Sentinel Lymph Node Micrometastases Research Articles

Sentinel lymph node biopsy for high-risk cutaneous squamous cell carcinoma: Analysis of recurrence-free survival

Background and aimCutaneous squamous cell carcinoma (CSCC) is a malignant epithelial cell tumor. CSCC has a tendency to spread via lymphogenic pathway. Metastases are found in 2%–6% of cases. Prognosis of patients with CSCC is directly related to the morphology and localization of primary tumor.The aim of this study was to evaluate the recurrence-free survival of patients with CSCC after tumor excision and SLNB as well as to analyze morphologic CSCC features related to patient recurrence-free survival. Materials and materialsA retrospective analysis of 51 patients with CSCC, who underwent surgical treatment between January 1, 2012, and December 31, 2014, in the Clinic of Plastic and Reconstructive Surgery, Hospital of the Lithuanian University of Health Sciences, was done. The diagnosis of CSCC was verified on a histological examination, and all patients had no clinical evidence of nodal or distant metastases on a physical examination or imaging studies. Sentinel lymph node biopsy (SLNB) was performed for low- and high-risk CSCC patients. ResultsA total of 51 patients were enrolled into the study (34 women and 17 men). Total of 68 lymph nodes were removed during sentinel lymph node biopsy. No micrometastases were identified. Until April 1, 2015, no relapse event was documented. The mean time after operation was 27.5 months. During the follow-up period, no distant metastases were identified. ConclusionsNo patient who had no micrometastases in sentinel lymph nodes developed local and distant CSCC metastases during the follow-up period. Our report supports the concept that SLNB can be applied for CSCC. It is obvious that larger prospective studies with longer follow-up period are needed to establish the efficacy of SLNB and define the optimal treatment of occult nodal metastasis for CSCC.

Recent advances in sentinel node biopsy in breast surgery.

Sentinel lymph node (SLN) biopsy has become the standard of care for early breast cancers throughout the world. It provides the breast cancer patients with the safety and benefit of a highly accurate and less-morbid axillary staging, thereby avoiding the uncomfortable side effects of unnecessary axillary dissection. Recently, SLN biopsy was successfully performed in patients undergoing neoadjuvant chemotherapy. However, the methods used for SLN biopsy, and for the evaluation of cancer metastasis in SLN are not still fully established. Ordinarily, a positive SLN (macrometastasis and micrometastasis) indicates further axillary lymph node dissection; however, recent reports have shown that this may not be true for all cases. Also, the prognostic significance of macrometastasis, micrometastasis and isolated tumor cells (ITC) in SLN are still unclear. In the first review, Dr. Motomura has presented an overview of the past, present, and future of SLN biopsy for breast cancers. The clinical significance of micrometastasis in sentinel nodes, the prevention of axillary lymph node dissection in patients with positive sentinel nodes, neoadjuvant chemotherapy and sentinel node biopsy, as well as future perspectives are discussed in this review. In the second review by Dr. Tsuda, the histopathological aspects of sentinel lymph nodes have been presented. He described the classification of macrometastasis, micrometastasis, and ITC, as well as the practice of intraoperative pathological diagnosis of SLN metastasis. In addition, the clinical implications of micrometastasis and ITCs in SLNs are discussed. In the third review, Dr. Tamaki described a recently developed new method for the detection of cancer metastasis in SLN; the one step nucleic acid amplification (OSNA) method. Based on several original articles, the reliability of the OSNA method has been compared with the histopathological method, and clinical use of OSNA method in SLN biopsy was presented. I advise the readers to read and compare the present issues and the past issues, entitled ‘‘Recent trends concerning sentinel lymph node biopsy for breast cancer and new methods for detection of metastasis’’ in Breast Cancer, Vol. 14, No. 4, 2007.

Sentinel lymph node biopsy using computed tomographic lymphography in patients with early tongue cancer

Conclusions: Because computed tomography (CT) lymphography provides preoperative images of anatomic relationships between a tumor, its associated lymph vessels, and the sentinel lymph node (SLN), it may aid in directing the SLN biopsy for management of early tongue cancer. Objectives: SLN biopsy using a radioisotope (RI) generally has been performed in head and neck cancer. However, this method can be performed only at institutions that are licenced for its use. In this study, we evaluated the utility of performing SLN biopsy in patients with early tongue cancer using the newly developed technique of CT lymphography. Methods: Enrolled in this study were 31 patients with T1N0 or T2N0 tongue cancer. CT images were obtained before and after injection of iopamidol into the peritumoral region and the SLN was identified as the first enhanced lymph node. SLN biopsy was performed using CT lymphographic guidance combined with blue dye injection. Results: The SLN was detected by CT lymphography in 28 cases (90.3%). By intraoperative frozen section examination, metastases to SLNs were found in 4 (14.3%) (T1N0, 1 patient; T2N0, 3 patients) of the 28 patients. Of these four, SLN micrometastases were found in one patient.

Predictive factors for additional non-sentinel lymph node involvement in breast cancer patients with one positive sentinel node.

The aim of this study was to identify a subgroup of breast cancer patients in whom it is possible to avoid axillary lymph node dissection (ALND) when the sentinel lymph node (SLN) is positive. A series of 292 patients treated with breast-conserving surgery or mastectomy underwent ALND after positive SLN detection. To correlate SLN metastasis with the chances of finding additional metastasis in non-SLNs we evaluated the main clinicopathological characteristics. No patients received adjuvant radiotherapy to the axillary region. Fifty-six patients (35.4%) with positive SLNs for macrometastases (n = 158) had additional metastases upon completion ALND compared with 7 patients (5.2%) with micrometastases in the SLN (n = 132). Cases with a higher number of positive axillary lymph nodes tended to have higher pT stage (p = 0.004). In multivariate analysis, pT was confirmed as an independent predictor of non-SLN metastases (OR = 2.40; 95% CI = 1.16-4.99). No patients with micrometastases in SLN and cancer lt;10 mm had additional positive non-SLNs. Our results, in agreement with the major published studies, suggest that ALND can be avoided in selected patients without the need for additional treatment to the axillary region.

Micrometastases in sentinel lymph node in endometrial cancer patients

Detection of micrometastases in sentinel lymph nodes (SLN) extends our knowledge of lymphatic spread in endometrial cancer, although its clinical significance has not yet been confirmed. The aim of study was to determine the incidence of SLN micrometastases and to analyze the association between micrometastases and disease relapse. Fifty-four patients with endometrioid endometrial cancer underwent routine surgical therapy and sentinel lymph node biopsy (SLNB). SLNB was performed using two techniques: cervical injection of 99mTc-labelled albumin or blue dye and fundal injection of blue dye. SLNs were subjected to ultrastaging with immunohistochemistry (AE1/AE3, 150µm). At least one SLN was detected in 51 patients (94.4%) and bilateral SLN detection was achieved in 80.4%. Nodal macrometastases were found in 3 patients (6.3%). SLNB enabled us to detect nodal macrometastases in 2 out of those 3 patients. In the third case, detection of SLN micrometastasis allowed to correctly determine the nodal status, thus avoiding the false negative result of SLNB. In 48 patients with detected 184 SLNs, there were 4 patients (8.3%) with micrometastases and 4 (8.3%) with ITC foci. No significant associations between the presence of risk factors (grade, myometrial invasion, cervical invasion, lymphovascular space invasion) and incidence of micrometastases and/or ITC foci in SLNs were found. Detection of micrometastases may result in lower false-negative rate, thus increasing SLNB safety.

Sentinel node navigation surgery for gastric cancer: Overview and perspective

The sentinel node (SN) technique has been established for the treatment of some types of solid cancers to avoid unnecessary lymphadenectomy. If node disease were diagnosed before surgery, minimal surgery with omission of lymph node dissection would be an option for patients with early gastric cancer. Although SN biopsy has been well ascertained in the treatment of breast cancer and melanoma, SN navigation surgery (SNNS) in gastric cancer has not been yet universal due to the complicated lymphatic flow from the stomach. Satisfactory establishment of SNNS will result in the possible indication of minimally invasive surgery of gastric cancer. However, the results reported in the literature on SN biopsy in gastric cancer are widely divergent and many issues are still to be resolved, such as the collection method of SN, detection of micrometastasis in SN, and clinical benefit. The difference in the procedural technique and learning phase of surgeons is also varied the accuracy of SN mapping. In this review, we outline the current status of application for SNNS in gastric cancer.

Biopathologic features and clinical significance of micrometatasis in the lymph node of early gastric cancer.

To evaluate the biopathologic features and clinical significance of nodal micrometastasis (MI) in early gastric cancer (EGC). Among 1022 EGC patients who underwent gastrectomy with lymphadenectomy of D1 + β or more from March 2001 to December 2005 at the Korean National Cancer Center, available nodal metastasis was found in 90 pT1N1 patients. Nodal metastasis was confirmed by immunohistochemistry (IHC) with cytokeratin and patients were classified into MI and macrometastasis (MA) groups based on the main tumor burden according to the 6(th) International Union Against Cancer/American Joint Committee on Cancer staging system; the main tumor burden with a diameter of greater than 0.2 mm but no greater than 2 mm as MI, and greater than 2 mm as MA of the representative metastatic node. Proliferative and apoptotic activities of the primary tumor and the nodal metastasis were measured by IHC with Ki-67 and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Biopathologic and clinical features of the patients were analyzed and compared between MI and MA groups. Patients with recurrence were compared with those without recurrence to identify risk factors for recurrence. Thirty-seven patients showed MI and the other 53 patients revealed MA in the lymph node; the incidence of patients with MI and MA was 41.1% and 58.9%. The main tumor burden was 0.9 and 4.6 mm in the representative metastatic node, respectively. Japanese N2 stations were more frequently involved in MA group (20.9%) than in MI group (10.3%) but the difference was not statistically different (P = 0.338). Proliferative and apoptotic activities of MI were decreased than those of MA (26.7% vs 40.5%, P = 0.004 and 1.0% vs 3.0%, P < 0.001, respectively). However, nodal MI in the current study showed a relatively high proliferative activity and an equivalent apoptotic activity compared to other cancers in the previously published studies. Recurrence was observed in 6 patients during the mean follow up period of 87.6 ± 26.2 mo. The recurrence was significantly associated with the presence of MA (P = 0.041) and lymphovascular invasion of the primary tumor (P = 0.032). Lymphadenectomy of D1 + β or more might be necessary in patients with MI in sentinel node to prevent recurrence by clearing MI involving Japanese N2 station.

One Step Nucleic Acid Amplification (OSNA) positive micrometastases and additional histopathological NSLN metastases: Results from a single institution over 53 months

IntroductionThe role of sentinel lymph node micrometastases on histopathological analysis is controversial in axillary staging and management in clinically node negative breast cancer. Long-term studies addressing the clinical relevance of occult breast cancer in sentinel lymph nodes based on molecular analysis are lacking. One Step Nucleic Acid Amplification (OSNA), a highly sensitive assay of cytokeratin 19 mRNA, is used intra-operatively for the detection of lymph node macro- and micrometastases in breast cancer. AimThe aim of this study is to review the rate of micrometastases and further histopathological NSLN metastases, in our unit following the introduction of OSNA in Guildford. MethodsData was collected prospectively from the period of introduction 01/12/2008 to 31/05/2013. All patients eligible for sentinel lymph node biopsy were offered OSNA and operations were performed by the consultant breast surgeons. Presence or absence of micro-metastases depends on the agreed cut-off point on the amplification curve. On detection of micrometastases (+) and positive but inhibited (i+) metastases, a level 1 axillary clearance (ANC) was performed and for a macrometastasis (++), a level 3 ANC was carried out. Results66% of the patients had negative SLN (n = 672) and 34% (n = 336) had positive sentinel lymph nodes who had further axillary surgery. Of these, 45% (n = 152/336) had macrometastases, 40% (n = 136/336) had micrometastases and 15% (48/336) had positive but inhibited results. There was no difference in the patient demographics and tumour characteristics in the various positive SLN groups. In patients with micrometastases, 15% (20/136) had further positive NLSNs and a further 6% (8/136) had >4 overall positive nodes (SLN + NSLN) thus requiring adjuvant supraclavicular/chest wall radiotherapy (p < 0.05). 25% of node positive patients had further NLSN metastases (85/336) and in these patients, the ratio of positive SLN/harvested SLN (+SLN/SLN) is constant at 1:1. This shows the likelihood of further positive NSLNs if all the harvested lymph nodes are positive. This linear trend is present in both micro-and macrometastases, thus correlating with the size and number of NSLN metastases. ConclusionOur study reflects the tumour burden of NSLNs based on the molecular analysis of the SLN. OSNA has the potential to accurately identify axillary micrometastases. Micro-metastases are important as some of the patients with micrometastases had overall four positive nodes [SLN + NSLN] (criteria for radiotherapy in the absence of other adverse clinicopathological features). Also, our study highlights certain factors that predict the NSLN metastases, pending validation by further prospective long-term data. This will allow accurate calculation of the axillary tumour burden, particularly in patients with micro-metastases.

148. Management of micro-metastasis in sentinel lymph node biopsy during breast cancer operation

Background: According to the results of ACOSOG Z0011 trial, ASCO and NCCN guideline showed that women with one to two metastatic SLNs planning to undergo breast-conserving surgery with whole-breast radiotherapy should not undergo ALND (in most cases). However, some prudent surgeons are still undergo ALND if SLN positive in accordance with Z0011 criteria. We evaluated the cases with micrometastasis in sentinel lymph node (SLN) during operation in our hospital.

290. Influence of micrometastasis in sentinel lymph nodes in colon cancer on prognosis and survival

Background: The sentinel node biopsy in colon cancer clearly increases detection of occult metastasis following ultrastaging of the sentinel nodes. The aim of this study was to investigate the prognostic impact and clinical relevance of micrometastasis found in the sentinel lymph nodes in colon cancer patients.

The impact of nodal tumour burden on lymphoscintigraphic imaging in patients with melanomas.

To retrospectively study the influence of nodal tumour burden on lymphoscintigraphic imaging in 509 consecutive patients with melanomas. Bidirectional lymphatic drainage, the clear depiction of an afferent lymphatic vessel, time to depiction of the first sentinel lymph node (SLN) and number of depicted and excised nodes were recorded. Nodal tumour load was classified as SLN-negative, SLN micrometastases or macrometastases. In the overall population, using multivariate regression analysis, a short SLN depiction time was significantly associated with the depiction of a greater number of radioactive nodes, a short distance between the primary tumour site and the nodal basin, younger age and lower nodal tumour burden. The proportion of patients with clear depiction of an afferent lymphatic vessel depended on the nodal tumour load (46% in SLN-negative patients, 57% in SLN positive patients, and 69% in patients with macrometastases; P = 0.009). Macrometastasis was significantly associated with delayed depiction of the first radioactive node and a greater number of depicted hotspots. In patients with clinically nonsuspicious nodes, i.e. the classical target group for SLN biopsy, clear depiction of an afferent vessel was significantly associated with a higher number of SLNs during dynamic acquisition, SLN micrometastasis and a higher overall number of metastatic lymph nodes after SLN biopsy plus completion lymphadenectomy. The excision of more than two SLNs did not increase the metastasis detection rate. In patients with bidirectional or tridirectional lymphatic drainage, the SLN positivity rates for the first, second and third basin were 25.4%, 11.7% and 0.0 %, respectively (P = 0.002). In patients with clinically nonsuspicious lymph nodes, clear depiction of an afferent lymph vessel may be a sign of micrometastasis. Macrometastasis is associated with prominent afferent vessels, delayed depiction of the first radioactive node and a higher number of depicted hotspots.

165. Can we safely avoid axillary clearance when sentinel node is minimally involved in early breast cancer?

Background: Sentinel Lymph Node Biopsy (SLNB) represents a minimally invasive technique for axillary staging in early breast cancer. SLNB is useful in surgical complications risk reducing compared to complete axillary lymph node dissection (CALND). Micrometastases (MM) prognostic value has been recently challenged. The 2011 St Gallen Consensus Conference recommended that micrometastases in a single sentinel node should not be an indication for axillary dissection irrespective of the type of breast surgery given.

Impact of sentinel node tumor burden on outcome of invasive breast cancer patients

BackgroundThe tumor status of the axillary lymph nodes is one of the most important prognostic factors in women with early breast cancer (BC). Sentinel lymph node (SLN) biopsy has become the standard staging procedure for patients with invasive BC, largely replacing axillary lymph nodes dissection (ALND). The exact impact on prognosis of SLN tumor burden is still object of controversy. The aim of this study was to correlate the tumor burden in the SLN with the outcome in a large cohort of women. Patients and methods1040 consecutive patients with clinical stage I–III invasive BC were prospectively collected on our Institutional BC database from January 2001 to January 2007. Patients were stratified into the following four groups based on the tumor burden of the SLN: macrometastases, tumor deposit ≥2 mm; micrometastases, tumor deposit ≥0.2 mm and <2 mm; isolated tumor cells (ITC), isolated tumor cells or tumor deposit <0.2 mm; negative, in case of patients with no evidence of tumor. ResultsAt a median follow-up of 8.5 years, the tumor burden of SLN metastases resulted significant predictor of DFS (P < 0.0001) and OS (P = 0.042). Multivariate analysis showed that the tumor burden of SLN metastases and Ki 67 proliferative index maintained the statistical significance. ConclusionPatients with SLN micrometastases or ITC, do not seem to have a worse DFS or OS compared with SLN negative cases. There is a significant decrease in DFS and OS in patients with macrometastatic disease in the SLN.

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.

In breast cancer patients sentinel lymph node metastasis characteristics predict further axillary involvement.

The aim of the study was to correlate various primary tumor characteristics with lymph node status, to examine sentinel lymph node (SLN) metastasis size and non-SLN axillary involvement, to look for a cut-off size/number value possibly predicting additional axillary involvement with more accuracy and to examine the relationship of SLN metastasis size to overall survival. Of 301 patients who underwent SLN biopsy, 75 had positive SLNs. The size of the metastases was measured. For different size categories, association with the prevalence of non-SLN metastases was assessed. Associations between metastasis size and tumor characteristics and overall survival (OS) were studied. The prevalence of axillary lymph node (ALN) involvement was not significantly different between cases with micrometastasis or macrometastasis in SLNs (p = 0.124). However, for metastases larger than 6, 7, and 8 mm, the prevalence of ALN involvement was significantly higher (p = 0.046, 0.022, and 0.025). OS was significantly lower in SLN-positive than in SLN-negative cases (p = 0.0375). Primary tumor size larger than 20 mm was associated with a significantly higher incidence of SLN metastasis (p < 0.001), and primary tumor size over 26 mm was associated with additional positive non-SLN (p < 0.001). Higher mitotic index (≥ 7) in primary tumors was significantly (p < 0.001) associated with ALN involvement in SLN-positive cases, whereas higher Ki67 labeling index was not significantly correlated with SLN or ALN involvement. Lymphovascular invasion (LVI) in primary tumors was significantly correlated with SLN positivity (p < 0.001) but not with further ALN involvement or OS. Tumor size and LVI are predictive for SLN metastasis. Mitotic index, primary tumor size, and larger volume SLN involvement are determinants of further ALN involvement. SLN metastasis size over 6 mm is a strong predictor of further axillary involvement. OS is shorter in the presence of positive SLN.

Management and results of treatment of breast cancer patients having sentinel lymph node micrometastases.

According to current therapeutic guidelines, finding micrometastases in the sentinel node (SLN) of a patient with non-advanced breast cancer is not an absolute indication for adjuvant axillary lymph node dissection (ALND). This work presents our experiences regarding this clinical problem. 1071 breast cancer patients were referred for sentinel node biopsy between January 2004 and December 2011. Metastases were found in 245 of the removed lymph nodes. In 49 patients lymph node changes turned out to be micrometastases or isolated tumor cells (ITC). ALND was performed in 38 cases of sentinel node micrometastases or ICTs. In three patients involvement of other axillary lymph nodes was found in the studied tissue material (7.9% vs. 37.9% for metastases >2mm). The remaining patients with micrometastases in the SLN (11/49) were treated conservatively. No local axillary recurrences or neoplastic metastases were found in this group of patients with SLN micrometastases. Mean follow-up period in patients who had undergone ALND was 18.0 months (4 to 60 months) and 21.4 months (9-40 months) in patients without ALND. Non-radical surgical treatment in the presence of SLN micrometastases in patients with non-advanced breast cancer does not lead to therapeutic failure (local axillary recurrences, distant metastases). Obtaining favorable outcomes of conservative treatment in the analyzed group of patients does not require additional modification of the adjuvant therapy.

No Axillary Lymph Node Dissection in Breast Cancer Patients with Sentinel Lymph Node Micrometastasis

Follow-up data of a series of 75 breast cancer patients with sentinel node (SN) micrometastases only (between 0.2 and 2 mm) and favorable histopathological features of the primary tumor (well-differentiated, T1 tumors without lymphovascular invasion) who refused completion axillary lymph node dissection (ALND) or who were unsuitable for surgery were assessed in order to detect the rate of axillary recurrence after an adjuvant chemoand/or hormonal adjuvant treatment was given. The great majority of patients (81.3%) did not undergo ALND due to the existence of favorable histopathologic factors while the rest were equally distributed among over 75-year-old women (10.6%) and patients at a high surgical risk due to comorbid conditions (9.3%). Sixty-six patients (88%) underwent conservative treatment (lumpectomy followed by adjuvant breast radiotherapy) while the remaining nine patients (12%) had total mastectomy; 72 out of 75 patients (96%) received some forms of adjuvant chemoand/or hormone-therapy. After a median follow-up of 38 months (range 12 - 84 months), nine out of 75 patients (12%) had a disease relapse, only one of them (1.3%) being affected by an axillary recurrence in the untreated axilla three years after primary surgery. On these grounds, completion ALND could be safely omitted in patients with SN micrometastasis and favorable histopathological characteristics of the primary neoplasm due to the very low rate of axillary recurrence with no detrimental effect on survival.

Abstract P1-01-25: Predictive factors of micrometastases in the sentinel node of patients affected by invasive early breast cancer

Abstract Aim: nodal metastatic involvement is the most important prognostic indicator in breast cancer. Sentinel node biopsy led to an increase in the detection of micrometastases. The aim of our analysis was to identify predictive factors of micrometastases and macrometastases of sentinel node. Materials and Methods: between January 2000 and December 2006, 675 patients were treated with breast surgery and sentinel node evaluation at University of Florence (Florence, Italy). Estrogen receptor status, progesterone receptor status, and Ki-67 labeling index determined with the MIB1 monoclonal antibody were assessed. HER2 immunohistochemistry (IHC) expression was scored as follows: 0, no staining or faint membrane staining; 1+, faint membrane staining in &amp;gt;10% of tumor cells, incomplete membrane staining; 2+, weak to moderate membrane staining in &amp;gt;10% of tumor cells; and 3+, intense circumferential membrane staining in &amp;gt;10% of tumor cells. HER2 scores of 0 and 1+ were considered negative. HER2 IHC 3+ and fluorescent in situ hybridization (FISH) – amplified tumors were considered positive. All IHC 2+ tumors and indeterminate tumors were tested for gene amplification by FISH. The sentinel node was examined by hematoxylin and eosin. The patients were divided into three groups based on AJCC TNM staging: sentinel node negative (n = 601); micrometastases if tumor deposit more than 0.2 mm but &amp;lt;2 mm (n = 20), and macrometastases if tumor deposit more than 2 mm (n = 53). Results: at the logistic regression with polytomous analyses (outcome micrometastases or macrometastases), age (p = 0.048), menopausal state (p = 0.013), breast quadrant (p = 0.005), lymph vascular invasion (p = 0.0001), post-surgical T stage (p = 0.0001), histotypes (p = 0.023), HER2 status (p = 0.02), Ki-67 proliferative index (p = 0.001) and nuclear grade (p = 0.024) were significantly correlated with sentinel node macrometastases. Sentinel node biopsy technique (cytological aspiration versus histological biopsy) was not associated with micrometastases (p = 0.89) or macrometastases (p = 0.48) occurrence. The only feature significantly associated with micrometastases in sentinel node was the lymph vascular invasion (p = 0.0001). Conclusion: the presence of micrometastases remained fairly constant over time if compared to macrometastases. In our experience the only feature significantly associated with micrometastases in sentinel node is the lymph vascular invasion. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-25.

Abstract AL-2: William L. McGuire memorial lecture – Local therapy in the molecular era: Relevant or relic?

Abstract Surgery has always been driven by disease burden; initially, to determine operability, and recently, to select patients for BCT. Systemic therapy also initially relied on disease burden (axillary nodes, tumor size), but gene profiles and molecular targets now predominate in selecting systemic therapy. Reliance on disease burden as a determinant of the intensity of local therapy is problematic as advanced imaging modalities and molecular pathology allow detection of increasingly smaller tumors. The application of management strategies proven beneficial for macroscopic tumor to subclinical disease has the potential for overtreatment as evidenced by increased mastectomy rates in patients undergoing preoperative MRI, and use of ALND and chemotherapy for sentinel node micrometastases. It is an appropriate time to ask how recognition of molecular subtypes and improvements in systemic therapy can be leveraged to improve local therapy outcomes and decrease the burden of therapy. Recognition that systemic therapy results in a major decrease in the rate of IBTR was the major impetus for SSO and ASTRO to commission a systemic review on margins for BCT in stage I and II breast cancer as the evidence base for a consensus conference. We concluded that evidence that margins more widely clear than no ink on tumor significantly improve local control was lacking and the routine practice of obtaining more widely clear margins is not indicated. Adoption of this approach has the potential to spare many women unnecessary surgery. The morbidity of ALND can also be avoided in many patients. The ACOSOG Z0011 trial showed no benefit to ALND for patients with 1 or 2 sentinel node metastases receiving WBRT and systemic therapy. There were many criticisms of this study, but 3 other prospective randomized trials (NSABP B04, NSABP B32, IBCSG 2013) demonstrate that residual axillary nodal disease does not translate to regional recurrence or a decrease in survival in a 1:1 ratio, and that systemic therapy greatly reduces the incidence of regional recurrence. In a prospective study of the applicability of Z0011 findings to an unselected population of women meeting study eligibility criteria, we found that only 16% of 287 consecutive patients had metastases in ≥3 sentinel nodes or matted nodes identified intraoperatively, sparing 84% ALND. These examples represent initial steps in reducing the morbidity of local therapy. Moving forward, it is appropriate to ask whether patients with favorable molecular profiles (luminal A), require the same local therapy as those with other molecular subtypes. More controversially, the success of HER2 blockade in improving survival raises the question of whether effective targeted therapy could allow a reduction in local therapy intensity. A major barrier to progress is the belief of many clinicians and patients that bigger surgery is better surgery. The full realization of multidisciplinary care will occur when improvements in outcomes with one modality result in studies examining the elimination of other treatments which may no longer be beneficial to patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr AL-2.