Breast Sentinel Lymph Node Research Articles

Evaluation of Breast Sentinel Lymph Node Coverage by Standard Radiation Therapy Fields

Biopsy of the breast sentinel lymph node (SLN) is now a standard staging procedure for early-stage invasive breast cancer. The anatomic location of the breast SLN and its relationship to standard radiation fields has not been described. A retrospective review of radiotherapy treatment planning data sets was performed in patients with breast cancer who had undergone SLN biopsy, and those with a surgical clip at the SLN biopsy site were identified. The location of the clip was evaluated relative to vertebral body level on an anterior-posterior digitally reconstructed radiograph, treated whole-breast tangential radiation fields, and standard axillary fields in 106 data sets meeting these criteria. The breast SLN varied in vertebral body level position, ranging from T2 to T7 but most commonly opposite T4. The SLN clip was located below the base of the clavicle in 90%, and hence would be excluded from standard axillary radiotherapy fields where the inferior border is placed at this level. The clip was within the irradiated whole-breast tangent fields in 78%, beneath the superior-posterior corner multileaf collimators in 12%, and outside the tangent field borders in 10%. Standard axillary fields do not encompass the lymph nodes at highest risk of containing tumor in breast cancer patients. Elimination of the superior-posterior corner MLCs from the tangent field design would result in inclusion of the breast SLN in 90% of patients treated with standard whole-breast irradiation.

Validation of clinical prediction rules for a low probability of nonsentinel and extensive lymph node involvement in breast cancer patients

Background Two recently developed clinical prediction rules aim to anticipate the lack of nonsentinel lymph node metastases and the involvement of less than 4 lymph nodes in breast cancer patients with positive sentinel lymph nodes (SLNs). Methods The University of Louisville Breast SLN Study clinical prediction rules were validated on an independent set of SLN-positive patients with tumors ≤15 mm. Results The data on 475 and 473 patients, respectively, were used for the validation. The areas under the receiver operating characteristic curves were similar to the originals for both predictive tools (.70 and .76). The lowest score of 1 identified 5 of 7 patients with disease limited to the SLNs and 161 of 165 as having less than 4 involved lymph nodes. Conclusions A subset of patients with SLN-only involvement and less than 4 metastatic lymph nodes can probably be identified by means of the Louisville clinical prediction rules, but prediction of the lack of non-SLN metastasis seems less reliable.

Breast cancer submicrometastasis detection in sentinel lymph node by molecular biology techniques: A new tumor staging method?

21120 Background: The purpose of this study was to analyze by molecular biology techniques (MBT) the presence of RNAm of mammaglobin (MAG) A and B in breast sentinel lymph nodes (SLN) by RT-PCR, and to correlate these findings with breast tumor characteristics. Methods: SLN from 51 patients with breast tumors smaller than or equal to 3 cm, with no palpable axillary lymphadenopathies were included. Hematoxylin-eosin (HE), immunohistochemistry study (IHC) and MBT were performed. Patients’ staging was assessed according to Saint Gallen's Consensus. Twenty-five patients had clinical follow-up. Results: HE showed metastasis in 4/51 cases, 5/51 were detected with IHC, and one of them negative for HE. MBT allowed the detection of 18/51 positive SN, which included the 5 above-mentioned cases. The other lymph nodes herein studied (33/51) showed no metastases with MBT. Patients’ mean age was 58 years, tumor's mean size was 0.96 cm. The average follow-up was 15 months (range: 1–29 months). The patient with a recurrence at 23 months of clinical follow-up was found to be the only one with HE (+), IHC (+), MAG-A (+) and MAG-B (+). Conclusions: SN study with HE fails to identify all SN with metastases. Immunohistochemistry and MBT increase metastasis detection. Multiplex RT-PCR technique for A and B MAG proves to be specific and sensitive. No direct relationship was found between the risk factors analyzed and the expression of MAG. Therefore, MAG could be used independently as a prognostic factor. The presence of hidden metastasis plays a significant role mainly in the overall survival rate of pre- and postmenopausal patients. This study will be useful to formulate hypotheses. Further research, including a larger population and a longer follow-up period, will be required to confirm these hypotheses. Should our findings be confirmed in the future, molecular biology determinations could modify patients staging and treatment. No significant financial relationships to disclose.

Implications of Transaxillary Breast Augmentation: Lifetime Probability for the Development of Breast Cancer and Sentinel Node Mapping Interference

Implications of Transaxillary Breast Augmentation: Lifetime Probability for the Development of Breast Cancer and Sentinel Node Mapping Interference

Loss of metastatic deposits in breast sentinel lymph nodes during intra-operative frozen section analysis

The intraoperative evaluation of sentinel lymph nodes is an ongoing debated issue. In this review we discuss different approaches to sentinel lymph node processing in an intra operative setting and in the consecutive embedding in paraffin. We propose a method, which uses routine intra operative examination of lymph nodes with stereo microscopy with selected frozen section analysis. We demonstrate preliminary data on a larger patient collective along with data on a control group. We could show in our study that a higher rate of metastates can be achieved avoiding intra operative frozen sections on grossly inconspicuous sentinel lymph nodes.

Pro: SLNB in DCIS

The role of sentinel node mapping and biopsy in the management of ductal carcinoma in situ (DCIS) remains controversial. A debate about the use of a staging technique for the evaluation of a malignancy without metastatic potential seems absurd. However, this debate is fueled by two factors. First, some patients diagnosed with DCIS will ultimately prove to have invasive carcinoma. Second, the status of the sentinel node is the most powerful predictor of prognosis and surgeons want to ensure that those patients with invasive carcinoma have sentinel node mapping for staging and treatment planning. In order to understand this debate an appreciation of the evolution of breast cancer management over the past decade is essential. The two most important historical events in this evolution have been the appreciation of the relationship of prior lumpectomy and its impact on lymphatic drainage from the breast to the sentinel node, and the increasing use of image guided core needle breast biopsies to sample mammographic abnormalities that may underestimate the extent of breast pathology. When Morton et al. 1 initially described the use of sentinel node mapping for melanoma, a minimally or undisturbed primary tumor site was considered essential for accurate identification of the sentinel node. In fact, a wide excision of a primary melanoma prior to referral for sentinel node mapping was considered a contraindication and these patients were denied sentinel node staging. When sentinel node mapping was initially described for breast carcinoma, a precise injection of colloid and/or dye around an intact primary tumor were considered important technical aspects in order to identify the correct sentinel node in the axilla. 2 Like melanoma patients, if the primary breast tumor was removed prior to referral for sentinel node mapping, the potential inaccuracy of the technique was used as a criterion to exclude patients from mapping. Mapping was done routinely at the time of DCIS management to avoid losing the opportunity to stage the axilla after excision when invasive carcinoma was subsequently identified. Subsequent experience in melanoma and breast sentinel node mapping has demonstrated that the technique is still accurate after wide excision of the primary tumor. 3,4 The evidence that mapping

Lymphoedema in young patients with breast cancer

Gross lymphoedema is a devastating complication in patients with breast cancer and more so in young women. These patients present with more advanced disease and suffer a higher incidence of loco-regional recurrence. Young women are also subject to more traumas to the lymphatics by virtue of their being more active. Treatment contributes to a higher incidence of lymphoedema in these patients. Thrombosis and infection may complicate intravenous chemotherapy, which damages lymphatic drainage. Modern radiotherapy delivers precise dosage and site targeting of treatment so that lymphoedema is less common. However, there is a tendency to return to aggressive treatment of the nodal areas. Early detection of breast cancer and sentinel lymph node biopsy will further decrease axillary dissection. Lymphoedema treatment consists mainly of compression therapy, manual lymphatic drainage and containment. Surgery is rarely required. Lymphoedema is a chronic condition that requires long-term care with patient compliance and active cooperation.

Indirect MR lymphangiography of the head and neck using conventional gadolinium contrast: A pilot study in humans

To evaluate indirect magnetic resonance lymphangiography (MR-LAG) using interstitial injection of conventional gadolinium contrast (gadoteridol and gadopentetate dimeglumine) for delineating the primary lymphatic drainage of head-and-neck sites. We performed head-and-neck MR-LAG in 5 healthy volunteers, with injection of dermal and mucosal sites. We evaluated the safety of the procedure, the patterns of enhancement categorized by injection site and nodal level, the time course of enhancement, the optimal concentration and volume of contrast, and the optimal imaging sequence. The worst side effects of interstitial contrast injection were brief, mild pain and swelling at the injected sites that were self-limited. MR-LAG resulted in consistent visualization of the primary lymphatic drainage pattern specific to each injected site, which was reproducible on repeated examinations. The best enhancement was obtained with injection of small volumes (0.3-0.5 mL) of either agent diluted, imaging within 5-15 min of injection, and a three-dimensional fast spoiled gradient echo sequence with magnetization transfer. We found head-and-neck MR-LAG to be a safe, convenient imaging method that provides functional information about the lymphatic drainage of injected sites. Applied to head-and-neck cancer, it has the potential to identify sites at highest risk of occult metastatic spread for radiotherapy or surgical planning, and possibly to visualize micrometastases.

Use of Radiotracer for Sentinel Lymph Node Mapping in Breast Cancer Optimizes Staging Independent of Site of Administration

In an effort to optimize sentinel lymph node (SLN) mapping for breast cancer, sites of mapping agent administration and types of mapping agents used continue to be evaluated. This study compares SLN mapping using peritumoral (PT) or subareolar (SA) injection of radiolabeled colloid and examines the relative contributions of radiotracer and blue dye to SLN identification. A retrospective review was performed of 456 patients with breast cancer and clinically negative axillae who underwent SLN mapping. Sequential groups of patients were injected with filtered Tc-99m SC, 326 peritumorally (group 1) and 130 subareolarly (group 2). All patients had intraoperative SA injection of 1% isosulfan blue dye. The SLN identification and isotope success rates were 97% and 96% in group 1 and 98% and 98% in group 2, respectively. Eighty-one patients (25%) in group 1 and 44 patients (34%) in group 2 had positive SLNs. Of these patients, 15% from group 1 and 14% from group 2 had only positive nodes detected by radiotracer, and 9 of these patients (6 from group 1 and 3 from group 2) had other nodes identified by both radiotracer and blue dye that were negative for metastases. Six percent of patients with positive SLNs were upstaged because of use of radiotracer. PT and SA injection of radiotracer have comparable success rates for axillary SLN identification. Given that 15% of patients in group 1 and 14% in group 2 had only positive SLNs detected by radiotracer, independent of site of administration, radiotracer remains essential for optimizing breast SLN mapping.

Molecular and Cellular Approaches to Patient Management in Oncology

Many of the techniques that are employed today by pathologists and oncologists to generate a diagnosis, prognosis or prediction of response have not changed over several decades. However, new molecular and cellular technologies will enable more precise and objective decision-making. This review will detail some of the more recent developments in these areas from Veridex, LLC, academic laboratories and other commercial entities. The discussion of molecular technologies will focus on breast sentinel lymph node biopsy, prostate biopsy, carcinoma of unknown primary, prediction of recurrence in lymph node negative colon and breast cancers and pharmacogenomics. The discussion of cellular technologies will focus on the use of circulating cells to serve in both prognostic and predictive capacities and on the use of molecular methods to interrogate the DNA and RNA isolated from these circulating cells.

The influence of radioisotope vehicle on breast sentinel node detection

Aim To assess the relationship between carrier molecule size and time elapsing between marker injection and sentinel node(s) biopsy in patients with breast cancer. Material The study performed on 122 women, in whom the sentinel node(s) was identified according to the procedure described below. In Group I ( n = 72 patients), SN identification was done with radioisotope marker of 400–3000 nm molecule size (tin colloid). In Group II ( n = 50 patients) radioisotope marker of <100 nm molecule size (colloidal albumin) was used. Methods All the patients of both groups received the markers with a single-point, intradermal, periareolar injection. Four hours after the injection (Group I – surgery in the next day) or immediately before the surgery (in this same day) (Group II), stationary lymphoscintigraphy was performed. Results Mean numbers of sentinel nodes identified with the radioisotope method in Groups I and II were 1.22 and 1.48, respectively. The difference was statistically significant ( p < 0.01). Conclusions There is a relationship between the radioisotope marker molecule size and the injection-to-intra-operative evaluation time. Administration of small molecule size radioisotope marker several hours prior to the planned surgery appears to be the optimum procedure in this method of SN identification in patients with breast cancer.

T2 Does dose matter in breast sentinel node imaging?

T2 Does dose matter in breast sentinel node imaging?

A GSO positron/single-photon imaging detector

We have developed and tested a GSO position sensitive gamma detector which can be used with positron and single-photon radionuclides for imaging breast cancer or sentinel lymph node detection. Because GSO has a relatively good energy resolution for annihilation gammas as well as low energy gamma photons, and does not contain any natural radioisotopes it can be used for positron imaging and lower energy single-photon imaging. The imaging detector consists of a GSO block, 2-inch square multichannel position sensitive photo-multiplier tube (PSPMT), and associated electronics. For the positron imaging, coincidence between the imaging detector and a single gamma probe is measured. For the single-photon imaging, a tungsten collimator is mounted in front of the imaging detector. With this configuration, it was possible to image both positron radionuclides and low energyu single-photon radionuclides.

Molecular analysis improves sensitivity of breast sentinel lymph node biopsy: Results of a multi-institutional prospective cohort study

Pathologic evaluation may lack the sensitivity required for accurate staging of the axilla in breast cancer patients. We have completed enrollment of a multi-institutional prospective cohort study designed to determine if molecular analyses can improve axillary staging. In subset analyses, we have attempted to address the following questions: (1) Does molecular analysis improve the sensitivity of sentinel lymph node biopsy (SLNB) and (2) is the sentinel lymph node (SLN) hypothesis valid at the molecular level? Four hundred eighty-nine subjects with T1, T2, or T3 breast cancer and no evidence of axillary lymph node (ALN) involvement were enrolled. ALNs were analyzed by routine pathology (hematoxylin-eosin staining), and by multimarker real-time reverse transcriptase-polymerase chain reaction analysis CRT-PCR to detect breast cancer metastases. Pathology and molecular data for both SLNs and nonsentinel ALNs were available for a subset of 207 subjects. The sensitivity of pathologic analysis of the SLN to predict the pathologic status of ALNs was 84.1%. The sensitivity of combining pathologic with molecular analysis of the SLN to predict the pathologic status of ALNs was 92.8%, a statistically significant increase in sensitivity (P = .031 by the McNemar test for correlated proportions). Finally, the sensitivity of combining pathologic with molecular analysis of the SLN to predict the pathologic or molecular status of ALNs was 85.4%. The combination of pathologic and molecular analysis of SLNs resulted in the highest sensitivity for prediction of the pathologic status of ALNs. The data also provide evidence that the SLN hypothesis remains valid at the molecular level.

Comparison of blue dye and isotope with blue dye alone in breast sentinel node biopsy

Sentinel lymph node biopsy (SNB) is rapidly gaining acceptance as an alternative to axillary dissection (AD) in patients with early breast cancer. Debate continues regarding the optimum technique for sentinel node (SN) mapping. We have used our series of 364 SNBs to compare two different techniques. A retrospective review of patients undergoing SNB by surgeons in our breast service. Overall results were analysed, with particular attention to those having blue dye alone and those having blue dye in combination with radio-labelled colloid. SNs were analysed using haematoxylin-eosin and immunohistochemical staining. SN identification rates were similar: 96% for dye alone and 89% for dye and colloid in combination. Twenty-one per cent of SN mapped with dye alone contained metastases, compared to 30% with dye and colloid in combination. The false-negative rate was correspondingly higher in the dye alone group (21 vs 2.8%). SNB using dye and colloid in combination was significantly superior to dye alone in this series. We advocate using both dye and colloid for intraoperative SN mapping.

Identification and Characterization of Optimal Gene Expression Markers for Detection of Breast Cancer Metastasis

Sentinel lymph node (SLN) status is highly predictive of overall axillary lymph node involvement in breast cancer. Historically, SLN-positive patients have undergone axillary lymph node dissection in a second surgery. Intraoperative SLN analysis could reduce the cost and complications of a second surgery; however, existing histopathological methods lack standardization and exhibit poor sensitivity. Rapid molecular methods may lead to improved intraoperative diagnosis of SLN metastasis. In this study, we used a genome-wide gene expression analysis of breast and other tissues to identify seven putative markers for detecting breast cancer metastasis. We assessed the utility of these markers for identifying clinically actionable metastases in lymph nodes through reverse transcriptase-polymerase chain reaction analysis of SLNs from 254 breast cancer patients. Polymerase chain reaction signals were compared to pathology on a per-patient basis. The optimal two-gene combination, mammaglobin and cytokeratin 19, detected clinically actionable metastasis in breast SLNs with 90% sensitivity and 94% specificity. Application of stringent criteria for identifying presumptive hematoxylin- and eosin-positive samples increased sensitivity and specificity to 91 and 97%, respectively. This study represents the first comprehensive demonstration of the utility of gene expression markers for detecting clinically actionable breast metastases. An intraoperative molecular assay using these markers has the potential to significantly reduce second surgeries for patients undergoing SLN dissection.

Breast Sentinel Lymph Node Navigation With Three-Dimensional Interstitial Multidetector-Row Computed Tomographic Lymphography

Three-dimensional multidetector-row computed tomographic lymphography (3D MDCT-LG) with interstitial injection of a widely available nonionic monometric contrast medium iopamidol was used for navigation of breast sentinel lymph node (SLN) biopsy. 3D MDCT-LG was obtained after massage of the interstitially injection sites of a total of 4-5 mL undiluted iopamidol at periareolar and peritumoral areas in 68 consecutive patients with early-stage breast cancer, using a 4 detector-row CT scanner. Drainage lymphatic patterns and SLN anatomy were assessed on 3D MDCT-LG images. 3D MDCT-LG-navigated SLN biopsy with combined use of blue dye was followed by backup axillary lymph node dissection to evaluate accuracy of SLN biopsy. The 3D MDCT-LG images clearly localized primary SLNs by visualizing the direct connection between these nodes and their afferent lymphatic vessels on detailed anatomy of the surrounding structures in all patients. Drainage lymphatic pathways on these images were classified into 4 patterns: single route/single SLN (39 cases, 57%), multiple routes/multiple SLNs (10 cases, 15%), single route/multiple SLNs (9 cases, 13%), and multiple routes/single SLN (10 cases, 15%). Under 3D MDCT-LG navigation, SLNs was found at the accurate location in all patients. With backup axillary lymph node dissection, metastasis was found in 14 (20%) patients, and 8 of these patients had metastasis only in the preoperatively identified SLNs. In other 5 positive patients, metastasis was found both in the SLN and non-SLNs. However, micrometastasis eventually was found only in non-SLN in an elderly patient. Overall, the sensitivity, false-negative rate, and accuracy of 3D CT-L-navigated SLN biopsy were 92% (13/14 patients), 7% (1/14 patients), and 98% (67/68 patients), respectively. Topographic 3D interstitial MDCT-LG can be a widely available and reliable navigator for breast SLN biopsy.

Evaluation of the sentinel lymph node mapping technique for breast cancer in a community-based teaching hospital

893 Background: The sentinel lymph node (SLN) procedure has been used with increasing frequency in patients diagnosed with early stage breast cancer. This review evaluated a community based teaching hospital’s experience with the sentinel lymph node biopsy technique. Methods: A retrospective medical record review utilizing the Surgical Registry at a community based teaching hospital and CPT4 codes specific for breast SLN biopsy were analyzed. This was followed by cross-referencing the identified information to the pathology information system and reviewing the final pathology and surgical reports. Results: From July 2002 through September 2003, 19 surgeons performed a total of 219 SLN procedures for breast cancer. Another 4 were attempted, but were unsuccessful in identifying the sentinel lymph node, hence,an axillary lymph node dissection (ALND) was performed. Of the 19 surgeons, 13 (68%) injected Tc99m followed by methylene or isosulfan blue dye. Intraoperatively, a gamma finder was utilized to identify the sentinel node (s). A frozen section was subsequently performed on any identified lymph node as well as for any palpably suspicious lymph node (s). If a sentinel node could not be identified, a level I and II axillary node dissection was performed. The number of SLN procedures performed by each surgeon ranged from one to 48. The mean number of SLN’s excised was 2.3, with a range of one to 7 nodes, with 4 or fewer lymph nodes removed in 90% of the patients. In the 50 patients with a positive SLN, 45 (90%) went on to ALND. In one case, the patient was on a clinical trial and was randomized to receive no further ALND. In the remaining 4 cases, the final pathology revealed 2 cases of micrometastatic disease and 2 cases of macroscopic disease. In 12 patients where an ALND was performed, no further positive nodes were identified. In an additional 6 cases, the SLN was negative on frozen section, but on final pathology, had a positive finding by Immunohistochemical analysis only. Conclusion: Evaluation of the SLN for breast cancer in this community based teaching hospital is similar to results reported in the literature. No significant financial relationships to disclose.

1–29 Intraoperative Cytologic Examination of Breast Sentinel Lymph Nodes: Test Utility and Patient Impact

1–29 Intraoperative Cytologic Examination of Breast Sentinel Lymph Nodes: Test Utility and Patient Impact

Injection of 99mTc-labeled sulfur colloid the day before operation for breast cancer sentinel lymph node mapping is as successful as injection the day of operation

Background We investigated whether the timing of injection of 99mTc-labeled sulfur colloid (radiocolloid) significantly influenced the success of breast cancer sentinel lymph node (SLN) mapping. Methods Review of a prospective SLN database. Five hundred forty-six consecutive breast SLN mapping patients were analyzed. A dual radiocolloid/blue dye technique was used in all patients. Results The SLN identification rate was similar among those patients injected the day prior (100%) and those injected the day of operation (99%, P = 0.14). A “hot” SLN was identified in 99% of patients injected the day prior and in 97% ( P = 0.17) injected the day of operation. The mean number of SLNs was greater among those injected the day prior (2.71) than among those injected the day of operation (2.33, P = 0.01). There were no differences in the rates of SLN metastases. Conclusions Radiocolloid injection the day before operation is an acceptable and logistically advantageous technique for breast cancer SLN mapping.