Skip to main content

Advertisement

SpringerLink
Log in

Nanoparticle-assisted axillary staging: an alternative approach after neoadjuvant chemotherapy in patients with pretreatment node-positive breast cancers

  • Clinical trial
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

In order to achieve an optimized method of axillary staging after neoadjuvant chemotherapy (NAC) in breast cancer patients with pretreatment positive axillary lymph nodes, we evaluated the feasibility and accuracy of nanoparticle-assisted axillary staging (NAAS) which combines carbon nanoparticles with standard sentinel lymph node biopsy (SLNB) with radioisotope and blue dye.

Methods

Invasive breast cancer patients with pre-NAC positive axillary lymph nodes who converted to ycN0 and received surgeries from November 2020 to March 2021 were included. All patients underwent ipsilateral NAAS followed by axillary lymph node dissection. Detection rate (DR), false-negative rate (FNR), negative predictive value (NPV) and accuracy of axillary staging were calculated.

Results

Eighty of 136 (58.8%) breast cancer patients converted to ycN0 after NAC and received NAAS. The DR, NPV and accuracy was 95.0%, 93.3% and 97.4% for NAAS, respectively. And the FNR was 4.2% (2/48) for NAAS, which was lower than that of standard dual-tracer SLNB (SD-SLNB) (9.5%, 4/42). Pretreatment clinical T4 classification was a risk factor for detection failure in NAAS (p = 0.016). When patients with pretreatment inflammatory breast cancers were excluded from analysis, FNR dropped to 2.2% (1/45) for NAAS.

Conclusion

NAAS revealed great performance in invasive breast cancer patients with pre-NAC positive axillary lymph nodes who converted to ycN0. The application of NAAS reached a better balance between more accurate axillary evaluation and less intervention.

Trial registration Chictr.org.cn (ChiCTR2000039814). Registered Nov 11, 2020.

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

Data availability

The data that support the findings of this study are available on reasonable request from the corresponding author.

References

  1. Siso C, de Torres J, Esgueva-Colmenarejo A, Espinosa-Bravo M, Rus N, Cordoba O, Rodriguez R, Peg V, Rubio IT (2018) Intraoperative ultrasound-guided excision of axillary clip in patients with node-positive breast cancer treated with neoadjuvant therapy (ILINA Trial): a new tool to guide the excision of the clipped node after neoadjuvant treatment. Ann Surg Oncol 25(3):784–791. https://doi.org/10.1245/s10434-017-6270-z

    Article  PubMed  Google Scholar 

  2. Diego EJ, McAuliffe PF, Soran A, McGuire KP, Johnson RR, Bonaventura M, Ahrendt GM (2016) Axillary staging after neoadjuvant chemotherapy for breast cancer: a pilot study combining sentinel lymph node biopsy with radioactive seed localization of pre-treatment positive axillary lymph nodes. Ann Surg Oncol 23(5):1549–1553. https://doi.org/10.1245/s10434-015-5052-8

    Article  PubMed  Google Scholar 

  3. Park S, Koo JS, Kim GM, Sohn J, Kim SI, Cho YU, Park BW, Park VY, Yoon JH, Moon HJ, Kim MJ, Kim EK (2018) Feasibility of charcoal tattooing of cytology-proven metastatic axillary lymph node at diagnosis and sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer patients. Cancer Res Treat 50(3):801–812. https://doi.org/10.4143/crt.2017.210

    Article  CAS  PubMed  Google Scholar 

  4. Caudle AS, Yang WT, Krishnamurthy S, Mittendorf EA, Black DM, Gilcrease MZ, Bedrosian I, Hobbs BP, DeSnyder SM, Hwang RF, Adrada BE, Shaitelman SF, Chavez-MacGregor M, Smith BD, Candelaria RP, Babiera GV, Dogan BE, Santiago L, Hunt KK, Kuerer HM (2016) 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 34(10):1072–1078. https://doi.org/10.1200/JCO.2015.64.0094

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Baker JL, Muhsen S, Zabor EC, Stempel M, Gemignani ML (2019) Does lymph node status prior to neoadjuvant chemotherapy influence the number of sentinel nodes removed? Ann Surg Oncol 26(2):336–342. https://doi.org/10.1245/s10434-018-7004-6

    Article  PubMed  Google Scholar 

  6. Shirzadi A, Mahmoodzadeh H, Qorbani M (2019) Assessment of sentinel lymph node biopsy after neoadjuvant chemotherapy for breast cancer in two subgroups: Initially node negative and node positive converted to node negative—a systemic review and meta-analysis. J Res Med Sci 24:18. https://doi.org/10.4103/jrms.JRMS_127_18

    Article  PubMed  PubMed Central  Google Scholar 

  7. Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, Leitch AM, Kuerer HM, Bowling M, Flippo-Morton TS, Byrd DR, Ollila DW, Julian TB, McLaughlin SA, McCall L, Symmans WF, Le-Petross HT, Haffty BG, Buchholz TA, Nelson H, Hunt KK, Alliance for Clinical Trials in Oncology (2013) Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA 310(14):1455–1461. https://doi.org/10.1001/jama.2013.278932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, Lebeau A, Liedtke C, von Minckwitz G, Nekljudova V, Schmatloch S, Schrenk P, Staebler A, Untch M (2013) Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol 14(7):609–618. https://doi.org/10.1016/S1470-2045(13)70166-9

    Article  PubMed  Google Scholar 

  9. Boileau JF, Poirier B, Basik M, Holloway CM, Gaboury L, Sideris L, Meterissian S, Arnaout A, Brackstone M, McCready DR, Karp SE, Trop I, Lisbona A, Wright FC, Younan RJ, Provencher L, Patocskai E, Omeroglu A, Robidoux A (2015) Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study. J Clin Oncol 33(3):258–264. https://doi.org/10.1200/JCO.2014.55.7827

    Article  PubMed  Google Scholar 

  10. Donker M, Straver ME, Wesseling J, Loo CE, Schot M, Drukker CA, van Tinteren H, Sonke GS, Rutgers EJ, Vrancken Peeters MJ (2015) Marking axillary lymph nodes with radioactive iodine seeds for axillary staging after neoadjuvant systemic treatment in breast cancer patients: the MARI procedure. Ann Surg 261(2):378–382. https://doi.org/10.1097/SLA.0000000000000558

    Article  PubMed  Google Scholar 

  11. Caudle AS, Yang WT, Mittendorf EA, Black DM, Hwang R, Hobbs B, Hunt KK, Krishnamurthy S, Kuerer HM (2015) Selective surgical localization of axillary lymph nodes containing metastases in patients with breast cancer: a prospective feasibility trial. JAMA Surg 150(2):137–143. https://doi.org/10.1001/jamasurg.2014.1086

    Article  PubMed  PubMed Central  Google Scholar 

  12. Simons JM, van Nijnatten T, van der Pol CC, Luiten E, Koppert LB, Smidt ML (2019) Diagnostic accuracy of different surgical procedures for axillary staging after neoadjuvant systemic therapy in node-positive breast cancer: a systematic review and meta-analysis. JAMA Surg 269(3):432–442. https://doi.org/10.1097/SLA.0000000000003075

    Article  Google Scholar 

  13. Natsiopoulos I, Intzes S, Liappis T, Zarampoukas K, Zarampoukas T, Zacharopoulou V, Papazisis K (2019) Axillary lymph node tattooing and targeted axillary dissection in breast cancer patients who presented as cN+ before neoadjuvant chemotherapy and became cN0 after treatment. Clin Breast Cancer 19(3):208–215. https://doi.org/10.1016/j.clbc.2019.01.013

    Article  PubMed  Google Scholar 

  14. Taback B, Jadeja P, Ha R (2018) Enhanced axillary evaluation using reflector-guided sentinel lymph node biopsy: a prospective feasibility study and comparison with conventional lymphatic mapping techniques. Clin Breast Cancer 18(5):e869–e874. https://doi.org/10.1016/j.clbc.2018.02.001

    Article  PubMed  Google Scholar 

  15. Mamtani A, Barrio AV, King TA, Van Zee KJ, Plitas G, Pilewskie M, El-Tamer M, Gemignani ML, Heerdt AS, Sclafani LM, Sacchini V, Cody HS 3rd, Patil S, Morrow M (2016) How often does neoadjuvant chemotherapy avoid axillary dissection in patients with histologically confirmed nodal metastases? Results of a prospective study. Ann Surg Oncol 23(11):3467–3474. https://doi.org/10.1245/s10434-016-5246-8

    Article  PubMed  PubMed Central  Google Scholar 

  16. Bryant JA, Siddiqi NJ, Loveday EJ, Irvine GH (2005) Presurgical, ultrasound-guided anchor-wire marking of impalpable cervical lymph nodes. J Laryngol Otol 119(8):627–628. https://doi.org/10.1258/0022215054516241

    Article  CAS  PubMed  Google Scholar 

  17. Wu X, Lin Q, Chen G, Lu J, Zeng Y, Chen X, Yan J (2015) Sentinel lymph node detection using carbon nanoparticles in patients with early breast cancer. PLoS ONE 10(8):e0135714. https://doi.org/10.1371/journal.pone.0135714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yang SX, Wei WS, Jiang QH, Zhou YF, Qu W, Tu JH, Ou-Yang QW, Zhou ZB, Ding HL, Xie CW (2018) Analysis of 246 sentinel lymph node biopsies of patients with clinical primary breast cancer by application of carbon nanoparticle suspension. J Obstet Gynaecol Res 44(6):1150–1157. https://doi.org/10.1111/jog.13635

    Article  CAS  PubMed  Google Scholar 

  19. Zhang L, Huang Y, Yang C, Zhu T, Lin Y, Gao H, Yang M, Cheng M, Wang K (2018) Application of a carbon nanoparticle suspension for sentinel lymph node mapping in patients with early breast cancer: a retrospective cohort study. World J Surg Oncol 16(1):112. https://doi.org/10.1186/s12957-018-1414-6

    Article  PubMed  PubMed Central  Google Scholar 

  20. Qin X, Yang M, Zheng X (2019) Comparative study of indocyanine green combined with blue dye with methylene blue only and carbon nanoparticles only for sentinel lymph node biopsy in breast cancer. Ann Surg Treat Res 97(1):1–6. https://doi.org/10.4174/astr.2019.97.1.1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mainiero MB (2010) Regional lymph node staging in breast cancer: the increasing role of imaging and ultrasound-guided axillary lymph node fine needle aspiration. Radiol Clin North Am 48(5):989–997. https://doi.org/10.1016/j.rcl.2010.06.010

    Article  PubMed  Google Scholar 

  22. Krishnamurthy S, Sneige N, Bedi DG, Edieken BS, Fornage BD, Kuerer HM, Singletary SE, Hunt KK (2002) Role of ultrasound-guided fine-needle aspiration of indeterminate and suspicious axillary lymph nodes in the initial staging of breast carcinoma. Cancer 95(5):982–988. https://doi.org/10.1002/cncr.10786

    Article  PubMed  Google Scholar 

  23. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. https://doi.org/10.1016/j.ejca.2008.10.026

    Article  CAS  Google Scholar 

  24. Ogawa Y, Ikeda K, Watanabe C, Kamei Y, Tokunaga S, Tsuboguchi Y, Inoue T, Fukushima H, Ichiki M (2018) Sentinel node biopsy for axillary management after neoadjuvant therapy for breast cancer: a single-center retrospective analysis with long follow-up. Surg Today 48(1):87–94. https://doi.org/10.1007/s00595-017-1558-y

    Article  PubMed  Google Scholar 

  25. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, von Minckwitz G (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384(9938):164–172. https://doi.org/10.1016/S0140-6736(13)62422-8

    Article  PubMed  Google Scholar 

  26. Hunt KK, Yi M, Mittendorf EA, Guerrero C, Babiera GV, Bedrosian I, Hwang RF, Kuerer HM, Ross MI, Meric-Bernstam F (2009) Sentinel lymph node surgery after neoadjuvant chemotherapy is accurate and reduces the need for axillary dissection in breast cancer patients. Ann Surg Oncol 250(4):558–566. https://doi.org/10.1097/SLA.0b013e3181b8fd5e

    Article  Google Scholar 

  27. Pilewskie M, Morrow M (2017) Axillary nodal management following neoadjuvant chemotherapy: a review. JAMA Oncol 3(4):549–555. https://doi.org/10.1001/jamaoncol.2016.4163

    Article  PubMed  PubMed Central  Google Scholar 

  28. Ersoy YE, Kadioglu H (2018) Review of novel sentinel lymph node biopsy techniques in breast cancer patients treated with neoadjuvant chemotherapy. Clin Breast Cancer 18(4):e555–e559. https://doi.org/10.1016/j.clbc.2018.01.004

    Article  PubMed  Google Scholar 

  29. Boughey JC, Ballman KV, Le-Petross HT, McCall LM, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, Feliberti EC, Hunt KK (2016) 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 Oncol 263(4):802–807. https://doi.org/10.1097/SLA.0000000000001375

    Article  Google Scholar 

  30. Choy N, Lipson J, Porter C, Ozawa M, Kieryn A, Pal S, Kao J, Trinh L, Wheeler A, Ikeda D, Jensen K, Allison K, Wapnir I (2015) Initial results with preoperative tattooing of biopsied axillary lymph nodes and correlation to sentinel lymph nodes in breast cancer patients. Ann Surg Oncol 22(2):377–382. https://doi.org/10.1245/s10434-014-4034-6

    Article  PubMed  Google Scholar 

  31. DeSnyder SM, Mittendorf EA, Le-Petross C, Krishnamurthy S, Whitman GJ, Ueno NT, Woodward WA, Kuerer HM, Akay CL, Babiera GV, Yang W, Lucci A (2018) Prospective feasibility trial of sentinel lymph node biopsy in the setting of inflammatory breast cancer. Clin Breast Cancer 18(1):e73–e77. https://doi.org/10.1016/j.clbc.2017.06.014

    Article  PubMed  Google Scholar 

  32. Karanlik H, Cabioglu N, Oprea AL, Ozgur I, Ak N, Aydiner A, Onder S, Bademler S, Gulluoglu BM (2021) Sentinel lymph node biopsy may prevent unnecessary axillary dissection in patients with inflammatory breast cancer who respond to systemic treatment. Breast Care 16(5):468–474. https://doi.org/10.1159/000512202

    Article  PubMed  Google Scholar 

  33. Kim HK, Ju YW, Lee JW, Kim KE, Jung J, Kim Y, Lee HB, Moon HG, Noh DY, Seo KS, Han W (2021) Association between number of retrieved sentinel lymph nodes and breast cancer-related lymphedema. J Breast Cancer 24(1):63–74. https://doi.org/10.4048/jbc.2021.24.e9

    Article  PubMed  PubMed Central  Google Scholar 

  34. Goldberg JI, Wiechmann LI, Riedel ER, Morrow M, Van Zee KJ (2010) Morbidity of sentinel node biopsy in breast cancer: the relationship between the number of excised lymph nodes and lymphedema. Ann Surg Oncol 17(12):3278–3286. https://doi.org/10.1245/s10434-010-1155-4

    Article  PubMed  Google Scholar 

  35. Kida K, Ishikawa T, Yamada A, Shimizu D, Tanabe M, Sasaki T, Ichikawa Y, Endo I (2015) A prospective feasibility study of sentinel node biopsy by modified indigocarmine blue dye methods after neoadjuvant chemotherapy for breast cancer. Eur J Surg Oncol 41(4):566–570. https://doi.org/10.1016/j.ejso.2014.10.066

    Article  CAS  PubMed  Google Scholar 

  36. Tee SR, Devane LA, Evoy D, Rothwell J, Geraghty J, Prichard RS, McDermott EW (2018) Meta-analysis of sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with initial biopsy-proven node-positive breast cancer. Br J Surg 105(12):1541–1552. https://doi.org/10.1002/bjs.10986

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by National Natural Science Foundation of China (32071284 and 81902686) and the Program of the Science and Technology Bureau of Sichuan (2019YFS0338).

Author information

Author notes

  1. Jiqiao Yang and Tao He contributed equally to this work.

Authors and Affiliations

  1. Department of Breast Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Alley, Chengdu, 610041, China

    Jiqiao Yang, Tao He, Yunhao Wu, Zhoukai Fu, Qing Lv, Shan Lu, Xiaodong Wang, Hongjiang Li, Jing Wang & Jie Chen

  2. Clinical Research Center for Breast Disease, West China Hospital, Sichuan University, Chengdu, China

    Jiqiao Yang

Authors
  1. Jiqiao Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tao He
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yunhao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhoukai Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qing Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shan Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaodong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hongjiang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jie Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the conception, design and interpretation of the data; the preparation of the manuscript; and the final editing and approval of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jie Chen.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

This study was approval by the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20200341).

Informed consent

Written informed consent was obtained from all patients.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, J., He, T., Wu, Y. et al. Nanoparticle-assisted axillary staging: an alternative approach after neoadjuvant chemotherapy in patients with pretreatment node-positive breast cancers. Breast Cancer Res Treat 192, 573–582 (2022). https://doi.org/10.1007/s10549-022-06539-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-022-06539-x

Keywords

Search

Navigation