Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy Is Accurate in Breast Cancer Patients with a Clinically Negative Axillary Nodal Status at Presentation

Background In breast cancer, neoadjuvant chemotherapy (NAC) is widely used in order to enable a conservative surgery. In patients treated with NAC, the use of sentinel lymph node (SLN) biopsy, which is a good predictor of the axillary nodal status in previously untreated patients, is still discussed. The aim of our study was to determine clinicopathological factors that may influence the accuracy of SLN biopsy after NAC. Methods Between March 2001 and December 2006, 129 patients with infiltrating breast carcinoma were studied prospectively. Preoperatively, all of them underwent NAC. At surgery, SLN biopsy followed by axillary lymph node (ALN) dissection was performed. Lymphatic mapping was done using the isotope method. Results The SLN identification rate was 93.8% (121/129). Fifty-six out of the 121 successfully mapped patients had positive ALN. Eight out of these 56 patients had tumor-free SLN (false-negative rate of 14.3%). The false-negative rate was correlated with larger tumor size (T1-T2 versus T3; P = 0.045) and positive clinical nodal status (N0 versus N1-N2; P = 0.003) before NAC. In particular, the false-negative rate was 0% (0/29) in N0 patients and 29.6% (8/27) in N1-N2 patients. Clinical and pathological responses to NAC did not influence the accuracy of SLN biopsy. Conclusion Our results show that clinical nodal status is the main clinicopathological factor influencing the false-negative rate of SLN biopsy after NAC for breast cancer. SLN biopsy after NAC can predict the ALN status with a high accuracy in patients who are clinically lymph node negative at presentation.     

Identifying Residual Nodal Disease in Sentinel Lymph Node Surgery After Neoadjuvant Chemotherapy for Breast Cancer

Annals of Surgical Oncology -     

Decreased Identification Rate of Sentinel Lymph Node after Neoadjuvant Chemotherapy

We prospectively studied the feasibility of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy by comparing the identification rate and the false-negative rate (FNR) with the results obtained from the patients without chemotherapy. From October 2001 to March 2003, a total of 284 consecutive patients who underwent SLNB and axillary lymph node dissection (ALND) at the Center for Breast Cancer, National Cancer Center were enrolled. Of the 284 patients, 54 underwent neoadjuvant chemotherapy prior to operation. The sentinel lymph node (SLN) was mapped by radioactive colloid alone or in combination with blue dye. All SLNs were evaluated by 2 mm serial sections after hematoxylin-eosin staining. The overall SLN identification rate was 91.9% (261/284): 72.2% (39/54) of the patients after chemotherapy and 96.5% (222/230) of the patients without chemotherapy. These results suggest that preoperative chemotherapy significantly affects lymphatic mapping (p< 0.001). Among the patients with chemotherapy, there were 3 false negatives in 39 successfully mapped tumors, yielding an FNR of 11.1% (3/27), a negative prediction value (NPV) of 80.0% (12/15), and an accuracy of 92.3% (36/39). There were 10 false negatives among 222 successfully detected patients without chemotherapy, yielding an FNR of 9.9% (10/101), an NPV of 92.4% (121/131), and an accuracy of 95.5% (212/222). These results were not statistically different when compared (p > 0.05). Although the SLN identification rate significantly decreased after neoadjuvant chemotherapy, SLNB could accurately predict axillary status. Thus SLNB can be an alternative to ALND even after neoadjuvant chemotherapy in cases of successful identification of the SLN.     

临床腋淋巴结阴性乳腺癌前哨淋巴结研究

目的：探讨前哨淋巴结活检术（ｓｅｎｔｉｎｅｌ ｌｙｍｐｈ ｎｏｄｅ ｂｉｏｐｓｙ, ＳＬＮＢ）在乳腺癌治疗中的应用。方法：使用专利蓝和美蓝染色,对１９９９年９月～２００１年４月连续收治的１４５例临床查体腋窝淋巴结阴性乳腺癌病人行前哨淋巴结活检术。结果：ＳＬＮＢ成功率为９６．５％（１４０／１４５）,假阴性率为２３．５％,准确率为９１．４％。病人年龄、肿瘤最大径、肿瘤部位、注射染料类型及是否活检对成功率和假阴性率无影响。结论：ＳＬＮＢ能够准确预测腋窝淋巴结的转移状况,在缩小手术范围、减少术后并发症的同时,提高了腋窝淋巴结分期的准确性;美蓝与专利蓝均可成功确定ＳＬＮ。     

Sentinel Node Biopsy Before Neoadjuvant Chemotherapy Spares Breast Cancer Patients Axillary Lymph Node Dissection

Background Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy, the sentinel node was identified in on average 89%, and the false-negative rate was on average 10%. Because of these mediocre results, no author dares to omit axillary clearance just yet. In our institute, sentinel lymph node biopsy is performed before neoadjuvant chemotherapy. The aim of this study was to evaluate our experience with this approach. Methods Sentinel node biopsy was performed before neoadjuvant chemotherapy in 25 T2N0 patients by using lymphoscintigraphy, a gamma ray detection probe, and patent blue dye. Axillary lymph node dissection was performed after chemotherapy if the sentinel node contained metastases. Results Ten patients had a tumor-positive axillary sentinel node, and one patient had an involved lateral intramammary node. Four patients had additional involved nodes in the completion lymph node dissection specimen. The other 14 patients (56%) had a tumor-negative sentinel node and did not undergo axillary lymph node dissection. No recurrences have been observed after a median follow-up of 18 months. Conclusions Fourteen (56%) of the 25 patients were spared axillary lymph node dissection when the sentinel node was found to be disease free. Performing sentinel node biopsy before neoadjuvant chemotherapy seems successful and reliable in patients with T2N0 breast cancer.     

Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Patients with Cytologically Proven Node-positive Breast Cancer at Diagnosis

Background

The performance of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NCT) was investigated in patients with locally advanced breast cancer (LABC).

Methods

After NCT of 178 patients with cytology-proven axillary/supraclavicular nodes metastasis at the time of diagnosis, SLNB using radioisotope was performed including completion node dissection between 2008 and 2011. The detection rate, sensitivity, false negative rate (FNR), negative predictive value (NPV) and accuracy of SLNB were analyzed.

Results

SLNB was successfully performed in 169 (94.9 %) patients. Tumor nonresponse and extensive residual nodal disease were found to be significantly associated with detection failure of sentinel nodes. Sensitivity, FNR, NPV, and accuracy of SLNB were 78.0, 22.0, 75.8, and 87.0 %, respectively, and a greater number of retrieved SLNs increased all four of these performance measures. Conversion to node-negative disease was achieved in 69 (40.8 %) patients: 24 % of patients with the luminal A subtype, 51.6 % of patients with the luminal B, 51.7 % of patients with the HER2-enriched, and 58.5 % of patients with the triple-negative breast cancer (TNBC) subtype. Luminal B, HER2-enriched, and TNBC subtypes showed comparable responses to NCT; however, the TNBC subtype had a significantly better FNR and accuracy.

Conclusions

SLNB was found to be technically feasible, but its routine use was not recommended for LABCs after NCT. However, acceptable performance was noted for locally advanced TNBCs, and thus SLNB might be safely considered in these selected patients.     

Predicting Non-sentinel Lymph Node Metastases in Patients with a Positive Sentinel Lymph Node After Neoadjuvant Chemotherapy

Background

The standard of care for breast cancer patients treated with neoadjuvant chemotherapy (NAC) who have a positive sentinel lymph node (+SLN) after NAC is completion axillary lymph node dissection (ALND). This study aimed to develop a nomogram to predict additional nodal disease in patients with +SLN after NAC.

Methods

The study reviewed patients 18 years of age or older who had invasive breast cancer treated with NAC followed by SLN surgery with +SLN and ALND between 2006 and 2017 at the authors’ institution. Factors predictive of positive non-SLNs were analyzed using uni- and multivariable logistic regression.

Results

The study identified 120 patients with +SLN after NAC and ALND. Of these patients, 30.8% were clinically node-negative (cN?), and 69.2% were clinically node-positive (cN+) before NAC. Tumor biology was human epidermal growth factor receptor 2-positive (HER2+) for 20%, hormone receptor-positive (HR+)/HER2? for 66.7%, and triple-negative breast cancer (TNBC) for 13.3% of the patients. Additional nodal disease was found on ALND for 63.3% of the patients. In the univariate analysis, the factors predictive of positive non-SLNs were biologic subtype (TNBC and HR+/HER2? vs HER2+; p?<?0.001), higher grade (p?=?0.047), higher pT category (p?=?0.02), SLN extranodal extension (p?=?0.03), larger SLN metastasis size (p?<?0.001), and higher number of +SLNs (p?=?0.02). The factors significant in the multivariable analysis included number of +SLNs, grade 3 vs grade 1 or 2, HER2+ versus HER2?, cN+ versus cN?, and larger SLN metastasis size. The resulting model showed excellent discrimination (area under the curve, 0.82; 95% confidence interval, 0.74–0.90) and good calibration (p?=?0.54, Hosmer–Lemeshow).

Conclusion

A clinical prediction model incorporating biologic subtype, grade, clinical node status, size of the largest SLN metastasis, and number of +SLNs can help physicians and patients estimate the likelihood of additional nodal disease and may be useful for guiding decision making regarding axillary management.

     

Comprehensive Axillary Evaluation in Neoadjuvant Chemotherapy Patients With Ultrasonography and Sentinel Lymph Node Biopsy

Background There is ongoing debate regarding the optimal sequence of sentinel lymph node (SLN) biopsy and neoadjuvant chemotherapy (CTX) for breast cancer. We report the accuracy of comprehensive pre–neoadjuvant CTX and post–neoadjuvant CTX axillary staging via ultrasound imaging, fine-needle aspiration (FNA) biopsy, and SLN biopsy.Methods From 2001 to 2004, 91 neoadjuvant CTX patients at the University of Michigan Comprehensive Cancer Center underwent axillary staging by ultrasonography, ultrasound-guided FNA biopsy, SLN biopsy, or a combination of these.Results Axillary staging was pathologically negative by pre–neoadjuvant CTX SLN biopsy in 53 cases (58%); these patients had no further axillary surgery. In 38 cases (42%), axillary metastases were confirmed at presentation by either ultrasound-guided FNA or SLN biopsy. These 38 patients underwent completion axillary lymph node dissection (ALND) after delivery of neoadjuvant CTX. Follow-up lymphatic mapping was attempted in 33 of these cases, and the SLN was identified in 32 (identification rate, 97%). One third of these cases were completely node negative on ALND. Residual metastatic disease was identified in 22 cases, and the SLN was falsely negative in 1 (4.5%).Conclusions Patients receiving neoadjuvant CTX can have accurate axillary nodal staging by ultrasound-guided FNA or SLN biopsy. In cases of documented axillary metastasis at presentation, repeat axillary staging with SLN biopsy can document the post–neoadjuvant CTX nodal status. This strategy optimizes pre–neoadjuvant CTX and post–neoadjuvant CTX staging information by distinguishing the patients who are node negative at presentation from those who have been downstaged to node negativity and offers the potential for avoiding unnecessary ALNDs in both of these patient subsets.Published by Springer Science+Business Media, Inc. © 2005 The Society of Surgical Oncology, Inc.     

Second Biopsy of Axillary Sentinel Lymph Node for Reappearing Breast Cancer After Previous Sentinel Lymph Node Biopsy

Background Sentinel lymph node biopsy (SLNB) is a safe and accurate axillary staging procedure for patients with primary operable breast cancer. An increasing proportion of these patients undergo breast-conserving surgery, and 5% to 15% will develop local relapses that necessitate reoperation. Although a previous SLNB is often considered a contraindication for a subsequent SLNB, few data support this concern. Methods Between January 2000 and June 2004, 79 patients who were previously treated at our institution with breast-conserving surgery and who had a negative SLNB for early breast cancer developed, during follow-up, local recurrence that was amenable to reoperation. Eighteen of these patients were offered a second SLNB because of a clinically negative axillary status an average of 26.1 months after the primary event. Results In all 18 patients (7 with ductal carcinoma-in-situ and 11 with invasive recurrences), preoperative lymphoscintigraphy showed an axillary sentinel lymph node, with a preoperative identification rate of 100%, and 1 or more SLNs (an average of 1.3 per patient) were surgically removed. Sentinel lymph node metastases were detected in two patients with invasive recurrence, and a complete axillary dissection followed. At a median follow up of 12.7 months, no axillary recurrences have occurred in patients who did not undergo axillary dissection. Conclusions Second SLNB after previous SLNB is technically feasible and likely effective in selected breast cancer patients. A larger population and longer follow-up are necessary to confirm these preliminary data.     

Beyond the False Negative Rate: Development of Quality Indicators for Sentinel Lymph Node Biopsy in Breast Cancer

Background  

Sentinel lymph node biopsy (SNLB) has been adopted as the standard method of axillary staging for women with clinically node-negative early-stage breast cancer. The false negative rate as a quality indicator is impractical given the need for a completion axillary dissection to calculate. The objective of this study was to develop practical quality indicators for SLNB using an expert consensus method and to determine if they were feasible to measure.     

Sentinel Lymph Node Biopsy Performed After Neoadjuvant Chemotherapy is Accurate in Patients with Documented Node-Positive Breast Cancer at Presentation

Background The optimal strategy for incorporating lymphatic mapping and sentinel lymph node biopsy into the management of breast cancer patients receiving neoadjuvant chemotherapy remains controversial. Previous studies of sentinel node biopsy performed following neoadjuvant chemotherapy have largely reported on patients whose prechemotherapy, pathologic axillary nodal status was unknown. We report findings using a novel comprehensive approach to axillary management of node-positive-patients receiving neoadjuvant chemotherapy. Methods We evaluated 54 consecutive breast cancer patients with biopsy-proven axillary nodal metastases at the time of diagnosis that underwent lymphatic mapping with nodal biopsy as well as concomitant axillary lymph node dissection after receiving neoadjuvant chemotherapy. All cases were treated at a single comprehensive cancer center between 2001 and 2005. Results The sentinel node identification rate after delivery of neoadjuvant chemotherapy was 98%. Thirty-six patients (66%) had residual axillary metastases (including eight patients that had undergone resection of metastatic sentinel nodes at the time of diagnosis), and in 12 cases (31%) the residual metastatic disease was limited to the sentinel lymph node. The final, post-neoadjuvant chemotherapy sentinel node was falsely negative in three cases (8.6%). The negative final sentinel node accurately identified patients with no residual axillary disease in 17 cases (32%). Conclusions Sentinel lymph node biopsy performed after the delivery of neoadjuvant chemotherapy in patients with documented nodal disease at presentation accurately identified cases that may have been downstaged to node-negative status and can spare this subset of patients (32%) from experiencing the morbidity of an axillary dissection.     

Impact of Omission of Axillary Lymph Node Dissection After Negative Sentinel Lymph Node Biopsy: 70-Month Follow-up

Background  

The objective of this study is to assess the oncologic safety of sentinel lymph node biopsy (SLNB), especially with regard to the axillary recurrence (AR) rate, and to determine the risk factors for AR and disease-free survival (DFS) and overall survival (OS) after negative SLNB.     

Sentinel Lymph Node Biopsy After Preoperative Chemotherapy for Breast Cancer: Findings from the Austrian Sentinel Node Study Group

Background  Sentinel lymph node biopsy (SLNB) has become an accurate alternative to axillary lymph node dissection for early breast cancer. However, data are still insufficient as regards the combination of SLNB with preoperative chemotherapy (PC). Methods  The Austrian Sentinel Node Study Group investigated 167 patients who underwent SLNB and axillary lymph node dissection after 3 to 6 courses of PC. SLNB was limited to patients with a clinically negative axilla after PC. Blue dye was used in 29 cases (17%), and tracers were used in 20 (12%). A combination of the two methods was applied in most patients (n = 120; 72%). Results  At least 1 sentinel lymph node (SLN) was identified in 144 patients (identification rate, 85%): in 86% by blue dye alone, in 65% by tracers alone, and in 88% by a combination of methods. The SLN was positive in 70 women (42%) and was the only positive node with otherwise negative axillary nodes in 39 patients (23%). In 6 cases, the SLN was diagnosed as negative although tumor infiltration was detected in an upper node of the axillary basin (false-negative rate, 8%; 6 of 76 patients; sensitivity, 92%). At least 62 patients (37%) were free of tumor cells in the SLN and in the axillary nodes. Conclusion  The results of SLNB after PC are comparable to the results of SLNB without PC. Further investigation in a prospective setting is warranted to confirm these promising results.     

Sentinel Node Lymph Node Surgery After Neoadjuvant Therapy: Principles and Techniques

Annals of Surgical Oncology - Surgical management of the axilla in breast cancer has been a topic of great interest. While sentinel lymph node biopsy (SLNB) is an established approach for patients...     

Lymphatic Mapping and Sentinel Lymph Node Biopsy

The status of the regional nodal basin remains the most important prognostic indicator of survival. The current standard of care for the management of invasive breast cancer is the complete removal of the tumor, with documentation of negative margins by either mastectomy or lumpectomy, followed by complete axillary lymph node dissection. Data suggest that complete lymph node dissection (CLND) provides better local control of the disease and may actually offer a survival advantage. Lymphatic mapping and sentinel lymph node (SLN) biopsy are clearly changing this long-held paradigm and have the potential to change the standard of surgical care of the breast cancer patient. The purpose of this report is to describe the lymphatic mapping experience at the H. Lee Moffitt Cancer Center and Research Institute. From April 1994 to January 1999, 1,147 consecutive breast cancer patients were enrolled in an institutional review board-approved lymphatic mapping protocol. Lymphatic mapping was performed using Tc99m-labeled sulfur colloid and isosulfan blue dye. An SLN was defined as any blue node and/or any hot node with ex vivo radioactivity counts >/=10 times an excised non-SLN or in situ radioactivity counts >/=3 times the background counts. Lymphatic mapping was successful in identifying the SLN in 1,098 of 1,147 (95.7%) cases. In the first 186 patients, all of whom underwent CLND following SLN biopsy, one false-negative biopsy was encountered for a false-negative rate of 0.83%. The method of diagnosis (excisional versus minimally invasive) does not appear to impact on lymphatic mapping. Tumor size, however, is directly related to the probability of axillary lymph node involvement. Advances in technology and the development of minimally invasive surgical techniques have heralded a new era in surgery. Lymphatic mapping and SLN biopsy may actually prove to be a more accurate method of identifying metastases to the axilla by allowing a more focused pathologic examination of the axillary node(s) at highest risk for metastasis. With adequate training, this technique can be readily implemented as a valuable tool in the surgical treatment of breast cancer.     

Patterns of Recurrence After Sentinel Lymph Node Biopsy for Breast Cancer

Background: Sentinel lymph node biopsy (SLNB) is gaining acceptance as an alternative to axillary lymph node dissection. The purpose of this study was to determine the frequency and pattern of disease recurrence after SLNB.Methods: Two-hundred twenty-two consecutive patients undergoing SLNB from April 6, 1998, to October 27, 1999, and who were 24 months out from their procedure were identified from a prospectively maintained database. Retrospective chart review and data analysis were performed to identify variables predictive of recurrence.Results: The median patient follow-up was 32 months (range, 24–43 months). A total of 159 patients (72%) were sentinel lymph node (SLN) negative and had no further axillary treatment. Five of these patients (3.1%) developed a recurrence (one local and four distant), with no isolated regional (axillary) recurrences. Sixty-three patients (28%) were SLN positive and underwent a subsequent axillary lymph node dissection. Six of these patients (9.5%) developed a recurrence (three local, one regional, and two distant). Pathologic tumor size (P < .001), lymphovascular invasion (P = .018), and a positive SLN (P = .048) were all statistically significantly associated with disease recurrence.Conclusions:With a minimum follow-up of 24 months, patients with a negative SLN and no subsequent axillary treatment demonstrate a low frequency of disease recurrence. This supports the use of SLNB as the sole axillary staging procedure in SLN-negative patients.     

Implications of Popliteal Lymph Node Detected by Sentinel Lymph Node Biopsy

BACKGROUND: Although there is lymphatic flow into the popliteal fossa from a skin tumor located in the lower leg, popliteal metastasis is extremely rare. Recently, sentinel lymph nodes outside traditional nodal basins have been identified. This study investigated the incidence of sentinel nodes in the popliteal region and the indication for biopsy. METHODS: Fourteen patients with various skin cancers involving the lower extremities (nine melanomas, four squamous cell carcinomas, and one sweat gland carcinoma) underwent lymphoscintigraphy and excision with sentinel lymph node biopsy. RESULTS: In all 14 patients, hot spots showed accumulation in the groin region. Five of 14 patients (36%) demonstrated popliteal sentinel nodes in addition to the inguinal nodes. Three of five popliteal sentinel nodes were histologically studied. A patient with acral melanoma demonstrated micrometastasis of melanoma cells in a popliteal node but not in the groin node. CONCLUSION: This study demonstrates that sentinel lymph nodes located in the popliteal fossa are frequently detected by lymphoscintigraphy and that biopsy should be performed if popliteal nodes are identified.