Sentinel Lymph Nodes In Breast Cancer Research Articles

12P - Outcome analysis of patients with breast cancer and positive sentinel node

12P - Outcome analysis of patients with breast cancer and positive sentinel node

Abstract P2-01-17: Total tumoral load as a prediction tool of non-sentinel node metastases in patients with early breast cancer and positive sentinel lymph node assesed by OSNA

Abstract Background: Total tumoral load (TTL) in the sentinel lymph nodes (SLN) assessed by the OSNA assay is a new variable that is able to predict the likelihood of more axillary metastasis. Compared with the number of positive SLNs, the TTL is independent of the number of metastatic SLNs and a better predictor of further nodal metastasis. Although establishing specific cutoff-points of the TTL can be questionable because they may change in the future and increasingly become more patient specific, we have seen that TTL <15.000 could be a good cut off by its high negative predictive value (NPV). Changes in practice have been occurred after the ACOSOG Z0011 trial and nowadays, patients with ≤ 2 positive SLNs may spare an axillary lymph node dissection (ALND) with no impact on the oncological outcome. In the Z0011, 27% of patients had additional non-SLN metastasis in the cALND. The objective of this study was to compare two methods of SLN metastatic burden, the TTL and the number of positive SLNs, for predicting non-SLN metastasis in patients with positive SLNs by OSNA. Methods: This is a retrospective cohort study of 145 consecutive patients with cT1-T2 invasive breast cancer with ultrasonographically node-negative treated between April 2010 to April 2013, where there is at least one positive SLN assesed by OSNA. We design a prediction tool based on the TTL results determined by OSNA to calculate the likelihood of not finding more positive non-SLN (http://www.vhebron.net/es/calculadora-risc-metastasi-2). Our group have demonstrated that TTL=15.000 could be a good cut off by its high NPV and sensitivity, 85.5% and 76.7%, respectively. Results: A total 325 SLNs were removed with a mean of 2.24. The type of SLN metastasis were macrometastasis in 85 patients (58.6%) and micrometastasis in 60 patients (41.4%). When considering patients with number of positive SLNs, of 109 patients with ≤2 positives SLNs and an cALND, 17 patients (22%) had non-SLN metastasis; and of 5 patients with ≥3 SLN, four (80%) had non-SLN metastasis. Taking the TTL results, of 51 patients with TTL <15.000 copies/µL with cALND (90.2% with one positive SLN), 7 patients (14%) had non-SLN metastasis, were a media of 2.2 extra non-SLN metastasis. Of 55 patients with TTL ≥15.000 copies/µL (with 1 or 2 positives SLNs) with cALND, 20 patients (36%) had non-SLN metastasis and there were a media of 2.5 non-SLN metastasis (range 1-8). Of 34 patients (62%) with one positive SLN with TTL ≥15.000 copies/µL, 12 patients (35%) had non-SLN metastasis; and of 21 patients with two positive SLN with TTL ≥15.000 copies/µL, eight patients (38%) had non-SLN metastasis. Conclusion: The total tumor load obtained by OSNA predicts non-SLN metastasis independent of the number of positive SLNs. The assess of the TTL in our cohort of patients show that patients with one or two positives SLNs with high TTL had high likelihood of non-SLN metastasis greater than 27% of Z0011 criteria. Prospective studies are needed to determine the clinical impact of this variable in patients outcome in the management of patients with SLN assesed by OSNA. Citation Format: Martin Espinosa-Bravo, Francesc Pérez-Ceresuela, Sebastian Diaz-Botero, Vicente Peg, Isabel T Rubio. Total tumoral load as a prediction tool of non-sentinel node metastases in patients with early breast cancer and positive sentinel lymph node assesed by OSNA [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-17.

Abstract P2-01-28: Prognosis of metastatic internal mammary sentinel nodes (IMSN) in breast cancer

Abstract Introduction: The presence of positive internal mammary nodes has historically been associated with a significant worse prognosis. Recent studies have also demonstrated a worse prognosis associated with drainage to the internal mammary nodes. Intense search for those nodes, biopsy, appropriate staging and modern treatment for positive IMSN might improve outcome. We sought to study the prognosis of pathologically positive IMSN at our institution. Methods: A retrospective analysis of a prospectively collected database including all breast cancer patients identified with an IMSN that was biopsied between 2005 and 2012 was performed. Demographics, histologic markers, patterns of recurrence as well as survival data were collected. Univariate and multivariate analysis were performed. Results: Thirteen of 82 patients with a biopsied IMSN were metastatic (16%). In 8 of those (62%), the biopsy resulted in a change in staging. In all cases of positive IMSN additional radiation to the internal mammary chain was added. Eighteen percent (18%) of positive nodes did not show drainage to the internal mammary basin during Lymphoscintigraphy. There was no statistical difference in regional and distant recurrences between the patients with positive IMSN and those with negative IMSN. Furthermore there was no difference in disease specific survival. Conclusions: Intense search for IMSN presence and biopsy of those nodes is associated with changes in staging and treatment for metastatic IMSN. In our study, pathologically positive IMSN were associated with a non- inferior prognosis than negative IMSN. Citation Format: Eli Avisar, Shai Libson, Eduardo Perez. Prognosis of metastatic internal mammary sentinel nodes (IMSN) in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-28.

Abstract P1-16-09: Magnetic sentinel node and occult lesion localization in breast cancer: Initial results of the MagSNOLL trial

Abstract Trial registration: ISRCTN: 68689512 MREC No: 13/LO/0636 UKCRN ID: 14979 INTRODUCTION: One-third of breast cancers diagnosed are non-palpable. These breast cancers require localization-guided surgery and axillary staging using sentinel lymph node biopsy (SLNB). We present our experience of the first 20 patients undergoing a novel technique of magnetic-guided lesion localization and concurrent SLNB, avoiding the need for wire-guided localization and radioisotopes. MATERIALS AND METHODS: Co-localization of the primary tumour and sentinel lymph nodes (SLNs) using a novel magnetic technique was initially undertaken on a protocol-driven predefined minimum of 10 patients with palpable breast cancers to assess the feasibility of the magnetic tracer to safely localize at the point of injection and concurrently drain to the lymphatics. In order to confirm proof of principle, the subsequent 20 patients with non-palpable breast cancers were analysed. An ultrasound-guided intra-tumoral injection of magnetic tracer was performed (0.5 mL Sienna+, Endomagnetics Ltd, UK). Once successful lesion localization was confirmed (peak magnetometer counts retained at the site of injection), the technique was undertaken in patients with non-palpable breast cancers awaiting wide local excision and SLNB. All patients underwent SLNB with the magnetic and combined technique (radioisotope and Patent Blue Dye). RESULTS: A total of 33 patients were recruited and 1 patient excluded due to breach of the trial protocol. This left a remainder of 32 patients for consideration, of which 12 patients (1 bilateral) possessed palpable breast cancer and 20 patients non-palpable breast cancer. Peak magnetometer counts were retained at the site of injection in all palpable (n=13) and non-palpable (n=20) breast cancers. Re-excisions (second operations) for involved margins were performed in 2 patients with non-palpable breast cancers (10%). The mean volume of excised specimens was 49 cm3 (SD 30.6). The SLN identification rate for the magnetic technique alone was 84% (28/33) overall and 85% (17/20) for non-palpable lesions. For the combined technique (radioisotope and blue dye) the SLN identification rate was 97% (32/33) overall and 100% (20/20) for non-palpable lesions. When the magnetic technique is combined with blue dye, the SLN identification rate overall was 97% (32/33) and for non-palpable breast cancers was 95% (19/20). The mean number of sentinel nodes excised was 1.75 versus 2.05 for the magnetic and combined techniques respectively. CONCLUSION: Magnetic lesion localization and concurrent SLNB is a feasible technique. Further optimisation and validation of this technique, in a larger trial, is required. Citation Format: Muneer Ahmed, Ashutosh Kothari, Hisham Hamed, Sumit Goyal, Tibor Kovacs, Anand David Purushotham, Bauke Anninga, Phillippa Young, Julie Scudder, Sarah McWililliams, Sarah Pinder, Quentin Pankhurst, Ian Monnypenny, Michael Douek. Magnetic sentinel node and occult lesion localization in breast cancer: Initial results of the MagSNOLL trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-16-09.

Magnetic sentinel node and occult lesion localization in breast cancer (MagSNOLL Trial).

Non-palpable breast cancers require localization-guided surgery and axillary staging using sentinel lymph node biopsy (SLNB). This study investigated the novel technique of magnetic-guided lesion localization and concurrent SLNB, which avoids the need for wire-guided localization and radioisotopes. An ultrasound-guided intratumoral injection of magnetic tracer (0·5 ml) was performed in a protocol-driven predefined minimum of ten patients with palpable breast cancer to assess the ability of the magnetic tracer safely to localize the tumour at the site of injection and concurrently drain to the lymphatics. Once successful lesion localization had been confirmed (peak magnetometer count retained at the centre of the tumour), the technique was undertaken in a further 20 patients with non-palpable breast cancers awaiting wide local excision and SLNB. All patients underwent SLNB with both the magnetic and standard dual (radioisotope and Patent Blue V dye) techniques. Thirty-two patients were recruited, of whom 12 (1 with bilateral disease) presented with palpable and 20 with non-palpable breast cancer. Peak magnetometer counts were retained at the tumour centre in all palpable (13) and non-palpable (20) breast cancers. Re-excisions for involved margins were necessary in two patients with non-palpable breast cancers. The sentinel lymph node identification rates were 28 of 33 procedures for the magnetic technique alone, 32 of 33 for the magnetic technique combined with blue dye, and 32 of 33 for the standard dual technique. Magnetic lesion localization is feasible, with intratumoral magnetic tracer injection combined with a periareolar injection of blue dye for subsequent SNLB.

Contrast-enhanced ultrasonography in qualitative diagnosis of sentinel lymph node metastasis in breast cancer: A meta-analysis.

This meta-analysis aims to determine the accuracy of contrast-enhanced ultrasonography (CEUS) in the qualitative diagnosis of metastatic sentinel lymph node (SLN) for patients with breast cancer. We screened PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases. All analyses were calculated using the STATA software, version 12.0 (Stata Corp, College Station, TX, USA). We calculated the summary statistics for sensitivity (Sen), specificity (Spe), positive and negative likelihood ratios (LR + /LR-), diagnostic odds ratio (DOR) and receiver operating characteristic (SROC) curve. Thirteen articles that met all inclusion criteria were included in this meta-analysis. A total of 876 breast cancer patients were assessed, including 372 patients with metastatic SLN and 504 patients without metastatic SLN. All SLN were histologically confirmed after conducting CEUS. The pooled Sen was 0.80 (95%CI = 0.76-0.84); the pooled Spe was 0.94 (95% CI = 0.91-0.96). The pooled LR + was 6.28 (95%CI = 3.61-10.92); the pooled negative LR - was 0.218 (95% CI = 0.10-0.31). The pooled DOR of CEUS in qualitative diagnosis of SLN metastasis was 49.10 (95% CI = 27.89-86.45). The area under the SROC curve was 0.937 (standard error [SE] =0.0128). Our meta-analysis suggests that CEUS may have high a diagnostic accuracy in testing for metastatic SLN in breast cancer. Thus, CEUS may be a good tool for differential diagnosis between metastatic and non-metastatic SLN.

Sentinel node in melanoma and breast cancer. Current considerations

The main objectives of sentinel node (SN) biopsy are to avoid unnecessary lymphadenectomies and to identify the 20–25% of patients with occult regional metastatic involvement. This technique reduces the associated morbidity from lymphadenectomy and increases the occult lymphatic metastases identification rate by offering the pathologist the lymph nodes with the highest probability of containing metastatic cells. Pre-surgical lymphoscintigraphy is considered a “road map” to guide the surgeon toward the sentinel nodes and to localize unpredictable lymphatic drainage patterns. The SPECT/CT advantages include a better SN detection rate than planar images, the ability to detect SNs in difficult to interpret studies, better SN depiction, especially in sites closer to the injection site and better anatomic localization. These advantages may result in a change in the patient's clinical management both in melanoma and breast cancer. The correct SN evaluation by pathology implies a tumoral load stratification and further prognostic implication. The use of intraoperative imaging devices allows the surgeon a better surgical approach and precise SN localization. Several studies report the added value of such devices for more sentinel nodes excision and a complete monitoring of the whole procedure. New techniques, by using fluorescent or hybrid tracers, are currently being developed.

Sentinel node in melanoma and breast cancer. Current considerations

The main objectives of sentinel node (SN) biopsy is to avoid unnecessary lymphadenectomies and to identify the 20-25% of patients with occult regional metastatic involvement. This technique reduces the associated morbidity from lymphadenectomy and increases the occult lymphatic metastases identification rate by offering the pathologist the or those lymph nodes with the highest probability of containing metastatic cells. Pre-surgical lymphoscintigraphy is considered a "road map" to guide the surgeon towards the sentinel nodes and to localize unpredictable lymphatic drainage patterns. The SPECT/CT advantages include a better SN detection rate than planar images, the ability to detect SNs in difficult to interpret studies, better SN depiction, especially in sites closer to the injection site and better anatomic localization. These advantages may result in a change in the patient's clinical management both in melanoma and breast cancer. The correct SN evaluation by pathology implies a tumoral load stratification and further prognostic implication. The use of intraoperative imaging devices allows the surgeon a better surgical approach and precise SN localization. Several studies reports the added value of such devices for more sentinel nodes excision and a complete monitoring of the whole procedure. New techniques, by using fluorescent or hybrid tracers, are currently being developed.

Clinical Significance of Extracapsular Invasion at Sentinel Lymph Nodes in Breast Cancer Patients with Sentinel Lymph Node Involvement.

A certain number of patients have extracapsular invasion (ECI) at the sentinel lymph node (SLN), but only a few reports describe its clinical significance. This study aimed to determine the clinical significance of ECI at SLN in breast cancer patients with involved SLN. This study evaluated ECI at SLN in 131 consecutive SLN-positive patients who underwent axillary lymph node dissection between 2003 and 2008 at the National Kyushu Cancer Center with regard to their long-term prognosis and non-SLN metastasis. Of the 131 patients, 46 (35 %) tested positive for ECI at SLN. Of these 46 patients, 61 % (28/46) had non-SLN metastasis compared with 28 % (24/85) in ECI-negative group (χ (2) test; P < 0.001). Multivariate analysis showed that ECI at SLN is significantly predictive for non-SLN metastasis [hazard ratio (HR) 3.2; 95 % confidence interval (CI) 1.4-7.1; P = 0.005]. The 5-year recurrence-free survival (RFS) rates were 71.3 % in the ECI-positive group and 89.9 %in the ECI-negative group (P = 0.001, log-rank test). Cox-regression analysis showed that ECI at SLN independently predicts lower RFS (HR 4.5; 95 % CI 1.8-11.7; P = 0.002). The findings show that ECI at SLN is an independent predictor of both non-SLN metastasis and poor prognosis for breast cancer patients with involved SLN. The clinical significance of ECI at SLN in operable-stage breast cancer warrants further study.

The use of indocyanine green to detect sentinel nodes in breast cancer: A prospective study

BackgroundAlthough Indocyanine green (ICG) is used to find sentinel nodes (SN) in patients with breast cancer (BC), its role in clinical practice is still debated, and needs a definitive validation to be included in the standard approach to finding sentinel nodes in breast cancer. Materials and methodsTo validate the ICG methods of detecting the SN in BC we have recently concluded a prospective validation trial. Patients with clinically node-negative, invasive early BC scheduled for breast surgery and SN biopsy were included in the trial. All the patients underwent SN detection using both the standard-of-care procedure using radioisotope technetium (99mTc) and the ICG, using the Photodynamic Eye camera. A comparison of the detection rate and the diagnostic accuracy of the two methods was performed to detect the equivalency of the two approaches. ResultsAt the end of the enrolment, 301 patients were considered eligible and included in the trial, and 589 nodes were removed. Five hundred and eighty-three nodes (99%) were identified with ICG (median 2 nodes per patient) and 452 (76.7%) were identified with 99mTc (median 2 nodes per patient). A concordance index of 98.75% (CI, 95% = 97.1%–99.5%) was detected. The dosage given ranged from 0.3 to 1.4 ml. ICG was used in all patients eligible for SN biopsy without any significant acute side effects. ConclusionsThe index of concordance between 99mTc and ICG seems to be extremely high, suggesting that ICG could be validated as an alternative method to 99mTc in the detection of SN in BC.

Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial

If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node, axillary lymph node dissection is the present standard. Although axillary lymph node dissection provides excellent regional control, it is associated with harmful side-effects. We aimed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects. Patients with T1-2 primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised, multicentre, open-label, phase 3 non-inferiority EORTC 10981-22023 AMAROS trial. Patients were randomly assigned (1:1) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node, stratified by institution. The primary endpoint was non-inferiority of 5-year axillary recurrence, considered to be not more than 4% for the axillary radiotherapy group compared with an expected 2% in the axillary lymph node dissection group. Analyses were by intention to treat and per protocol. The AMAROS trial is registered with ClinicalTrials.gov, number NCT00014612. Between Feb 19, 2001, and April 29, 2010, 4823 patients were enrolled at 34 centres from nine European countries, of whom 4806 were eligible for randomisation. 2402 patients were randomly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy. Of the 1425 patients with a positive sentinel node, 744 had been randomly assigned to axillary lymph node dissection and 681 to axillary radiotherapy; these patients constituted the intention-to-treat population. Median follow-up was 6·1 years (IQR 4·1-8·0) for the patients with positive sentinel lymph nodes. In the axillary lymph node dissection group, 220 (33%) of 672 patients who underwent axillary lymph node dissection had additional positive nodes. Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group. 5-year axillary recurrence was 0·43% (95% CI 0·00-0·92) after axillary lymph node dissection versus 1·19% (0·31-2·08) after axillary radiotherapy. The planned non-inferiority test was underpowered because of the low number of events. The one-sided 95% CI for the underpowered non-inferiority test on the hazard ratio was 0·00-5·27, with a non-inferiority margin of 2. Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year, 3 years, and 5 years. Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1-2 primary breast cancer and no palpable lymphadenopathy. Axillary radiotherapy results in significantly less morbidity. EORTC Charitable Trust.

Prognosis of metastatic internal mammary sentinel nodes (IMSN) in breast cancer.

103 Background: The presence of positive internal mammary nodes has historically been associated with a significant worse prognosis. Recent studies have also demonstrated a worse prognosis associated with drainage to the internal mammary nodes. Intense search for those nodes, biopsy, appropriate staging and modern treatment for positive IMSN might improve outcome. We sought to study the prognosis of pathologically positive IMSN at our institution. Methods: A retrospective analysis of a prospectively collected database including all breast cancer patients identified with an IMSN that was biopsied between 2005 and 2012 was performed. Demographics, histologic markers, patterns of recurrence as well as survival data were collected. Univariate and multivariate analysis were performed. Results: Thirteen of 82 patients with a biopsied IMSN were metastatic (16%). In 8 of those (62%), the biopsy resulted in a change in staging. In all cases of positive IMSN additional radiation to the internal mammary chain was added. Eighteen percent (18%) of positive nodes did not show drainage to the internal mammary basin during Lymphoscintigraphy. There was no statistical difference in regional and distant recurrences between the patients with positive IMSN and those with negative IMSN. Furthermore there was no difference in disease specific survival. Conclusions: Intense search for IMSN presence and biopsy of those nodes is associated with changes in staging and treatment for metastatic IMSN. In our study, pathologically positive IMSN were associated with a non- inferior prognosis than negative IMSN.

Diagnostic validity of the intraoperative analysis in frozen section of the sentinel lymph node in the surgical management of breast cancer

ObjectiveThe method for intraoperative sentinel lymph node (SLN) evaluation has still not been established in breast cancer staging. This study has evaluated the diagnostic validity and impact of intraoperative analysis using the frozen section (FS) of SLN. Material and methodsWe performed a descriptive study of the diagnostic validity of the FS of the SLN in patients with breast cancer and selective sentinel node biopsy (SSNB) from October 2006 to October 2012. The diagnostic validity indexes were evaluated using sensitivity, specificity, positive and negative predictive values and global value. The final histopathological results of the biopsies was considered as the gold standard. ResultsA total of 370 patients were studied. Sensitivity and specificity for detection of metastasis using FS of the SLN were 67% and 100%, respectively. Global diagnostic validity was 95%. There was a correlation between detection of metastasis and tumor size (p<0.05). Twelve of the 15 patients with SLN micro-metastases underwent axillary lymph node dissection (ALND). Metastatic lymph nodes were not found in any of them. ConclusionsIntraoperative FS examination of the SLN is a useful and reliable predictor of axillary lymph node staging in patients with initial stages of breast cancer. FS reduces the number of second interventions, at least for most patients who have breast cancer and unequivocal evidence of positive lymph node disease.

Validez diagnóstica del análisis intraoperatorio mediante sección en congelación del ganglio centinela en el manejo quirúrgico del cáncer de mama

The method for intraoperative sentinel lymph node (SLN) evaluation has still not been established in breast cancer staging. This study has evaluated the diagnostic validity and impact of intraoperative analysis using the frozen section (FS) of SLN.We performed a descriptive study of the diagnostic validity of the FS of the SLN in patients with breast cancer and selective sentinel node biopsy (SSNB) from October-2006 to October-2012. The diagnostic validity indexes were evaluated using sensitivity, specificity, positive and negative predictive values and global value. Gold standard was considered as the final histopathological results of the biopsies.A total of 370 patients were studied. Sensitivity and specificity for detection of metastasis by FS in the SLN were 67% and 100%, respectively. Global diagnostic validity was 95%. There was a correlation between detection of metastasis and tumor size (p<0.05). Twelve of the 15 patients with SLN micro-metastases underwent axillary lymph node dissection (ALND). Metastatic lymph nodes were not found in any of them.Intraoperative FS examination of the SLN is a useful and reliable predictor of axillary lymph node staging in patients with initial stages of breast cancer. FS reduces the need for second interventions, at least for most patients who have breast cancer with identifiable positive SLN and unequivocal evidence of positive lymph node disease.

Experience at the district hospital: Assessment of the sonographically occult macro metastases following sentinel node biopsy. Do we over treat the axilla?

Introduction: Assessment of the sentinel nodes in breast cancer identifies patients who may benefit from further axillary surgery and adjuvant chemotherapy. Sentinel lymph node biopsy is appropriate for the patients with clinically and radiologically normal axilla.

Histologic evaluation of sentinel and non-sentinel axillary lymph nodes in breast cancer by multilevel sectioning and predictors of non-sentinel metastasis.

Sentinel lymph node (SLN) provides accurate nodal staging for breast cancer. This technique has been introduced in Siriraj Hospital since 1998. The goal of this study is to assess its accuracy in predicting the state of the axilla, and compare the results of standard examination and multilevel sectioning. A retrospective analysis of 195 breast cancer patients who underwent both SLN biopsy (using dye alone as the lymphatic mapping) and axillary node dissection during 1998-2002 were analyzed. All slides including SLNs and the non-SLNs (NSLNs) were reviewed and multilevel study was performed on all SLNs and NSLNs [four levels of hematoxylin-eosin (HE) at 200 µm interval and keratin stains on the first and fourth levels]. Of 195 patients, 30% of cases were SLN-positive (32 NSLN-positive and 27 NSLN-negative). Additional study could detect positive axillary nodes 10.8% (4 SLN-positive and 5 NSLN-positive) more than standard HE stain. The false negative rate increased from 20.3% to 24.1%. The concordance between SLN and NSLN statuses was 89.7%. The sensitivity was 75.9%. By multivariate analysis, the significant predictors for axillary node metastasis were tumor size of more than 2.2 cm, histologic type of invasive ductal carcinoma (IDC), not otherwise specified (NOS) and lymphovascular invasion (LVI). By univariable analysis, the significant predictors of NSLN metastasis after positive-SLN were outer location of the tumor, LVI and perinodal extension. In conclusion, use of multilevel and immunohistochemistry increased detection of positive-SLNs. Caution should be kept in accepting SLN biopsy using peritumoral dye technique alone as the procedure for staging due to a high false-negative rate. The concordance rate of 89.7% confirmed the reliability of SLN. Outer location of tumor, LVI and perinodal extension is significant predictors of positive-NSLN after positive-SLN.

Lymphoscintigraphy with peritumoral injection versus lymphoscintigraphy with subdermal periareolar injection of technetium-labeled human albumin to identify sentinel lymph nodes in breast cancer patients

Preoperative lymphoscintigraphy is without doubt a valid method for the detection of the sentinel lymph node (SLN). There has been considerable debate regarding the optimal site for the introduction of the tracer; various sites include peritumoral (PT), periareolar (PA), subdermal, and intradermal injection. To evaluate retrospectively the lymphoscintigraphic identification rate of peritumoral (PT) injection versus subdermal periareolar (PA) injection in the detection of SLNs in breast cancer. Between October 2002 and December 2011, a cohort of 906 consecutive patients with biopsy proven breast cancer underwent 914 SLN biopsy procedures. A total of 339 procedures (Group A) were performed using a PT deep injection of radiotracer while 575 procedures (Group B) adopted a subdermal PA injection of radiotracer towards the upper outer quadrant, regardless of the site of the carcinoma. All the patients underwent synchronous excision of the breast cancer and SLN biopsy. SLNs were identified in the lymphoscintigram in 308/339 cases (90.85%) of Group A (PT injection) and in 537/575 cases (93.39%) of Group B (PA injection). Furthermore, in 2/339 patients (0.58%) of Group A, internal mammary lymph nodes were found at lymphoscintigraphy, whereas no internal mammary sentinel nodes were found in the Group B patients. The intraoperative identification rate of axillary SLNs was 99.41% (337 of 339) in the Group A patients and 99.65% (573 of 575) in the Group B patients. There was no significant difference in the two groups between the incidence of the number of SLNs detected and the incidence of identification of positive SLNs. PT versus PA injection of radiotracer showed comparable success rates for axillary SLN identification, and can be considered a rapid and reliable method.

Non-Axillary Sentinel Node in Breast Cancer. Are we Staging Correctly? A Multicenter Study

Purpose: The study of the sentinel lymph node is the best technique to stage, have a prognosis and decide the adequate treatment in breast cancer. The usual technique implies studding the axillary lymph node. Our work tries to identify affected nodes in other regions apart from the axilla and its possible impact in staging and treatment. Methods: The sentinel lymph node technique was performed on 1660 patients included in an observational and multicentric study designed to observe the presence of metastatic cells in axillary and non-axillary lymph nodes. Results: In 19% of the patients the sentinel lymph node was detected in non-axillary regions. In these cases metastatic cells were more frequent which could suppose a change in the stage and/or treatment. As protective factor against non-axillary nodes involvement we found the localization of the cancer in external quadrants while youth and injecting the tracer inside the tumor were found to be risk factors. Conclusions: Detecting and studding non-axillary lymph nodes in breast cancer leads to a more precise staging of the disease which could imply a change in the optimal treatment.

The impact of method of biopsy on the incidence of breast cancer sentinel lymph node metastases

The dislocation of the malignant cells along the needle tract during breast cancer (BC) diagnosis has been demonstrated by several studies. However, the published experiences that relate the diagnostic technique with sentinel node (SN) involvement are few and controversial. The aim of our analysis was to evaluate the impact of different techniques for preoperative BC biopsy among prognostic factors of metastases occurrence in SN. We reviewed the institutional clinical database of our Center. A total of 674 patients were diagnosed between February 1999 and December 2006 with invasive BC. SN metastases classification followed the 2002 American Joint Committee on Cancer (AJCC) TNM pathological staging: macrometastases, micrometastases, isolated tumor cells or negative. Only macrometastases and micrometastases were considered positive. Concerning fine-needle aspiration cytology, we used disposable needles of the size of 21-27G. For percutaneous biopsy we used cutting needle type "tru-cut"; the Gauge needle ranged between 14 and 20. At univariate analysis of specific parameters using positive SN as outcome, percutaneous diagnostic technique did not affect significantly the SN positivity (p=0.60). At multivariate models only central quadrant lesion (p=0.005) and lymph vascular invasion (LVI) presence (p<0.0001) maintained the statistical significance as risk factor for positive SN status. Polytomic logistics models showed that only LVI maintained the statistical significance both for prediction of micrometastases and macrometastases. Our analysis showed that different techniques used for BC diagnosis did not influence SN status.

Abstract P1-01-12: Intraoperative detection of sentinel lymph nodes in breast cancer patients using ultrasonography-guided direct indocyanine green dye-marking by real-time virtual sonography constructed with three-dimensional computed tomography-lymphography

Abstract Purpose: This study aims to determine the utility of ultrasonography (US)-guided direct dye-marking of sentinel lymph nodes (SLNs) by real-time virtual sonography (RVS) constructed with three-dimensional (3D) computed tomography (CT)-lymphography (LG). Patients and Methods: We identified SLNs in 258 clinically node-negative breast cancer patients using an RVS system to display in real time a virtual multiplanar reconstruction CT image obtained from CT volume data corresponding to the same cross-sectional image from US. CT volume data were obtained using our original 3D CT-LG, which accurately detects SLNs in breast cancer. We then perform US-guided dye-marking close to SLNs using indocyanine green (ICG). Subsequently, indigo carmine blue dye was injected into the subareolar and peritumoral areas around each primary tumor. All patients underwent SLN biopsy and SLN metastases were examined pathologically. Results: In all 258 patients, we were able to detect the same SLNs visualized on 3DCT-LG, using the RVS system. We detected ICG close to SLNs in 257 of 258 patients (99.6%) during SLN biopsy. In 25 patients (9%), we failed to follow the blue lymphatic route stained by indigo carmine and SLNs were not stained by indigo carmine, but easily detected SLNs by ICG marking. Conclusion: US-guided direct ICG dye-marking of SLNs using this RVS system seems useful for the detection of SLNs, allowing easy detection of SLNs even when the stained lymphatic route is not followed. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-12.