Skip to main content

Advertisement

SpringerLink
Log in

Use of imaging prediction model for omission of axillary surgery in early-stage breast cancer patients

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

Abstract

Purpose

To develop a prediction model incorporating clinicopathological information, US, and MRI to diagnose axillary lymph node (LN) metastasis with acceptable false negative rate (FNR) in patients with early stage, clinically node-negative breast cancers.

Methods

In this single center retrospective study, the inclusion criteria comprised women with clinical T1 or T2 and N0 breast cancers who underwent preoperative US and MRI between January 2017 and July 2018. Patients were temporally divided into the development and validation cohorts. Clinicopathological information, US, and MRI findings were collected. Two prediction models (US model and combined US and MRI model) were created using logistic regression analysis from the development cohort. FNRs of the two models were compared using the McNemar test.

Results

A total of 964 women comprised the development (603 women, 54 ± 11 years) and validation (361 women, 53 ± 10 years) cohorts with 107 (18%) and 77 (21%) axillary LN metastases in each cohort, respectively. The US model consisted of tumor size and morphology of LN on US. The combined US and MRI model consisted of asymmetry of LN number, long diameter of LN, tumor type, and multiplicity of breast cancers on MRI, in addition to tumor size and morphology of LN on US. The combined model showed significantly lower FNR than the US model in both development (5% vs. 32%, P < .001) and validation (9% vs. 35%, P < .001) cohorts.

Conclusion

Our prediction model combining US and MRI characteristics of index cancer and LN lowered FNR compared to using US alone, and could potentially lead to avoid unnecessary SLNB in early stage, clinically node-negative breast cancers.

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
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ALND:

Axillary lymph node dissection

AUC:

Area under the receiver operating characteristics curve

FNR:

False negative rate

HER2:

Human epidermal growth factor type 2

HR:

Hormone receptor

LN:

Lymph node

SLNB:

Sentinel lymph node biopsy

References

  1. Galimberti V, Cole BF, Viale G, Veronesi P, Vicini E, Intra M, Mazzarol G, Massarut S, Zgajnar J, Taffurelli M, Littlejohn D, Knauer M, Tondini C, Di Leo A, Colleoni M, Regan MM, Coates AS, Gelber RD, Goldhirsch A, International Breast Cancer Study Group T (2018) 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 19:1385–1393. https://doi.org/10.1016/S1470-2045(18)30380-2

    Article  PubMed  Google Scholar 

  2. Giuliano AE, Ballman KV, McCall L, Beitsch PD, Brennan MB, Kelemen PR, Ollila DW, Hansen NM, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, Hunt KK, Morrow M (2017) Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA 318:918–926. https://doi.org/10.1001/jama.2017.11470

    Article  PubMed  PubMed Central  Google Scholar 

  3. Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, McCall LM, Morrow M (2011) Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA 305:569–575. https://doi.org/10.1001/jama.2011.90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gentilini O, Botteri E, Dadda P, Sangalli C, Boccardo C, Peradze N, Ghisini R, Galimberti V, Veronesi P, Luini A, Cassano E, Viale G, Veronesi U (2016) Physical function of the upper limb after breast cancer surgery. Results from the SOUND (sentinel node vs. Observation after axillary Ultra-souND) trial. Eur J Surg Oncol 42:685–689. https://doi.org/10.1016/j.ejso.2016.01.020

    Article  CAS  PubMed  Google Scholar 

  5. Rao R, Euhus D, Mayo HG, Balch C (2013) Axillary node interventions in breast cancer: a systematic review. JAMA 310:1385–1394. https://doi.org/10.1001/jama.2013.277804

    Article  CAS  PubMed  Google Scholar 

  6. Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thurlimann B, Senn HJ, Panel M (2015) Tailoring therapies--improving the management of early breast cancer: St Gallen International Expert Consensus on the primary therapy of early breast cancer 2015. Ann Oncol 26:1533-1546 https://doi.org/10.1093/annonc/mdv221

  7. Giuliano AE, Connolly JL, Edge SB, Mittendorf EA, Rugo HS, Solin LJ, Weaver DL, Winchester DJ, Hortobagyi GN (2017) Breast Cancer-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 67: 290-303 https://doi.org/10.3322/caac.21393

  8. Hersh EH, King TA (2021) De-escalating axillary surgery in early-stage breast cancer. Breast S0960–9776(21):01020–01021. https://doi.org/10.1016/j.breast.2021.11.018

    Article  Google Scholar 

  9. Mittendorf EA, Chavez-MacGregor M, Vila J, Yi M, Lichtensztajn DY, Clarke CA, Giordano SH, Hunt KK (2017) Bioscore: a staging system for breast cancer patients that reflects the prognostic significance of underlying tumor biology. Ann Surg Oncol 24:3502–3509. https://doi.org/10.1245/s10434-017-6009-x

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lyman GH, Somerfield MR, Bosserman LD, Perkins CL, Weaver DL, Giuliano AE (2017) Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of clinical oncology clinical practice guideline update. J Clin Oncol 35:561–564. https://doi.org/10.1200/JCO.2016.71.0947

    Article  PubMed  Google Scholar 

  11. Gentilini O, Veronesi U (2012) 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 21:678–681. https://doi.org/10.1016/j.breast.2012.06.013

    Article  PubMed  Google Scholar 

  12. Reimer T, Stachs A, Nekljudova V, Loibl S, Hartmann S, Wolter K, Hildebrandt G, Gerber B (2017) Restricted axillary staging in clinically and sonographically node-negative early invasive breast cancer (c/iT1-2) in the context of breast conserving therapy: first results following commencement of the Intergroup-Sentinel-Mamma (INSEMA) Trial. Geburtshilfe Frauenheilkd 77:149–157. https://doi.org/10.1055/s-0042-122853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Jung JG, Ahn SH, Lee S, Kim EK, Ryu JM, Park S, Lim W, Jung YS, Chung IY, Jeong J, Chang JH, Shin KH, Chang JM, Moon WK, Han W (2022) No axillary surgical treatment for lymph node-negative patients after ultra-sonography [NAUTILUS]: protocol of a prospective randomized clinical trial. BMC Cancer 22:189. https://doi.org/10.1186/s12885-022-09273-1

    Article  PubMed  PubMed Central  Google Scholar 

  14. van Roozendaal LM, Vane MLG, van Dalen T, van der Hage JA, Strobbe LJA, Boersma LJ, Linn SC, Lobbes MBI, Poortmans PMP, Tjan-Heijnen VCG, Van de Vijver K, de Vries J, Westenberg AH, Kessels AGH, de Wilt JHW, Smidt ML (2017) Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013–08). BMC Cancer 17:459. https://doi.org/10.1186/s12885-017-3443-x

    Article  PubMed  PubMed Central  Google Scholar 

  15. Alvarez S, Anorbe E, Alcorta P, Lopez F, Alonso I, Cortes J (2006) Role of sonography in the diagnosis of axillary lymph node metastases in breast cancer: a systematic review. AJR Am J Roentgenol 186:1342–1348. https://doi.org/10.2214/AJR.05.0936

    Article  PubMed  Google Scholar 

  16. Harnan SE, Cooper KL, Meng Y, Ward SE, Fitzgerald P, Papaioannou D, Ingram C, Lorenz E, Wilkinson ID, Wyld L (2011) Magnetic resonance for assessment of axillary lymph node status in early breast cancer: a systematic review and meta-analysis. Eur J Surg Oncol 37:928–936. https://doi.org/10.1016/j.ejso.2011.07.007

    Article  CAS  PubMed  Google Scholar 

  17. Kuijs VJ, Moossdorff M, Schipper RJ, Beets-Tan RG, Heuts EM, Keymeulen KB, Smidt ML, Lobbes MB (2015) The role of MRI in axillary lymph node imaging in breast cancer patients: a systematic review. Insights Imaging 6:203–215. https://doi.org/10.1007/s13244-015-0404-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Mango VL, Pilewskie M, Jochelson MS (2021) To look or not to look? Axillary imaging: less may be more. J Breast Imaging 3:666–671

    Article  Google Scholar 

  19. Rauch GM, Kuerer HM, Jochelson MS (2021) To look or not to look? Yes to nodal ultrasound! J Breast Imaging 3:659–665

    Article  Google Scholar 

  20. Saksena M, Jimenez R, Coopey S, Harris K (2021) Axillary ultrasound evaluation in breast cancer patients: a multidisciplinary viewpoint and middle ground. J Breast Imaging 3:672–675

    Article  Google Scholar 

  21. Chang JM, Leung JWT, Moy L, Ha SM, Moon WK (2020) Axillary nodal evaluation in breast cancer: state of the art. Radiology 295:500–515. https://doi.org/10.1148/radiol.2020192534

    Article  PubMed  Google Scholar 

  22. Eom YH, Kim EJ, Chae BJ, Song BJ, Jung SS (2015) The distance between breast cancer and the skin is associated with axillary nodal metastasis. J Surg Oncol 111(7):824–828. https://doi.org/10.1002/jso.23898

    Article  PubMed  Google Scholar 

  23. Bae MS, Shin SU, Song SE, Ryu HS, Han W, Moon WK (2018) Association between US features of primary tumor and axillary lymph node metastasis in patients with clinical T1–T2N0 breast cancer. Acta Radiol 59(4):402–408. https://doi.org/10.1177/0284185117723039)

    Article  PubMed  Google Scholar 

  24. Krag DN, Anderson SJ, Julian TB (2010) Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol 11(10):927–933

    Article  PubMed  PubMed Central  Google Scholar 

  25. Members of the German AGO Breast Committee: Diagnosis and treatment of patients with primary and metastatic breast cancer. Guidelines of the AGO breast committee 2018. www.ago-online.de.

  26. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN guidelines). Breast cancer, Version 3. 2023.

  27. Rotili A , Pesapane F, Penco S, et al. (2019) Analysis of the preoperative axillary ultrasound in 685 Women with T1 breast cancer: can we move away from sentinel lymph node biopsy in women with early breast cancer?. Radiological Society of North America 2019 Scientific Assembly and Annual Meeting, December 1–6, 2019, Chicago IL. www.archive.rsna.org/2019/19003664.html. Accessed Sep 9 2021.

  28. Baltzer PA, Dietzel M, Burmeister HP, Zoubi R, Gajda M, Camara O, Kaiser WA (2011) Application of MR mammography beyond local staging: is there a potential to accurately assess axillary lymph nodes? Evaluation of an extended protocol in an initial prospective study. AJR Am J Roentgenol 196:W641-647. https://doi.org/10.2214/AJR.10.4889

    Article  PubMed  Google Scholar 

  29. Byon JH, Park YV, Yoon JH, Moon HJ, Kim EK, Kim MJ, You JK (2021) Added value of MRI for invasive breast cancer including the entire axilla for evaluation of high-level or advanced axillary lymph node metastasis in the Post-ACOSOG Z0011 trial era. Radiology 300:46–54. https://doi.org/10.1148/radiol.2021202683

    Article  PubMed  Google Scholar 

  30. Lyman GH, Giuliano AE, Somerfield MR, Benson AB 3rd, Bodurka DC, Burstein HJ, Cochran AJ, Cody HS 3rd, Edge SB, Galper S, Hayman JA, Kim TY, Perkins CL, Podoloff DA, Sivasubramaniam VH, Turner RR, Wahl R, Weaver DL, Wolff AC, Winer EP, American Society of Clinical O (2005) American society of clinical oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol 23:7703–7720. https://doi.org/10.1200/JCO.2005.08.001

    Article  PubMed  Google Scholar 

  31. Di Micco R, Gentilini OD (2020) Axillary observation alone versus sentinel node biopsy: past, present and future perspectives. Minerva Chir 75:392–399. https://doi.org/10.23736/S0026-4733.20.08528-4

    Article  PubMed  Google Scholar 

  32. del Riego J, Diaz-Ruiz MJ, Teixido M, Ribe J, Vilagran M, Canales L, Sentis M, Grup de Mama V-O-B (2016) The impact of preoperative axillary ultrasonography in T1 breast tumours. Eur Radiol 26:1073–1081. https://doi.org/10.1007/s00330-015-3901-2

    Article  PubMed  Google Scholar 

  33. Garcia Fernandez A, Fraile M, Gimenez N, Rene A, Torras M, Canales L, Torres J, Barco I, Gonzalez S, Veloso E, Gonzalez C, Cirera L, Pessarrodona A (2011) Use of axillary ultrasound, ultrasound-fine needle aspiration biopsy and magnetic resonance imaging in the preoperative triage of breast cancer patients considered for sentinel node biopsy. Ultrasound Med Biol 37:16–22. https://doi.org/10.1016/j.ultrasmedbio.2010.10.011

    Article  PubMed  Google Scholar 

  34. Panda SK, Goel A, Nayak V, Shaik Basha S, Pande PK, Kumar K (2019) Can preoperative ultrasonography and MRI replace sentinel lymph node biopsy in management of axilla in early breast cancer-a prospective study from a tertiary cancer center. Indian J Surg Oncol 10:483–488. https://doi.org/10.1007/s13193-019-00924-7

    Article  PubMed  PubMed Central  Google Scholar 

  35. Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, Muss HB, Smith BL, Hudis CA, Winer EP, Wood WC (2013) Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol 31:2382–2387. https://doi.org/10.1200/JCO.2012.45.2615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Cataliotti L, Westenberg AH, Klinkenbijl JH, Orzalesi L, Bouma WH, van der Mijle HC, Nieuwenhuijzen GA, Veltkamp SC, Slaets L, Duez NJ, de Graaf PW, van Dalen T, Marinelli A, Rijna H, Snoj M, Bundred NJ, Merkus JW, Belkacemi Y, Petignat P, Schinagl DA, Coens C, Messina CG, Bogaerts J, Rutgers EJ (2014) 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 15:1303–1310. https://doi.org/10.1016/S1470-2045(14)70460-7

    Article  PubMed  PubMed Central  Google Scholar 

  37. Harada T, Tanigawa N, Matsuki M, Nohara T, Narabayashi I (2007) Evaluation of lymph node metastases of breast cancer using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging. Eur J Radiol 63:401–407. https://doi.org/10.1016/j.ejrad.2007.02.010

    Article  PubMed  Google Scholar 

  38. Kamitani T, Hatakenaka M, Yabuuchi H, Matsuo Y, Fujita N, Jinnouchi M, Nagao M, Shirahane K, Tokunaga E, Honda H (2013) Detection of axillary node metastasis using diffusion-weighted MRI in breast cancer. Clin Imaging 37:56–61. https://doi.org/10.1016/j.clinimag.2012.02.014

    Article  PubMed  Google Scholar 

  39. Luciani A, Dao TH, Lapeyre M, Schwarzinger M, Debaecque C, Lantieri L, Revelon G, Bouanane M, Kobeiter H, Rahmouni A (2004) Simultaneous bilateral breast and high-resolution axillary MRI of patients with breast cancer: preliminary results. AJR Am J Roentgenol 182:1059–1067. https://doi.org/10.2214/ajr.182.4.1821059

    Article  PubMed  Google Scholar 

  40. Scaranelo AM, Eiada R, Jacks LM, Kulkarni SR, Crystal P (2012) Accuracy of unenhanced MR imaging in the detection of axillary lymph node metastasis: study of reproducibility and reliability. Radiology 262:425–434. https://doi.org/10.1148/radiol.11110639

    Article  PubMed  Google Scholar 

Download references

Funding

This research is supported by two grants of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No. HI20C2092), and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No. HI19C0481, HC19C0110). The funding source was not involved in the study design, and has no role in data collection, data analysis and interpretation, or decision to submit results for presentation or publication.

Author information

Authors and Affiliations

  1. Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea

    Soo-Yeon Kim, Yeon Soo Kim, Su Min Ha, Su Hyun Lee, Nariya Cho, Woo Kyung Moon & Jung Min Chang

  2. Department of Radiology, Seoul National College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea

    Soo-Yeon Kim, Yeon Soo Kim, Su Min Ha, Su Hyun Lee, Nariya Cho, Woo Kyung Moon & Jung Min Chang

  3. Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea

    Soo-Yeon Kim, Yeon Soo Kim, Su Min Ha, Su Hyun Lee, Nariya Cho, Woo Kyung Moon & Jung Min Chang

  4. Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea

    Yunhee Choi

  5. Department of Surgery, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea

    Wonshik Han & Hong‑Kyu Kim

Authors
  1. Soo-Yeon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yunhee Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yeon Soo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Su Min Ha
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Su Hyun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wonshik Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hong‑Kyu Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nariya Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Woo Kyung Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jung Min Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S-YK and JMC: contributed to the study conception and design. Image analysis was performed by S-YK, JMC, YSK, SMH, and SHL. Statistical analysis was performed by YC, S-YK, and JMC. The first draft of the manuscript was written by S-YK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jung Min Chang.

Ethics declarations

Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of our institution (No. 2004-155-1118).

Informed consent

Informed consent was waived by the institutional review board.

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 18 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

Kim, SY., Choi, Y., Kim, Y.S. et al. Use of imaging prediction model for omission of axillary surgery in early-stage breast cancer patients. Breast Cancer Res Treat 199, 489–499 (2023). https://doi.org/10.1007/s10549-023-06952-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-023-06952-w

Keywords

Search

Navigation