Rationale and Objectives
Breast cancer is the leading cause of mortality in women worldwide. Lymphatic mapping with sentinel node biopsy has the potential to reduce the morbidity associated with breast cancer staging in women after neoadjuvant therapy.
Materials and Methods
A systematic search of world literature between 1996 and 2007 of sentinel node mapping in patients with early-stage breast carcinoma after chemotherapy was undertaken. Potentially eligible studies were identified using database-specific search strategies incorporating appropriate Boolean combinations of the keywords sentinel node biopsy or sentinel node localization or lymphatic mapping; breast cancer or malignancy or neoplasm; and preoperative or neoadjuvant chemotherapy. The electronic searches were augmented with a manual search of reference lists from identified articles. Successful lymph node mapping, defined as successful identification rate (SIR), and false-negative rate (FNR) was summarized using a bivariate random effects mixed model. The extent of heterogeneity was assessed using the inconsistency statistic. The effect of study level covariates, such as use of immunohistochemistry or dual mapping technique, and individual quality criteria, such as study design or multi-institution participation, on SIR and FNR were analyzed using metaregression.
Results
A total of 24 trials of 1799 subjects were reported that met eligibility criteria. All studies identified were published between 2000 and 2007. Lymph node involvement was found in 758 patients (37%) and ranged from 25% to 96% across studies. The proportion of patients who had successful lymph node mapping ranged from 63% to 100%, with 79% of studies reporting a rate of less than 95%. The summary successful identification rate was 0.896 (95% confidence interval [CI] 0.860–0.923) with moderate heterogeneity. The summary FNR was 0.084 (95% CI 0.064–0.109) with no significant heterogeneity. Increasing prevalence of lymph node involvement and same-day mapping and lymph node dissection both significantly reduced the FNR.
Conclusions
The present systematic review demonstrates robust estimates of successful identification rate and false-negative rates of sentinel lymph node mapping and biopsy after neoadjuvant therapy for early-stage breast cancer patients. With a 90% SIR and 8% FNR, this technique is a reliable tool for planning treatment in this population as an alternative to completion axillary lymph node dissection.
Breast cancer is the leading cause of cancer mortality in women worldwide, according to the World Health Organization . Most patients are currently diagnosed with localized non-metastatic breast cancer (Stages 0–1) on mammography . The most important determinant of prognosis for breast cancer patients are tumor size and the status of the axillary lymph nodes . The presence of regional metastases in the axillary basin reduces a patients’ 5-year survival by approximately 28% to 40% . Staging of the axilla was formerly performed at surgery with a level I and II axillary lymph node dissection. Axillary lymph node dissection has significant side effects of lymphedema and arm swelling . Since the early 1990s, sentinel lymph node mapping and subsequent biopsy has shown much promise in the axillary staging and surgical management of breast cancer . The sentinel node biopsy is based on the sentinel node hypothesis proposed by Cabanas . The aim of the technique is to demonstrate which patients have axillary metastasis and resulting direct subsequent lymph node dissection. Many studies have demonstrated the accuracy of sentinel lymph node mapping in the staging of early breast cancer . Reported identification rates and false-negative rates (FNR) in patients who have not received chemotherapy range from 84% to 100% and 0% to 13%, respectively . Sentinel lymph node mapping is rapidly replacing axillary lymph node dissection in the primary staging of breast cancer .
Preoperative (or neoadjuvant) chemotherapy has become the standard of care in patients with locally advanced breast cancer (Stage IIIB) and is being used increasingly in patients with localized non-metastatic disease (Stages 0–1) . Although it has not improved the survival rate compared to adjuvant chemotherapy, neoadjuvant chemotherapy can decrease the magnitude of the operative procedure required, converting many patients from mastectomy to breast conservation surgery . The use of sentinel lymph node mapping in patients after preoperative chemotherapy has been proposed, but its role is less certain. Studies in the literature report identification rates of 76.3% to 100% and accuracies of 79% to 98% . The question of whether sentinel node biopsy is feasible and accurate after neoadjuvant chemotherapy is one of great importance because neoadjuvant chemotherapy has been shown to downstage axillary lymph nodes in a significant proportion of patients .
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Methods
Study Search Strategy
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Study Selection Criteria
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Data Extraction
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Assessment of Methodological Quality and Publication Bias
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Summary of Diagnostic Test Performance
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Sensitivity Analyses of Study-level Characteristics and Summary Performance
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Exploratory Analyses
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Results
Study Identification
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Study Characteristics
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Table 1
Individual Study Characteristics and Performance
Author Year Journal Origin Mean Age Number of Patients NPV SIR FNR Aihara et al 2004Journal of Surgical Oncology Japan 62 endo, 47 chemo 16 endo, 20 chemo 0.929 0.85 0.08 Balch et al 2003Annals of Surgical Oncology USA 51 32 0.923 0.97 0.05 Brady et al 2002The Breast Journal USA 44 14 1 0.93 0.00 Cohen et al 2000The American Journal of Surgical Pathology USA 45 ∗ 38 0.813 0.82 0.20 Fernandez et al 2000Nuclear Medicine Communications Spain 55 36 0.778 0.94 0.25 Haid et al 2001Cancer Austria 53 33 1 0.88 0.00 Jones et al 2005American Journal of Surgery USA N/A 36 0.846 0.81 0.16 Khan et al 2005Annals of Surgical Oncology USA 40 ∗ 33 0.857 0.96 0.05 Kinoshita et al 2007Breast Cancer Japan 50.2 104 0.938 0.94 0.19 Lang et al 2004Journal of the American College of Surgery USA 51 ∗ 53 0.967 0.94 0.04 Lee et al 2007Breast Cancer Results Treatment Korea 46.1 219 0.868 0.78 0.16 Mahmounas et al 2005Journal of Clinical Oncology USA N/A 428 0.931 0.80 0.11 Miller et al 2002Annals of Surgical Oncology USA N/A 35 1 0.86 0.00 Nason et al 2000Cancer USA N/A 82 0.571 0.80 0.33 Patel et al 2004The American Surgeon USA N/A 42 1 0.95 0.00 Piato et al 2002European Journal of Surgical Oncology Brazil N/A 42 0.885 0.98 0.17 Reitsamer et al 2003Journal of Surgical Oncology Austria 31–74 41 0.917 0.63 0.07 Schwartz et al 2003The Breast Journal USA 50 21 0.909 1.00 0.09 Shimazu et al 2004Cancer Japan 51.3 47 0.733 0.94 0.12 Stearns et al 2002Annals of Surgical Oncology USA 46 34 0.875 0.85 0.06 Tafra et al 2001American Journal of Surgery USA N/A 29 1 0.93 0.00 Tanaka et al 2006Oncology Reports Japan N/A 70 0.958 0.90 0.03 Tausch et al 2006Annals of Surgical Oncology Austria 50 ∗ 167 0.931 0.84 0.06 Yu et al 2006Annals of Surgical Oncology Taiwan 42.6 127 0.912 0.91 0.08
Chemo: chemotherapy; Endo: endocrine therapy; FNR: false-negative rate; NPV: negative predictive value; SIR: identification rate.
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Assessment of Quality
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Table 2
Quality Characteristics by Study
Author Year Prospective Study Design Size >30 Verification Test Index Test Reference Test Subjects Report Consecutive Broad Blind Multiple Institutions Aihara et al 2004 Yes Yes Yes Yes Yes Yes No Yes No No Not described Balch et al 2003 Yes Yes Yes Yes Yes Yes No Yes Yes No Single institution, multiple surgeons Brady et al 2002 No No Yes Yes Yes No No Yes Yes No Single institution, single surgeon Cohen et al 2000 Yes Yes Yes Yes Yes Yes No Yes Yes No Single institution Fernandez et al 2000 Yes Yes Yes Yes Yes Yes No Yes Yes No Single institution Haid et al 2001 Yes Yes Yes Yes Yes Yes No No Yes No Single institution Jones et al 2005 No Yes Yes No No No Yes Yes Yes No Multicenter trial Khan et al 2005 No Yes Yes Yes Yes Yes Yes Yes Yes No Single institution Kinoshita et al 2007 Yes Yes Yes Yes No Yes Yes Yes Yes No Single institution Lang et al 2004 Yes Yes Yes Yes Yes Yes No Yes Yes No Single institution Lee et al 2007 Yes Yes Yes Yes Yes Yes Yes Yes Yes No Single institution, multiple surgeons Mahmounas et al 2005 Yes Yes Yes Yes Yes Yes No Yes Yes No Multicenter trial Miller et al 2002 Yes Yes Yes Yes Yes No No Yes Yes No Single institution Nason et al 2000 Yes Yes Yes Yes Yes Yes No Yes Yes No Single institution, multiple surgeons Patel et al 2004 No Yes Yes Yes Yes Yes No No Yes No Single institution, multiple surgeons Piato et al 2002 Yes Yes Yes Yes Yes Yes No Yes Yes No Single institution Reitsamer et al 2003 Yes Yes Yes Yes Yes Yes No Yes Yes No Not described Schwartz et al 2003 Yes No Yes Yes Yes Yes No Yes Yes No Single institution, single surgeon Shimazu et al 2004 Yes Yes Yes Yes Yes Yes No Yes Yes No Single institution Stearns et al 2002 Yes No Yes Yes Yes Yes Yes Yes Yes No Single institution, multiple surgeons Tafra et al 2001 Yes No Yes Yes Yes Yes No Yes Yes No Multicenter trial Tanaka et al 2006 Yes Yes Yes Yes Yes Yes Yes Yes Yes No Single institution Tausch et al 2006 No Yes Yes Yes Yes No Yes Yes Yes No Multicenter trial Yu et al 2006 Yes Yes Yes Yes Yes Yes Yes Yes Yes No Single institution
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Summary of Diagnostic Test Performance
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Sensitivity Analyses of Study-level Characteristics and Summary Performance
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Table 3
Effect of Study-level Covariates on Successful Identification Rates and False-negatives Rates
Successful Identification Rate False-Negative Rate Covariate Covariate = Yes Covariate = No Covariate = Yes Covariate = No Dual mapping technique 0.898 0.877 0.095 0.066 Immunohistochemistry 0.857 0.929 0.087 0.071 Same-day mapping and axillary node dissection ∗ 0.900 0.893 0.058 0.115 Use of gamma probe 0.884 0.889 0.088 0.066 Peritumoral injection 0.889 0.884 0.067 0.116
The estimates of each parameter in the presence or absence of each covariate were evaluated using univariate metaregression.
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Assessment of Publication Bias
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Exploratory Analyses
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Discussion
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Conclusion
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Appendix 1
Individual quality criteria in assessment of studies
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