Skip to main content

Advertisement

SpringerLink
Log in

Intraoperative Pathology Assessment May Lead to Overtreatment of the Axilla in Clinically Node-Negative Breast Cancer Patients Undergoing Upfront Mastectomy

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Randomized trials have established the safety of observation or axillary radiation (AxRT) as an alternative to axillary lymph node dissection (ALND) in patients with limited nodal disease who undergo upfront surgery. Variability remains in axillary management strategies in cN0 patients undergoing mastectomy found to have one to two positive sentinel lymph nodes (SLNs). We examined the impact of intraoperative pathology assessment in axillary management in a national cohort of AMAROS-eligible mastectomy patients.

Methods

The National Cancer Database was used to identify AMAROS-eligible cT1-2N0 breast cancer patients undergoing upfront mastectomy and SLN biopsy (SLNB) and found to have one to two positive SLNs, from 2018 to 2019. We constructed a variable defining intraoperative pathology as ‘not performed/not acted on’ if ALND was either not performed or performed at a later date than SLNB, or ‘performed/acted on’ if SLNB and ALND were completed on the same day. Adjusted multivariable analysis examined predictors of treatment with both ALND and AxRT.

Results

Overall, 8222 patients with cT1-2N0 disease underwent upfront mastectomy and had one to two positive SLNs. Intraoperative pathology was performed/acted on in 3057 (37.2%) patients. These patients were significantly more likely to have both ALND and AxRT than those without intraoperative pathology (41.0% vs. 4.9%; p < 0.001). On multivariate analysis, the strongest predictor of receiving both ALND and AxRT was use of intraoperative pathology (odds ratio 8.99, 95% confidence interval 7.70–10.5; p < 0.001).

Conclusions

We advocate that consideration should be made for omission of routine intraoperative pathology in mastectomy patients likely to be recommended postmastectomy radiation to minimize axillary overtreatment with both ALND and AxRT in appropriate patients.

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

Similar content being viewed by others

References

  1. Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981–22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014;15(12):1303–10. https://doi.org/10.1016/S1470-2045(14)70460-7.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Giuliano AE, Ballman K, McCall L, Beitsch P, Whitworth PW, Blumencranz P, 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(3):413–20. https://doi.org/10.1097/SLA.0000000000001863.

    Article  PubMed  Google Scholar 

  3. Galimberti V, Cole BF, Viale G, Veronesi P, Vicini E, Intra M, et al.,International Breast Cancer Study Group Trial 23-01. Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23–01): 10-year follow-up of a randomised, controlled phase 3 trial. Lancet Oncol. 2018;19(10):1385–93. https://doi.org/10.1016/S1470-2045(18)30380-2.

    Article  PubMed  Google Scholar 

  4. Sávolt Á, Péley G, Polgár C, Udvarhelyi N, Rubovszky G, Kovács E, et al. Eight-year follow up result of the OTOASOR trial: the optimal treatment of the axilla - surgery or radiotherapy after positive sentinel lymph node biopsy in early-stage breast cancer: a randomized, single centre, phase III, non-inferiority trial. Eur J Surg Oncol. 2017;43(4):672–9. https://doi.org/10.1016/j.ejso.2016.12.011.

    Article  PubMed  Google Scholar 

  5. Milgrom S, Cody H, Tan L, Morrow M, Pesce C, Setton J, et al. Characteristics and outcomes of sentinel node-positive breast cancer patients after total mastectomy without axillary-specific treatment. Ann Surg Oncol. 2012;19(12):3762–70. https://doi.org/10.1245/s10434-012-2386-3.

    Article  PubMed  Google Scholar 

  6. FitzSullivan E, Bassett RL, Kuerer HM, Mittendorf EA, Yi M, Hunt KK, et al. Outcomes of sentinel lymph node-positive breast cancer patients treated with mastectomy without axillary therapy. Ann Surg Oncol. 2017;24(3):652–9. https://doi.org/10.1245/s10434-016-5605-5.

    Article  PubMed  Google Scholar 

  7. Cody HS 3rd. Extending ACOSOG Z0011 to encompass mastectomy: what happens without RT? Ann Surg Oncol. 2017;24(3):621–3. https://doi.org/10.1245/s10434-016-5608-2.

    Article  PubMed  Google Scholar 

  8. Gao W, Lu S, Zeng Y, Chen X, Shen K. Axilla lymph node dissection can be safely omitted in patients with 1–2 positive sentinel nodes receiving mastectomy: a large multi-institutional study and a systemic meta-analysis. Breast Cancer Res Treat. 2022;196(1):129–41. https://doi.org/10.1007/s10549-022-06727-9.

    Article  PubMed  Google Scholar 

  9. Kantor O, Means J, Grossmith S, Dey T, Bellon JR, Mittendorf EA, et al. Optimizing axillary management in clinical T1–2N0 mastectomy patients with positive sentinel lymph nodes. Ann Surg Oncol. 2022;29(2):972–80. https://doi.org/10.1245/s10434-021-10726-3.

    Article  PubMed  Google Scholar 

  10. Raber BM, Lin H, Shen Y, Shaitelman SF, Bedrosian I. Trends in regional nodal management of breast cancer patients with low nodal burden. Ann Surg Oncol. 2019;26(13):4346–54. https://doi.org/10.1245/s10434-019-07901-y.

    Article  PubMed  Google Scholar 

  11. Hennigs A, Köpke M, Feißt M, Riedel F, Rezai M, Nitz U, et al. Which patients with sentinel node-positive breast cancer after breast conservation still receive completion axillary lymph node dissection in routine clinical practice? Breast Cancer Res Treat. 2019;173(2):429–38. https://doi.org/10.1007/s10549-018-5009-2.

    Article  CAS  PubMed  Google Scholar 

  12. Stafford AP, Hoskin TL, Day CN, Sanders SB, Boughey JC. Contemporary axillary management in cT1-2N0 breast cancer with one or two positive sentinel lymph nodes: factors associated with completion axillary lymph node dissection within the national cancer database. Ann Surg Oncol. 2022;29(8):4740–9. https://doi.org/10.1245/s10434-022-11759-y.

    Article  PubMed  Google Scholar 

  13. McLaughlin SA, Brunelle CL, Taghian A. Breast cancer-related lymphedema: risk factors, screening, management, and the impact of locoregional treatment. J Clin Oncol. 2020;38(20):2341–50. https://doi.org/10.1200/JCO.19.02896.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Gregorowitsch ML, Verkooijen HM, Houweling A, Fuhler N, Koelemij R, Schoenmaeckers EJP, et al., UMBRELLA Study Group. Impact of modern-day axillary treatment on patient reported arm morbidity and physical functioning in breast cancer patients. Radiother Oncol. 2019;131:221–8. https://doi.org/10.1016/j.radonc.2018.07.006.

    Article  PubMed  Google Scholar 

  15. Johnson AR, Kimball S, Epstein S, Recht A, Lin SJ, Lee BT, et al. Lymphedema incidence after axillary lymph node dissection: quantifying the impact of radiation and the lymphatic microsurgical preventive healing approach. Ann Plast Surg. 2019;82(3):S234–41. https://doi.org/10.1097/SAP.0000000000001864.

    Article  CAS  PubMed  Google Scholar 

  16. Williams AD, Khan AJ, Sevilimedu V, Barrio AV, Morrow M, Mamtani A. Omission of intraoperative frozen section may reduce axillary overtreatment among clinically node-negative patients having upfront mastectomy. Ann Surg Oncol. 2022;29(13):8037–43. https://doi.org/10.1245/s10434-022-12238-0.

    Article  PubMed  Google Scholar 

  17. Bilimoria KY, Bentrem DJ, Stewart AK, Winchester DP, Ko CY. Comparison of commission on cancer-approved and -nonapproved hospitals in the United States: implications for studies that use the national cancer data base. J Clin Oncol. 2009;27(25):4177–81. https://doi.org/10.1200/JCO.2008.21.7018.

    Article  PubMed  Google Scholar 

  18. Bartels SAL, Donker M, Poncet C, Sauvé N, Straver ME, van de Velde CJH, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981–22023 AMAROS trial. J Clin Oncol. 2022. https://doi.org/10.1200/JCO.22.01565.

    Article  PubMed  Google Scholar 

  19. Tinterri C, Gentile D, Gatzemeier W, Sagona A, Barbieri E, Testori A, et al., SINODAR-ONE Collaborative Group. Preservation of axillary lymph nodes compared with complete dissection in T1–2 breast cancer patients presenting one or two metastatic sentinel lymph nodes: the SINODAR-ONE Multicenter randomized clinical trial. Ann Surg Oncol. 2022;29(9):5732–44. https://doi.org/10.1245/s10434-022-11866-w.

    Article  PubMed  Google Scholar 

  20. McLaughlin SA, Staley AC, Vicini F, Thiruchelvam P, Hutchison NA, Mendez J, Feldman SM, et al. Considerations for clinicians in the diagnosis, prevention, and treatment of breast cancer-related lymphedema: recommendations from a multidisciplinary expert ASBrS panel: part 1: definitions, assessments, education, and future directions. Ann Surg Oncol. 2017;24(10):2818–26. https://doi.org/10.1245/s10434-017-5982-4.

    Article  PubMed  Google Scholar 

  21. National Comprehensive Cancer Network Guideline. Breast cancer. Version 4 2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed 9 Apr 2023

  22. Cortina CS, Bergom C, Craft MA, Fields B, Brazauskas R, Currey A, et al. A national survey of breast surgeons and radiation oncologists on contemporary axillary management in mastectomy patients. Ann Surg Oncol. 2021;28(10):5568–79. https://doi.org/10.1245/s10434-021-10441-z.

    Article  PubMed  Google Scholar 

  23. Moossdorff M, Nakhlis F, Hu J, Barry WT, Losk K, Haskett C, et al. The potential impact of AMAROS on the management of the axilla in patients with clinical T1–2N0 Breast cancer undergoing primary total mastectomy. Ann Surg Oncol. 2018;25(9):2612–9. https://doi.org/10.1245/s10434-018-6519-1.

    Article  PubMed  Google Scholar 

  24. Grossmith S, Nguyen A, Hu J, Plichta JK, Nakhlis F, Cutone L, et al. Multidisciplinary management of the axilla in patients with cT1-T2 N0 breast cancer undergoing primary mastectomy: results from a prospective single-institution series. Ann Surg Oncol. 2018;25(12):3527–34. https://doi.org/10.1245/s10434-018-6525-3.

    Article  PubMed  Google Scholar 

  25. Davis J Jr, Boughey JC, Hoskin TL, Day CN, Cheville JC, Piltin MA, et al. Locoregional management of the axilla in mastectomy patients with one or two positive sentinel nodes: the role of intraoperative pathology. Clin Breast Cancer. 2021;21(5):458–65. https://doi.org/10.1016/j.clbc.2021.02.013.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

RP and CG acknowledge the Pamela and Nick Gelsomini Breast Surgical Oncology Fellowship Fund for support, and EAM acknowledges support as the Rob and Karen Hale Distinguished Chair in Surgical Oncology.

Author information

Authors and Affiliations

  1. Division of Breast Surgery, Department of Surgery, Brigham and Women’s Hospital, Boston, MA, USA

    Robert M. Pride MD, Charity C. Glass MD, MPP, Faina Nakhlis MD, Alison Laws MD, MPH, Elizabeth A. Mittendorf MD, PhD, MHCM, Tari A. King MD & Olga Kantor MD, MS

  2. Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA

    Robert M. Pride MD, Charity C. Glass MD, MPP, Faina Nakhlis MD, Alison Laws MD, MPH, Elizabeth A. Mittendorf MD, PhD, MHCM, Tari A. King MD & Olga Kantor MD, MS

  3. Harvard Medical School, Boston, MA, USA

    Faina Nakhlis MD, Alison Laws MD, MPH, Elizabeth A. Mittendorf MD, PhD, MHCM, Tari A. King MD & Olga Kantor MD, MS

  4. Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA

    Anna C. Weiss MD

  5. Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, USA

    Jennifer R. Bellon MD

Authors
  1. Robert M. Pride MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Charity C. Glass MD, MPP
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Faina Nakhlis MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alison Laws MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anna C. Weiss MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jennifer R. Bellon MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Elizabeth A. Mittendorf MD, PhD, MHCM
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tari A. King MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Olga Kantor MD, MS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Olga Kantor MD, MS.

Ethics declarations

Disclosure

Elizabeth A. Mittendorf reports compensated service on scientific advisory boards for Astra Zeneca, BioNTech and Merck; uncompensated service on steering committees for Bristol Myers Squibb and Roche/Genentech; and institutional research support from Roche/Genentech (via SU2C grant) and Gilead. She also reports research funding from Susan Komen for the Cure, for which she serves as a Scientific Advisor, and uncompensated participation as a member of the American Society of Clinical Oncology Board of Directors. Tari A. King reports speaker honoraria and an advisory board role for Exact Sciences, and is on the global advisory board of Besins Healthcare. Robert M. Pride, Charity C. Glass, Faina Nakhlis, Alison Laws, Anna C. Weiss, Jennifer R. Bellon, and Olga Kantor report no disclosures.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 27 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pride, R.M., Glass, C.C., Nakhlis, F. et al. Intraoperative Pathology Assessment May Lead to Overtreatment of the Axilla in Clinically Node-Negative Breast Cancer Patients Undergoing Upfront Mastectomy. Ann Surg Oncol 30, 5978–5987 (2023). https://doi.org/10.1245/s10434-023-13898-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-023-13898-2

Search

Navigation