Sentinel Lymph Node Surgery After Neoadjuvant Chemotherapy in Patients With Node-Positive Breast Cancer The ACOSOG Z1071 (Alliance) Clinical Trial

Department of Surgery, Mayo Clinic, Rochester, Minnesota.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 10/2013; 310(14):1455-1461. DOI: 10.1001/jama.2013.278932
Source: PubMed


IMPORTANCE Sentinel lymph node (SLN) surgery provides reliable nodal staging information with less morbidity than axillary lymph node dissection (ALND) for patients with clinically node-negative (cN0) breast cancer. The application of SLN surgery for staging the axilla following chemotherapy for women who initially had node-positive cN1 breast cancer is unclear because of high false-negative results reported in previous studies. OBJECTIVE To determine the false-negative rate (FNR) for SLN surgery following chemotherapy in women initially presenting with biopsy-proven cN1 breast cancer. DESIGN, SETTING, AND PATIENTS The American College of Surgeons Oncology Group (ACOSOG) Z1071 trial enrolled women from 136 institutions from July 2009 to June 2011 who had clinical T0 through T4, N1 through N2, M0 breast cancer and received neoadjuvant chemotherapy. Following chemotherapy, patients underwent both SLN surgery and ALND. Sentinel lymph node surgery using both blue dye (isosulfan blue or methylene blue) and a radiolabeled colloid mapping agent was encouraged. MAIN OUTCOMES AND MEASURES The primary end point was the FNR of SLN surgery after chemotherapy in women who presented with cN1 disease. We evaluated the likelihood that the FNR in patients with 2 or more SLNs examined was greater than 10%, the rate expected for women undergoing SLN surgery who present with cN0 disease. RESULTS Seven hundred fifty-six women were enrolled in the study. Of 663 evaluable patients with cN1 disease, 649 underwent chemotherapy followed by both SLN surgery and ALND. An SLN could not be identified in 46 patients (7.1%). Only 1 SLN was excised in 78 patients (12.0%). Of the remaining 525 patients with 2 or more SLNs removed, no cancer was identified in the axillary lymph nodes of 215 patients, yielding a pathological complete nodal response of 41.0% (95% CI, 36.7%-45.3%). In 39 patients, cancer was not identified in the SLNs but was found in lymph nodes obtained with ALND, resulting in an FNR of 12.6% (90% Bayesian credible interval, 9.85%-16.05%). CONCLUSIONS AND RELEVANCE Among women with cN1 breast cancer receiving neoadjuvant chemotherapy who had 2 or more SLNs examined, the FNR was not found to be 10% or less. Given this FNR threshold, changes in approach and patient selection that result in greater sensitivity would be necessary to support the use of SLN surgery as an alternative to ALND. TRIAL REGISTRATION Identifier: NCT00881361.

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Available from: Henry Mark Kuerer, Jul 12, 2014
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    • ", its accuracy is considered insufficient in clinically node positive patients [14]. Two prospective trials reported a false negative rate of 12.6–14.2% of this approach [13] [14]. A noninvasive technique would be preferable, as it would strongly reduce morbidity by omitting the need for any invasive procedure [15]. "
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    ABSTRACT: Objective To provide a systematic review of studies comparing the diagnostic performance of noninvasive techniques and axillary lymph node dissection in the identification of initially node positive patients with pathological complete response of axillary lymph nodes to neoadjuvant systemic therapy. Methods PubMed and Embase databases were searched until May 21st, 2014. First, duplicate studies were eliminated. Next, study abstracts were read by two readers to assess eligibility. Studies were selected based on predefined inclusion criteria. Of these, data extraction was performed by two readers independently. Results Of the 987 abstracts that were considered for inclusion, four were eligible for final analysis, which included a total of 572 patients. The diagnostic performance of clinical examination, axillary ultrasound, breast MRI, whole body 18F-FDG PET-CT, and a prediction model to identify patients with pathological complete response were investigated. Studies were often limited by small sample size. Furthermore, systemic therapy regimens and definitions of clinical and pathological complete response were variable, refraining further pooling of data. The reported positive predictive value of different techniques to identify patients with axillary pathological complete response after neoadjuvant systemic therapy varied between 40-100%. Conclusion At present, there is no accurate noninvasive restaging technique able to identify patients with complete axillary response after neoadjuvant systemic therapy
    European Journal of Radiology 10/2014; 84(1). DOI:10.1016/j.ejrad.2014.09.020 · 2.37 Impact Factor
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    • "Although SLNB can be safely performed before preoperative chemotherapy, it requires an additional operation and patients with initial node-positive disease cannot benefit from downstaging by preoperative chemotherapy.20–22 However, SLNB performed after preoperative chemotherapy is associated with higher false-negative rates, especially in patients with originally node-positive cancer.23–25 "
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    ABSTRACT: Two decades ago, lymphatic mapping of sentinel lymph nodes (SLN) was introduced into surgical cancer management and was termed sentinel node navigated surgery. Although this technique is now routinely performed in the management of breast cancer and malignant melanoma, it is still under investigation for use in other cancers. The radioisotope technetium ((99m)Tc) and vital blue dyes are among the most widely used enhancers for SLN mapping, although near-infrared fluorescence imaging of indocyanine green is also becoming more commonly used. (99m)Tc-tilmanocept is a new synthetic radioisotope with a relatively small molecular size that was specifically developed for lymphatic mapping. Because of its small size, (99m)Tc-tilmanocept quickly migrates from its site of injection and rapidly accumulates in the SLN. The mannose moieties of (99m)Tc-tilmanosept facilitate its binding to mannose receptors (CD206) expressed in reticuloendothelial cells of the SLN. This binding prevents transit to second-echelon lymph nodes. In Phase III trials of breast cancer and malignant melanoma, and Phase II trials of other malignancies, (99m)Tc-tilmanocept had superior identification rates and sensitivity compared with blue dye. Trials comparing (99m)Tc-tilmanocept with other (99m)Tc-based agents are required before it can be routinely used in clinical settings.
    OncoTargets and Therapy 06/2014; 7:1151-8. DOI:10.2147/OTT.S50394 · 2.31 Impact Factor
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    • "Recently, studies have evaluated SLNB after neoadjuvant therapy in patients with an initially positive axilla.29–31 Both the ACOSOG Z1071 clinical study30 and the SENTINA study31 obtained higher-than-expected false negative rates (12.6 and 14.2 %, respectively). It would be premature to change standard clinical practices now. "
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    ABSTRACT: Axillary reverse mapping (ARM) is a new technique developed with the aim of reducing lymphedema rates by preserving lymphatic drainage of the upper limbs during sentinel lymph node biopsy and axillary lymph node dissection (ALND). However, it is unclear whether preservation of these lymph nodes affects oncological risk. The present study evaluated the presence of metastases in ARM nodes. A total of 45 patients underwent ARM during ALND. Blue dye was used for ARM nodes localization. All axillary lymph nodes, including ARM nodes, were removed and sent separately for pathological evaluation of metastases. ARM identification was achieved in 40/45 patients (88.9 %). The average number of removed ARM nodes was 1.9. ARM nodes metastasis occurred in 10 of 40 patients (25 %). Patients with an axilla extensively affected by cancer had an elevated risk of metastasis to the arm's lymph nodes (p < 0.001). The rate of arm lymph nodes compromised by metastases calls into question the viability of the ARM technique. Larger studies may point to particular patient profiles for which ARM can be safely use.
    Annals of Surgical Oncology 03/2014; 21(7). DOI:10.1245/s10434-014-3626-5 · 3.93 Impact Factor
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