Sentinel node biopsy in breast cancer has a greater node positivity rate than axillary node sample: Results from a retrospective analysis

Background

Sentinel node biopsy as a surgical method of axillary staging for early breast cancer has been widely accepted as an alternative to traditional four-node axillary node sampling, and is the recommended technique by the Association of Breast Surgery in the United Kingdom. In selected units axillary sampling has been compared with either radioisotope sentinel node or blue dye only techniques with comparable node positivity rates. There are no studies directly comparing combined method sentinel node biopsy (SNB) with conventional axillary (four) node sampling (ANS).

Methods

Data for all patients undergoing axillary staging by axillary node sample or sentinel node biopsy were collected, including those proceeding to axillary clearance as a second procedure, but excluding those undergoing axillary clearance as a first procedure.

Results

From January 2005 to January 2011, 641 axillary staging procedures were performed (SNB n = 231 (36.0%), ANS n = 410 (64.0%)). Baseline tumour characteristics were similar for the two groups except for a higher frequency of breast conservation in the SNB group (95.6 vs. 75.6%; p < 0.0001). The proportion of cases with positive nodes was higher in the SNB group (20.8 vs. 14.4%; p = 0.042). In patients who had presented with symptomatic disease, there was a significantly higher node positivity rate with SNB (30.9%) than with ANS (15.5%; p = 0.002), despite similar baseline characteristics in both groups.

Conclusion

Combined method sentinel node biopsy is more sensitive at detecting low volume axillary disease than traditional four-node sample.     

Ultrasound and fine needle aspiration cytology of the axilla in the pre-operative identification of axillary nodal involvement in breast cancer

Aims

Pre-operative diagnosis of axillary nodal involvement in breast cancer allows one-stage axillary surgery. We evaluated the efficacy of axillary ultrasound (US) with US guided fine needle aspiration cytology (FNAC) in the diagnosis of axillary nodal involvement.

Methods

Over a 13-month period, we performed US of 369 axillae in patients with screen-detected (n = 278) and symptomatic (n = 91) invasive carcinoma of the breast, at the same time as US of the primary tumour. If abnormal lymph nodes were demonstrated, a single US guided FNAC of the most abnormal node was performed. US and FNAC results were compared with the final histology of the surgically excised lymph nodes.

Results

Among the 369 axillae studied, 102 had nodal macrometastases and 38 (37%) were identified by US guided FNAC. The rate was 33% in screen-detected and 44% in symptomatic patients. Sensitivity increased with increasing numbers of positive axillary nodes, and the more abnormal the appearances of the nodes on US.

Conclusion

US with FNAC of the most abnormal node allows pre-operative detection of a third of node positive axillae in screen-detected and over 40% of those with symptomatic breast cancer, allowing one-stage axillary surgery avoiding the sentinel node biopsy step in these patients.     

Validation of a technique using microbubbles and contrast enhanced ultrasound (CEUS) to biopsy sentinel lymph nodes (SLN) in pre-operative breast cancer patients with a normal grey-scale axillary ultrasound

Background

In patients with breast cancer, grey-scale ultrasound often fails to identify lymph node (LN) metastases. We aimed to validate the technique of contrast-enhanced ultrasound (CEUS) as a test to identify sentinel lymph node (SLN) metastases and reduce the numbers of patients requiring a completion axillary node clearance (ANC).

Methods

371 patients with breast cancer and a normal axillary ultrasound were recruited. Patients received periareolar intra-dermal injection of microbubble contrast agent. Breast lymphatics were visualised by CEUS and followed to identify and biopsy axillary SLN. Patients then underwent standard tumour excision and either SLN excision (benign biopsy) or axillary clearance (malignant biopsy) with subsequent histopathological analysis.

Results

The technique failed in 46 patients, 6 patients had indeterminate biopsy results and 24 patients were excluded. In 295 patients with a conclusive SLN biopsy, the sensitivity of the technique was 61% and specificity 100%. Given a benign SLN biopsy result, the post-test probability that a patient had SLN metastases was 8%. 35 patients were found to have SLN metastases and had a primary ANC (29 macrometastases and 6 micrometastases/ITC). There were 22 false negative results (10 macrometastases and 12 micrometastases). Macrometastases in core biopsy specimens correlated with LN macrometastases on surgical excision.

Conclusion

Pre-operative biopsy of SLN reduced the numbers of patients requiring completion ANC. Despite the low sensitivity, only 22 patients (8%) with a benign SLN biopsy were subsequently found to have LN metastases. Without the confirmation of macrometastases on core biopsy specimens, patients with micrometastases/ITC may be inadvertently selected for primary ANC.     

Risk Stratification of Patients With Early Breast Cancer

BackgroundSentinel lymph node biopsy (SLNB) is the standard procedure performed to stage the axillae, and axillary node clearance (ANC) or radiotherapy is the treatment for nodal involvement. The aims of this study were to assess (1) the role of preoperative axillary ultrasonography (US), (2) the number of positive lymph nodes on ANC after either positive SLNB results or preoperative ultrasonographically guided nodal biopsy, and (3) the role of ANC in patients with node-positive breast cancer.Patients and MethodsAll patients with invasive breast cancer and axillary node involvement (but clinically negative nodes on presentation) who underwent ANC between January 2008 and December 2009 were identified, and information regarding clinicopathologic parameters and the nodal yield was collected. ANC was performed for 3 groups: patients with micrometastasis seen in SLNB specimens, macrometastasis seen in SLNB specimens, and positive axillary nodes detected on US biopsy.ResultsANC was performed 141 times over the 2-year period. Forty-two percent of axillary node involvement was diagnosed by biopsy or preoperative US, and 40% of these patients received neoadjuvant chemotherapy. The remainder of cases were diagnosed by SLNB: 30% had micrometastases and 70% had macrometastases. Fifty percent of cancers with an ultrasonographic diagnosis of lymph node involvement were high grade and 56% had 4 or more positive nodes on ANC; this was significantly higher than in patients with positive SLNB results (P = .0001). Only 20% of patients with macrometastases on SLNB had 4 or more positive nodes in comparison with 56% with positive axillary lymph nodes by US (P < .0001).ConclusionThe routine use of preoperative axillary US and biopsy of abnormal nodes helps in identifying high-risk patients and thus aids in planning treatment.     

The feasibility of sentinel node biopsy in the previously treated breast

Purpose

Sentinel lymph node biopsy (SNB) has been a standard technique in early breast cancer. However, it is not clear that the SNB procedure can be applied to second breast cancer or recurrence occurring in the previously treated breast. The purpose of this study was to clarify the feasibility of the SNB procedure in breast cancer occurring in the previously treated breast, and to investigate the factors related to altered lymphatic flow.

Patients and methods

Between April 2004 and December 2006, 1490 patients underwent the breast SNB procedure. Among them, 31 patients had a history of previous treatments in the same breast. Recent excision biopsy cases were not included in this group. All patients had previous breast-conserving surgery in the same breast. Sixteen patients had axillary dissection, 3 had SNB, and 12 had no axillary treatment. Ten patients had received radiation therapy to the breast and axilla. Visualization of axillary nodes, internal mammary nodes and contralateral axillary nodes was evaluated and compared with pathological results.

Results

Axillary nodes were visualized in 23 patients, internal mammary nodes in 7 patients, and contralateral axillary nodes in 7 patients. The patients with previous axillary dissection exhibited altered lymph node distribution, but did not show involvement of contralateral axillary nodes. Visualization of contralateral axillary nodes occurred in 7 of the 10 patients with previous irradiation to breast irrespective of axillary dissection. Twenty-eight patients underwent SNB, 4 of whom showed cancer-positive nodes. Three patients were cancer-positive in non-ipsilateral axillary nodes (one patient showed positive opposite axillary node and two patients showed positive internal mammary nodes).

Conclusion

Previous axillary dissection or irradiation to the breast greatly influences lymphatic flow. Irradiation to the breast may be a strong factor for the visualization of contralateral axillary nodes. Despite the frequent alteration of lymphatic flow, SNB seems to be feasible in secondary or recurrent breast cancer patients.     

Staging and management of axillary lymph nodes in patients with local recurrence in the breast or chest wall after a previous negative sentinel node procedure

Objective

To evaluate axillary staging and management in patients with local recurrence (LR) after a previous negative sentinel lymph node biopsy (SNB).

Methods

Between 1999 and 2008, 130 patients with previous negative SNB developed a LR of breast or chest wall. After examination of clinical records, 70 patients met the inclusion criteria and remained available for analysis.

Results

Thirty-seven patients were treated with axillary lymph node dissection (ALND), followed by axillary radiotherapy in 9 cases. In 26 of these 37 patients no positive axillary lymph nodes were found. Nineteen patients received no treatment of the axilla at all. Of those, 9 were older than 70 years of age at diagnosis of LR. In 13 patients a second SNB was attempted, but was successful in only 5 cases. Eight patients underwent a complementary ALND. Overall, positive lymph nodes were detected in 13 of the 50 patients who underwent axillary staging, either by SNB or ALND. The median length of follow-up of the 70 patients following their diagnosis of LR was 24 months (range 2–81 months). During this follow-up period one patient developed an axillary recurrence. This was a patient who refused to undergo ALND but was given locoregional radiotherapy instead.

Conclusions

In the absence of guidelines for staging and management of the axilla at time of LR of breast or chest wall, many different strategies are being used. Considering the high rate of positive axillary lymph nodes in these patients, repeat surgical staging is appropriate.     

Quantitation of sentinel node metastatic burden and Her-2/neu over-expression accurately predicts residual axillary nodal involvement and extranodal disease in breast cancer

Background data

Recent literature has suggested that completion axillary lymph node dissection (ALND) in breast carcinoma patients with positive SLN may not be necessary. However, a method for determining the risk of non-SLN or extranodal disease remains to be established.

Aims

To determine if pathological variables from primary tumors and sentinel lymph node (SLN) metastases could predict the probability of non-sentinel lymph node (NSLN) metastases and extranodal disease in patients with breast carcinoma and SLN metastases.

Methods

84 women with T1-3 breast cancer and clinically-negative axillae underwent completion ALND. Maximum diameter and width of SLN metastases were measured to calculate metastatic area. When multiple SLNs contained metastases, areas were summed to calculate the Total Metastatic Area (TMA). Multiple linear regression models were used to identify predictive factors.

Results

Her-2/neu over-expression increased the odds of NSLN metastases (OR 4.3, p = 0.01) and extranodal disease (OR 7.9, p < 0.001). Independent SLN predictors were ≥1 positive SLN (OR, 7.35), maximum diameter and area of SLN metastases (OR 2.26, 1.85 respectively) and TMA (OR, 2.12). Maximum metastatic diameter/SLN diameter (OR 3.71, p = 0.04) and the area of metastases/SLN area (OR 3.4, p = 0.04) were predictive. For every 1 mm increase in diameter of SLN metastases, the odds of NSLN extranodal disease increased by 8.5% (p = 0.02). TMA >0.40 cm² was an independent predictor for NSLN metastases and extranodal disease.

Conclusion

Her-2/neu over-expression and parameters assessing metastatic burden in the SLN, particularly TMA, predicted the presence of NSLN involvement and extranodal disease in patients with breast carcinoma and SLN metastases.     

The role of sentinel node biopsy in ductal carcinoma in situ of the breast

Aim

Sentinel node biopsy (SNB) is an accepted alternative to lymphadenectomy in the case of invasive breast carcinoma, although the sentinel node's role in ductal carcinoma in situ (DCIS) diagnosed on core needle biopsy has not been well defined nevertheless guidelines recommend this procedure. The purpose of this study was to determine the diagnostic value of sentinel nodes in female patients with primary DCIS using core needle stereotactic biopsy.

Material and methods

Between the years 2000 and 2005, 261 patients were diagnosed with DCIS by core needle biopsy. In this group, 183 patients underwent SNB to determine lymph node involvement. Those patients with metastases to the sentinel node underwent axillary lymphadenectomy.

Results

In the group of 183 patients that underwent SNB, 10 patients (5.5%) showed metastases to the sentinel lymph node. Histopathological studies of the primary lesions of these 10 patients revealed invasive ductal carcinoma in 6 cases (3.5%) and 1 case (0.5%) of invasive lobular carcinoma. Only 3 of the patients (1.5%) were given a final diagnosis of DCIS with metastases to sentinel lymph nodes, of which 2 cases were DCIS and 1 case was DCIS with microinvasion. Axillary lymphadenectomy performed on patients with abnormal SNB showed involvement of other axillary lymph nodes in 4 patients.

Conclusions

SNB as a diagnostic tool in DCIS remains controversial as the number of cases of axillary lymph node metastases is minuscule. The biggest clinical challenge in this situation is a group of patients with primary diagnosis of DCIS in which invasive components are seen by mammotomic biopsy.     

Intraoperative evaluation of axillary sentinel lymph nodes using touch imprint cytology and immunohistochemistry. Part II. Results.

AIM: In order to operate selectively on positive axillae during the initial operative session for early breast cancer, an accurate and rapid intraoperative method to examine an axillary node sample (ANS) or a sentinel node biopsy (SNB) is required. The aim of this study was to determine the feasibility and accuracy of Immunohistochemistry (IHC)-stained touch imprints in detecting metastatic axillary nodes intraoperatively. MATERIAL AND METHODS: Four hundred and thirty-two axillary nodes from 52 patients (23 axillary node clearance (ANC), 15 ANS and 14 SNB) were bisected, imprinted and stained with anti-cytokeratin 19 IHC. Results were compared with those of routine haematoxylin and eosin (H&E)-stained sections. RESULTS: IHC imprints detected 32 positive nodes from 12 patients. H&E sections detected 31 positive nodes from 11 patients. IHC imprints missed metastases in three nodes and missed the diagnosis of positive axillae in two patients. H&E missed metastases in four nodes and missed the diagnosis of positive axillae in 3 patients. On a node-basis, sensitivities were 91.4 and 88.5%, negative predictive values (NPV) were 99.2 and 99.0% and overall accuracies were 99.3 and 99.1% for IHC imprints and H&E sections, respectively. On a patient-basis, sensitivities were 85.7 and 78.5%, NPVs were 95.2 and 93.1% and overall accuracies were 96.1 and 94.2% for IHC imprints and H&E sections respectively. There were no false positives. Interpretation of the results by a non-histopathologist was concordant with that of a histopathologist. Results might be obtained within 30-45 min depending on the number of examined nodes. CONCLUSION: Intraoperative IHC staining of touch imprints of axillary sentinel nodes is feasible and is a reliable method for evaluating axillary nodes. Slides can be reliably interpreted by a trained non-histopathologist.     

The sensitivity of pre-operative axillary staging in breast cancer: Comparison of invasive lobular and ductal carcinoma

Introduction

Axillary ultrasound (AUS) with fine-needle aspiration (FNA) biopsy of abnormal lymph nodes is important for pre-operative staging and planning the surgical management of the axilla. Invasive lobular carcinoma (ILC) metastases are thought to be difficult to detect because the cells are small and on cytology resemble lymphocytes. To investigate this we directly compared the sensitivity of pre-operative axillary staging between ILC and invasive ductal carcinoma (IDC).

Method

Consecutive patients that presented in a single breast unit with pure IDC between April 2005 and December 2006 and pure ILC between January 2008 and December 2012 were retrospectively identified from pathology records. Pre-operative axillary ultrasound and FNA biopsy results were compared with post-operative histopathology from the sentinel node biopsy (SNB) or axillary lymph node dissection (ALND).

Results

A total of 275 and 142 axillae were identified in the IDC and ILC groups respectively. In the node positive patients there was no significant difference in the sensitivity of AUS (IDC vs. ILC; 58.7% vs. 52.8%). However, there was a significant difference in the sensitivity of ultrasound-guided FNA biopsy of abnormal nodes (IDC vs. ILC; 98.4% vs. 53.6%; p < 0.001).

Conclusion

AUS has comparative sensitivities between IDC and ILC populations. In contrast, FNA biopsy of abnormal axillary nodes is clearly less sensitive in the ILC group. In these patients, who have abnormal AUS, we suggest that a core biopsy is required to improve the pre-operative staging and prevent unnecessary surgical procedures.     

Perioperative diagnosis of the positive axilla in breast cancer: A safe, time efficient algorithm

Background

This study evaluates the combined role of axillary ultrasound (Ax US), fine needle aspiration (FNAC) and intraoperative frozen section analysis of the sentinel node (FS SN) in a practical, time efficient algorithm to reduce the requirement for reoperation for axillary clearance in breast cancer in a busy tertiary unit.

Methods

Between October 2007 and June 2009 188 women underwent Ax US as a first investigation for nodal status. Suspicious nodes were biopsied, negative axillae proceeded to FS SN at time of primary breast surgery. All confirmed positive cases proceeded to immediate axillary clearance.

Results

93 women had positive axillary nodes at final histology. Ax US + FNAC identified 59 positive axillae and had a sensitivity of 63.4% and specificity of 100%. FS SN identified a further 26 cases with a sensitivity of 76.5% and specificity of 100%. Overall, only 8 women required reoperation for axillary clearance. Sensitivity for the combined procedures was 91.4%. Commencement of adjuvant therapy was significantly less in those women identified earlier compared to those requiring a second operation (23.3 days vs 49.0 days, p < 0.005).

Conclusion

95.7% of cases were diagnosed accurately in the perioperative period, preventing delay to triage to definitive oncological care and reducing requirement for costly reoperation.     

Axillary Surgery Following Neoadjuvant Chemotherapy – Multidisciplinary Guidance From the Association of Breast Surgery,Faculty of Clinical Oncology of the Royal College of Radiologists,UK Breast Cancer Group,National Coordinating Committee for Breast Pathology and British Society of Breast Radiology

AimsThese multidisciplinary guidelines aim to provide clinically helpful, evidence-based recommendations on the surgical management of the axilla in patients who have received neo-adjuvant chemotherapy for early breast cancer.Materials & methodsFollowing a review of published evidence, a writing group representing all disciplines quorate within a breast cancer multidisciplinary meeting prepared the guidelines.Key recommendationsIn patients presenting with clinically node negative axillae, sentinel node biopsy (SNB) may be performed prior to or on completion of neo-adjuvant chemotherapy (NACT). In patients presenting with clinically node positive axillae, SNB may be safely considered following completion of NACT. Four nodes should be removed with dual mapping. If evidence of complete pathological response of previous metastases is seen, axillary radiotherapy may be offered. If residual cancer (isolated tumour cells, micro- or macrometastes) is seen within the SNB, offer axillary node dissection.     

Completion axillary dissection can safely be omitted in screen detected breast cancer patients with micrometastases. A decade's experience from a single institution

Background

The need for completion axillary lymph node dissection (ALND) in breast cancer patients with micrometastases in the sentinel nodes (SNs) is controversial. The aim of this retrospective observational study is to determine if the method of detection of early breast cancer is predictive for additional positive nodes in patients with micrometastases in the SNs.

Methods

Between 2001 and 2011 a total of 1993 women with primary unilateral breast cancer had surgery at Skåne University Hospital, Lund. Of 1993 patients, 1458 had an SN biopsy and nearly all patients with micro- and macrometastases had ALND.

Results

Micrometastases defined as >0.2 mm/>200 cells and ≤2.0 mm were found in 62 of 757 screen-detected patients and in 81 of 701 patients with symptomatic breast cancer. Only 3 of the screen-detected patients with micrometastases, all with tumour size >15 mm (range 18–39 mm), had metastases in the completion ALND whereas this was found in 18 of the symptomatic patients with micrometastases (p = 0.01), (tumour size, range 10–30 mm). Logistic regression analysis adjusted for method of detection, tumour size and histological grade showed 5 times higher odds for further metastases in ALND in patients with symptomatic presentation vs. screen-detected breast cancer.

Conclusion

Despite the small number of patients with micrometastases in this large cohort of breast cancer patients, these results support the contention that completion ALND can safely be omitted in screen-detected breast cancer patients with micrometastases in the SNs.     

The real-time intra-operative evaluation of sentinel lymph nodes in breast cancer patients using One Step Nucleic Acid Amplification (OSNA) and implications for clinical decision-making

Introduction

One Step Nucleic Acid Amplification (OSNA) method for the intraoperative analysis of sentinel lymph nodes (SLNs) in breast cancer, obviates a second operation to the axilla and thereby expedites progression to adjuvant therapy. Recent NICE guidelines have approved OSNA as a method of sentinel node diagnosis to support the above case.¹

Method

This is a single centre prospective cohort analysis of all patients undergoing breast cancer surgery including sentinel node biopsy from February 2010 to June 2012. Patients with negative SLN(s) on OSNA had no further axillary surgery. A validation phase was performed prior to using OSNA routinely. Those with micrometastases underwent a level 1 clearance, and >one SLN with macrometastases, underwent treatment by level 2 axillary dissection. The length of time from sentinel node retrieval to OSNA result was recorded.

Results

Four hundred and forty nodes were analysed in 212 patients with a mean age of 55 years (range 24–98). The sensitivity and specificity of OSNA was 93% and 94% respectively in cases of macrometastases. The process required additional median anaesthesia time of 20 min (range −48 to +65 min). Non-sentinel node positivity was 5% and 48% for micrometastasis and macrometastasis respectively.

Conclusion

OSNA identified 62 of 212 patients with at least one positive sentinel node, thereby sparing 29% from a second procedure to clear the axilla subsequently. The median waiting time of 20 min for node results from completion of breast procedure is acceptable and allows for an efficient operating list. OSNA can be incorporated into routine practice and with improved methods of imaging preoperatively, can be an excellent adjunct to the breast cancer patient pathway of care.     

Minimal access breast surgery – A single breast incision for breast conservation surgery and sentinel lymph node biopsy

Aims

Minimal access breast surgery (MABS) is a procedure that completes breast conservation surgery (BCS) and sentinel node biopsy (SNB) through a single incision. It allows access to axillary sentinel nodes via the breast incision and also provides access to the internal mammary nodes (IMN) as well as other nodal sites when needed. The aims of this study are to describe the MABS approach and to evaluate its safety and efficacy in cases undergoing BCS and SNB (axillary or IMN) for treatment of breast cancer.

Methods

The surgical technique for MABS is described. One hundred and three consecutive clinically lymph node negative patients undergoing BCS and SNB (axillary or IMN) were considered for MABS. Cases were classified according to the location of sentinel nodes dissected (axillary, internal mammary or other), the location of the tumour and whether MABS was used. The success of MABS was calculated based on the number of cases where BCS and SNB were completed through a single breast incision. Number of lymph nodes (LN) retrieved, rate of LN positivity, aesthetics and complications were documented.

Results

Eighty-six percent of cases of BCS with axillary-only SNB were completed with MABS. For cases of BCS with axillary and IMN SNB, MABS was successful for BCS and IMN SNB in 97% of cases and for BCS and SNB from both nodal regions in 63%. There was only one case, a woman with breast prostheses, who required three separate incisions. When axillary-only SNB cases were completed with MABS, an average of 2.9 axillary LN per case with a 29% axillary LN positivity rate was seen. When axillary and IMN SNB were completed with MABS for both regions, an average of 3.0 axillary LN per case were retrieved with an axillary LN positivity rate of 65%. When separate axillary and breast incisions were made, 2.7 LN per case were removed with an axillary LN positivity rate of 30%. Aesthetics were excellent and there were no complications associated with reaching the nodes through the breast incision.

Conclusion

MABS is a feasible option for the majority of women undergoing BCS and SNB and it does not compromise the success of SNB.     

Intra-operative imprint cytology for assessing the sentinel node in breast cancer – Results of its routine use over 8 years

Introduction

Intra-operative imprint cytology (IIC) for analysing sentinel lymph node/s (SLN) in breast cancer allows definitive axillary surgery as a one-step procedure. Most reported studies are research oriented. This study reports long-term results of IIC done as routine clinical practice.

Materials and methods

Eight hundred ninety-six female, operable breast cancer patients underwent SLN biopsy over an 8-year period (January 1999–December 2006). Data were extracted retrospectively from medical records. SLNs were sent intra-operatively to the laboratory where they were bisected, touch imprinted and stained with Hematoxylin & Eosin. Patients with positive IIC had axillary clearance. Formal histological analyses of SLNs were compared with IIC findings. The impact of routine pre-operative axillary ultrasound (introduced in 2003) on IIC sensitivity and specificity was also assessed.

Results

Median age was 61 years (26–89) and median tumour size was 18 mm (2–100). A total of 244/896 patients had SLN metastases on final paraffin histology of which 177 were correctly detected by IIC (67 false negatives). 39/67 false negatives could be attributed to sampling error. The overall sensitivity and specificity of IIC for the identification of SLN metastases was 73% and 100%, respectively. The sensitivity of IIC after introduction of pre-operative axillary ultrasound decreased from 75% to 71%.

Discussion

Routine use of IIC for analysis of the SLN in breast cancer allows complete axillary surgery during a single anaesthetic for a majority of patients undergoing SLN biopsy. Almost two thirds of positive axillae were spared a second operation. False negative results are frequent and patients should be warned about the potential need for further axillary surgery.     

Observational study of blue dye-assisted four-node sampling for axillary staging in early breast cancer

Background

The use of radioisotopes (RIs) is regulated and not all institutions have nuclear medicine facilities for sentinel node biopsy (SNB). We previously reported blue dye-assisted four-node axillary sampling (4NAS/dye) to be a suitable method for detecting sentinel nodes (SNs) without RIs. Here, we present an interim report on an observational study of this technique.

Methods

From May 2003 to June 2008, 234 early breast cancer patients underwent SNB with 4NAS/dye. Lymphatic mapping was performed by injection of patent blue, and axillary sampling was performed until 4 SNs were detected. Patients with metastatic SNs underwent axillary lymph node dissection (ALND) at levels I and II, while SN-negative patients did not undergo further axillary procedures.

Results

The SN identification rate was 99%. In total, 44 patients were diagnosed with metastatic disease by using the 4NAS/dye technique and underwent ALND; the remaining 189 patients did not undergo ALND (the SNB group). After a median follow-up period of 54 months, only 1 patient (0.5%) in the SNB group developed axillary recurrence. For the 4NAS/dye procedure, blue SNs were harvested in 220 patients (94%) and only unstained SNs were harvested in 13 patients (6%). Among the 44 patients with SN metastases, foci were found in blue SNs in 37 patients (84%), while they were found in only unstained SNs in 7 patients (16%).

Conclusions

SNB with 4NAS/dye is a safe and reliable technique for treatment of early breast cancer patients. This technique may be particularly useful for surgeons who do not have access to radioisotope facilities.     

A differential intra-operative molecular biological test for the detection of sentinel lymph node metastases in breast carcinoma. An extended experience from the first UK centre routinely offering the service in clinical practice

Introduction

One-Step Nucleic acid Amplification (OSNA) is a molecular biological assay of cytokeratin-19 (a breast epithelial marker) mRNA. It can be employed intra-operatively for detection of lymph node metastases in breast carcinoma. Patients with positive sentinel nodes may proceed to axillary lymph node dissection (ALND) level I or higher dependent upon the OSNA quantitative result, during the same surgical procedure, avoiding a second operation and eliminating the technical difficulties possibly associated with delayed ALND.

Aims

Our Breast Unit was the first in the UK to implement this novel technique in routine practice. This study reviews our first 44-month data following introduction of OSNA “live” on whole sentinel nodes following an extensive validation study (Snook et al.).⁹

Methods

Data was collected prospectively from the period of introduction 01/12/2008 to 30/08/2012. All patients eligible for sentinel node biopsy were offered OSNA and operations were performed by five consultant breast surgeons. On detection of macro-metastasis a level II/III and for a micro-metastasis a level I ALND was performed.

Results

A total of 859 patients (1709 sentinel lymph nodes) were analysed. All except one were females. The majority underwent wide local excision (73.4%, n = 631) or mastectomy 25% (n = 215) and 1.6% (13) underwent SLN biopsy alone. IDC was seen in 79% (n = 680) of the patients and 53.5% (n = 460) had grade II tumours. One-third (30.8%, n = 265) had positive sentinel nodes and had further axillary surgery at the time of SLN biopsy. Of these, 47% (n = 125/265) had macro-metastases, 38% (n = 101/265) had micro-metastases and 14.7% (n = 39/265) had “positive but inhibited” results. Positive non-sentinel lymph nodes (NSLN) were seen in 35% (44/125) of those with macro-metastases; 17.8% (18/101) of the patients with micro-metastases and 10.2% (4/39) of the “positive but inhibited” group.

Conclusion

In our series over a third of our patients had positive lymph nodes detected with OSNA allowing them to proceed directly to axillary surgery at the same operation. This technique eliminates the need for a second operation in sentinel lymph node positive patients and avoids the anxiety waiting for histological results.     

Internal mammary lymph drainage and sentinel node biopsy in breast cancer – A study on 1008 patients

Introduction

Nowadays, axillary sentinel node (SN) biopsy is a standard procedure in the staging of breast cancer. Although the internal mammary (IM) lymph node status is a major independent prognostic factor in breast cancer patients, sampling of IM sentinel nodes (IMSNs) is not performed routinely. The aim of this study was to determine the likelihood of finding IM lymph node metastases in case of IM hotspots on lymphoscintigraphy and evaluate the relevance of IMSN biopsy as a method to improve staging.

Patients and methods

Between April 1997 and May 2006, a total of 1008 consecutive patients with clinically node-negative operable primary breast cancer were enrolled in a prospective study on SN biopsy. Both axillary and IMSNs were sampled, based on lymphoscintigraphy, intraoperative gamma probe detection and blue dye mapping, using 10 mCi (370 MBq) ^99mTc-nanocolloid injected peritumorally, and 0.5–1.0 ml Patent Blue V injected intradermally.

Results

Lymphoscintigraphy showed axillary sentinel nodes in 98% (989/1008) and IMSNs in 20% of the patients (196/1008). Sampling the IM basin, as based on the results of lymphoscintigraphy, was successful in 71% of the patients (139/196) and revealed metastases in 22% (31/139). In 29% of the patients with positive IMSNs (9/31) no axillary metastases were found.

Conclusion

Evaluation of IMSNs improves nodal staging in breast cancer. Patients with IM hotspots on lymphoscintigraphy have a substantial risk (22%) of metastatic involvement of the IM chain. In addition, true IM node-negative patients can be spared the morbidity associated with adjuvant radiotherapy.     

The significance of immunohistochemistry positivity in sentinel nodes which are negative on haematoxylin and eosin in breast cancer

Introduction

Sentinel lymph node (SLN) biopsy allows a more detailed examination of a smaller number of lymph nodes in patients with clinically node negative breast cancer. Immunohistochemistry detects small tumour burden not routinely seen on haematoxylin and eosin (H&E). The significance of such findings remains to be fully elucidated.

Aim

To assess the axillary disease burden of patients in whom the sentinel lymph node biopsy was positive on immunohistochemistry and negative on H and E.

Methods

An analysis of patients who underwent SLN mapping for breast cancer at St Vincent's University Hospital from January 1st, 2000 to December 31st, 2006 was conducted. All SLNs were assessed by serial H&E and IHC sections. Patients with micrometastases (0.2–2 mm) underwent a completion axillary lymph node dissections (CLND). Patients with ITC (<0.2 mm) were individually discussed and a CLND was performed selectively based on additional clinicopathological criteria and patient preference. Analysis of the additional nodes from CLND was performed. Patients were followed for a median of 27 months (range 12–72 months).

Results

1076 patients who underwent SLN were included for analysis. 211 (20%) had a positive SLN biopsy using H&E. Forty-nine patients (5%) had a negative SLN on H&E which was positive on IHC. Of these, 15 had micrometastases and underwent a CLND. Two had further axillary nodal disease. ITC were found in the remaining 34 patients. Sixteen of these patients underwent a CLND. Five of this group had further nodal disease.

Conclusion

Micrometastases and isolated tumour cells, detected only by immunohistochemical analysis of sentinel lymph nodes, are associated with further positive nodes in the axilla in up to 15% of patients. This upstaging of disease may impact upon patient outcome.