title: Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study.
abstract: BACKGROUND
  The optimum timing of sentinel-lymph-node biopsy for breast cancer patients treated with neoadjuvant chemotherapy is uncertain. The SENTINA (SENTinel NeoAdjuvant) study was designed to evaluate a specific algorithm for timing of a standardised sentinel-lymph-node biopsy procedure in patients who undergo neoadjuvant chemotherapy.
  
  
  METHODS
  SENTINA is a four-arm, prospective, multicentre cohort study undertaken at 103 institutions in Germany and Austria. Women with breast cancer who were scheduled for neoadjuvant chemotherapy were enrolled into the study. Patients with clinically node-negative disease (cN0) underwent sentinel-lymph-node biopsy before neoadjuvant chemotherapy (arm A). If the sentinel node was positive (pN1), a second sentinel-lymph-node biopsy procedure was done after neoadjuvant chemotherapy (arm B). Women with clinically node-positive disease (cN+) received neoadjuvant chemotherapy. Those who converted to clinically node-negative disease after chemotherapy (ycN0; arm C) were treated with sentinel-lymph-node biopsy and axillary dissection. Only patients whose clinical nodal status remained positive (ycN1) underwent axillary dissection without sentinel-lymph-node biopsy (arm D). The primary endpoint was accuracy (false-negative rate) of sentinel-lymph-node biopsy after neoadjuvant chemotherapy for patients who converted from cN1 to ycN0 disease during neoadjuvant chemotherapy (arm C). Secondary endpoints included comparison of the detection rate of sentinel-lymph-node biopsy before and after neoadjuvant chemotherapy, and also the false-negative rate and detection rate of sentinel-lymph-node biopsy after removal of the sentinel lymph node. Analyses were done according to treatment received (per protocol).
  
  
  RESULTS
  Of 1737 patients who received treatment, 1022 women underwent sentinel-lymph-node biopsy before neoadjuvant chemotherapy (arms A and B), with a detection rate of 99.1% (95% CI 98.3-99.6; 1013 of 1022). In patients who converted after neoadjuvant chemotherapy from cN+ to ycN0 (arm C), the detection rate was 80.1% (95% CI 76.6-83.2; 474 of 592) and false-negative rate was 14.2% (95% CI 9.9-19.4; 32 of 226). The false-negative rate was 24.3% (17 of 70) for women who had one node removed and 18.5% (10 of 54) for those who had two sentinel nodes removed (arm C). In patients who had a second sentinel-lymph-node biopsy procedure after neoadjuvant chemotherapy (arm B), the detection rate was 60.8% (95% CI 55.6-65.9; 219 of 360) and the false-negative rate was 51.6% (95% CI 38.7-64.2; 33 of 64).
  
  
  CONCLUSIONS
  Sentinel-lymph-node biopsy is a reliable diagnostic method before neoadjuvant chemotherapy. After systemic treatment or early sentinel-lymph-node biopsy, the procedure has a lower detection rate and a higher false-negative rate compared with sentinel-lymph-node biopsy done before neoadjuvant chemotherapy. These limitations should be considered if biopsy is planned after neoadjuvant chemotherapy.
  
  
  BACKGROUND
  Brustkrebs Deutschland, German Society for Senology, German Breast Group.
authors.affiliation: Interdisciplinary Breast Centre, Department of Gynaecology and Obstetrics, Klinikum Esslingen, Esslingen, Germany. t.kuehn@klinikum-esslingen.de
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kuehn
authors.forename: Ingo
authors.initials: I
authors.lastname: Bauerfeind
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Barbara
authors.initials: B
authors.lastname: Fleige
authors.forename: Maik
authors.initials: M
authors.lastname: Hausschild
authors.forename: Gisela
authors.initials: G
authors.lastname: Helms
authors.forename: Annette
authors.initials: A
authors.lastname: Lebeau
authors.forename: Cornelia
authors.initials: C
authors.lastname: Liedtke
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Valentina
authors.initials: V
authors.lastname: Nekljudova
authors.forename: Sabine
authors.initials: S
authors.lastname: Schmatloch
authors.forename: Peter
authors.initials: P
authors.lastname: Schrenk
authors.forename: Annette
authors.initials: A
authors.lastname: Staebler
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D005188:False Negative Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology / Q000601:surgery*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D021701:Sentinel Lymph Node Biopsy; D055815:Young Adult