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Sentinel lymph node mapping in breast cancer patients following neoadjuvant chemotherapy: systematic review and meta-analysis about head to head comparison of cN0 and cN + patients

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Abstract

Purpose

The effectiveness of sentinel lymph node (SLN) mapping and biopsy following neoadjuvant chemotherapy (NAC) in axillary lymph node staging of breast cancer (BCa) patients with initial clinical node positive status (cN +) compared to clinical node negative status (cN0) is not yet known. The aim of this meta-analysis was to compare the accuracy of SLN mapping following NAC in cN + and cN0 BCa patients.

Methods

PubMed and Scopus were comprehensively reviewed to retrieve all the studies that performed SLN mapping/biopsy and standard axillary lymph node dissection on cN0 and cN + BCa patients following NAC. Pooled detection and false negative rates for N0 and N + patients including 95% confidence interval values (95% CI) were evaluated. Odds ratio (OR) and risk difference (RD) of SLN detection failure and false negative results were compared between two groups.

Results

A total of 27 articles were included for SLN detection rate evaluation and 17 for false negative assessment. The OR and RD of detection failure in N + group compared with N0 group following NAC were 2.22 (p = 0.00, 95% CI 1.4–3.4) and 4% (p = 0.00, 95% CI 2–6%), respectively. The OR and RD of false negative rate were 1.6 (p = 0.01, 95% CI 1–2.6) and 8% (p = 0.02, 95% CI 1–14%), respectively.

Conclusion

SLN mapping in BCa patients following NAC shows high risk of detection failure and high false negative rate of SLN biopsy in cN + patients. In comparison with cN0 BCa patients, SLN mapping and biopsy after NAC was associated with almost two times higher odds of detection failure and false negative results in cN + patients; therefore, this method should not be recommended in this group of patients.

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References

  1. Puig CA, Hoskin TL, Day CN, Habermann EB, Boughey JC. National trends in the use of neoadjuvant chemotherapy for hormone receptor-negative breast cancer: a national cancer data base study. Ann Surg Oncol. 2017;24(5):1242–50. https://doi.org/10.1245/s10434-016-5733-y.

    Article  PubMed  Google Scholar 

  2. Tonellotto F, Bergmann A, de Souza AK, de Aguiar SS, Bello MA, Thuler LCS. Impact of number of positive lymph nodes and lymph node ratio on survival of women with node-positive breast cancer. Eur J Breast Health. 2019;15(2):76.

    Article  Google Scholar 

  3. DiSipio T, Rye S, Newman B, Hayes S. Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. Lancet Oncol. 2013;14(6):500–15.

    Article  Google Scholar 

  4. Abass MO, Gismalla MD, Alsheikh AA, Elhassan MM. Axillary lymph node dissection for breast cancer: efficacy and complication in developing countries. J Glob Oncol. 2018;4:1–8.

    PubMed  Google Scholar 

  5. Krag DN, Weaver DL, Alex JC, Fairbank J, et al. Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol. 1993;2(6):335–40.

    Article  CAS  Google Scholar 

  6. Solà M, Recaj M, Castellà E, Puig P, Gubern JM, Julian JF, Fraile M. Sentinel node biopsy in special histologic types of invasive breast cancer. J Breast Health. 2016;12(2):78.

    Article  Google Scholar 

  7. Güven HE, Kültüroğlu MO, Gülçelik MA, Özaslan C. Sentinel Lymph node metastasis in invasive lobular carcinoma of the breast. Eur J Breast Health. 2018;14(2):117.

    PubMed  PubMed Central  Google Scholar 

  8. Miltenburg DM, Miller C, Karamlou TB, Brunicardi FC. Meta-analysis of sentinel lymph node biopsy in breast cancer. J Surg Res. 1999;84(2):138–42. https://doi.org/10.1006/jsre.1999.5629.

    Article  CAS  PubMed  Google Scholar 

  9. Sadeghi R, Treglia G. Systematic reviews and meta-analyses of diagnostic studies: a practical guideline. Clin Transl Imaging. 2017;5(2):83–7.

    Article  Google Scholar 

  10. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2000. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 28 July 2021.

  11. Agresti A. An introduction to categorical data analysis. John Wiley & Sons; 2018.

    Google Scholar 

  12. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.

    Article  CAS  Google Scholar 

  13. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.

    Article  Google Scholar 

  14. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.

    Article  CAS  Google Scholar 

  15. Duval S, Tweedie R. A nonparametric “trim and fill” method of accounting for publication bias in meta-analysis. J Am Stat Assoc. 2000;95(449):89–98.

    Google Scholar 

  16. Yu Y, Cui N, Li HY, Wu YM, Xu L, Fang M, Sheng Y. Sentinel lymph node biopsy after neoadjuvant chemotherapy for breast cancer: retrospective comparative evaluation of clinically axillary lymph node positive and negative patients, including those with axillary lymph node metastases confirmed by fine needle aspiration. BMC Cancer. 2016;16(1):808. https://doi.org/10.1186/s12885-016-2829-5.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Vu HN, Shoemaker RR, O’Connor PF, Wan W, Fratkin MJ. Intraoperative radiocolloid injection for sentinel node biopsy postneoadjuvant chemotherapy. J Surg Res. 2015;198(1):149–54. https://doi.org/10.1016/j.jss.2015.05.020.

    Article  PubMed  Google Scholar 

  18. Vriens B, Keymeulen K, Kroep JR, Charehbili A, Peer PG, de Boer M, Aarts MJB, Heuts EM, Tjan-Heijnen VCG. Axillary staging in breast cancer patients treated with neoadjuvant chemotherapy in two Dutch phase III studies. Oncotarget. 2017;8(28):46557–64. https://doi.org/10.18632/oncotarget.15101.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Tanaka Y, Maeda H, Ogawa Y, Nishioka A, Itoh S, Kubota K, Ue H, Nakatani K, Sasaguri S. Sentinel node biopsy in breast cancer patients treated with neoadjuvant chemotherapy. Oncol Rep. 2006;15(4):927–31.

    PubMed  Google Scholar 

  20. Takahashi M, Jinno H, Hayashida T, Sakata M, Asakura K, Kitagawa Y. Correlation between clinical nodal status and sentinel lymph node biopsy false negative rate after neoadjuvant chemotherapy. World J Surg. 2012;36(12):2847–52. https://doi.org/10.1007/s00268-012-1704-z.

    Article  PubMed  Google Scholar 

  21. Shimazu K, Tamaki Y, Taguchi T, Akazawa K, Inoue T, Noguchi S. Sentinel lymph node biopsy using periareolar injection of radiocolloid for patients with neoadjuvant chemotherapy-treated breast carcinoma. Cancer. 2004;100(12):2555–61. https://doi.org/10.1002/cncr.20242.

    Article  PubMed  Google Scholar 

  22. Reitsamer R, Peintinger F, Rettenbacher L, Prokop E. Sentinel lymph node biopsy in breast cancer patients after neoadjuvant chemotherapy. J Surg Oncol. 2003;84(2):63–7. https://doi.org/10.1002/jso.10294.

    Article  PubMed  Google Scholar 

  23. Rebollo-Aguirre A, Gallego-Peinado M, Menjón-Beltrán S, García-García J, Pastor-Pons E, Chamorro-Santos C, Ramos-Font C, Salamanca-Ballesteros A, Llamas-Elvira J, Olea-Serrano N. Biopsia del ganglio centinela en pacientes con cáncer de mama operable tratadas con quimioterapia neoadyuvante. Revista Española de Medicina Nuclear e Imagen Molecular. 2012;31(3):117–23.

    Article  CAS  Google Scholar 

  24. Piñero-Madrona A, Escudero-Barea MJ, Fernández-Robayna F, Alberro-Adúriz JA, García-Fernández A, Vicente-García F, Dueñas-Rodriguez B, Lorenzo-Campos M, Caparrós X, Cansado-Martínez MP. Biopsia selectiva del ganglio centinela tras quimioterapia neoadyuvante en el cáncer de mama: resultados del estudio GEICAM 2005–07. Cir Esp. 2015;93(1):23–9.

    Article  Google Scholar 

  25. Pecha V, Kolarik D, Kozevnikova R, Hovorkova K, Hrabetova P, Halaska M, Sottner O, Trnkova M, Petruzelka L, Kolarova H. Sentinel lymph node biopsy in breast cancer patients treated with neoadjuvant chemotherapy. Cancer. 2011;117(20):4606–16. https://doi.org/10.1002/cncr.26102.

    Article  PubMed  Google Scholar 

  26. Nason KS, Anderson BO, Byrd DR, Dunnwald LK, Eary JF, Mankoff DA, Livingston R, Schmidt RA, Jewell KD, Yeung RS, Moe RE. Increased false negative sentinel node biopsy rates after preoperative chemotherapy for invasive breast carcinoma. Cancer. 2000;89(11):2187–94.

    Article  CAS  Google Scholar 

  27. Najim O, Dockx Y, Huyghe I, van den Wyngaert T, Papadimitriou K, Tjalma WAA, Huizing MT. The predictive value of sentinel node biopsy in early breast cancer after neo-adjuvant chemotherapy: a prospective study. Eur J Obstet Gynecol Reprod Biol. 2018;229:108–11. https://doi.org/10.1016/j.ejogrb.2018.06.040.

    Article  PubMed  Google Scholar 

  28. Mamounas EP, Brown A, Anderson S, Smith R, Julian T, Miller B, Bear HD, Caldwell CB, Walker AP, Mikkelson WM, Stauffer JS, Robidoux A, Theoret H, Soran A, Fisher B, Wickerham DL, Wolmark N. 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(12):2694–702. https://doi.org/10.1200/jco.2005.05.188.

    Article  PubMed  Google Scholar 

  29. Lang JE, Esserman LJ, Ewing CA, Rugo HS, Lane KT, Leong SP, Hwang ES. Accuracy of selective sentinel lymphadenectomy after neoadjuvant chemotherapy: effect of clinical node status at presentation. J Am Coll Surg. 2004;199(6):856–62. https://doi.org/10.1016/j.jamcollsurg.2004.08.023.

    Article  PubMed  Google Scholar 

  30. Kinoshita T, Takasugi M, Iwamoto E, Akashi-Tanaka S, Fukutomi T, Terui S. Sentinel lymph node biopsy examination for breast cancer patients with clinically negative axillary lymph nodes after neoadjuvant chemotherapy. Am J Surg. 2006;191(2):225–9. https://doi.org/10.1016/j.amjsurg.2005.06.049.

    Article  PubMed  Google Scholar 

  31. Julian TB, Dusi D, Wolmark N. Sentinel node biopsy after neoadjuvant chemotherapy for breast cancer. Am J Surg. 2002;184(4):315–7. https://doi.org/10.1016/s0002-9610(02)00955-8.

    Article  PubMed  Google Scholar 

  32. Jones JL, Zabicki K, Christian RL, Gadd MA, Hughes KS, Lesnikoski BA, Rhei E, Specht MC, Dominguez FJ, Smith BL. A comparison of sentinel node biopsy before and after neoadjuvant chemotherapy: timing is important. Am J Surg. 2005;190(4):517–20. https://doi.org/10.1016/j.amjsurg.2005.06.004.

    Article  PubMed  Google Scholar 

  33. Han A, Moon HG, Kim J, Ahn SK, Park IA, Han W, Noh DY. Reliability of sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer patients. J Breast Cancer. 2013;16(4):378–85. https://doi.org/10.4048/jbc.2013.16.4.378.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Gimbergues P, Abrial C, Durando X, Le Bouedec G, Cachin F, Penault-Llorca F, Mouret-Reynier MA, Kwiatkowski F, Maublant J, Tchirkov A, Dauplat J. Sentinel lymph node biopsy after neoadjuvant chemotherapy is accurate in breast cancer patients with a clinically negative axillary nodal status at presentation. Ann Surg Oncol. 2008;15(5):1316–21. https://doi.org/10.1245/s10434-007-9759-z.

    Article  CAS  PubMed  Google Scholar 

  35. Classe JM, Bordes V, Campion L, Mignotte H, Dravet F, Leveque J, Sagan C, Dupre PF, Body G, Giard S. 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(5):726–32. https://doi.org/10.1200/jco.2008.18.3228.

    Article  PubMed  Google Scholar 

  36. Cao XS, Li HJ, Cong BB, Sun X, Qiu PF, Liu YB, Wang CJ, Wang YS. Axillary and internal mammary sentinel lymph node biopsy in breast cancer after neoadjuvant chemotherapy. Oncotarget. 2016;7(45):74074–81. https://doi.org/10.18632/oncotarget.12615.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Andreis D, Bonardi S, Allevi G, Aguggini S, Gussago F, Milani M, Strina C, Spada D, Ferrero G, Ungari M, Rocca A, Nanni O, Roviello G, Berruti A, Harris AL, Fox SB, Roviello F, Polom K, Bottini A, Generali D. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with T2 to T4, N0 and N1 breast cancer. Breast. 2016;29:55–61. https://doi.org/10.1016/j.breast.2016.07.003.

    Article  CAS  PubMed  Google Scholar 

  38. Zhang K, Zhu Q, Sheng D, Li J, Chang C. A new model incorporating axillary ultrasound after neoadjuvant chemotherapy to predict non-sentinel lymph node metastasis in invasive breast cancer. Cancer Manag Res. 2020;12:965–72. https://doi.org/10.2147/cmar.s239921.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Kahler-Ribeiro-Fontana S, Pagan E, Magnoni F, Vicini E, Morigi C, Corso G, Intra M, Canegallo F, Ratini S, Leonardi MC. Long-term standard sentinel node biopsy after neoadjuvant treatment in breast cancer: a single institution ten-year follow-up. Eur J Surg Oncol.  2021;47(4):804–12. https://doi.org/10.1016/j.esjo.2020.10.014.

  40. Classe JM, Loaec C, Gimbergues P, Alran S, de Lara CT, Dupre PF, Rouzier R, Faure C, Paillocher N, Chauvet MP, Houvenaeghel G, Gutowski M, De Blay P, Verhaeghe JL, Barranger E, Lefebvre C, Ngo C, Ferron G, Palpacuer C, Campion L. Sentinel lymph node biopsy without axillary lymphadenectomy after neoadjuvant chemotherapy is accurate and safe for selected patients: the GANEA 2 study. Breast Cancer Res Treat. 2019;173(2):343–52. https://doi.org/10.1007/s10549-018-5004-7.

    Article  PubMed  Google Scholar 

  41. Baker JL, Muhsen S, Zabor EC, Stempel M, Gemignani ML. Does lymph node status prior to neoadjuvant chemotherapy influence the number of sentinel nodes removed? Ann Surg Oncol. 2019;26(2):336–42. https://doi.org/10.1245/s10434-018-7004-6.

    Article  PubMed  Google Scholar 

  42. Javan H, Gholami H, Assadi M, Pakdel AF, Sadeghi R, Keshtgar M. The accuracy of sentinel node biopsy in breast cancer patients with the history of previous surgical biopsy of the primary lesion: systematic review and meta-analysis of the literature. Eur J Surg Oncol (EJSO). 2012;38(2):95–109.

    Article  CAS  Google Scholar 

  43. Kermani AT, Bagheri R, Tehranian S, Shojaee P, Sadeghi R, Krag DN. Accuracy of sentinel node biopsy in the staging of non-small cell lung carcinomas: systematic review and meta-analysis of the literature. Lung Cancer. 2013;80(1):5–14.

    Article  Google Scholar 

  44. Tehranian S, Treglia G, Krag DN, Kakhki VRD, Zakavi SR, Sadeghi R, Keshtgar M. Sentinel node mapping in anal canal cancer: systematic review and meta-analysis. J Gastrointestinal & Liver Dis. 2013;22(3):321–8.

  45. Kadkhodayan S, Shiravani Z, Hasanzadeh M, Sharifi N, Yousefi Z, Fattahi A, Sadeghi R. Lymphatic mapping and sentinel node biopsy in endometrial cancer—a feasibility study using cervical injection of radiotracer and blue dye. Nucl Med Rev. 2014;17(2):55–8.

    Article  Google Scholar 

  46. Kakhki VRD, Bagheri R, Tehranian S, Shojaei P, Gholami H, Sadeghi R, Krag DN. Accuracy of sentinel node biopsy in esophageal carcinoma: a systematic review and meta-analysis of the pertinent literature. Surg Today. 2014;44(4):607–19.

    Article  Google Scholar 

  47. Hassanzadeh M, Farahabadi EH, Yousefi Z, Kadkhodayan S, Zarifmahmoudi L, Sadeghi R. Lymphatic mapping and sentinel node biopsy in ovarian tumors: a study using intra-operative Tc-99m-Phytate and lymphoscintigraphy imaging. J Ovarian Res. 2016;9(1):55.

    Article  Google Scholar 

  48. National Comprehensive Cancer Network. Breast Cancer (Version 5.2021). https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed 28 June 2021.

  49. Mamounas EP, Brown A, Anderson S, Smith R, Julian T, Miller B, Bear HD, Caldwell CB, Walker AP, Mikkelson WM. 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(12):2694–702.

    Article  Google Scholar 

  50. Mocellin S, Goldin E, Marchet A, Nitti D. Sentinel node biopsy performance after neoadjuvant chemotherapy in locally advanced breast cancer: a systematic review and meta-analysis. Int J Cancer. 2016;138(2):472–80.

    Article  CAS  Google Scholar 

  51. Goyal A. New technologies for sentinel lymph node detection. Breast Care. 2018;13(5):349–53.

    Article  Google Scholar 

  52. Koukouraki S, Sanidas E, Askoxilakis J, Stathaki M, Charalambakis V, Daboudi M, Voutoufianaki I, Kafousi M, Stathopoulos E, Tsiftsis D. Is there any benefit from sentinel lymph node biopsy using the combined radioisotope/dye technique in breast cancer patients with clinically negative axilla? Nucl Med Commun. 2009;30(1):48–53.

    Article  Google Scholar 

  53. Kataria K, Srivastava A, Qaiser D. What is a false negative sentinel node biopsy: definition, reasons and ways to minimize it? Indian J Surg. 2016;78(5):396–401.

    Article  Google Scholar 

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Funding

No funds, Grants, or other support was received. The authors have no relevant financial or non-financial interests to disclose.

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Authors and Affiliations

  1. Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Leili Zarifmahmoudi, Atena Aghaee & Ramin Sadeghi

  2. Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland

    Giorgio Treglia

  3. Academic Education, Research and Innovation Area, Ente Ospedaliero Cantonale, Bellinzona, Switzerland

    Giorgio Treglia

  4. Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland

    Giorgio Treglia

  5. Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland

    Giorgio Treglia

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  1. Leili Zarifmahmoudi
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  2. Atena Aghaee
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  4. Ramin Sadeghi
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RS: conception and manuscript draft. LZ: literature search and data analysis. AA: manuscript draft and revision. GT: revision.

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Correspondence to Giorgio Treglia.

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Zarifmahmoudi, L., Aghaee, A., Treglia, G. et al. Sentinel lymph node mapping in breast cancer patients following neoadjuvant chemotherapy: systematic review and meta-analysis about head to head comparison of cN0 and cN + patients. Breast Cancer 29, 50–64 (2022). https://doi.org/10.1007/s12282-021-01280-7

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