ArticlesSentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study
Introduction
Axillary-lymph-node status is one of the strongest prognostic factors for patients with breast cancer and it guides adjuvant local and systemic treatment decisions. In recent years, sentinel-lymph-node biopsy has replaced full axillary-lymph-node dissection as a staging procedure for patients who undergo primary surgery and have clinically negative lymph nodes. Sentinel-lymph-node biopsy provides an accurate assessment of histological nodal status and is associated with less acute and chronic morbidity than axillary-lymph-node dissection.1, 2, 3 Neoadjuvant chemotherapy is established for treatment of locally advanced disease and is being used increasingly for early-stage breast cancer.4 This therapeutic approach provides in-vivo chemosensitivity testing and prognostic information. Patients with an unfavourable tumour-to-breast ratio can be downstaged to allow less radical surgery and to increase the rate of breast-conserving treatment.5, 6
Timing of sentinel-lymph-node biopsy in the neoadjuvant setting is controversial. Reliable data for the detection rate, accuracy (the false-negative rate), and the number of regional relapses are available for when biopsy is done before systemic adjuvant treatment in patients with clinically node-negative (cN0) disease,7, 8 but limited data are available in the context of neoadjuvant chemotherapy. One advantage of doing sentinel-lymph-node biopsy before neoadjuvant chemotherapy is that knowledge of the initial histological nodal status can be used to guide postoperative locoregional treatment decisions. However, the best surgical approach in the axilla for the 20–40% of patients with initially positive lymph nodes (cN+) who are downstaged after neoadjuvant chemotherapy to a clinically negative lymph node status (ycN0) is unclear.5, 6 In this population, biopsy done after neoadjuvant chemotherapy would increase the overall rate of axilla-conserving treatment. Furthermore, growing evidence suggests that the nodal stage after neoadjuvant chemotherapy reflects prognosis more accurately than does initial axillary status9 and could, in the near future, lead to tailoring of regional treatment.10
The feasibility and accuracy of doing sentinel-lymph-node biopsy after neoadjuvant chemotherapy is of some concern. For example, lymphatic drainage from the breast could be impaired, thus hampering detection of the sentinel lymph node. Furthermore, tumour regression in the axilla could follow a non-uniform pattern, leading to an unacceptable false-negative rate. Many cohort studies have been done of sentinel-lymph-node biopsy after neoadjuvant chemotherapy, and findings of three meta-analyses showed detection rates of 63–100% and false-negative rates of 0–39%.11, 12, 13 However, most of these trials were either retrospective or single-centre in design and included only a few patients who had predominantly cN0 disease before neoadjuvant chemotherapy. A few, small, retrospective series have been published of patients who presented initially with cN+ disease and converted to negative axillary status after neoadjuvant chemotherapy; detection rates were 77·6–98·0% of patients and false-negative rates were registered for 5·6–35·5%.14, 15, 16, 17, 18, 19 In a prospective multicentre study of sentinel-lymph-node biopsy after neoadjuvant chemotherapy,20 the detection rate was 94·6% for patients with cN0 disease before neoadjuvant chemotherapy and 81·5% for those who presented initially with cN+ status; false negatives were noted in 9·4% and 15·0%, respectively. However, the low statistical power of this study precludes reliable evidence for subgroups of patients who initially have cN0 or cN+ disease.
Khan and colleagues21 reported 33 patients undergoing a second sentinel-lymph-node biopsy after neoadjuvant chemotherapy. These patients had initially presented with a clinically negative axilla before neoadjuvant chemotherapy but were found to have an involved sentinel lymph node at a first sentinel-lymph-node biopsy done before neoadjuvant chemotherapy. The detection rate for this second sentinel-lymph-node biopsy was 97·0% and the false-negative rate was 4·5%.21
The SENTINA (SENTinel NeoAdjuvant) study was designed to provide reliable data for the feasibility and accuracy of a standardised sentinel-lymph-node biopsy procedure in different settings before and after neoadjuvant chemotherapy. We included several clinical scenarios, with the aim to ascertain the best timing strategy for sentinel-lymph-node biopsy in breast cancer patients treated with neoadjuvant chemotherapy.
Section snippets
Study design
The SENTINA study is a four-arm, prospective, multicentre cohort study undertaken at 103 centres in Germany and Austria. We enrolled patients with breast cancer who were scheduled for neoadjuvant chemotherapy, which had to include at least six cycles of an anthracycline-based regimen recommended by German guidelines for use in the neoadjuvant setting. All patients provided written informed consent. The protocol was reviewed by a central ethics committee (University of Tübingen) and approved by
Results
Between September, 2009, and May, 2012, 2234 patients entered the trial, and of these, 1737 women from 103 institutions fulfilled criteria for the final per-protocol analysis (figure 2). A median of eight (range 1–138) patients were accrued per institution. Nine institutions accrued more than 50 patients each.
1022 (59%) of 1737 patients in the per-protocol analysis presented initially with an unsuspicious clinical lymph-node status and underwent sentinel-lymph-node biopsy before neoadjuvant
Discussion
Our findings show that sentinel lymph nodes were detected in almost all patients who were clinically node-negative and underwent sentinel-lymph-node biopsy before neoadjuvant chemotherapy (ie, those women in arms A and B), whereas the detection rate was 80·1% for patients who converted after chemotherapy from clinically positive to negative axillary status (ie, those in arm C). The overall false-negative rate was 14·2% for patients who converted, and it was around 20% if only one or two
References (28)
- et al.
Shoulder-arm morbidity following axillary dissection and sentinel node only biopsy for breast cancer
Eur J Surg Oncol
(2002) - et al.
Recommendation from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives, 2006
Ann Oncol
(2007) - et al.
Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 phase III trial
Lancet Oncol
(2007) - et al.
Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial
Lancet Oncol
(2010) - et al.
Breast cancer sentinel node identification and classification after neoadjuvant chemotherapy: systematic review and meta analysis
Acad Radiol
(2009) - et al.
Accuracy of sentinel node biopsy after neoadjuvant chemotherapy in breast cancer patients: a systematic review
Eur J Cancer
(2009) - et al.
Lymphatic mapping and sentinel lymph node biopsy in early stage breast carcinoma: a metaanalysis
Cancer
(2006) - et al.
Shoulder-arm morbidity in patients with sentinel node biopsy and complete axillary dissection: data from a prospective randomised trial
Eur J Surg Oncol
(2009) - et al.
Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18
J Clin Oncol
(1997) - 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)
Incidence and prognostic significance of complete axillary downstaging after primary chemotherapy in breast cancer patients with T1 to T3 tumors and cytologically proven axillary metastatic lymph nodes
J Clin Oncol
Using chemotherapy response to personalise choices regarding locoregional therapy: a new era in breast cancer treatment?
J Clin Oncol
Meta-analysis of sentinel lymph node biopsy after preoperative chemotherapy in patients with breast cancer
Br J Surg
Sentinel node identification rate, but not accuracy, is significantly decreased after preoperative chemotherapy in axillary node-positive patients
Breast Cancer Res Treat
Cited by (1087)
The use of blue dye alone for sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with initially node-positive breast cancer
2024, European Journal of Surgical OncologyEfficacy of Targeted Axillary Dissection With Radar Reflector Localization Before Neoadjuvant Chemotherapy
2024, Journal of Surgical Research