.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    Article  CAS  PubMed  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Article  CAS  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. 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.

    Article  Google Scholar 

  14. Mauriac L, MacGrogan G, Avril A, et al. Neoadjuvant chemotherapy for operable breast carcinoma larger than 3 cm: a unicentre randomized trial with a 124-month median follow-up. Institut Bergonie Bordeaux Groupe Sein (IBBGS). Ann Oncol. 1999;10:47–52.

    Article  CAS  PubMed  Google Scholar 

  15. Ring A, Webb A, Ashley S, et al. Is surgery necessary after complete clinical remission following neoadjuvant chemotherapy for early breast cancer? J Clin Oncol. 2003;21:4540–5.

    Article  CAS  PubMed  Google Scholar 

  16. •• Clouth B, Chandrasekharan S, Inwang R, et al. The surgical management of patients who achieve a complete pathological response after primary chemotherapy for locally advanced breast cancer. Eur J Surg Oncol. 2007;33:961–6. Single-institution retrospective series exploring the safety of omitting further breast surgery through the novel use of tumor bed biopsies following neoadjuvant chemotherapy to assess for pathologic complete response.

    Article  CAS  PubMed  Google Scholar 

  17. Daveau C, Savignoni A, Abrous-Anane S, et al. Is radiotherapy an option for early breast cancers with complete clinical response after neoadjuvant chemotherapy? Int J Radiat Oncol Biol Phys. 2011;79:1452–9.

    Article  PubMed  Google Scholar 

  18. Dialani V, Chadashvili T, Slanetz PJ. Role of imaging in neoadjuvant therapy for breast cancer. Ann Surg Oncol. 2015;22:1416–24.

    Article  PubMed  Google Scholar 

  19. Network NCC. Clinical practice guidelines in oncology. Breast Cancer Version 2.2016. Preoperative Systemic Therapy: Surgical Treatment Response. 2016.

  20. Croshaw R, Shapiro-Wright H, Svensson E, et al. Accuracy of clinical examination, digital mammogram, ultrasound, and MRI in determining postneoadjuvant pathologic tumor response in operable breast cancer patients. Ann Surg Oncol. 2011;18:3160–3.

    Article  PubMed  Google Scholar 

  21. Peintinger F, Kuerer HM, Anderson K, et al. Accuracy of the combination of mammography and sonography in predicting tumor response in breast cancer patients after neoadjuvant chemotherapy. Ann Surg Oncol. 2006;13:1443–9.

    Article  PubMed  Google Scholar 

  22. Schott AF, Roubidoux MA, Helvie MA, et al. Clinical and radiologic assessments to predict breast cancer pathologic complete response to neoadjuvant chemotherapy. Breast Cancer Res Treat. 2005;92:231–8.

    Article  CAS  PubMed  Google Scholar 

  23. Helvie MA, Joynt LK, Cody RL, et al. Locally advanced breast carcinoma: accuracy of mammography versus clinical examination in the prediction of residual disease after chemotherapy. Radiology. 1996;198:327–32.

    Article  CAS  PubMed  Google Scholar 

  24. Schulz-Wendtland R. Neoadjuvant chemotherapy—monitoring: clinical examination, ultrasound, mammography, MRI, elastography: only one, only few or all? Eur J Radiol. 2012;81(Suppl 1):S147–8.

    Article  PubMed  Google Scholar 

  25. Huber S, Wagner M, Zuna I, et al. Locally advanced breast carcinoma: evaluation of mammography in the prediction of residual disease after induction chemotherapy. Anticancer Res. 2000;20:553–8.

    CAS  PubMed  Google Scholar 

  26. Adrada BE, Huo L, Lane DL, et al. Histopathologic correlation of residual mammographic microcalcifications after neoadjuvant chemotherapy for locally advanced breast cancer. Ann Surg Oncol. 2015;22:1111–7.

    Article  PubMed  Google Scholar 

  27. Kim YS, Chang JM, Moon HG, et al. Residual mammographic microcalcifications and enhancing lesions on MRI after neoadjuvant systemic chemotherapy for locally advanced breast cancer: correlation with histopathologic residual tumor size. Ann Surg Oncol. 2016;23:1135–42.

    Article  PubMed  Google Scholar 

  28. Weiss A, Lee KC, Romero Y, et al. Calcifications on mammogram do not correlate with tumor size after neoadjuvant chemotherapy. Ann Surg Oncol. 2014;21:3310–6.

    Article  PubMed  Google Scholar 

  29. Marinovich ML, Houssami N, Macaskill P, et al. Meta-analysis of magnetic resonance imaging in detecting residual breast cancer after neoadjuvant therapy. J Natl Cancer Inst. 2013;105:321–33.

    Article  CAS  PubMed  Google Scholar 

  30. Marinovich ML, Sardanelli F, Ciatto S, et al. Early prediction of pathologic response to neoadjuvant therapy in breast cancer: systematic review of the accuracy of MRI. Breast. 2012;21:669–77.

    Article  CAS  PubMed  Google Scholar 

  31. Hylton NM, Blume JD, Bernreuter WK, et al. Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy—results from ACRIN 6657/I-SPY TRIAL. Radiology. 2012;263:663–72.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Loo CE, Straver ME, Rodenhuis S, et al. Magnetic resonance imaging response monitoring of breast cancer during neoadjuvant chemotherapy: relevance of breast cancer subtype. J Clin Oncol. 2011;29:660–6.

    Article  PubMed  Google Scholar 

  33. McGuire KP, Toro-Burguete J, Dang H, et al. MRI staging after neoadjuvant chemotherapy for breast cancer: does tumor biology affect accuracy? Ann Surg Oncol. 2011;18:3149–54.

    Article  PubMed  Google Scholar 

  34. • De Los Santos JF, Cantor A, Amos KD, et al. Magnetic resonance imaging as a predictor of pathologic response in patients treated with neoadjuvant systemic treatment for operable breast cancer. Translational Breast Cancer Research Consortium trial 017. Cancer. 2013;119:1776–83. Large multicentre retrospective study and one of the first in recent literature to demonstrate differences in performance of MRI for predicting pathologic complete response to neoadjuvant therapy among different biologic subtypes of breast cancer.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Keune JD, Jeffe DB, Schootman M, et al. Accuracy of ultrasonography and mammography in predicting pathologic response after neoadjuvant chemotherapy for breast cancer. Am J Surg. 2010;199:477–84.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Jochelson MS, Lampen-Sachar K, Gibbons G, et al. Do MRI and mammography reliably identify candidates for breast conservation after neoadjuvant chemotherapy? Ann Surg Oncol. 2015;22:1490–5.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Umphrey H, Bernreuter W, Bland K, et al. Abstract P3-03-03: a tri-modality imaging assessment algorithm to evaluate neoadjuvant therapy response in patients with operable breast cancer. Cancer Res. 2012;72:P3-03-03.

    Article  Google Scholar 

  38. •• 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. Multicentre, retrospective analysis evaluating the predictive value of minimally invasive biopsy techniques for determining pathologic complete response to neoadjuvant chemotherapy. Reported improved accuracy with a vacuum-assisted biopsy, which shows promise as a future tool to accurately identify candidates for non-operative management.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. van la Parra RF, Kuerer HM. Selective elimination of breast cancer surgery in exceptional responders: historical perspective and current trials. Breast Cancer Res. 2016;18:28.

    Article  Google Scholar 

  40. 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.

    Article  CAS  PubMed  Google Scholar 

  41. Boileau JF, Poirier B, Basik M, et al. Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study. J Clin Oncol. 2015;33:258–64.

    Article  PubMed  Google Scholar 

  42. Boughey JC, McCall LM, Ballman KV, et al. Tumor biology correlates with rates of breast-conserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer: findings from the ACOSOG Z1071 (Alliance) prospective multicenter clinical trial. Ann Surg. 2014;260:608–14. discussion 614-606

    Article  PubMed  PubMed Central  Google Scholar 

  43. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  44. 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.

    Article  PubMed  Google Scholar 

  45. King TA, Morrow M. Surgical issues in patients with breast cancer receiving neoadjuvant chemotherapy. Nat Rev Clin Oncol. 2015;12:335–43.

    Article  PubMed  Google Scholar 

  46. Xing Y, Foy M, Cox DD, et al. Meta-analysis of sentinel lymph node biopsy after preoperative chemotherapy in patients with breast cancer. Br J Surg. 2006;93:539–46.

    Article  CAS  PubMed  Google Scholar 

  47. Hunt KK, Yi M, Mittendorf EA, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy is accurate and reduces the need for axillary dissection in breast cancer patients. Ann Surg. 2009;250:558–66.

    PubMed  Google Scholar 

  48. Mamounas EP, Brown A, Anderson S, et al. Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2005;23:2694–702.

    Article  PubMed  Google Scholar 

  49. 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.

    Article  PubMed  Google Scholar 

  50. Alvarado R, Yi M, Le-Petross H, et al. The role for sentinel lymph node dissection after neoadjuvant chemotherapy in patients who present with node-positive breast cancer. Ann Surg Oncol. 2012;19:3177–84.

    Article  PubMed  Google Scholar 

  51. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Mamounas EP, Anderson SJ, Dignam JJ, et al. Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27. J Clin Oncol. 2012;30:3960–6.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Fisher B, Jeong JH, Anderson S, et al. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. 2002;347:567–75.

    Article  PubMed  Google Scholar 

  54. • Giuliano AE, Ballman K, McCall L, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: long-term follow-up from the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 randomized trial. Ann Surg. 2016;264:413–20. Updated analysis of an important clinical trial which redefined axillary management in patients with up to two positive sentinel nodes by demonstrating no difference in local recurrence-free survival between those who received sentinel lymph node dissection and those who underwent further axillary surgery.

    Article  PubMed  Google Scholar 

  55. International Breast Cancer Study G, Rudenstam CM, Zahrieh D, et al. Randomized trial comparing axillary clearance versus no axillary clearance in older patients with breast cancer: first results of International Breast Cancer Study Group Trial 10-93. J Clin Oncol. 2006;24:337–44.

    Article  Google Scholar 

  56. Gentilini O, Veronesi U. Abandoning sentinel lymph node biopsy in early breast cancer? A new trial in progress at the European Institute of Oncology of Milan (SOUND: Sentinel node vs Observation after axillary UltraSouND). Breast. 2012;21:678–81.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, McGill University, Montreal, QC, Canada

    Stephanie M. Wong & Mark Basik

  2. Hazelrig-Salter Radiation Oncology Center, The University of Alabama at Birmingham, Birmingham, AL, USA

    Jennifer De Los Santos

  3. Department of Oncology, McGill University, Montreal, Canada

    Mark Basik

  4. Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, H3T1E2, Montreal, QC, Canada

    Mark Basik

Authors
  1. Stephanie M. Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer De Los Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark Basik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark Basik.

Ethics declarations

Conflict of Interest

Stephanie M. Wong, Jennifer De Los Santos and Mark Basik declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Local-Regional Evaluation and Therapy

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wong, S.M., De Los Santos, J. & Basik, M. Eliminating Surgery in Early-Stage Breast Cancer: Pipe-Dream or Worthy Consideration in Selected Patients?. Curr Breast Cancer Rep 9, 148–155 (2017). https://doi.org/10.1007/s12609-017-0242-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12609-017-0242-y

Keywords

Search

Navigation