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Positive predictive value of axillary lymph node cortical thickness and nodal, clinical, and tumor characteristics in newly diagnosed breast cancer patients

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Abstract

Purpose

Axillary lymph nodes (LNs) with cortical thickness > 3 mm have a higher likelihood of malignancy. To examine the positive predictive value (PPV) of axillary LN cortical thickness in newly diagnosed breast cancer patients, and nodal, clinical, and tumor characteristics associated with axillary LN metastasis.

Methods

Retrospective review of axillary LN fine needle aspirations (FNAs) performed 1/1/2018–12/31/2019 included 135 axillary FNAs in 134 patients who underwent axillary surgery. Patient demographics, clinical characteristics, histopathology, and imaging features were obtained from medical records. Hypothesis testing was performed to identify predictors of axillary LN metastasis.

Results

Cytology was positive in 72/135 (53.3%), negative in 61/135 (45.2%), and non-diagnostic in 2/135 (1.5%). At surgery, histopathology was positive in 84 (62.2%) and negative in 51 (37.8%). LN cortices were thicker in metastatic compared to negative nodes (p < 0.0001). PPV of axillary LNs with cortical thickness ≥ 3 mm, ≥ 3.5 mm, ≥ 4 mm and, ≥ 4.25 mm was 0.62 [95% CI 0.53, 0.70], 0.63 [0.54, 0.72], 0.67 [0.57, 0.76] , and 0.74 [0.64, 0.83], respectively. At multivariable analysis, abnormal hilum (OR = 3.44, p = 0.016) and diffuse cortical thickening (OR = 2.86, p = 0.038) were associated with nodal metastasis.

Conclusion

In newly diagnosed breast cancer patients, increasing axillary LN cortical thickness, abnormal fatty hilum, and diffuse cortical thickening are associated with nodal metastasis. PPV of axillary LN cortical thickness ≥ 3 mm and ≥ 3.5 mm is similar but increases for cortical thickness ≥ 4 mm. FNA of axillary LNs with cortex < 4 mm may be unnecessary for some patients undergoing sentinel LN biopsy.

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Data availability

The datasets generated during and/or analyzed during the current study are not publically available due to HIPPA and IRB but are available from the corresponding author on reasonable request.

Abbreviations

LN :

Lymph node

PPV :

Positive predictive value

CI :

Confidence interval

FNA :

Fine needle aspiration

IDC :

Invasive ductal carcinoma

ILC :

Invasive lobular carcinoma

IDLC :

Invasive carcinoma with ductal and lobular features

DCIS :

Ductal carcinoma in situ

SLNB :

Sentinel lymph node biopsy

ALND :

Axillary lymph node dissection

US :

Ultrasound

References

  1. Carter CL, Allen C, Henson DE (1989) Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 63:181–187

    Article  CAS  PubMed  Google Scholar 

  2. Collan YU, Eskelinen MJ, Nordling SA, Lipponen P, Pesonen E, Kumpusalo LM, Pajarinen P, Kettunen KO (1994) Prognostic studies in breast cancer. Multivariate combination of nodal status, proliferation index, tumor size, and DNA ploidy. Acta Oncol 33:873–878. https://doi.org/10.3109/02841869409098449

    Article  CAS  PubMed  Google Scholar 

  3. Rivadeneira DE, Simmons RM, Christos PJ, Hanna K, Daly JM, Osborne MP (2000) Predictive factors associated with axillary lymph node metastases in T1a and T1b breast carcinomas: analysis in more than 900 patients. J Am Coll Surg 191:1–6. https://doi.org/10.1016/s1072-7515(00)00310-0

    Article  CAS  PubMed  Google Scholar 

  4. Pilewskie ML, Morrow M (2014) Management of the clinically node-negative axilla: what have we learned from the clinical trials? Oncology 28:371–378

    PubMed  Google Scholar 

  5. Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP, Ashikaga T, Weaver DL, Mamounas EP, Jalovec LM, Frazier TG, Noyes RD, Robidoux A, Scarth HM, Wolmark N (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 11:927–933. https://doi.org/10.1016/S1470-2045(10)70207-2

    Article  PubMed  PubMed Central  Google Scholar 

  6. Bromham N, Schmidt-Hansen M, Astin M, Hasler E, Reed MW (2017) Axillary treatment for operable primary breast cancer. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD004561.pub3

    Article  PubMed  PubMed Central  Google Scholar 

  7. Garcia-Etienne CA, Ferrari A, Della Valle A, Lucioni M, Ferraris E, Di Giulio G, Squillace L, Bonzano E, Lasagna A, Rizzo G, Tancredi R, Scotti Foglieni A, Dionigi F, Grasso M, Arbustini E, Cavenaghi G, Pedrazzoli P, Filippi AR, Dionigi P, Sgarella A (2020) Management of the axilla in patients with breast cancer and positive sentinel lymph node biopsy: An evidence-based update in a European breast center. Eur J Surg Oncol 46:15–23. https://doi.org/10.1016/j.ejso.2019.08.013

    Article  PubMed  Google Scholar 

  8. 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 

  9. 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 

  10. Magnoni F, Galimberti V, Corso G, Intra M, Sacchini V, Veronesi P (2020) Axillary surgery in breast cancer: An updated historical perspective. Semin Oncol 47:341–352. https://doi.org/10.1053/j.seminoncol.2020.09.001

    Article  PubMed  Google Scholar 

  11. 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 O, (2013) Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA 310:1455–1461. https://doi.org/10.1001/jama.2013.278932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sacre RA (1986) Clinical evaluation of axillary lymph nodes compared to surgical and pathological findings. Eur J Surg Oncol 12:169–173

    CAS  PubMed  Google Scholar 

  13. Marino MA, Avendano D, Zapata P, Riedl CC, Pinker K (2020) Lymph node imaging in patients with primary breast cancer: concurrent diagnostic tools. Oncologist 25:e231–e242. https://doi.org/10.1634/theoncologist.2019-0427

    Article  PubMed  Google Scholar 

  14. Weiss A, King C, Vincuilla J, Parker T, Portnow L, Nakhlis F, Dominici L, Mittendorf EA, King TA (2022) Rates of pathologic nodal disease among cN0 and cN1 patients undergoing routine axillary ultrasound and neoadjuvant chemotherapy. Breast Cancer Res Treat 195:181–189. https://doi.org/10.1007/s10549-022-06677-2

    Article  CAS  PubMed  Google Scholar 

  15. Mainiero MB, Cinelli CM, Koelliker SL, Graves TA, Chung MA (2010) Axillary ultrasound and fine-needle aspiration in the preoperative evaluation of the breast cancer patient: an algorithm based on tumor size and lymph node appearance. AJR Am J Roentgenol 195:1261–1267. https://doi.org/10.2214/AJR.10.4414

    Article  PubMed  Google Scholar 

  16. Leenders MW, Broeders M, Croese C, Richir MC, Go HL, Langenhorst BL, Meijer S, Schreurs WH (2012) Ultrasound and fine needle aspiration cytology of axillary lymph nodes in breast cancer. To do or not to do? Breast 21:578–583. https://doi.org/10.1016/j.breast.2012.05.008

    Article  CAS  PubMed  Google Scholar 

  17. Preda T, McGrath R, Bingham J, Fawcett A, O’Dea C, Bochner M, Gill PG, Kollias J (2020) How much does axillary ultrasound contribute in women undergoing breast-conserving surgery with no palpable axillary nodes? ANZ J Surg 90:1146–1150. https://doi.org/10.1111/ans.15680

    Article  PubMed  Google Scholar 

  18. Hieken TJ, Trull BC, Boughey JC, Jones KN, Reynolds CA, Shah SS, Glazebrook KN (2013) Preoperative axillary imaging with percutaneous lymph node biopsy is valuable in the contemporary management of patients with breast cancer. Surgery 154:831–838. https://doi.org/10.1016/j.surg.2013.07.017

    Article  PubMed  Google Scholar 

  19. Liu M, Yang Y, Xie F, Guo J, Wang S, Yang H, Wang S (2019) Could axillary clearance be avoided in clinically node-negative breast cancer patients with positive nodes diagnosed by ultrasound guided biopsy in the post-ACOSOG Z0011 era? PLoS ONE. https://doi.org/10.1371/journal.pone.0210437

    Article  PubMed  PubMed Central  Google Scholar 

  20. Pilewskie M, Mautner SK, Stempel M, Eaton A, Morrow M (2016) Does a positive axillary lymph node needle biopsy result predict the need for an axillary lymph node dissection in clinically node-negative breast cancer patients in the ACOSOG Z0011 era? Ann Surg Oncol 23:1123–1128. https://doi.org/10.1245/s10434-015-4944-y

    Article  PubMed  Google Scholar 

  21. National Comprehensive Cancer Network: Breast Cancer (Version 4.2022). In:

  22. Mittendorf EA, Kantor O, Weiss A, Richardson E, Garrido-Castro A, Portnow LH, Krop IE, Lin NU, Winer EP, Tolaney SM, King TA (2023) Nodal positivity in early-stage triple-negative breast cancer: implications for preoperative immunotherapy. Ann Surg Oncol 30:100–106. https://doi.org/10.1245/s10434-022-12357-8

    Article  PubMed  Google Scholar 

  23. Weiss A, Martinez-Saez O, Waks AG, Laws A, McGrath M, Tarantino P, Portnow L, Winer E, Rey M, Tapia M, Prat A, Partridge AH, Tolaney SM, Cejalvo JM, Mittendorf EA, King TA (2023) Nodal positivity and systemic therapy among patients with clinical T1–T2N0 human epidermal growth factor receptor-positive breast cancer: Results from two international cohorts. Cancer 129:1836–1845. https://doi.org/10.1002/cncr.34750

    Article  CAS  PubMed  Google Scholar 

  24. 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 

  25. 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 95:982–988. https://doi.org/10.1002/cncr.10786

    Article  PubMed  Google Scholar 

  26. Tahir M, Osman KA, Shabbir J, Rogers C, Suarez R, Reynolds T, Bucknall T (2008) Preoperative axillary staging in breast cancer-saving time and resources. Breast J 14:369–371. https://doi.org/10.1111/j.1524-4741.2008.00600.x

    Article  PubMed  Google Scholar 

  27. Liu XS (2017) Common language effect size for multiple treatment comparisons. Meas Eval Couns Dev 48:238–243. https://doi.org/10.1177/0748175615578739

    Article  Google Scholar 

  28. 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 263:802–807. https://doi.org/10.1097/SLA.0000000000001375

    Article  PubMed  Google Scholar 

  29. Simons JM, van Pelt M, Marinelli A, Straver ME, Zeillemaker AM, Pereira Arias-Bouda LM, van Nijnatten TJA, Koppert LB, Hunt KK, Smidt ML, Luiten EJT, van der Pol CC (2019) Excision of both pretreatment marked positive nodes and sentinel nodes improves axillary staging after neoadjuvant systemic therapy in breast cancer. Br J Surg 106:1632–1639. https://doi.org/10.1002/bjs.11320

    Article  CAS  PubMed  Google Scholar 

  30. Cho N, Moon WK, Han W, Park IA, Cho J, Noh DY (2009) Preoperative sonographic classification of axillary lymph nodes in patients with breast cancer: node-to-node correlation with surgical histology and sentinel node biopsy results. AJR Am J Roentgenol 193:1731–1737. https://doi.org/10.2214/AJR.09.3122

    Article  PubMed  Google Scholar 

  31. Zhu Y, Zhou W, Zhou JQ, Fei XC, Ye TJ, Huang O, Chen XS, Zhan WW (2016) Axillary staging of early-stage invasive breast cancer by ultrasound-guided fine-needle aspiration cytology: which ultrasound criteria for classifying abnormal lymph nodes should be adopted in the post-ACOSOG Z0011 trial era? J Ultrasound Med 35:885–893. https://doi.org/10.7863/ultra.15.06019

    Article  PubMed  Google Scholar 

  32. Ewing DE, Layfield LJ, Joshi CL, Travis MD (2015) Determinants of false-negative fine-needle aspirates of axillary lymph nodes in women with breast cancer: lymph node size, cortical thickness and hilar fat retention. Acta Cytol 59:311–314. https://doi.org/10.1159/000440797

    Article  PubMed  Google Scholar 

  33. Schmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O’Shaughnessy J, Investigators K (2020) Pembrolizumab for early triple-negative breast cancer. N Engl J Med 382:810–821. https://doi.org/10.1056/NEJMoa1910549

    Article  CAS  PubMed  Google Scholar 

  34. Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, Chien AJ, Forero-Torres A, Ellis E, Han H, Clark A, Albain K, Boughey JC, Jaskowiak NT, Elias A, Isaacs C, Kemmer K, Helsten T, Majure M, Stringer-Reasor E, Parker C, Lee MC, Haddad T, Cohen RN, Asare S, Wilson A, Hirst GL, Singhrao R, Steeg K, Asare A, Matthews JB, Berry S, Sanil A, Schwab R, Symmans WF, van ’t Veer L, Yee D, DeMichele A, Hylton NM, Melisko M, Perlmutter J, Rugo HS, Berry DA, Esserman LJ, (2020) Effect of pembrolizumab plus neoadjuvant chemotherapy on pathologic complete response in women with early-stage breast cancer: an analysis of the ongoing phase 2 adaptively randomized I-SPY2 trial. JAMA Oncol 6:676–684. https://doi.org/10.1001/jamaoncol.2019.6650

    Article  PubMed  Google Scholar 

  35. Abe H, Schmidt RA, Kulkarni K, Sennett CA, Mueller JS, Newstead GM (2009) Axillary lymph nodes suspicious for breast cancer metastasis: sampling with US-guided 14-gauge core-needle biopsy–clinical experience in 100 patients. Radiology 250:41–49. https://doi.org/10.1148/radiol.2493071483

    Article  PubMed  Google Scholar 

  36. Bedi DG, Krishnamurthy R, Krishnamurthy S, Edeiken BS, Le-Petross H, Fornage BD, Bassett RL Jr, Hunt KK (2008) Cortical morphologic features of axillary lymph nodes as a predictor of metastasis in breast cancer: in vitro sonographic study. AJR Am J Roentgenol 191:646–652. https://doi.org/10.2214/AJR.07.2460

    Article  PubMed  Google Scholar 

  37. Chung HL, Tso HH, Middleton LP, Sun J, Leung JWT (2022) Axillary nodal metastases in invasive lobular carcinoma versus invasive ductal carcinoma: comparison of node detection and morphology by ultrasound. AJR Am J Roentgenol 218:33–41. https://doi.org/10.2214/AJR.21.26135

    Article  PubMed  Google Scholar 

  38. Balasubramanian I, Fleming CA, Corrigan MA, Redmond HP, Kerin MJ, Lowery AJ (2018) Meta-analysis of the diagnostic accuracy of ultrasound-guided fine-needle aspiration and core needle biopsy in diagnosing axillary lymph node metastasis. Br J Surg 105:1244–1253. https://doi.org/10.1002/bjs.10920

    Article  CAS  PubMed  Google Scholar 

  39. Bhandari A, Xia E, Wang Y, Sindan N, Kc R, Guan Y, Lin Y-L, Wang X, Zhang X, Wang O (2018) Impact of sentinel lymph node biopsy in newly diagnosed invasive breast cancer patients with suspicious node: a comparative accuracy survey of fine-needle aspiration biopsy versus core-needle biopsy. Am J of Transl Res 10:1860–1873

    CAS  Google Scholar 

  40. Rautiainen S, Masarwah A, Sudah M, Sutela A, Pelkonen O, Joukainen S, Sironen R, Karja V, Vanninen R (2013) Axillary lymph node biopsy in newly diagnosed invasive breast cancer: comparative accuracy of fine-needle aspiration biopsy versus core-needle biopsy. Radiology 269:54–60. https://doi.org/10.1148/radiol.13122637

    Article  PubMed  Google Scholar 

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Author notes

  1. Anne-Sophie T. Loonis and Allyson L. Chesebro have contributed equally to this work.

Authors and Affiliations

  1. Division of Breast Imaging, Department of Radiology, Brigham and Women’s Hospital, 75 Francis St, Boston, MA, 02115, USA

    Anne-Sophie T. Loonis, Allyson L. Chesebro, Camden P. Bay, Leah H. Portnow, Anna Weiss, Sona A. Chikarmane & Catherine S. Giess

  2. Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA

    Anne-Sophie T. Loonis, Allyson L. Chesebro, Leah H. Portnow, Sona A. Chikarmane & Catherine S. Giess

  3. Takeda Pharmaceuticals, Cambridge, MA, USA

    Camden P. Bay

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

    Anna Weiss

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

    Anna Weiss

  6. Division of Surgical Oncology, Department of Surgery, University of Rochester, Rochester, NY, USA

    Anna Weiss

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Contributions

All authors contributed equally to the study conception and design. Material preparation, data collection, and analysis were performed by Allyson L. Chesebro MD, Anne-Sophie T. Loonis MD, and Camden P. Bay PhD. The first draft of the manuscript was written by Anne-Sophie T. Loonis MD and Allyson L. Chesebro MD and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Allyson L. Chesebro.

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This study was approved by the appropriate institutional review board with waiver of informed consent (IRB protocol number 17-109).

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Loonis, AS.T., Chesebro, A.L., Bay, C.P. et al. Positive predictive value of axillary lymph node cortical thickness and nodal, clinical, and tumor characteristics in newly diagnosed breast cancer patients. Breast Cancer Res Treat 203, 511–521 (2024). https://doi.org/10.1007/s10549-023-07155-z

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