The role of sentinel lymph node biopsy in Paget's disease of the breast.

BACKGROUND: Sentinel lymph node (SLN) biopsy has become a standard of care for axillary lymph node staging in breast cancer and appears suitable for virtually all patients with clinically node-negative (cN0) invasive disease. However, its role in Paget's disease of the breast, a condition in which invasion may or may not be present, remains undefined. METHODS: Among 7,083 consecutive SLN biopsy procedures, we retrospectively identified 39 patients with Paget's disease of the breast. Nineteen patients had no associated clinical/radiographic features ("Paget's only"), and 20 patients had associated clinical/radiographic findings ("Paget's with findings"). RESULTS: The mean ages for the Paget's alone and with findings groups were 63.6 and 49.6 years, respectively. The use of breast conservation therapy was 32% in the Paget's alone group and 10% in the Paget's with findings group. Invasive carcinoma was found in 27% of patients in the Paget's alone group and 55% of patients in the Paget's with findings group. The success rate of SLN biopsy was 98%, and the mean number of SLNs removed was 3 in both groups. In the entire cohort of Paget's disease, 28% (11/39) of the patients had positive SLNs (11%, Paget's alone; 45%, Paget's with findings). CONCLUSION: In our "Paget's only" cohort, invasive cancer was found in 27% of cases and positive SLNs in 11%. SLN biopsy should be considered in all patients with Paget's disease of the breast, whether associated clinical/radiographic findings are present.

Pleomorphic adenoma of the breast: case report and review of the literature.

Pleomorphic adenoma of the breast (PAB) is a very rare neoplasm. Although quite unique in its morphology, PAB shares some similarities with adenomyoepithelioma and is considered by some authors as a variant of this entity. Cytologic diagnosis of this lesion can be very challenging, especially when limited sampling is available. The differential diagnosis of PAB includes metaplastic carcinoma. On cytologic material, fibroadenoma and phyllodes tumor should also be considered within the differential diagnosis. We report the findings in a case of PAB, initially misdiagnosed as mucinous carcinoma on fine-needle aspiration, and review the literature regarding this entity. Correct identification of this benign mammary neoplasm is important to avoid unnecessarily aggressive treatment.

A selection algorithm for internal mammary sentinel lymph node biopsy in breast cancer.

Internal mammary lymph-node (IMN) metastases in breast carcinomas have a major influence on survival, comparable with the influence of axillary lymph-node metastases (ALNM). Prospective, randomized trials have demonstrated that complete IMN dissection as part of extended radical mastectomy does not improve overall or disease-free survival. In the subset of patients with tumours 1cm or less in size and no ALNM, information on IMN status would provide important information. In these cases, the presence of IMN metastases would change the staging from stage I to stage IIIB, according to the current tumour, node and metastasis classification. More importantly, it would influence these patients' adjuvant treatment. Lymphatic mapping for sentinel lymph-node (SLN) biopsy has demonstrated extra-axillary drainage in up to 35% of patients. Recent reports have demonstrated the feasibility of internal mammary sentinel lymph-node (IM-SLN) biopsy. Here we review the general prognostic and clinical significance of tumor location and lymph-node metastases in breast cancer and discuss the specific factors associated with IMN identification, metastases and treatment in the pre-SLN and SLN eras. Based on our review, we propose an algorithm for a selective approach to IM-SLN in breast cancer.

A trend analysis of the relative value of blue dye and isotope localization in 2,000 consecutive cases of sentinel node biopsy for breast cancer.

BACKGROUND: Among the advocates of blue dye, isotope, or combined dye-isotope mapping of the sentinel lymph node (SLN) for breast cancer, there is no universal consensus as to which technique is optimal and whether the relative value of each method changes with increasing experience. The objective of this study was to examine the relative contributions of blue dye and radioisotope to successful identification of the SLN as the SLN-mapping technique evolved over our first 2,000 consecutive cases. STUDY DESIGN: Using the first 2,000 consecutive SLN biopsy procedures for breast cancer, performed by eight surgeons (none previously experienced in SLN techniques) at one institution, using a combined technique of blue dye and isotope mapping, we report the institutional learning curve and the relative contributions of dye and isotope to identifying both the SLN and the positive SLN, by increments of 500 cases. RESULTS: Comparing the first 500 with the most recent 500 cases, success in identifying the SLN by blue dye did not improve with experience, although success in isotope localization steadily increased, from 86% to 94% (p < 0.00005). With the increasing success of isotope mapping, the marginal benefit of blue dye (the proportion of cases in which the SLN was identified by blue dye alone) steadily declined, from 9% to 3% (p = 0.0001). Parallel to this trend, the proportion of positive SLNs identified by blue dye did not change with experience (89% to 90%), but isotope success steadily increased, from 88% to 98% (p = 0.0015). The proportion of positive SLNs identified by blue dye alone declined from 12% to 2% (p = 0.0015). CONCLUSIONS: Using a combined technique of blue dye and radioisotope mapping, and with refinement of the radioisotope technique, we report 97% success identifying the SLN. Although we continue to recommend the use of both methods in SLN mapping for breast cancer, we observe with experience a declining marginal benefit for blue dye.

Intradermal isotope injection is superior to intramammary in sentinel node biopsy for breast cancer.

BACKGROUND: The optimal sentinel lymph node (SLN) biopsy technique remains undefined in breast cancer. Injecting radiotracer or blue dye by a variety of routes seems to stage the axilla with comparable accuracy, and we have hypothesized that the dermal and the parenchymal lymphatics of the breast drain to the same SLN in most patients. Two previous studies from our institution support this concept: (1) a single-surgeon series of 200 consecutive SLN biopsy procedures demonstrating a high dye-isotope concordance for both intradermal (ID) and intraparenchymal (IP) isotope injection, and (2) a series of 100 procedures validated by a backup axillary dissection (ALND) in which the false-negative rate following ID isotope injection was comparable to that of our previous results with IP injection. Here, we directly compare the results of SLN biopsy using either ID or IP isotope injection for our entire experience of SLN biopsy procedures in which a backup ALND was done. METHODS: This is a retrospective, nonrandomized study of 298 clinical stage I to II breast cancer patients having SLN biopsy with a backup ALND planned in advance, comparing the results of ID (n = 164) and IP (n = 134) isotope injection. All patients had IP injection of blue dye. Endpoints included (1) successful SLN identification, (2) false-negative rate, (3) dye-isotope concordance, and (4) the SLN/axillary background isotope count ratio. RESULTS: ID isotope was more successful than IP, identifying the SLN in 98% versus 89% of cases, respectively. False-negative results (4.8% vs 4.4%) and dye-isotope concordance (92% vs 93%) were comparable between the 2 groups, and SLN/axillary background isotope count ratios were significantly higher with ID than with IP injection (288/1 vs 59/1). CONCLUSIONS: ID isotope injection identifies the SLN more often than IP, stages the axilla with comparable accuracy, and is associated with higher levels of SLN isotope uptake. The dermal and parenchymal lymphatics of the breast drain to the same axillary SLN in most breast cancer patients, and ID isotope injection is the procedure of choice in this setting.

Percutaneous biopsy and sentinel lymphadenectomy: minimally invasive diagnosis and treatment of nonpalpable breast cancer.

OBJECTIVE: The purpose of this study was to determine the usefulness of the combination of percutaneous imaging-guided large-core breast biopsy and sentinel lymphadenectomy in the diagnosis and treatment of nonpalpable invasive breast cancer. MATERIALS AND METHODS: Retrospective review revealed 200 consecutive nonpalpable breast cancers diagnosed by percutaneous imaging-guided large-core biopsy and treated with surgery that included sentinel lymphadenectomy. Percutaneous breast biopsy was performed with stereotactic or sonographic guidance with an automated core needle or vacuum-assisted biopsy probe. Sentinel lymphadenectomy was performed with intradermal injection of a radioisotope and intraparenchymal injection of blue contrast agent. Technical success was defined as identification of sentinel nodes at surgery. Medical records were reviewed. RESULTS: Technical success rate was 200 (100%) of 200. In 158 (79%) of 200 cancers, sentinel nodes were tumor-free, and axillary dissection was avoided. In three (2%) of 200 carcinomas, the sentinel nodes were negative for tumor, but nonsentinel nodes suspicious on intraoperative palpation were excised and found by frozen section analysis to contain tumor. Tumor was found in sentinel nodes in 39 (20%) of 200 carcinomas; axillary dissection, performed in 31 of these 39 women, revealed additional tumor in nonsentinel nodes in seven (23%). A single surgical procedure was performed for 164 (82%) of 200 carcinomas; the breast was preserved in 191 (96%) of these 200 carcinomas. CONCLUSION: Percutaneous imaging-guided large-core breast biopsy and sentinel lymphadenectomy provide a minimally invasive approach to the diagnosis and treatment of women with nonpalpable invasive breast cancers.

Localization of the sentinel node in breast cancer: identical results with same-day and day-before isotope injection.

BACKGROUND: Although the technique of sentinel lymph node (SLN) biopsy in breast cancer is not fully standardized, an increasing number of centers map the SLN by using radioisotope supplemented by blue dye, and most have injected isotope on the day of surgery. Here we directly compare the results of same-day and day-before isotope injection in a large series of breast cancer patients having SLN biopsy with our mature technique. METHODS: Starting with our 961st SLN procedure for breast cancer, 1320 consecutive patients had SLN biopsy after the injection of unfiltered 99mTc-labeled sulfur colloid given as a single-site, low-volume (0.05 ml) intradermal injection: 933 on the day of surgery (1-day protocol) and 387 on the day before (2-day protocol). All had intraparenchymal injection of blue dye. RESULTS: The two groups were comparable in age, tumor location, histopathologic characteristics, and number of SLNs identified. LSG taken at 2 hours in the 2-day protocol was positive more often than LSG performed at 30 minutes in the 1-day protocol, and nonaxillary sites of lymphatic drainage were seen in <1% of each group. Absolute isotope counts and the ratio of SLN to axillary background counts were similar. Isotope localization of the SLN succeeded in a comparable fraction of patients, as did SLN identification overall. CONCLUSIONS: The results of SLN mapping with same-day and day-before injection of radioisotope are virtually identical. The logistical advantages of day-before injection do not compromise the success of the procedure.

Highest isotope count does not predict sentinel node positivity in all breast cancer patients.

BACKGROUND: Radioisotope mapping is an essential technical component of sentinel lymph node (SLN) biopsy, and most authors define isotope success by an arbitrary threshold SLN-to-background ratio. Few studies have examined the degree to which the relative level of SLN counts correlates with the presence of metastasis. Having removed the SLN with the highest counts, how far should the surgeon persist in removing additional SLN which contain much lower levels of isotope? METHODS: We performed SLN biopsy, using both radioisotope and blue dye, in 2285 consecutive patients with stage I-II breast cancer. Successful isotope localization was defined as an ex vivo SLN-to-axillary background count ratio of at least 4:1, and enhanced pathologic analysis (serial sections and immunohistochemistry) was used throughout. RESULTS: Among the 1566 patients with more than one SLN site identified, the SLN contained metastasis in 463 (30%). In 369 (80%) of these SLN-positive cases, the SLN with the highest count contained tumor, but in 94 (20%) it was benign. Among these 94: (1) the counts of the hottest benign SLN exceeded those of the histologically positive SLN by a ratio of at least 10:1 in 31% (29 of 94) of cases, (2) the counts of the positive SLN were < 4:1 those of the axillary background in 16% (15 of 94) of cases, and (3) blue dye failed to identify 27% of positive SLN. No optimum ratio of SLN-to-SLN or SLN-to-background counts identified the positive SLN in all cases. CONCLUSION: Although the SLN with the highest counts is positive in 80% of breast cancer patients with multiple SLN, neither a relatively high isotope count nor the presence of blue dye consistently predict SLN positivity in all breast cancer patients. For maximum accuracy, SLN biopsy requires (1) the removal of all nodes containing isotope regardless of the relative magnitude of counts, (2) the concurrent use of blue dye to salvage those procedures in which isotope fails, and (3) the removal of all clinically suspicious non-SLN.

The breast cancer patient with multiple sentinel nodes: when to stop?

BACKGROUND: During sentinel lymph node (SLN) biopsy for breast cancer, most authors report identifying a mean of 1 to 3 SLNs, but a range of 1 to 8 (or more) SLNs per patient. A significant minority of patients have 4 or more SLNs. Here we seek to determine the significance for the breast cancer patient of finding multiple SLNs, and whether there is an optimal threshold number of SLNs that should be removed. STUDY DESIGN: 1,561 patients who underwent successful SLN biopsy using blue dye and radioisotope in combination. Each SLN site was categorized prospectively by the operating surgeon as a dye success, an isotope success, or both. All SLNs containing counts at least four times greater than the postexcision axillary background were considered to be isotope successes. RESULTS: Fifteen percent of patients (241) had multiple (>3) SLNs. Ninety-eight percent of node-positive patients (440 of 449) were identified within the first three SLN sites examined. In 2% of all SLN positive patients (9 of 449) or 4% of patients with multiple SLN (9 of 241), a positive SLN was detected at site four or more. In eight patients the first positive SLN was found at sites four or more. Blue dye and isotope were equally effective in identifying metastases in patients with multiple SLNs. CONCLUSIONS: Fifteen percent of patients having SLN biopsy for breast cancer have multiple SLNs. Although 98% of positive SLNs were identified within the first three sites sampled, a small number of patients had their first positive SLN at sites 4 to 8. These data suggest that there is no absolute upper threshold for the number of SLNs that should be removed. Sampling a few additional SLNs probably adds little morbidity to the procedure, yet may significantly alter the treatment of some individuals. SLN biopsy should be continued until all blue and hot nodes are removed.

Lymphovascular invasion enhances the prediction of non-sentinel node metastases in breast cancer patients with positive sentinel nodes.

BACKGROUND: Fifty percent of patients with sentinel lymph node (SLN) metastases have no metastatic disease in non-SLNs on axillary lymph node dissection (ALND). The goal of this study is to determine which patients have metastatic disease limited to the SLN, and, therefore, may not require completion ALND. METHODS: Of the first 1000 patients undergoing SLN biopsy at Memorial Sloan-Kettering Cancer Center, using a combined blue dye and isotope technique, 231 (26%) had positive SLN. Of these, 206 underwent completion ALND. They are the study group for this report. RESULTS: The likelihood of non-SLN metastasis was inversely related to three clinicopathologic variables: tumor size < or = 1.0 cm; absence of lymphovascular invasion (LVI); and SLN micrometastases (< or = 2 mm). None of 24 patients with all three predictive factors had non-SLN metastases, whereas 58% of patients with none of the factors had disease in the non-SLN. CONCLUSION: Patients with small breast cancers, no LVI, and SLN micrometastases have a low risk of non-SLN metastases, and may not require completion ALND.

Clinical aspects of sentinel node biopsy.

Sentinel lymph node (SLN) biopsy requires validation by a backup axillary dissection in a defined series of cases before becoming standard practice, to establish individual and institutional success rates and the frequency of false negative results. At least 90% success in finding the SLN with no more than 5-10% false negative results is a reasonable goal for surgeons and institutions learning the technique. A combination of isotope and dye to map the SLN is probably superior to either method used alone, yet a wide variety of technical variations in the procedure have produced a striking similarity of results. Most breast cancer patients are suitable for SLN biopsy, and the large majority reported to date has had clinical stage T1-2N0 invasive breast cancers. SLN biopsy will play a growing role in patients having prophylactic mastectomy, and in those with 'high-risk' duct carcinoma in situ, microinvasive cancers, T3 disease, and neoadjuvant chemotherapy. SLN biopsy for the first time makes enhanced pathologic analysis of lymph nodes logistically feasible, at once allowing greater staging accuracy and less morbidity than standard methods. Retrospective data suggest that micrometastases identified in this way are prognostically significant, and prospective clinical trials now accruing promise a definitive answer to this issue.

Complementarity of blue dye and isotope in sentinel node localization for breast cancer: univariate and multivariate analysis of 966 procedures.

BACKGROUND: The hypothesis that sentinel lymph node (SLN) mapping in breast cancer patients is optimized by combining blue dye and isotope is reasonable and intuitive. Despite this, few studies examine in detail the factors contributing to the success of these techniques, either individually or in combination. METHODS: During a time period of 21/2 years, 1000 consecutive patients at Memorial Sloan-Kettering Cancer Center had SLN mapping performed by using both blue dye and isotope, with preoperative lymphoscintigraphy (LSG). Among the 966 patients with invasive cancer, 12 variables were examined for their correlation with the success of SLN localization by blue dye, by isotope, and by the combined method, using univariate and multivariate models. RESULTS: By univariate analysis, blue dye success was more frequent in association with: a positive LSG (P = .02), age < or = 60 (P < .0005), a previous surgical biopsy (P = .03), and an outer quadrant tumor (P < .0005). Isotope success was more frequent with a positive LSG (P < .0005), age < or = 60 (P = .004), and intradermal isotope injection (P < .0005). Combined (dye and/or isotope) success was more frequent when there was a positive LSG (P < .0005), age < or = 60 (P = .006) and intradermal isotope injection (P < .0005). In multivariate analysis, blue dye success remained uniquely associated with outer quadrant tumor location (P < .0005), and isotope success was uniquely associated with intradermal isotope injection (P = .012). Combined success was more frequent with a positive LSG (P < .0005), age < or = 60 (P = .033), and intradermal isotope injection (P = .003). CONCLUSIONS: The five variables associated with successful SLN localization by blue dye or by isotope overlap but are not identical. Only three of these, intradermal isotope injection, a positive LSG, and age < 60, predicted success by the dye-isotope combination in the multivariate model. Dye and isotope complement each other, and SLN biopsy for breast cancer should use both.

Intradermal isotope injection: a highly accurate method of lymphatic mapping in breast carcinoma.

BACKGROUND: The combined approach of radioactive tracer and blue-dye mapping of sentinel lymph nodes (SLN) has evolved into a safe and effective alternative to routine axillary node dissection in specific patient populations with breast carcinoma. The optimal route of injection for the isotope has not been clearly defined. To assess the intradermal route of isotope injection, we prospectively evaluated 100 patients with biopsy-proven invasive breast carcinoma with SLN biopsy followed by planned axillary node dissection. METHODS: All patients were given an intradermal injection of Tc-99m sulfur colloid and an intraparenchymal injection of blue dye. All patients underwent a complete axillary node dissection. Each sentinel node was serially sectioned and examined by immunohistochemistry. RESULTS: Sentinel nodes were successfully identified in 99% of cases. Forty-six patients had axillary metastases; of these, four had falsely negative sentinel nodes (false-negative rate, 9%). The false-negative rate was 0 of 24 (0%) for T1 tumors, 2 of 18 (11%) for T2 tumors, and 2 of 4 (50%) for T3 tumors. Three of four patients with false negatives had palpable, clinically suspicious axillary nodes found intraoperatively. If these cases are excluded, the accuracy of the procedure was 100% for T1 and T2 tumors. Of the 42 positive axillae identified by SLNB (true positives), 40 were localized using the intradermal injection of radioisotope; in 13 of these cases, this was the only method that identified the true-positive node. CONCLUSION: These data demonstrate that intradermal injection of radioactive tracer is an effective method of localizing the SLN in cases involving small breast cancers. Further investigation is warranted before this technique is adopted for use in larger breast cancers. Intraoperative examination and biopsy of any suspicious nonsentinel nodes are critical.

Sentinel lymph node biopsy in patients with male breast carcinoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is now a widely implemented technique for evaluating the axilla in women with early stage breast carcinoma. Men who develop breast carcinoma are at similar risk as their female counterparts of developing the morbidities related to axillary dissection. SLNB is aimed at preventing these morbidities. In this study, the authors evaluated the role of SLNB in the treatment of men with early stage breast carcinoma. METHODS: Among the 1692 patients who underwent SLNB at the Memorial Sloan-Kettering Cancer Center, 16 men with breast carcinoma were identified. The charts and records of these 16 patients were reviewed retrospectively. RESULTS: The mean patient age was 57.2 years. The mean tumor size was 1.3 cm. In 15 of 16 patients (93.75%) and in all patients with T1 tumors, one or more sentinel lymph nodes were successfully identified. SLNB failed in one patient, who had a T2 tumor (3 cm). Ten of the 15 patients had negative sentinel lymph nodes (66.7%). Four of these patients had no additional lymph nodes removed, whereas six patients had additional lymph nodes removed, all of which were negative. Two patients (13.3%) had positive sentinel lymph nodes on frozen-section analysis and underwent immediate completion axillary dissection: Both had additional positive lymph nodes. Three patients (20.0%) had positive sentinel lymph nodes on further sectioning or immunohistochemistry, and two patients underwent completion axillary dissection: Neither patient had additional positive lymph nodes. The third patient had one immunohistochemically positive lymph node and did not undergo completion axillary dissection. CONCLUSIONS: SLNB for patients with breast carcinoma was as successful in men as it has been shown to be in women and may be offered as a management option to men with early stage breast carcinoma by surgeons who are experienced with the technique.

Sentinel lymphadenectomy accurately predicts nodal status in T2 breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has emerged as a reliable, accurate method of staging the axilla for early breast cancer. Although widely accepted for T1 lesions, its use in larger tumors remains controversial. This study was undertaken to define the role of SLNB for T2 breast cancer. STUDY DESIGN: From a prospective breast sentinel lymph node database of 1,627 patients accrued between September 1996 and November 1999, we identified 223 patients with clinical T1-2N0 breast cancer who underwent 224 lymphatic mapping procedures and SLNB followed by a standard axillary lymph node dissection (ALND). Preoperative lymphatic mapping was performed by injection of unfiltered technetium 99 sulfur colloid and isosulfan blue dye. Data about patient and tumor characteristics and the status of the sentinel lymph nodes and the axillary nodes were analyzed. Statistics were performed using Fisher's exact test. RESULTS: Two hundred four of 224 sentinel lymph node mapping procedures (91%) were successful. Median tumor size was 2.0 cm (range 0.2 to 4.8 cm). One hundred forty-five of the 204 patients had T1 lesions and 59 patients had T2 lesions. There were 92 pathologically positive axillae, 5 (5%) of which were not evident either by SLNB or by intraoperative clinical examination. The false-negative rate and accuracy were not significantly different between the two groups, but axillary node metastases were observed more frequently with T2 than with T1 tumors (p = 0.005); other factors, including patient age, prior surgical biopsy, upper-outer quadrant tumor location, and tumor lymphovascular invasion were not associated with a higher incidence of false-negative SLNB in either T1 or T2 tumors. CONCLUSIONS: SLNB is as accurate for T2 tumors as it is for T1 tumors. Because no tumor or patient characteristics predict a high false-negative rate, all patients with T1-2N0 breast cancer should be considered candidates for the procedure. Complete clinical examination of the axilla should be undertaken to avoid missing palpable axillary nodal metastases.