Sentinel Lymph Nodes In Breast Cancer Research Articles

Fallacies of preoperative lymphoscintigraphy in detecting sentinel node in breast cancer

BackgroundPreoperative lymphoscintigraphy is one of the three methods of evaluating sentinel nodes in patients with breast cancer; however, it has been reported to have a high false negative rate.Case presentationsWe report here two cases where the preoperative lymphoscintigraphy was found to be fallacious. A 44-year-old female with T2N0 breast cancer underwent preoperative lymphoscintigraphy with Tc99 sulfur colloid which failed to show any uptake in axilla or internal mammary chain. Intraoperative scintigraphy with blue dye and hand held gamma probe identified sentinel lymph node in axilla. Another patient with T2N0 lesion underwent preoperative lymphoscintigraphy which showed a sentinel lymph node in axilla and another in supraclevicular fossa. Intraoperative scintigraphy failed to show supraclevicular node however axillary node was correctly identified.ConclusionThese two cases further strengthen the need to carry out triple test in identification of sentinel lymph node in patients with breast cancer. It also demonstrates the fallacies of preoperative lymphoscintigraphy.

The reliability and accuracy of intraoperative imprint cytology of sentinel lymph nodes in breast cancer

Sentinel lymph node (SLN) biopsy is a new component of the surgical treatment of breast cancer that accurately predicts axillary status. In this study the authors evaluated the accuracy of intraoperative imprint cytology (IC) in comparison with definitive histologic evaluation of SLN in breast cancer patients. A total 413 women with breast carcinoma and clinically negative axillary nodes underwent breast surgery and SLN biopsy. Mapping of SLN involved injection of (99m)Technecium labelled human albumin nanocolloid particles and Patent Blue dye. At the Department of Pathology, SLNs were bisected along its major axis. Both halves were imprinted 2-4 times on the slides and immediate staining with Hemacolor (Merck Germany) was performed for intraoperative examination. Imprint node negative women underwent no further surgery, while node positive women proceeded to full axillary clearance. Histological analysis of the SLN involved serial sectioning of the whole node with H&E and immunostaining for cytokeratin. Definitive histology revealed metastases (pN+) in 159/413 patients (38.5%): 69 (16.7%) macro metastases, 57 (13.8%) micro metastases, and 33 (8%) women with only isolated IHC positive cells or positive cell groups smaller than 0.2 mm (pNO sn+). The other 254 women had negative SLN biopsy. Imprint cytology detected 54/69 macro metastases, and 4/57 micro metastases. In the group with negative SLN (254), 2 cases were ''false positives''. Imprint of SLN biopsy can identify a negative axilla with high accuracy (specificity 99.2%). Overall sensitivity is only 36.5%, but macrometastases are detected in 77% which is important for performing ALDN in one session with operation of primary tumour.

Localization of sentinel nodes in breast cancer: novel method and device to help pen marking of active nodes during gamma camera imaging

Gamma camera imaging with Tc-99m marking is a widely used method to locate sentinel lymph nodes (SNs) in breast cancer patients. Prior to SN biopsy, the anterior and lateral location of the SN is marked on the patient's skin using an ink pen. The pen marks guide the surgeon during an operation. However, in many cases the marking is difficult due to limited space under the detectors of a gamma camera. The aim of this study was to improve the pen marking method. Eleven female patients were imaged 3–4 h after injection of Tc-99m labelled Nanocol©. Injection was performed to parenchyma surrounding the breast tumour. To facilitate pen marking, two polycarbonate (PC) plates with 40 × 32 holes (spacing = 10 mm) were engineered for anterior and lateral side imaging and then installed on the bed of a dual-head gamma camera. Two drops of Tc-99m were placed into the top corners of both the PC plates, in order to trace the corresponding x–y coordinates first from the acquired images and then from the plates. After imaging, the x–y coordinates of the SN(s) were determined from the anterior and lateral side images. Subsequently, the location of each SN was marked with an ink pen on the skin through the small holes in the PC plates. According to the surgeon's evaluation, the distance between the marks and the true location of the SNs was 4.5 ± 6.9 mm. Measurements with a custom made phantom revealed that the accuracy of the novel method was significantly (P = 0.06) higher as compared with the traditional method (2.7 ± 3.0 mm versus 9.2 ± 3.0 mm). In addition, we were not able to mark the weakest activity (0.02 MBq) with the traditional method. Taken together, the marking process was considerably easier with the novel method, it had better accuracy and sensitivity than the traditional method and the device is simple enough to be adapted for most gamma cameras.

Update on detection of sentinel lymph nodes in patients with breast cancer

Sentinel lymph node biopsy is now the practice of choice for the management of many patients with breast cancer. This was not true in the early 1990s, when the first such procedures were performed and protocols for such were refined often. This was also not true in the first years of the 21st century, when a decade of collective experience and information acquired from numerous clinical investigations dictated additional subtle and not-so-subtle refinements of the procedures. However, it is true today; reports of the latest round of clinical investigations indicate that there are several breast cancer sentinel node procedures that result in successful identification of potential sentinel nodes in nearly all patients who are eligible for such procedures. A significant component of many of these successful sentinel node procedures is a detection and localization protocol that involves radiotracer methodologies, including radiopharmaceutical administration, preoperative nuclear medicine imaging, and intraoperative gamma counting. The present state and roles of nuclear medicine protocols used in breast cancer sentinel lymph node biopsy procedures is reviewed with emphasis on discussion of recent results, unresolved issues, and future considerations. Included are brief reviews of present radiotracer and blue-dye techniques for node localization, including remarks about injection strategies, counting probe technology, and radiation safety. Included also are discussions of on-going investigations of the implications of the presence of micrometastases; of the management value of detection, localization, and excision of extra-axillary nodes such as internal mammary nodes; and of the broad range of recurrence rates presently being reported. Remarks on the present and possible near- and long-term roles for nuclear medicine in the staging of breast cancer patients including comments on positron emission tomography and intraoperative imaging conclude the article.

Modifications of the learning curve guidelines for breast cancer sentinel node biopsy

Background Guidelines for the learning period of sentinel lymph node biopsy in breast cancer do not address important details such as the false negative rate way of calculation and the number of patients with positive axilla that should be included among the cases of this period. The aim of this study was to identify refinement points which should be included in the guidelines. Methods We studied 138 breast cancer cases of the sentinel lymph node biopsy learning period of three surgeons. The sentinel node was identified using isosulfan blue or technetium sulfur colloid or both. All patients underwent complementary axillary dissection. Results All three surgeons (A, B, C) fulfilled the guidelines' false negative rate criteria of 5, 0 and 5%, respectively, after 20 cases. However, only six, 10 and 10 cases with positive axilla, respectively, were included and the false negative rates using only these cases were 17, 0 and 10%, respectively. Conclusions Current guidelines may lead surgeons to inappropriate conclusions about their ability to perform sentinel lymph node biopsy with an acceptable false negative rate. The learning period should include as many cases with positive axilla as possible and the false negative rate should be calculated only on those patients.

The sentinel node in breast cancer: an update

There has been rapid acceptance of sentinel lymph node biopsy into the management of breast cancer over the past 10 years. This article seeks to highlight the controversies and to summarise its current status.

Areolar-Cutaneous Junction Injection Boosts Activity in Sentinel Node by More than 50 Times Compared to Perilesional Injection: Implications for Morbidity Reduction

The combination of concurrently administered perilesional radiotracer injections and areolar-cutaneous junction radiotracer injections during one imaging session in the detection of sentinel nodes (SN) in breast cancer is new. A case is presented where the perilesional injections of radiotracer produced a faint node. Subsequently, 45 minutes later, the same patient received an injection of radiotracer at the areolar-cutaneous junction, which "boosted" the activity in the original SN by more than 50 times. This case illustrates the marked improvement in SN counts that can occur with the addition of areolar-cutaneous junction injections to perilesional injections. The perilesional component of this hybrid injection technique maintains the ability to visualize internal mammary and extra-axillary SN. Even more importantly, these "hotter" nodes have significant implications for morbidity reduction, the main goal of sentinel lymph node biopsy in itself.

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.

Sentinel Lymph Node Metastases Detected by Immunohistochemistry Only Do Not Mandate Complete Axillary Lymph Node Dissection in Breast Cancer

The significance of breast cancer sentinel lymph node (SLN) metastases detected only by immunohistochemistry staining (IHC) remains poorly understood. This study attempted to quantify the risk of non-SLN metastases. A prospectively collected database of 750 consecutive SLN biopsy procedures in breast cancer patients was reviewed. Medical records were reviewed to supplement the database. SLNs were identified in 738 (98.4%) of these procedures in 723 patients. Of these, 151 patients (20.5%) had metastases detected by hematoxylin and eosin staining (H&E), and 33 (4.6%) of the 718 with known IHC staining results had metastases detected by IHC only. Twenty-eight (84.8%) of 33 patients with IHC-detected metastases underwent complete axillary lymph node dissection (CALND). The median primary tumor size was 2.0 cm among those undergoing CALND and 0.9 cm among the five patients treated without CALND (P = .10). Two of the 28 patients (7.1%) had additional metastases detected with CALND. These patients had a T3 or T4 invasive lobular primary tumor. Of 24 patients with T1 or T2 primary tumors and IHC-detected metastases who underwent CALND, none had additional metastases detected. Median follow-up was 14.5 months. All patients with IHC-detected SLN metastases were treated with adjuvant systemic therapy. None of the five patients with IHC-detected metastases not undergoing CALND has subsequently manifested clinical axillary disease. CALND could have been or was safely omitted in 29 of 29 patients with T1 or T2 primary tumors and metastases detected by IHC. Such patients should be counseled about this low risk before CALND is recommended.

Intraoperative Examination of Sentinel Nodes in Breast Cancer: Is the Glass Half Full or Half Empty?

Intraoperative identification of positive sentinel lymph nodes in patients with breast cancer may avoid a return to the operating room. In a group of 402 consecutive patients with primary breast cancer who underwent sentinel lymph node biopsy, an intraoperative examination (IE) was obtained in 236 cases either by frozen section (FS; n = 68) or by touch preparation cytology (TP; n = 168). IE had an accuracy of 89% (209 of 236), but it identified only 52 of 77 positive cases (sensitivity, 68%). There were 25 false-negative cases (13.7%), of which 7 were macrometastases and 18 by micrometastases (P < .001). Six macrometastases were missed by TP and one by FS (P = .9). There were two false-positive cases (3.7%). Overall, 48 (20%) of 236 patients avoided a delayed return to the operating room for a completion lymphadenectomy because of IE findings. This occurred in 10% of patients with tumors <1 cm in diameter, in 20% of those with tumors between 1 and 2 cm, and in 34% of those with tumors >2 cm in diameter (P = .05). The cost savings for the Italian Health System amounted to 198,040 (US$223,794) in these patients. IE has acceptable sensitivity for lymph node macrometastases, but it is a weak tool for diagnosing micrometastases. FS and TP are roughly equivalent. IE allows management changes, because approximately 20% of all patients are expected to undergo synchronous axillary dissection, and it is particularly helpful in T2 patients. This may allow substantial cost savings for the health-care system.

Lumpectomy margins are affected by tumor size and histologic subtype but not by biopsy technique

Objective The effect of the type of biopsy (needle vs. excisional) on lumpectomy margin status has not been well established. The objective of this study was to determine whether needle biopsy is associated with a higher positive margin rate at time of lumpectomy. Methods We evaluated this hypothesis in the setting of a prospective multi-institutional study. A total of 3975 patients were enrolled in the University of Louisville Breast Cancer Sentinel Lymph Node Study from May 7, 1998 to June 3, 2003. Patients who underwent lumpectomy at the time of their sentinel lymph node biopsy were the focus of this analysis. Patients with clinical stage T1 N0 and T2 N0breast cancer were eligible; 29 patients were found to have T3 tumors on final pathology. Pathologists at each institution defined margin positivity, and tumor at the inked margin of resection was the study guideline. Results Median patient age was 59 years, and median tumor size was 1.5 cm. A total of 2658 patients underwent lumpectomy with the following results. The cancer of 1515 patients was diagnosed by fine-needle or core-needle biopsy and of 821 patients was diagnosed by excisional biopsy; in 322 patients the method of diagnosis was unknown. The type of previous biopsy did not significantly affect the positive-margin rate at the time of lumpectomy (13.3% vs. 11.0% for needle and excisional biopsy, respectively, P = 0.107). However, patients with larger tumors were more often found to have a positive margin (11.4% vs. 13.9% vs. 27.6% for T1, T2, and T3 tumors, respectively; P = 0.010). No difference was found in margin status after excision of palpable versus nonpalpable tumors (10.6% vs. 10.9%, respectively, P = 0.743). Histologic subtype, however, did affect margin status (15.8% vs. 9.8% positive margins for lobular vs. ductal type, respectively, P = 0.003). Conclusions In this multi-institutional study, increasing tumor size and lobular histologic subtype were associated with a greater likelihood of a positive margin. The type of biopsy, needle or excisional, had no effect on the ability to achieve negative margins.

A concordance study of subareolar and subdermal injections for breast cancer sentinel lymph node mapping

Background There is disagreement regarding the preferred injection site for breast sentinel lymph node mapping. Methods The concordance of blue staining and radioactivity in the sentinel nodes of 730 consecutive patients was analyzed based on injection of mapping agents into the same or separate intradermal and subareolar sites. Results There were no significant differences in identification rates or the mean number of sentinel nodes whether agents were injected into the same or separate sites. In each group, a concordant sentinel node (both blue and “hot”) was identified in >90% of patients ( P = not significant). There were no significant differences in the percentage of sentinel nodes identified as both blue and hot. Conclusions Separate subdermal and subareolar injections of mapping agents drain to the same sentinel node as often as injections into the same location. These two injection techniques appear to result in the identification of the same sentinel nodes.

Meta-analysis of non-sentinel node metastases associated with micrometastatic sentinel nodes in breast cancer.

The need for further axillary treatment in patients with breast cancer with low-volume sentinel node (SN) involvement (micrometastases or smaller) is controversial. Twenty-five studies reporting on non-SN involvement associated with low-volume SN involvement were identified using Medline and a meta-analysis was performed. The weighted mean estimate for the incidence of non-SN metastases after low-volume SN involvement is around 20 per cent, whereas this incidence is around 9 per cent if the SN involvement is detected by immunohistochemistry (IHC) alone. Subset analyses suggest that studies with axillary dissection after any type of SN involvement result in somewhat higher estimates than studies allowing omission of axillary clearance, as do studies with more detailed histological evaluation of the SN compared with those with a less intensive histological protocol. Higher-quality papers yield lower pooled estimates than lower-quality papers. The risk of non-SN metastasis with a low-volume metastasis in the SN is around 10-15 per cent, depending on the method of detection of SN involvement. This should be taken into account when assessing the risk of omission of axillary dissection after a positive SN biopsy yielding micrometastatic or immunohistochemically positive SNs.

Clinical considerations in breast cancer sentinel lymph node mapping: A moffitt review

Lymphatic mapping redefined the clinical significance of axillary lymph nodes in the treatment of breast cancer. Current literature supports the concept that any patient diagnosed with invasive breast cancer should in fact have their sentinel lymph nodes evaluated. However, there are many cases of " special situations in lymphatic mapping " . These special situations mark an important point that should be considered: When and who should undergo lymphatic mapping? A summary of these considerations/cases will be the focus of this report.

Sentinel node in breast cancer. Histological study of 67 cases

The extirpation of the sentinel node is a widespread surgical technique whose aim is to avoid axillary resection in patients with breast cancer at early stages. Determination of tumoral infiltration can be evident in the case of macrometastasis (>2mm), or difficult to detect in micrometastasis (<2mm). For this reason we use a protocol of serialized sections, to increase our capacity for detecting micrometastasis. Realisation of this protocol is highly laborious and represents a high cost, thus its effectiveness and efficacy must be studied. We reviewed 67 sentinel nodes corresponding to 48 patients with breast cancer treated at our hospital in the last three years. All the samples received at the Pathology Unit were included. Serialized sections of three microns were made on each node and with a depth of 40 microns between them. A total of fourteen cuts were made. Every five cuts there was an alternation of immunostaining with a cocktail of queratines (AE1/AE3) and with haemotoxylin-eosin. Sixty-seven sentinel nodes were extirpated from 48 patients. Fourteen positive (20%) were detected. Of these metastases, 6 were macrometastases >2mm, 5 were micrometastases <2mm and 3 were isolated cellular groups (between 0.2 and 2mm). In 6 cases (43%), the metastases only became evident with queratine staining in serialized cuts. Axillary resection was carried out in 44 cases. The histological study of the sentinel nodes makes it possible to evaluate the status of tumoral infiltration of the axillary ganglions and to greatly reduce axillary lymphadenectomies. The conventional study of the sentinel node (with a single section) is insufficient for the diagnosis of tumoral infiltration. In our series, histological study using a protocol of serialized sections has enabled us to detect some 43% of metastases in the sentinel node that were not evident in the initial section.

Role of three axillary lymph node sampling for predicting non-sentinel node metastases in patients with breast cancer and positive sentinel node

Role of three axillary lymph node sampling for predicting non-sentinel node metastases in patients with breast cancer and positive sentinel node

Role of three axillary lymph node sampling for predicting non-sentinel node metastases in patients with breast cancer and positive sentinel node

694 Background: Half of breast cancer patients with positive sentinel node (SN)s do not have further metastatic non-SNs and do not need to undergo axillary lymph node dissection (ALND). This study evaluated the usefulness of three axillary lymph node (ALN) sampling for predicting non-SN metastases in breast cancer patients with SN metastases. Methods: SN biopsy was performed in patients with clinically node-negative breast cancer using dye and radioisotope. When SNs were diagnosed as metastasis-positive by intraoperative imprint cytology, three ALN sampling was performed, followed by ALND. The metastatic status of sampled nodes was compared with that of non-SNs. Imprint cytological evaluation was also performed for the sampled nodes and was compared with the final histological results of the sampled nodes. Results: Between 2001 and 2003, 252 patients underwent SN biopsy. Of 39 (16%) patients with positive imprint cytology, 36 (14%) were diagnosed as tumor positive on final histological examination and ana...

Intraoperative imprint cytology of sentinel nodes in breast cancer.

Sentinel node (SN) biopsy is a new standard of care for axillary node staging in patients with early-stage, clinically node-negative breast cancer. A second operation can be avoided when the results are available intraoperatively. However, there is no standard intraoperative method for SN assessment. The aim of this study was to evaluate intraoperative imprint cytology (IC) for the detection of SN involvement in patients with early-stage breast cancer. One hundred eighty-five consecutive patients with a breast tumor underwent SN biopsy with intraoperative IC. The SN was bisected and a touch preparation was made with a glass slide, on both sides of the cut. Permanent sections were evaluated with H&E and immunohistochemical staining. The IC results were compared with the final histologic results. The sensitivity, specificity, accuracy, and positive and negative predictive values of IC were 33.3, 78.4, 78.9, 90, and 77.5%, respectively. IC was more sensitive for macrometastases than for micrometastases. In the 118 patients studied after the learning phase, 9 patients with a positive SN by IC avoided a second operation. Intraoperative IC of SNs appears to be reasonably reliable in patients with breast cancer, permitting axillary dissection during the same surgical procedure when positive. In contrast, sensitivity for detection of micrometastases is low.

Update on the NSABP and ACOSOG Breast Cancer Sentinel Node Trials

Sentinel lymph node biopsy in women with breast cancer has become routine in many surgical practices; yet basic questions regarding the procedure remain unanswered. The National Surgical Adjuvant Bowel and Breast Project (NSABP) and the American College of Surgeons Oncology Group (ACOSOG) trials address the issues of morbidity, efficacy, safety, and the significance of low-volume disease. NSABP B-32 randomizes women to sentinel lymph node biopsy followed by a standard level I and II axillary dissection or sentinel lymph node biopsy without dissection unless metastatic disease is noted by H&E examination. Overall survival, disease-free survival, and morbidity serve as end points. Further pathologic evaluation of the lymph nodes with immunohistochemistry will be performed by the study center. This study is nearing its anticipated accrual goal. Patients enrolled in the now-closed ACOSOG Z0010 trial underwent bone marrow aspiration just prior to sentinel node biopsy. Immunocytochemical analysis of the marrow will be compared to sentinel lymph node (SLN) biopsy to determine prognostic accuracy. ACOSOG Z0011 randomizes women undergoing breast-conserving therapy with low-volume axillary disease to completion axillary dissection or observation. Overall survival, disease-free survival, local regional control, and morbidity serve as end points. This trial is currently enrolling patients.

Optimal surgeon experience for breast cancer sentinel node biopsy: how can surgeons stay up-to-date?

Optimal surgeon experience for breast cancer sentinel node biopsy: how can surgeons stay up-to-date?