Paget's disease in the era of sentinel lymph node biopsy

BACKGROUND: Paget's disease of the breast is an uncommon cancer. "Breast cancer" management has evolved to include sentinel lymph node biopsy (SLNB). Our objective is to determine utilization of SLNB in the surgical algorithm of Paget's disease. METHODS: After institutional review board approval, a database review of patients with Paget's disease was conducted. Patient demographics, tumor characteristics, treatment including use of SLNB, and survival were reviewed. Patient characteristics and outcomes were analyzed by using contingency table chi-square, pooled t tests, and log-rank tests for comparisons. RESULTS: Fifty-four patients with Paget's disease were identified and divided into 2 cohorts (18 no SLNB and 36 SLNB). The mean age was 66 years for the no-SLNB group and 60 years for the SLNB group (P = .17). Paget's disease only was present in 33%, Paget's disease + DCIS in 41%, and Paget's disease + invasive cancer in 26%. The mean invasive tumor size was 1.62 cm in the no-SLNB group and 1.59 cm in the SLNB group (P = .96). For invasive disease, ER/PR status was similar, but Her2 was more likely to be overexpressed in SLNB (P = .04). Surgery choice ranged from "no surgery" to lumpectomy to mastectomy. Axillary staging was performed in 45 of 54 patients, with 11% in both cohorts having nodal disease. A sentinel lymph node was identified in 97% of patients. Five-year overall and disease-free survival was 100% in the no-SLNB group and 88% in the SLNB group (P = .97) and 76% in the no-SLNB group and 84% in the SLNB group (P = .88), respectively. CONCLUSIONS: Paget's disease remains rare but should be treated similar to other "breast cancer." SLNB should be performed to evaluate the axilla when invasive disease is identified or a mastectomy is planned.     

Axillary Recurrence After Negative Sentinel Node Biopsy in a Patient with Breast Cancer: Report of a Case

We report a case of axillary recurrence after sentinel node biopsy without axillary lymph node dissection in a patient with breast cancer. A hot and dye-stained node was identified at the primary operation and then at the time of axillary recurrence. Sentinel node biopsy is a promising alternative to axillary lymph node dissection in patients with breast cancer because of the low associated incidence of axillary recurrence.     

前哨淋巴结活检术替代腋窝淋巴结清扫术在乳腺癌中的临床应用

目的探讨前哨淋巴结活检术（SLNB）替代腋窝淋巴结清扫术（ALND）在早期乳腺癌患者中的应用价值和安全性。方法对2003年1月到2005年12月期间行前哨淋巴结活检术替代腋窝清扫术的125例患者作为研究组,对同一时期行腋窝清扫术且术后病理淋巴结阳性个数≤1的45例患者作为对照组;比较两组患者术后上肢并发症的发生情况及腋窝复发情况。结果SLNB替代ALND术后上肢麻木、肿胀、疼痛、僵硬、上肢活动受限及肌力减退方面的并发症均明显较ALND少,在随访36．5个月中,仅出现一例腋窝复发。结论前哨淋巴结活检术替代腋窝淋巴结清扫术术后并发症明显减少,腋窝复发率低,是早期乳腺癌患者的安全分期手术。     

原发性乳腺癌患者非哨兵淋巴结转移预测因素的研究

目的探讨原发性乳腺癌患者哨兵淋巴结活检(SLNB)后，哨兵淋巴结(SN)转移者非哨兵淋巴结(NSN)转移相关的临床及组织学因素。方法252例确诊为原发性乳腺癌患者SLNB后行腋窝淋巴结清扫，所有的腋窝淋巴结(SN及NSN)均行常规组织学检查。应用X^2检验分析年龄，肿瘤大小，肿瘤位置，病理类型，受体状态和SN转移数目与NSN转移的关系。结果SLNB成功率94％，假阴性率7．4％。随着原发肿瘤的增大，NSN转移的可能性增加：T1a T1b期肿瘤NSN转移率为0；T1c期为42％；T2期为87％。只有1个SN转移的患者NSN转移率明显低于多个SN转移的患者(27％vs46％)。结论NSN转移的可能性随着原发肿瘤的增大和多个SN转移而增加，而患者的年龄，肿瘤的位置，病理类型和受体状态不影响NSN转移的可能性。     

Regional recurrence in the era of sentinel lymph node biopsy

Background

The incidence of all-location regional recurrence after sentinel lymph node biopsy is not well documented. This study attempts to identify risk factors.

Methods

A prospectively maintained database was queried to identify patients with a regional recurrence of breast cancer after a first operation for invasive unilateral breast cancer. Patients with regional recurrence were compared with those alive and disease free at 5 years.

Results

Twenty-one of 1,060 patients (2%) experienced a regional recurrence. Most patients (95%) underwent sentinel lymph node biopsy as their axillary staging. Those with regional recurrences had larger tumors (P < .001), higher stage disease (P < .001), more estrogen receptor– and triple-negative breast cancers (P < .001), and more positive lymph nodes (P = .007). Mastectomy (P = .001) and receipt of neoadjuvant and/or chemotherapy (P < .001) were more common among those with regional recurrences.

Conclusions

Regional recurrence of breast cancer occurs infrequently. Risk factors include high-risk cancers, higher stage at presentation, nodal involvement, and need for therapies reflecting higher risk biology.     

Diminishing morbidity with the increased use of sentinel node biopsy in breast carcinoma

Background

Sentinel lymph node biopsy has largely replaced axillary node dissection in the staging of women with clinically negative axillas. The aim of this study was to compare the morbidity of sentinel node biopsy only, sentinel node biopsy followed by axillary dissection, and axillary node dissection only.

Methods

Retrospective review of a prospectively maintained database of patients who underwent sentinel lymph node biopsy, axillary lymph node dissection, or both between June 1996 and August 2008 was performed. The incidence of postoperative complications, including arm cellulitis, diminished shoulder range of motion, axillary hematoma, intercostal brachial nerve injury, pulmonary embolus or deep-vein thrombosis, lymphocele requiring aspiration, wound dehiscence, and wound infection, was compared among the 3 groups using Fisher's exact test.

Results

Of the 6,847 axillary operations performed, 2,745 (40%) were sentinel node biopsy only, 1,825 (27%) were sentinel lymph node biopsy followed by completion axillary dissection, and 2,277 (33%) were axillary dissection only. The mean node retrieval was 2 for sentinel node biopsy, 13 for sentinel node biopsy and completion axillary dissection, and 14 for axillary dissection. The mean age was 58 years. The overall complication rate was higher during the first half of the study period than during the second half (9.9% vs 3.9%, P < .0001). Axillary dissection had the highest overall complication rate (11.1%), followed by sentinel node biopsy and completion axillary dissection (7.3%), followed by sentinel node biopsy alone (2.6%) (P < .0001). Significantly less shoulder range of motion limitation, axillary hematoma, and lymphocele requiring aspiration were seen after sentinel node biopsy alone than after sentinel node biopsy plus completion axillary dissection or axillary dissection alone (P < .0001). Wound infection was also significantly less common after sentinel node biopsy than after axillary dissection (P = .02). No difference was seen in incidence of postoperative pulmonary embolus or deep-vein thrombosis, arm cellulitis, intercostal brachial nerve injury, or wound dehiscence.

Conclusions

Sentinel lymph node biopsy is less morbid than sentinel node biopsy followed by completion axillary dissection and axillary node dissection alone. The morbidity of axillary surgery has decreased over time.     

Sentinel node biopsy in breast cancer revisited

The axilla has long been a focus of clinicians' attention in the management of breast cancer. The approach to the axilla has undergone dramatic changes over the last century, from radical and extended radical excisions, through the introduction of sentinel node biopsy for node negative patients to the current situation where selective management of those with nodal involvement is being introduced.The introduction of lymphatic mapping and sentinel node biopsy in the 1990's has been key to the major changes that have occurred. In less than 20 years it has moved from a hypothesis to a situation where it is the default approach to almost all clinically node negative patients and is being considered in other situations where axillary clearance was previously considered standard. This article reviews the development and introduction of sentinel node biopsy, its current uncertainties and limitations, and possible future developments.     

The future of surgery in the treatment of breast cancer

The role of surgery cannot be discussed independently, but in relationship to the other modalities of treatment. Sentinel lymph node mapping and biopsy has revolutionized the role of surgery in axillary staging. Techniques of sentinel node mapping, the timing relative to chemotherapy, possible contraindications, and the necessity of completion axillary dissection are all under active investigation. The next few years will see continued changes in this important technique. Techniques of localizing clinically occult tumors are numerous and under study. These are not yet at the level of Phase III comparative trials. Induction chemotherapy has long been standard care for women with locally advanced breast cancer. It has not become standard care for Stage I or II breast cancers that meet criteria for adjuvant therapy. The ability to significantly downsize 80% of breast cancers is reason enough to make it usual practice for women who are certain to receive chemotherapy, if only for the cosmetic advantage that would accrue. Much has been made of the use of thermal ablation of small breast cancers by small probes introduced by skin puncture. In initial trials the lesions were excised after being heated or frozen. Current studies are leaving the destroyed tissue in place and following for evidence of control or recurrence. The value of this approach in terms of cosmesis is unproven, and the timing of its introduction when small tumors are being evaluated for margins and genetic markers, make it difficult to imagine broad acceptance. Finally, the role of prophylactic surgery for women at increased risk remains a difficult equation, compounded of alternatives such as chemoprevention, availability and effectiveness of surveillance techniques, and the level of fear and anxiety of the patient.     

Implementation of sentinel lymph node biopsy for breast cancer by surgeons in the Department of Defense

BACKGROUND: Sentinel lymph node biopsy (SLNB) for the evaluation of women with invasive breast cancer is rapidly gaining acceptance. The purpose of this study was to assess how surgeons in the Department of Defense (DOD) are incorporating SLNB into practice. METHODS: Surgeons at all DOD hospitals were telephonically surveyed regarding their current practices with SLNB. RESULTS: Of 66 DOD hospitals 23 (35%) are currently performing SLNB. Eleven hospitals (11 of 23, 48%) are academic centers, while 12 (12 of 23, 52%) are not teaching facilities. Seventeen (17 of 23, 77%) are in the learning phase of SLNB and follow SLNB with an axillary dissection. Eighteen (18 of 23, 78%) of facilities have surgeons who learned the procedure in residency/fellowship training. Sixteen (16 of 23, 70%) use a combination of isosulfan blue dye and sulfur colloid radioisotope. Surgeons performing SLNB are not aware of the method of examination of the sentinel node at their institution at 6 of 23 (26%) of hospitals. CONCLUSIONS: Increasing numbers of surgeons in the DOD Healthcare System are performing SLNB. The majority learned the procedure in residency or fellowship and are using a combination of blue dye and radioisotope for the performance of SLNB.     

Predictors of nonsentinel lymph node metastasis in breast cancer patients

BACKGROUND: In order to define a future subset of breast cancer patients in whom the axilla may be staged by sentinel lymph node biopsy alone, the conditions under which nonsentinel axillary lymph node metastases occur must be delineated. METHODS: A prospective database including 212 breast cancer patients who underwent sentinel lymph node biopsy followed by completion axillary dissection at our institution was reviewed. A multivariate, logistic, stepwise regression was performed to evaluate the relationship between nonsentinel lymph node metastasis and patient age, primary tumor size, presence of lymphatic invasion, use of radioisotope to identify the sentinel node and degree of metastasis in the sentinel node. RESULTS: Tumor size greater than 2 cm, lymphatic invasion of the primary tumor, macrometastasis in the sentinel node, and use of radioisotope all positively correlated independently with metastasis in the nonsentinel lymph node (P = 0.0001, P = 0.0483, P = 0.0008, P = 0.0271, respectively). CONCLUSIONS: Predictors of nonsentinel axillary node metastasis exist and are important in defining those patients in whom a sentinel lymph node biopsy alone may not be adequate.     

Axillary sentinel lymph node identification using superparamagnetic iron oxide versus radioisotope in early stage breast cancer: The UK SentiMag trial (SMART study)

Background & ObjectivesSentinel lymph node biopsy (SLNB) is an accurate and reliable method for staging the axilla in early breast cancer. The gold standard technique for localizing the sentinel lymph node (SLN) is the use of radioisotope with or without blue dye. However, this technique has its limitations. Various alternatives have been explored to overcome the disadvantages of the standard SLNB technique and superparamagnetic iron oxide mapping agents have garnered significant attention. The SMART study aims to compare the magnetic technique using the superparamagnetic iron oxide particles (SPIO, Sienna+®) to the radioisotope technique (Tc99) +/− blue dye, for SLN identification in patients with early breast cancer.MethodsA prospective, multicenter study was done that recruited 109 clinically node-negative early-stage breast cancer patients from five centres in the United Kingdom (UK). The patients received radioisotope ± blue dye injections, followed by intraoperative injection of magnetic tracer prior to SLNB. The sentinel node identification rate was compared between the magnetic and standard techniques to evaluate detection rate (per patient and per node), non-inferiority and concordance.ResultsData was analysed for 107 patients. The per patient detection rate was 98.13% (105/107) when using the magnetic tracer and 92.26% (103/107) when using the standard technique. The nodal detection rate was 93.07% (188/202 nodes) when using the magnetic tracer and 96.53% (195/202) when using the standard technique. Of the 31 patients with positive sentinel lymph nodes (SLNs), all 31 (100%) were detected by both techniques.ConclusionOur study demonstrates that the magnetic technique is a feasible method for SLNB, with an identification rate that is not inferior to the standard technique. The magnetic technique offers a suitable alternative to the standard technique thereby avoiding the need for the complexities of nuclear medicine, the hazards of radiation and the anaphylaxis risk of blue dye.     

乳晕真皮内注射蓝色染料法前哨淋巴结活检的应用

目的 探讨使用乳晕真皮内注射蓝色染料法前哨淋巴结活检在早期乳腺癌治疗中的作用和价值。方法 回顾性分析25例早期乳腺癌患者应用乳晕真皮内注射蓝色染料法前哨淋巴结活检的临床结果。结果 25例患者中成功检测出前哨淋巴结者24例,检出率为96．0％。共检出前哨淋巴结62枚,平均每例2．5枚。病理结果中HE染色5例淋巴结有转移,免疫组化染色7例阳性。本组前哨淋巴结检出的灵敏度为87．5％;准确性96．0％;假阴性率12．5％;假阳性率0。结论 应用乳晕真皮内注射蓝色染料法前哨淋巴结活检在早期乳腺癌治疗中同样可以取得较高的检出率和准确性。     

Sentinel node biopsy in early breast cancer. A review on recent and ongoing randomized trials

IntroductionSentinel Lymph Node Biopsy (SLNB) is regarded as the standard procedure for nodal staging in patients with early breast cancer. In the last decade several randomized trials have been evaluating its role and indications.Materials and methodsThis article reviews recent and ongoing randomized trials on SLNB.ResultsFour randomized controlled trials have recently shown evidence that SLNB either alone or followed by radiation therapy is effective for the management in patients with low axillary tumor burden in early breast cancer. Nine randomized controlled trials on SLNB are ongoing: four assessing its role in case of positive sentinel node, three evaluating whether SLNB itself can be omitted when the preoperative nodal imaging is negative, two are studying SLNB in the neoadjuvant setting.Discussion and conclusionSLNB either alone or with axillary radiotherapy has been shown to be non-inferior to complete axillary dissection in terms of local recurrence, disease-free survival and overall survival in early breast cancer with minimally metastatic axilla. So far, results from ongoing trials are going to confirm the appropriate treatment in patients with limited axillary nodal involvement, the role and the timing of SLNB within the neoadjuvant setting and to define whether surgery can be avoided in the axilla in early stage breast cancer patients with negative preoperative imaging.     

The value of sentinel lymph node biopsy in elderly breast cancer patients

BACKGROUND: Although sentinel lymph node biopsy has been accepted as a useful procedure for certain breast cancer patients, the value of this procedure in the elderly remains unknown. We undertook this study to evaluate changes in adjuvant treatment attributable to sentinel lymph node biopsy. METHODS: A total of 104 patients > or =65 years underwent sentinel lymph node biopsy plus lumpectomy or mastectomy for the treatment of clinically node-negative invasive breast cancer. Demographic, pathologic, and treatment data were evaluated using an SAS software package (SAS, Cary, North Carolina). RESULTS: Twenty-nine of 104 patients (28%) had metastatic disease in > or =1 sentinel lymph node. Nonsurgical treatment was modified in 38% of patients because of sentinel lymph node biopsy results. Changes included adjuvant chemotherapy and/or hormonal therapy, adjuvant axillary radiotherapy, and decisions against adjuvant therapy. CONCLUSIONS: These data suggest that sentinel lymph node biopsy in elderly breast cancer patients is beneficial.     

Considerations for sentinel lymph node biopsy in breast cancer patients with biopsy proven axillary disease prior to neoadjuvant treatment

Background

Axillary disease can be downstaged with neoadjuvant treatment for breast cancer. We attempted to identify factors to consider in determining whether to perform a sentinel lymph node biopsy in patients with biopsy proven axillary metastases (cN+) prior to neoadjuvant treatment.

Advantage of sentinel lymph node biopsy before neoadjuvant chemotherapy in breast cancer treatment

Lymph node status is a key factor in determining the stage of breast cancer and the most appropriate therapy and for predicting the outcome of patients. Accurate identification of sentinel lymph nodes (SLNs) preoperatively is of clinical importance. Sentinel lymph node biopsy (SLNB) causes less lymph edema of the upper arm than axillary lymph node dissection (ALND) with a high accuracy rate and low false-negative rate (FNR). Neoadjuvant chemotherapy (NAC) can be given not only to patients with locally advanced breast cancer, but also to those with axillary lymph node metastasis and an operable tumor. However, SLNB after NAC results in a lower identification rate and a higher FNR than SLNB before treatment. Recently, a hybrid imaging device has been developed, which consists of single photon emission computed tomography (CT, SPECT) and a low-dose CT installed on the same platform. This imaging system offers an easy and safe method of performing SLNB under local anesthesia. To identify the initial cancer stage in patients who will be treated by systemic therapy before surgery, SLNB should be performed prior to systemic treatments, using a well-developed navigating tool, such as SPECT/CT.     

Outcomes of sentinel node biopsy for breast cancer in British Columbia, 1996 to 2001

BACKGROUND: This study evaluated the outcomes of the first 5 years of sentinel node biopsy (SNB) in British Columbia (BC), Canada, 1996 to 2001. METHODS: There were 547 SNB procedures for breast cancer performed by 29 surgeons at 12 hospitals in BC between October 1996 and July 2001. Identification, accuracy, and false-negative rates were determined and correlated to patient, tumor, and surgical factors with the chi-square test. RESULTS: SNB mapping was performed using blue dye alone (15%), radiopharmaceutical alone (6%), or both (79%). A completion axillary dissection was performed in 93%. A median of 2 (range 1 to 16) sentinel nodes was biopsied. The overall identification rate was 88%, accuracy was 92%, and false-negative rate was 22%. All rates were improved in younger (age <50 years) compared with older women. A positive lymphoscintiscan and the mapping agent used were associated with higher identification rates but not accuracy or false negative rates. Increasing surgeon experience was not significantly associated with improvements in identification or false-negative rates. CONCLUSIONS: The potential of SNB was not fully translated into surgical practice in BC by 2001.     

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.     

Sentinel lymph node biopsy after neoadjuvant chemotherapy in a patient with operable breast cancer

PURPOSE: This study was undertaken to assess the feasibility of performing a sentinel lymph node biopsy (SLNB) for a patient with operable breast cancer after undergoing neoadjuvant chemotherapy (NAC). METHOD: Between January 2002 and December 2003, women with primary breast cancer who had a breast tumor measuring larger than 3 cm in unilateral diameter were eligible for NAC. All patients who had completed NAC underwent lymphatic mapping with labeled (99m)Tc phytate on the day before surgery. Sentinel lymph node biopsy followed by a full axillary lymph node (AXLN) dissection (ALND) was performed in all patients. Sentinel lymph nodes (SLN) were sent for a frozen-section examination. RESULTS: The rate of SLN identification was 71%. Both the sensitivity and negative predictive value of SLNB were 100%. The false negative rate was 0%. When candidates for SLNB were restricted to patients with a breast tumor measuring less than 3 cm and clinically negative nodes after NAC, the rate of SLN identification increased to 93% from 71% while still maintaining the 0% false negative rate. CONCLUSION: Sentinel lymph node biopsy after NAC is therefore considered to be a feasible and accurate method to predict the AXLN status in patients who have a breast tumor measuring less than 3 cm in unilateral diameter and a clinically negative AXLN status at the time of surgery after NAC.     

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.Presented at the 54th Annual Meeting of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001.