Micrometastatic Sentinel Lymph Node Research Articles

Prise en charge axillaire dans le cancer du sein : enquête de pratique française

ObjectiveTo establish an inventory concerning the consistency of current medical practices in the management of axillary support for non-metastatic breast cancer since the publication of the ACOSOG-Z0011 randomized trial. Patients and methodsA descriptive survey practice using a questionnaire sent by email was conducted in medical care teams for breast cancer. ResultsForty-eight medical teams across the French territory answered to the questionnaire. It has been noted that 72.9% of medical teams have said to consistently achieve an additional axillary lymph node dissection (ALND) in case of macrometastatic sentinel node (SN), 12.5% in case of micrometastatic SN and only 2.1% in isolated tumor cells SN. The majority of medical teams (61.9%) claimed they did not perform the procedure GS before or after neoadjuvant chemotherapy (NAC). The SN biopsy was performed in only 29.1% of teams before and 9% after NAC, outside study. Axillary irradiation was performed in case of macrometastatic SN without complementary by 27.1% of interviewed medical teams and by 4.1% in the case of micrometastic SN. Discussion and conclusionThis survey of practice in patients with breast cancer highlights the evolution of medical practice for the axillary management in France. It also illustrates the diversity of practices in medical teams and the significant compensatory increase in the expansion of radiation fields in patients with metastatic SN without additional ALND.

Axillary dissection in the micrometastatic sentinel node in breast cancer?

Axillary dissection in the micrometastatic sentinel node in breast cancer?

Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23–01): a phase 3 randomised controlled trial

For patients with breast cancer and metastases in the sentinel nodes, axillary dissection has been standard treatment. However, for patients with limited sentinel-node involvement, axillary dissection might be overtreatment. We designed IBCSG trial 23-01 to determine whether no axillary dissection was non-inferior to axillary dissection in patients with one or more micrometastatic (≤2 mm) sentinel nodes and tumour of maximum 5 cm. In this multicentre, randomised, non-inferiority, phase 3 trial, patients were eligible if they had clinically non-palpable axillary lymph node(s) and a primary tumour of 5 cm or less and who, after sentinel-node biopsy, had one or more micrometastatic (≤2 mm) sentinel lymph nodes with no extracapsular extension. Patients were randomly assigned (in a 1:1 ratio) to either undergo axillary dissection or not to undergo axillary dissection. Randomisation was stratified by centre and menopausal status. Treatment assignment was not masked. The primary endpoint was disease-free survival. Non-inferiority was defined as a hazard ratio (HR) of less than 1·25 for no axillary dissection versus axillary dissection. The analysis was by intention to treat. Per protocol, disease and survival information continues to be collected yearly. This trial is registered with ClinicalTrials.gov, NCT00072293. Between April 1, 2001, and Feb 28, 2010, 465 patients were randomly assigned to axillary dissection and 469 to no axillary dissection. After the exclusion of three patients, 464 patients were in the axillary dissection group and 467 patients were in the no axillary dissection group. After a median follow-up of 5·0 (IQR 3·6-7·3) years, we recorded 69 disease-free survival events in the axillary dissection group and 55 events in the no axillary dissection group. Breast-cancer-related events were recorded in 48 patients in the axillary dissection group and 47 in the no axillary dissection group (ten local recurrences in the axillary dissection group and eight in the no axillary dissection group; three and nine contralateral breast cancers; one and five [corrected] regional recurrences; and 34 and 25 distant relapses). Other non-breast cancer events were recorded in 21 patients in the axillary dissection group and eight in the no axillary dissection group (20 and six second non-breast malignancies; and one and two deaths not due to a cancer event). 5-year disease-free survival was 87·8% (95% CI 84·4-91·2) in the group without axillary dissection and 84·4% (80·7-88·1) in the group with axillary dissection (log-rank p=0·16; HR for no axillary dissection vs axillary dissection was 0·78, 95% CI 0·55-1·11, non-inferiority p=0·0042). Patients with reported long-term surgical events (grade 3-4) included one sensory neuropathy (grade 3), three lymphoedema (two grade 3 and one grade 4), and three motor neuropathy (grade 3), all in the group that underwent axillary dissection, and one grade 3 motor neuropathy in the group without axillary dissection. One serious adverse event was reported, a postoperative infection in the axilla in the group with axillary dissection. Axillary dissection could be avoided in patients with early breast cancer and limited sentinel-node involvement, thus eliminating complications of axillary surgery with no adverse effect on survival. None.

Multi-Institutional Comparison of Non-sentinel Lymph Node Predictive Tools in Breast Cancer Patients with High Predicted Risk of Further Axillary Metastasis

Although axillary lymph node dissection (ALND) has been the standard intervention in breast cancer patients with sentinel lymph node (SLN) metastasis, only a small proportion of patients benefit from this operation, because most do not harbor additional metastases in the axilla. Several predictive tools have been constructed to identify patients with low risk of non-SLN metastasis who could be candidates for the omission of ALND. In the present work, predictive nomograms were used to predict a high (>50 %) risk of non-SLN metastasis in order to identify patients who would most probably benefit from further axillary treatment. Data of 1000 breast cancer patients with SLN metastasis and completion ALND from 5 institutions were tested in 4 nomograms. A subset of 313 patients with micrometastatic SLNs were also tested in 3 different nomograms devised for the micrometastatic population (the high risk cut-off being 20 %). Patients with a high predicted risk of non-SLN metastasis had higher rates of metastasis in the non-SLNs than patients with low predicted risk. The positive predictive values of the nomograms ranged from 44 % to 64 % with relevant inter-institutional variability. The nomograms for micrometastatic SLNs performed much better in identifying patients with low risk of non-SLN involvement than in high-risk-patients; for the latter, the positive predictive values ranged from 13 % to 20 %. The nomograms show inter-institutional differences in their predictive values and behave differently in different settings. They are worse in identifying high risk patients than low-risk ones, creating a need for new predictive models to identify high-risk patients.

Evaluation of a multiparametric system able to predict nonsentinel lymph node status in breast cancer patients with a micrometastatic sentinel node assessed by the one step nucleic acidamplification (OSNA) assay.

1050 Background: Axillary lymph node dissection (ALND) may not be necessary in women with breast cancer (BC) who have micrometastasis in a sentinel lymph node (SLN), owing to the low risk of non-SLN (NSLN) involvement. In our Institute we validated and adopted the molecular diagnostic tool OSNA based on the quantitative measurement of Cytokeratin 19 (CK19) mRNA.The aims of our work in a subgroup of women with micrometastatic SLN, were: 1) to correlate the copy numbers of CK19 mRNA with the risk of additional positive NSLNs; 2) to assess the relationships between the molecular subtype classification and the probability of a positive ALND; 3) to verify whether a combination of the new above mentioned parameters is able to identify a subgroup of patients with a micrometastatic SLN and a negligible risk of positive NSLNs in whom ALND may be avoided. Methods: The SLN lysates from 709 patients were analyzed by OSNA assay. We considered only patients with a micrometastatic SLN (copy numbers between 250 and 5000/μL) and the probability of having a positive ALND was calculated by the logistic regression model. This series of BC patients were divided into four main subtypes taking in account the BC classification as defined by a combination of estrogen, progesteron receptors and HER2 status. Results: OSNA positivity for micrometastasis was reported in 91/709 cases (12,8%).The number of patients with positive ALND was 20 (22%). The statistical analyses showed that the metastatic involvement of NSLNs is associated with SLNs with a high copy numbers (>2000) of CK19 mRNA together with HER2 subtype. Otherwise none of the luminal A patients with a positive SLN but presenting a copy number <1000, had a positive NSLNs. Conclusions: We showed that biologically-driven analyses may be able to build new models with higher performance in terms of breast cancer axillary status prediction after positive SLN biopsy for micrometastasis. The copy numbers of CK19 mRNA and the molecular subtypes are more advantageous than traditional parameters because they are not pathologist-dependent and therefore they are more reliable and reproducible.

P3-07-02: Prediction of Non-Sentinel Lymph Node Status in Breast Cancer Patients with a Micrometastatic Sentinel Lymph Node Determined by the One Step Nucleic Acid Amplification (OSNA) Assay.

Abstract Background Axillary lymph node dissection (ALND) may not be necessary in women with breast cancer (BC) who have micrometastasis in a sentinel lymph node (SLN), owing to the low risk of non-SLN (NSLN) involvement. In our Institute we validated and adopted the new molecular diagnostic tool OSNA (One Step Nucleic Acid Amplification) based on the quantitative measurement of Cytokeratin 19 (CK19) mRNA. The aims of our work in a subgroup of women with micrometastatic SLN, were: 1) to correlate the copy numbers of CK19 mRNA with the risk of additional positive NSLNs; 2) to assess the relationships between the molecular subtype classification based on the immunohistochemistry phenotypic patterns and the probability of a positive ALND; 3) to verify whether a combination of the new above mentioned parameters is able to identify a subgroup of patients with a micrometastatic SLN and a negligible risk of positive NSLNs in whom ALND may be avoided. Material and Methods: The intraoperative clinical study was conducted on 901 fresh SLNs from 709 consecutive patients with clinically node negative BC. The SLN lysates were analyzed by OSNA assay. If the CK19 mRNA copy number/mL lysate was less than 250 copies/mL, the result was regarded as negative (−); copy numbers between 250 and 5000/mL were regarded as micrometastasis (+), and copy numbers greater than 5000/mL as macrometastasis (++). We analyzed only patients with a micrometastatic SLN. Complementary ALND was performed concurrently in case of OSNA assay positivity and the probability of having a positive lymph node axillary dissection was calculated by the unconditional logistic regression model. This series of BC patients were divided into four main subtypes taking in account the BC classification as defined by a combination of estrogen, progesteron receptors and HER2 status evaluated by immunohistochemistry (IHC) and confirmed by FISH in case of IHC-HER2 2+. Results: OSNA positivity for micrometastasis was reported in 91/709 cases (12,8%).The number of patients with positive ALND was 20 (22%). The statistical analyses showed that the metastatic involvement of NSLNs is associated with SLNs with a high copy numbers (>2000) of CK19 mRNA together with luminal B subtype. Otherwise none of the luminal A patients with a positive SLN but presenting a copy number <1000, had a positive NSLNs. Conclusions: We showed that biologically-driven analyses may be able to build new models with higher performance in terms of breast cancer axillary status prediction after positive SLN biopsy for micrometastasis. The copy numbers of CK19 mRNA and the molecular subtypes are more advantageous than traditional parameters because they are not pathologist-dependent and therefore they are more reliable and reproducible. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-02.

Prognosis and non-sentinel lymph node status of the breast cancer patients with micrometastatic sentinel lymph nodes.

140 Background: Sentinel lymph node biopsy (SLNB) is a more sensitive and accurate nodal staging procedure than axillary lymph node dissection (ALND). Because of detailed pathologic evaluation in SLNs, more nodal micrometastases have been identified. However, it remains controversial whether to perform ALND for patients with micrometastases in SLNs and their prognostic significance is also a matter of debate. The purpose of this study is to determine the non-sentinel lymph node (NSLN) status and prognosis of the patients with micrometastatic SLNs. Methods: A prospective database of 1,012 clinically node-negative, T1-T2 breast cancer patients, who underwent SLNB from January 2002 to Dec 2010 at Keio University Hospital was analyzed. SLNs were detected using a combined method of isosulfun blue dye and small-sized technetium-99m-labeled tin colloid. Intraoperative frozen examination was performed with hematoxylin and eosin (HE) staining. SLNs, fixed and embedded in paraffin, were additionally diagnosed with HE staining and immunohistochemical (IHC) analysis. Results: Micrometastases in SLNs were found in 69 (6.8%) of 1,012 patients. Thirty eight (55.1%) of 69 patients with micrometastatic SLNs underwent immediate or delayed ALND and revealed no NSLN metastasis. Among 31 (44.9%) patients with micrometastatic SLNs who omitted ALND and axillary radiation therapy, no axillary lymph node recurrence has been observed after a median follow-up of 50 months, although 29 patients (93.5%) in these 31 patients received adjuvant systemic therapy. There is no significant difference in recurrence free survival between the patients with micrometastatic and negative SLNs (98.0% vs. 95.7%, respectively). Conclusions: These date suggested that it may not be necessary to perform ALND for the patients with micrometastatic SLNs and the presence of micrometastases in SLNs may not worsen prognosis with proper systemic therapy.

Semi‐quantitative evaluation of CD44+/CD24− tumor cell distribution in breast cancer tissue using a newly developed fluorescence immunohistochemical staining method

CD44(+) /CD24(-) tumor cells are reported to contain cancer stem cells in breast cancer. The main purpose of the present study is to develop an immunohistofluorescence method that can quantitatively analyze CD44(+) /CD24(-) tumor cell distribution in breast cancer tissue and help better define the role of CD44(+) /CD24(-) tumor cells in breast cancer. The samples used were from 21 primary breast cancer patients who underwent neoadjuvant chemotherapy and 17 cases with sentinel lymph nodes that had lymph node micrometastasis. CD44(+) /CD24(-) tumor cells were distinguished at a single cell level using improved triple-staining immunohistofluorescence and a simulated laser capture microdissection method. The percentage of CD44(+) /CD24(-) cells significantly increased following neoadjuvant chemotherapy treatment (0.93% and 2.78%, before and after, respectively, P = 0.0043). The percentage of CD44(+) /CD24(-) cells was also significantly high in micrometastatic sentinel lymph nodes (0.49% and 1.91%, primary tumors and lymph nodes, respectively, P = 0.0246). The CD44(+) /CD24(-) tumor cell distribution was heterogeneous in both breast cancer tissue and lymph node metastasis. In a xenograft model using immunodeficient mice, the hedgehog signaling inhibitor cyclopamine repressed the tumorigenicity of CD44(+) /CD24(-) cells. Our results suggest that this semi-quantitative immunohistochemical analysis is valuable for detecting a small population of cells in cancer tissues and that the hedgehog signaling pathway inhibitor cyclopamine is useful for regulating the CD44(+) /CD24(-) tumor cells in breast cancer.

Comparative Validation of Online Nomograms for Predicting Nonsentinel Lymph Node Status in Sentinel Lymph Node–Positive Breast Cancer

Completion axillary lymph node dissection is recommended for patients with metastases to the sentinel lymph node (SLN) in breast cancer although nonsentinel lymph nodes (NSLN) are often negative for tumor. Online nomograms are available to predict risk of NSLN disease. To compare the accuracy of the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram (using 9 variables) with the Stanford nomogram (using 3 variables) in predicting NSLN metastasis. A single academic center. Prospectively maintained database of patients with breast cancer who underwent SLN biopsy from October 1, 1999, through January 31, 2008. Risk of NSLN metastasis was calculated using each nomogram's online calculator. Results from the axillary lymph node dissection were reviewed for positive NSLNs. Nomograms were evaluated using the area under the receiver operating characteristic curve, false-negative rates, positive predictive value, and calibration plot. Nomogram scores and axillary lymph node dissection results. Of 579 patients who underwent SLN biopsy, 179 (30.9%) had a positive SLN. For 123 patients who underwent axillary lymph node dissection, the area under the curve for the MSKCC and Stanford nomograms was 0.72 and 0.70, respectively. False-negative rates for nomogram values of 10% or less were low (4.1% for the MSKCC and 7.8% for the Stanford). The positive predictive value for nomogram probabilities of 80% or greater was higher for MSKCC than for Stanford (90.9% vs 61.8%). The Stanford nomogram performed more accurately in low-risk patients with isolated tumor cells or micrometastatic SLN disease; however, the MSKCC nomogram more accurately predicted NSLN outcomes across the entire study population. Although the MSKCC and Stanford nomograms performed similarly on the basis of the area under the curve, the MSKCC nomogram was consistently more reliable in predicting actual NSLN outcomes.

Axillary lymph node dissection in the case of sentinel lymph node micrometastatic invasion: evaluation of three predictive models

Objective To evaluate three predictive risk models of non-sentinel lymph node (NSLN) involvement in the case of micrometastatic sentinel node (SLN) involvement for breast cancer. Study design This retrospective study included 72 successive patients with micrometastatic SLN involvement who had surgery between March 1996 and October 2007. All patients had undergone immediate or delayed axillary lymph node dissection (ALND). The Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram, the Stanford nomogram and the Tenon score were applied to the population to calculate the probability of NSLN involvement. Results For the MSKCC nomogram with a threshold value of 10%, sensitivity was 50%, specificity was 70% and the negative predictive value (NPV) was 89%. The area under the receiver operating characteristic curve (AUC) was 0.6 (significant). Use of this nomogram would have avoided ALND in 49 out of 72 (68%) patients, but five out of 10 (50%) patients with NSLN involvement would not have been detected. With a threshold value of 7%, the AUC was 0.69, sensitivity was 90% and NPV was 97%. ALND would have been avoided in 31 out of 72 (43%) patients, with a 3% chance of leaving metastases when abstaining from ALND. For the Tenon score with a threshold value of 3.5, sensitivity was 50%, specificity was 72% and the AUC was 0.62. This was not clinically applicable because eight out of 10 (80%) patients with NSLN involvement would not have been detected. For the Stanford nomogram, the results could not be interpreted because the AUC was not significant. Conclusion None of the tested models are sufficiently reliable for use in daily practice. The MSKCC nomogram showed the most encouraging results, especially for a threshold value of 7%, but this has not been validated in the literature. Complete axillary dissection should be performed in the case of micrometastatic SLN involvement until more data become available.

Prognosis and nonsentinel lymph node status of the patients with breast cancer with micrometastatic sentinel lymph nodes.

e11503 Background: Sentinel lymph node biopsy (SLNB) is a more sensitive and accurate nodal staging procedure than axillary lymph node dissection (ALND). Because of detailed pathologic evaluation in SLNs, more nodal micrometastases have been identified. However, it remains controversial whether to perform ALND for patients with micrometastases in SLNs and their prognostic significance is also a matter of debate. The purpose of this study is to determine the non-sentinel lymph node (NSLN) status and prognosis of the patients with micrometastatic SLNs. Methods: A prospective database of 1,012 clinically node-negative, T1-T2 breast cancer patients, who underwent SLNB from January 2002 to Dec 2010 at Keio University Hospital was analyzed. SLNs were detected using a combined method of isosulfun blue dye and small-sized technetium-99m-labeled tin colloid. Intraoperative frozen examination was performed with hematoxylin and eosin (HE) staining. SLNs, fixed and embedded in paraffin, were additionally diagnosed wi...

Interest of axillary lymph node dissection in the case of micrometastatic invasion of the sentinel lymph node: Evaluation of three predicting models of risk of nonsentinel lymph node involvement.

e11568 Background: To evaluate three predicting risk models of non sentinel lymph node (NSLN) involvement in case of micrometastatic sentinel node (SLN) involvement for breast cancer. Methods: This retrospective study included 72 successive patients with a micrometastatic SLN involvement who had surgery between March 1996 and October 2007. All patients had an immediately or delayed axillary lymph node dissection (ALND). The MSKCC nomogram, the Stanford nomogram and the Tenon score were applied to our population in order to calculate the probability of NSLN involvement. Statistical analysis with establishment of a ROC curve was applied to each model. Results: Concerning the MSKCC nomogram, w ith a threshold value of 10%, sensitivity was 50%, specificity was 70%, and negative predictive value (NPV) was 89%. The area under the ROC curve (AUC) was 0.6 (significant). ALND was avoided in 49 patients (68%) but it failed to detect 5 out of 10 (50%) patients with NSLN involvement. When using a threshold of 7%, the AUC was 0.69 with a sensitivity of 90% and a NPV of 97%. It avoided 31 out of 72 ALND (43%) while having only 3% chance of leaving metastasis when abstaining from ALND. Concerning the Tenon score, using a threshold of 3.5, the sensitivity lowered to 50% while the specificity was 72% and the AUC 0.62. It was not clinically applicable because 8 out of 10 patients (80%) with NSLN involved were spared from a necessary ALND. Concerning the Stanford nomogram, our results were not interpretable because the AUC was not significant. Conclusions: None of these three models was sufficiently reliable to be used in the daily practice. The MSKCC nomogram showed the most encouraging results especially for a threshold of 7% which is not validated in the literature. Completion axillary dissection should be performed as a standard of management in case of micrometastatic SLN involvement until more available data.

Can we avoid axillary dissection in the micrometastatic sentinel node in breast cancer?

There is considerable interest in foregoing axillary dissection (AD) when the sentinel node (SN) is positive in early breast cancer, particularly when involvement is minimal (micrometastases or isolated tumor cells). To address this issue we analyzed outcomes in patients with a single micrometastatic SN who did not receive AD. We selected 377 consecutive patients treated at the European Institute of Oncology between 1999 and 2007 for invasive breast cancer. Classical and competing risks survival analyses were performed to estimate prognostic factors for axillary recurrence, first events and overall survival. Median age was 53years (range 26-80); median follow-up was 5years (range 1-9). Most (91.8%) patients received conservative surgery; 209 (55.4%) had only one SN (range 1-8). Five-year overall survival was 97.3%. There were 10 local events, 2 simultaneous local and axillary events, 6 axillary recurrences and 12 distant events. The cumulative incidence of axillary recurrence was 1.6% (95% CI 0.7-3.3). By multivariable analysis, tumor size and grade were significantly associated with axillary recurrence. The high five-year survival and low cumulative incidence of axillary recurrence in this cohort provide justification for the increasingly common practice of foregoing AD in women with minimal SN involvement, and suggest in particular that AD can safely be avoided in women with small, low-grade tumors. Nevertheless, a subset of patients might be at high risk of developing overt axillary disease and efforts should be made to identify such patients by ancillary analyses of the results of ongoing or recently published clinical trials.

P248 Clinicopathological characteristics of the breast cancer patients with micrometastatic sentinel lymph nodes

P248 Clinicopathological characteristics of the breast cancer patients with micrometastatic sentinel lymph nodes

Non-Sentinel Lymph Node Status and Prognosis of Breast Cancer Patients with Micrometastatic Sentinel Lymph Nodes

Background: The prognostic significance of sentinel lymph node (SLN) micrometastases and the need for axillary lymph node dissection (ALND) on patients with micrometastases in SLNs remain controversial. Methods: A prospective database of 657 breast cancer patients who underwent SLN biopsy (SLNB) was analyzed. SLNs were detected using a combined method of isosulfan blue dye and small-sized technetium-99m-labeled tin colloid. Results: Micrometastases in SLNs were found in 50 (7.6%) of 657 patients. Twenty-nine (58.0%) of 50 patients with micrometastatic SLNs underwent ALND and no further metastases were found in non-sentinel lymph nodes. Among 21 patients (42.0%) with micrometastatic SLNs who decided to forego ALND, no axillary lymph node recurrence has been observed during a median follow-up time of 47 months. There is no significant difference in recurrence-free survival between the patients with micrometastatic and negative SLNs (p = 0.90). Conclusions: These data suggest that it may not be necessary to perform ALND on patients with micrometastases in SLNs and that the presence of micrometastases in SLNs may not be associated with prognosis.

Significance of Sentinel Lymph Node Micrometastases in Patients With Breast Cancer

TO THE EDITOR: Hansen et al report an interesting analysis of the significance of micrometastatic sentinel lymph node (SLN) involvement in breast cancer. They conclude that patients with isolated tumor cells (ITCs) and micrometastatic tumor deposits measuring smaller than 2 mm (American Joint Committee on Cancer nodal stage pN0[i ] and pN1mi) do not have worse 8-year disease-free survival or overall survival compared with SLN-negative patients (pN0). However, they do demonstrate significantly reduced survival for patients with SLN metastases larger than 2 mm (pN1). This is in contrast with a large recently published retrospective review from the Netherlands, which demonstrated reduced 5-year disease-free survival in patients with both ITCs and micrometastatic disease in the SLN. We are concerned by Hansen et al’s failure to include details of the primary tumor characteristics (ie, tumor grade and receptor status) in their report. Table 3 reveals that only 54% of SLN-negative patients received adjuvant hormone therapy (tamoxifen group and chemotherapy and tamoxifen group) compared with 76.1%, 72.2%, and 66.9% for the groups with ITCs, micrometastases, and macrometastases, respectively. Is this because the SLN-negative patients were not routinely administered adjuvant hormone therapy or because estrogen receptor–negative patients are over-represented in this group? If the latter is true, the SLN-negative group would be expected to have a worse prognosis. In the multivariate analysis, SLN status was categorized as macrometastatic or all others. Patients with ITCs and micrometastases represented only 22.2% of this group. The majority of patients in this comparative group were SLN negative (pN0). It is not surprising that a difference was found when they were compared with the macrometastatic group. The number of patients in the ITC and micrometastatic groups who developed a failure event (ie, disease recurrence or death) is rather small (Fig 3 of Hansen et al), and the CIs for disease-free and overall survival for these groups are likely to be large. Therefore, it is not possible to convincingly argue that patients with ITCs and micrometastatic tumor deposits do not have worse prognosis than patients with macrometastatic disease in the SLN. The significance of finding ITCs or micrometastatic disease burden in the SLN of patients with breast cancer remains a considerable management dilemma. SLN status is an important determinant for adjuvant therapy decision making, and additional studies are required to better understand the biologic significance of low-volume disease in the SLN.

Non-sentinel lymph node status and prognosis of the breast cancer patients with micrometastatic sentinel lymph nodes

e11504 Background: Sentinel lymph node biopsy (SLNB) has become a standard therapy for clinically node-negative breast cancer patients and improvements of histopathological and molecular analysis of sentinel lymph node (SLN) have increased the rate of micrometastases identified. However it remains controversial whether to perform axillary lymph node dissection (ALND) for patients with micrometastases in SLNs and their prognostic significance is also a matter of debate. The purpose of this study is to determine the non- sentinel lymph node (NSLN) status and prognosis of the patients with micrometastatic SLNs. Methods: A prospective database of 666 breast cancer patients with the tumor size less than 3cm and clinical negative node, who underwent SLNB from January 2002 to July 2007 at Keio University Hospital was analyzed. SLNs were detected using a combined method of isosulfun blue dye and small-sized technetium-99m-labeled tin colloid. SLNs were diagnosed with standard hematoxylin and eosin (HE) staining and immunohistochemical (IHC) analysis. Results: Micrometastases in SLNs were found in 50 (7.5%) of 666 patients. Twenty nine (58.0%) of 50 patients with micrometastatic SLNs underwent ALND and revealed no NSLN metastasis. Among 21 (42.0%) patients with micrometastatic SLNs who skipped ALND, no axillary lymph node recurrence has been observed in the median follow-up time of 43 months, although 20 patients (95.2%) in 21 patients received adjuvant systemic therapy. There is no significant difference in recurrence free survival between the patients with micrometastatic and negative SLNs (98.0% vs. 95.7%, respectively). Conclusions: These date suggested that it may not be necessary to perform ALND for the patients with micrometastases in SLNs and the presence of micrometastases in SLNs may not be associated with prognosis. No significant financial relationships to disclose.

Critical study of our initial experience of 993 sentinel node biopsies for breast surgery

Identification of sentinel node (SN) involvement predictive factors, non-sentinel node involvement predictive factors, selective prognosis of each group of patients by study of breast surgery cases with sentinel node sampling. Prospective monocentric registering of 993 sentinel node samples routinely taken between January 2001 and October 2005, covering technical aspects of detection (colorimetric and radio-isotope), pathological results (serial sections 5 Mmicro thick prior to staining hematoxylin-eosine-saffron and if necessary, by immune histochemistry cytokeratine high molecular weight), therapeutics and follow-up (average period: 32 months (3-69). Seven hundred and sixteen patients (72.1%) were free of sentinel node involvement. Among positive sentinel node patients (27.9%), 14.5% presented macrometastasis, 11% micrometastasis and 2.4% isolated tumor cells (CTI). Sentinel node involvement risk factors included: related to clinical features, age (2 years younger in the micrometastatic group compared to the macrometastatic group); related to tumor caracteristics, size (12.15 mm for the negative SN group, 15.4 mm for the micrometastatic group and 16.25 mm for the macrometastatic group), grading (a majority of grade I encountered with micrometastasis versus macrometastasis) and multifocality (macrometastasis SN associated with multilocular tumor in 77.8% cases, micro metastasis SN in 22.2% cases and negative SN in 6.7% cases). Predictive factors do not differ for micro- or macrometastasic involvement. Among features concerning secondary axillary dissection, 47.1% (66/140) were positive with a macrometastatic SN, 12.1% (13/107) with micrometastic SN. Predictive factors of positive secondary axillary dissection were tumor size, grading, micrometastasis size and micrometastasis multifocality. With a 32 months mean follow-up, the positive micrometastasis sub-group (with or without positive secondary axillary dissection) expressed one only metastatic recurrence (0.9%); on the contrary, three patients (2.1%) issued from the macrometastatic SN group, expressed metastatic recurrence. One only local axillary recurrence (0.14%) occurred among negative SN (717 cases); no axillary recurrence occurred among the 30 patients without secondary axillary dissection (CTI [22 cases], micrometastatic SN group [5 cases] and macrometastatc group [3 cases]). First, 72.1% of T0 or T1 tumors, avoid adverse axillary dissection effects. Second, micrometastatic involvement predictive factors do not differ from macrometastatic ones and those of positive secondary axillary dissection among micrometastatic SN do not appear clearly : the risk of axillary recurrence is low: at the very most, it seems possible to propose a safe guideline, avoiding secondary axillary dissection only for selected group of lower risk patients: tumoral size < 10 mm, grade I, monocentric SN involvement. Third, it is not possible to differentiate a selective prognosis between negative, CTI, micrometastatic and macrometastatic SN subgroups probably because of a short follow-up. Fourth, teaching through companionship is fully valided by the secondary minimal rate of axillary recurrence.

Sentinel node mapping performed before preoperative chemotherapy may avoid axillary dissection in breast cancer patients with negative or micrometastatic sentinel nodes

Background Sentinel node (SN) biopsy after preoperative chemotherapy (PC) in breast cancer patients is associated with a lower identification rate (IR) and an increased false-negative rate (FNR) compared with SN biopsy in untreated patients. Our aims were to examine the feasibility of SN mapping before PC and the possibility to assess the lymph node status after chemotherapy through a follow-up lymphatic mapping. Methods SN biopsy was performed in 45 clinically node-negative breast cancer patients before PC. A follow-up lymphatic mapping was done after completion of chemotherapy and irrespective of the lymph node status was followed by axillary lymph node dissection (ALND). Results SN mapping before chemotherapy identified a mean of 2.3 SNs in all patients (IR 100%). Nineteen patients revealed a negative SN; 26 patients had a positive SN (micrometastasis found in 6/26 patients). After PC follow-up lymphatic mapping was successful in 29 of 45 patients (IR 64%). IR for follow-up mapping was 80% for patients with a negative or micrometastatic SN before chemotherapy compared with 45% for patients with macrometastatic SNs ( P = .027, Fisher exact test). None of the patients with a negative or micrometastatic SN before chemotherapy revealed positive lymph nodes after PC ( P = .031, McNemar test) and the FNR for follow-up lymphatic mapping in these patients was 0%. Contrary to that, 15 of 20 patients with a macrometastasis before PC had positive nodes after chemotherapy, and the FNR of follow-up mapping in these patients was 50%. Conclusions Patients with a negative SN before PC may forego complete ALND after PC, whereas this may not be valid for patients with macrometastatic SNs. Follow-up lymphatic mapping in patients with positive nodal status before chemotherapy is associated with a low IR and a high FNR.

Comparative Evaluation of an Extensive Histopathologic Examination and a Real-Time Reverse-Transcription-Polymerase Chain Reaction Assay for Mammaglobin and Cytokeratin 19 on Axillary Sentinel Lymph Nodes of Breast Carcinoma Patients

To assess the accuracy of a commercially available real-time reverse-transcription-polymerase chain reaction assay for mammaglobin and cytokeratin 19 mRNAs [GeneSearch Breast Lymph Node (BLN) Assay, Veridex LLC, Warren, NJ] in the detection of axillary sentinel lymph nodes (SLNs) metastases in patients with breast carcinoma. Because of the lack of standardized and widely accepted protocols for a truly accurate histopathologic examination of SLN, the relative merits of alternative assays based on the identification of tumor specific mRNA markers deserve further assessment. : A prospective series of 293 consecutive SLNs from 293 patients was evaluated. The BLN assay results were compared with those of an extensive histopathologic examination of the entire SLNs performed on serial frozen sections cut at 40 to 50 microm intervals. The BLN assay correctly identified 51 of 52 macrometastatic and 5 of 20 micrometastatic SLNs, with a sensitivity of 98.1% to detect metastases larger than 2 mm, 94.7% for metastases larger than 1 mm, and 77.8% for metastases larger than 0.2 mm. The overall concordance with histopathology was 90.8%, with specificity of 95.0%, positive predictive value of 83.6%, and negative predictive value of 92.9%. When the results were evaluated according to the occurrence of additional metastases to non-SLN in patients with histologically positive SLNs, the assay was positive in 33 (91.7%) of the 36 patients with additional metastases and in 22 (66.6%) of the 33 patients without further echelon involvement. The sensitivity of the reverse-transcription -polymerase chain reaction assay is comparable to that of the histopathologic examination of the entire SLN by serial sectioning at 1.5 to 2 mm.