Swedish prospective multicenter trial on the accuracy and clinical relevance of sentinel lymph node biopsy before neoadjuvant systemic therapy in breast cancer

Linda Zetterlund, Fuat Celebioglu, Rimma Axelsson, Jana de Boniface, Jan Frisell, Linda Zetterlund, Fuat Celebioglu, Rimma Axelsson, Jana de Boniface, Jan Frisell

Abstract

Purpose: The timing of sentinel lymph node biopsy (SLNB) in the context of neoadjuvant systemic therapy (NAST) in breast cancer is still controversial. SLNB before NAST has been evaluated in few single-institution studies in which axillary lymph node dissection (ALND), however, was commonly not performed in case of a negative SLNB. We investigated the potential clinical relevance of SLNB before NAST by performing ALND in all patients after NAST.

Methods: This national multicenter trial prospectively enrolled clinically node-negative breast cancer patients planned for NAST at 13 recruiting Swedish hospitals between October 2010 and December 2015. SLNB before NAST was followed by ALND after NAST in all individuals. Repeat SLNB after NAST was encouraged but not mandatory.

Results: SLNB before NAST was performed in 224 patients. The identification rate was 100% (224/224). The proportion of patients with a negative SLNB before NAST but positive axillary lymph nodes after NAST was 7.4% (nine of 121 patients, 95% CI 4.0-13.5). Among those with a positive SLNB before NAST, 23.2% (86/112) had further positive lymph nodes after NAST.

Conclusions: In clinically node-negative patients, SLNB before NAST is highly reliable. With this sequence, ALND and regional radiotherapy can be safely omitted in patients with a negative SLNB provided good clinical response to NAST. Additionally, SLNB-positive patients upfront will receive correct nodal staging unaffected by NAST and be consequently offered adjuvant locoregional treatment according to current guidelines pending the results of ongoing randomized trials.

Trial registration: ClinicalTrials.gov NCT02031042.

Keywords: Breast cancer; False negative rate; Identification rate; Neoadjuvant systemic therapy; Pre-treatment; Sentinel lymph node biopsy.

Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This trial was approved by the Regional Ethics Committee in Stockholm (2010/441-31/4) and the Radiation Protection Committee at Södersjukhuset.

Informed consent

Written informed consent was obtained from all individual participants before inclusion.

Figures

Fig. 1
Fig. 1
CONSORT diagram. NAST neoadjuvant systemic therapy, SLNB sentinel lymph node biopsy, ALND axillary lymph node dissection

References

    1. Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP, et al. 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. 2010;11(10):927–933. doi: 10.1016/S1470-2045(10)70207-2.
    1. Schule J, Frisell J, Ingvar C, Bergkvist L. Sentinel node biopsy for breast cancer larger than 3 cm in diameter. Br J Surg. 2007;94(8):948–951. doi: 10.1002/bjs.5713.
    1. Kuerer HM, Sahin AA, Hunt KK, Newman LA, Breslin TM, Ames FC, et al. Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Ann Surg. 1999;230(1):72–78. doi: 10.1097/00000658-199907000-00011.
    1. Sackey H, Magnuson A, Sandelin K, Liljegren G, Bergkvist L, Fulep Z, et al. Arm lymphoedema after axillary surgery in women with invasive breast cancer. Br J Surg. 2014;101(4):390–397. doi: 10.1002/bjs.9401.
    1. Schrenk P, Tausch C, Wolfl S, Bogner S, Fridrik M, Wayand W. Sentinel node mapping performed before preoperative chemotherapy may avoid axillary dissection in breast cancer patients with negative or micrometastatic sentinel nodes. Am J Surg. 2008;196(2):176–183. doi: 10.1016/j.amjsurg.2007.08.068.
    1. Schrenk P, Hochreiner G, Fridrik M, Wayand W. Sentinel node biopsy performed before preoperative chemotherapy for axillary lymph node staging in breast cancer. Breast J. 2003;9(4):282–287. doi: 10.1046/j.1524-4741.2003.09406.x.
    1. Menard JP, Extra JM, Jacquemier J, Buttarelli M, Lambaudie E, Bannier M, et al. Sentinel lymphadenectomy for the staging of clinical axillary node-negative breast cancer before neoadjuvant chemotherapy. Eur J Surg Oncol. 2009;35(9):916–920. doi: 10.1016/j.ejso.2008.11.002.
    1. Jones JL, Zabicki K, Christian RL, Gadd MA, Hughes KS, Lesnikoski BA, et al. A comparison of sentinel node biopsy before and after neoadjuvant chemotherapy: timing is important. Am J Surg. 2005;190(4):517–520. doi: 10.1016/j.amjsurg.2005.06.004.
    1. Ollila DW, Neuman HB, Sartor C, Carey LA, Klauber-Demore N. Lymphatic mapping and sentinel lymphadenectomy prior to neoadjuvant chemotherapy in patients with large breast cancers. Am J Surg. 2005;190(3):371–375. doi: 10.1016/j.amjsurg.2005.01.044.
    1. van Rijk MC, Nieweg OE, Rutgers EJ, Oldenburg HS, Olmos RV, Hoefnagel CA, et al. Sentinel node biopsy before neoadjuvant chemotherapy spares breast cancer patients axillary lymph node dissection. Ann Surg Oncol. 2006;13(4):475–479. doi: 10.1245/ASO.2006.07.025.
    1. Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013;310(14):1455–1461. doi: 10.1001/jama.2013.278932.
    1. Xing Y, Foy M, Cox DD, Kuerer HM, Hunt KK, Cormier JN. Meta-analysis of sentinel lymph node biopsy after preoperative chemotherapy in patients with breast cancer. Br J Surg. 2006;93(5):539–546. doi: 10.1002/bjs.5209.
    1. van Deurzen CH, Vriens BE, Tjan-Heijnen VC, van der Wall E, Albregts M, van Hilligersberg R, et al. Accuracy of sentinel node biopsy after neoadjuvant chemotherapy in breast cancer patients: a systematic review. Eur J Cancer. 2009;45(18):3124–3130. doi: 10.1016/j.ejca.2009.08.001.
    1. Classe JM, Bordes V, Campion L, Mignotte H, Dravet F, Leveque J, et al. 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):726–732. doi: 10.1200/JCO.2008.18.3228.
    1. Lyman GH, Temin S, Edge SB, Newman LA, Turner RR, Weaver DL, et al. Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2014;32(13):1365–1383. doi: 10.1200/JCO.2013.54.1177.
    1. Network NCC. NCCN Clinical Practice Guidelines in Oncology, Version 2.2016 Invasive Breast Cancer. 2016
    1. Fontein DB, van de Water W, Mieog JS, Liefers GJ, van de Velde CJ (2013) Timing of the sentinel lymph node biopsy in breast cancer patients receiving neoadjuvant therapy—recommendations for clinical guidance. Eur J Surg Oncol 39(5):417–424
    1. van Rijk MC, Deurloo EE, Nieweg OE, Gilhuijs KG, Peterse JL, Rutgers EJ, et al. Ultrasonography and fine-needle aspiration cytology can spare breast cancer patients unnecessary sentinel lymph node biopsy. Ann Surg Oncol. 2006;13(1):31–35. doi: 10.1245/ASO.2005.01.024.
    1. Leenders MW, Broeders M, Croese C, Richir MC, Go HL, Langenhorst BL, et al. Ultrasound and fine needle aspiration cytology of axillary lymph nodes in breast cancer. To do or not to do? Breast (Edinburgh, Scotland) 2012;21(4):578–583. doi: 10.1016/j.breast.2012.05.008.
    1. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981;47(1):207–214. doi: 10.1002/1097-0142(19810101)47:1<207::AID-CNCR2820470134>;2-6.
    1. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer (Oxford, England: 1990) 2009;45(2):228–247. doi: 10.1016/j.ejca.2008.10.026.
    1. Sataloff DM, Mason BA, Prestipino AJ, Seinige UL, Lieber CP, Baloch Z. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. J Am Coll Surg. 1995;180(3):297–306.
    1. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–1474. doi: 10.1245/s10434-010-0985-4.
    1. Bossuyt V, Provenzano E, Symmans WF, Boughey JC, Coles C, Curigliano G, et al. Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration. Ann Oncol. 2015;26(7):1280–1291.
    1. AJCC. Breast cancer staging AJCC 7th edition: American Joint Committee on Cancer 2009[updated 2016. 7th. ]
    1. Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013;14(7):609–618. doi: 10.1016/S1470-2045(13)70166-9.
    1. Kim T, Giuliano AE, Lyman GH. Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: a metaanalysis. Cancer. 2006;106(1):4–16. doi: 10.1002/cncr.21568.
    1. Neuman H, Carey LA, Ollila DW, Livasy C, Calvo BF, Meyer AA, et al. Axillary lymph node count is lower after neoadjuvant chemotherapy. Am J Surg. 2006;191(6):827–829. doi: 10.1016/j.amjsurg.2005.08.041.
    1. Belanger J, Soucy G, Sideris L, Leblanc G, Drolet P, Mitchell A, et al. Neoadjuvant chemotherapy in invasive breast cancer results in a lower axillary lymph node count. J Am Coll Surg. 2008;206(4):704–708. doi: 10.1016/j.jamcollsurg.2007.10.016.
    1. Khan A, Sabel MS, Nees A, Diehl KM, Cimmino VM, Kleer CG, et al. Comprehensive axillary evaluation in neoadjuvant chemotherapy patients with ultrasonography and sentinel lymph node biopsy. Ann Surg Oncol. 2005;12(9):697–704. doi: 10.1245/ASO.2005.09.007.
    1. Galimberti V, Ribeiro Fontana SK, Maisonneuve P, Steccanella F, Vento AR, Intra M, et al. Sentinel node biopsy after neoadjuvant treatment in breast cancer: five-year follow-up of patients with clinically node-negative or node-positive disease before treatment. Eur J Surg Oncol. 2016;42(3):361–368. doi: 10.1016/j.ejso.2015.11.019.
    1. Andersson Y, de Boniface J, Jonsson PE, Ingvar C, Liljegren G, Bergkvist L, et al. Axillary recurrence rate 5 years after negative sentinel node biopsy for breast cancer. Br J Surg. 2012;99(2):226–231. doi: 10.1002/bjs.7820.
    1. Galimberti V, Cole BF, Zurrida S, Viale G, Luini A, Veronesi P, et al. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial. Lancet Oncol. 2013;14(4):297–305. doi: 10.1016/S1470-2045(13)70035-4.
    1. 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):413–420. doi: 10.1097/SLA.0000000000001863.
    1. Chapman CH, Jagsi R. Postmastectomy radiotherapy after neoadjuvant chemotherapy: a review of the evidence. Oncology (Williston Park, NY) 2015;29(9):657–666.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel