Are 3 sentinel nodes sufficient?

HYPOTHESIS: It has recently been proposed that only 3 sentinel lymph nodes (SLNs) are required for an adequate SLN biopsy. Others have advocated removing all nodes that are blue, hot, at the end of a blue lymphatic channel, or palpably suspicious or that have radioactive counts of 10% or greater of the most radioactive SLN. Our objective was to determine the false-negative rate (FNR) associated with limiting SLN biopsy to 3 nodes. DESIGN: Multicenter prospective study. SETTING: Both academic and private practice. PATIENTS: A total of 4131 patients underwent SLN biopsy followed by completion axillary node dissection. MAIN OUTCOME MEASURE: The FNR associated with 3-node SLN biopsy. RESULTS: Of the 4131 patients in this study, an SLN was identified in 3882 (94.0%). The median number of SLNs identified was 2; more than 3 SLNs were removed in 738 patients (17.9%). Of the patients in whom a SLN was identified, 1358 (35.0%) were node positive. The overall FNR in this study was 7.7%. In 89.7% of node-positive patients, a positive SLN was found in the first 3 SLNs removed. If SLN biopsy had been limited to the first 3 nodes, the FNR would be 10.3% (P = .005 compared with removing >3 SLNs). The FNR increased with the strategy of limiting SLN biopsy to fewer SLNs (P<.001). CONCLUSION: Removing only 3 SLNs cannot be recommended, because it is associated with a substantially increased FNR.

Factors predicting failure to identify a sentinel lymph node in breast cancer.

BACKGROUND: Although sentinel lymph node (SLN) biopsy is widely accepted as a minimally invasive method of nodal staging, failure to identify an SLN mandates a level I/II axillary node dissection. The purpose of this study was to elucidate factors that independently predict failure to identify an SLN. METHODS: Using a large multicenter prospective study of SLN biopsy for patients with invasive breast cancer, we performed univariate and multivariate regression analyses to determine clinicopathologic factors predictive of failure to identify an SLN. RESULTS: Of the total 4131 patients in the study, an SLN was not identified in 249 (6.0%). Tumor location (P = .409), biopsy type (P = .079), surgery type (P = .380), and histologic subtype (P = .999) were not significant predictors of failure to identify an SLN. On multivariate analysis, age greater than 60 years (OR = 1.469; 95% CI, 1.116-1.934, P = .006), nonpalpable tumors (OR = 0.639; 95% CI, 0.479-0.852, P = .002), injection technique with blue dye alone (OR = 0.389, 95% CI, 0.259-5.86, P < .001), and surgical experience of less than 10 SLN biopsy cases (OR = 1.886; 1.428-2.492, P < .001) were significant independent predictors of failure to identify an SLN. Optimal SLN biopsy technique using an intradermal and/or subareolar injection of radioactive colloid and blue dye can improve SLN identification rates regardless of patient and tumor characteristics. CONCLUSIONS: Patient age and tumor palpability significantly affect the ability to identify an SLN in patients with breast cancer. Optimal injection technique can significantly improve sentinel node identification rate regardless of these factors.

Biopsy type does not influence sentinel lymph node status.

BACKGROUND: This study sought to determine whether the type of biopsy examination independently affects sentinel lymph node (SLN) status in breast cancer patients. METHODS: A prospective multicenter study of patients who had SLN biopsy examination followed by axillary node dissection was analyzed to determine whether the type of biopsy examination influenced SLN status. RESULTS: Of the 3853 patients studied, 32% had a positive SLN. Patients were diagnosed by fine-needle (N = 293), core-needle (N = 2154), excisional (N = 1386), or incisional (N = 20) biopsy procedures. The rates of SLN positivity for these groups were 45%, 32%, 29%, and 65%, respectively (P < .001). Other factors predictive of SLN status included: patient age (P < .001), tumor size (P < .001), tumor palpability (P < .001), number of SLN removed (P < .001), type of surgery (mastectomy vs. lumpectomy) (P < .001), histologic subtype (P = .048), and the use of immunohistochemistry (P < .001). All of these factors remained significant in the multivariate model except for histologic subtype and biopsy examination type. CONCLUSIONS: Biopsy examination type does not independently influence the risk for nodal metastasis.

Effect of lymphoscintigraphy drainage patterns on sentinel lymph node biopsy in patients with breast cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy examination is an accepted method of staging breast cancer patients. SLN biopsy examination in patients with drainage to the internal mammary chain (IMC) nodes is controversial. METHODS: A prospective study of SLN biopsy examination followed by axillary dissection was analyzed to determine how surgeons manage patients with IMC drainage and the rates of axillary SLN identification and positivity in these cases. RESULTS: Lymphoscintigraphy was performed in 2196 (53.2%) of the 4131 patients in this study. IMC drainage was noted in 80 patients (3.6%). An axillary SLN was identified in 29 of the 40 patients with IMC drainage alone (72.5%). The rate of finding a positive axillary lymph node did not differ based on the lymphoscintigraphic pattern (P = .470). CONCLUSIONS: Most surgeons do not perform IMC SLN biopsy procedures. Even when lymphoscintigraphy shows isolated drainage to IMC nodes, axillary SLNs usually are identified. Lymphoscintigraphy therefore has limited usefulness.

Surgeon and community factors affecting breast cancer sentinel lymph node biopsy.

BACKGROUND: We sought to determine whether the results of sentinel lymph node (SLN) biopsy are related to practice and community factors. METHODS: This prospective study included more than 300 surgeons from a variety of practice environments. Most surgeons had minimal experience with SLN biopsy prior to this study. Patients underwent attempted SLN biopsy, followed by completion axillary dissection. Univariate and multivariate analyses were performed to assess factors related to the SLN identification rate and the false negative rate. RESULTS: A total of 4131 patients were enrolled. SLN identification rate was 93%; the false negative (FN) rate was 7.9%. The only factor that was significantly associated with improved SLN identification rate (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.12 to 2.36, P = .0126) and FN rate (OR 2.39, 95% CI 1.32 to 4.79, P = .0073) was surgeon experience (>20 SLN cases). CONCLUSIONS: Surgeon experience is the major factor that contributes to improved SLN biopsy results. SLN biopsy can be performed equally well by community and academic surgeons.

Margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive breast cancer: American Society of Clinical Oncology endorsement of the Society of Surgical Oncology/American Society for Radiation Oncology consensus guideline.

PURPOSE: The Society of Surgical Oncology (SSO)/American Society for Radiation Oncology (ASTRO) guideline on surgical margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive breast cancer was considered for endorsement. METHODS: The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing practice guidelines developed by other organizations. ASCO staff reviewed the SSO/ASTRO guideline for developmental rigor; an ASCO ad hoc review panel of experts reviewed the guideline content. RESULTS: The ASCO ad hoc guideline review panel concurred that the recommendations are clear, thorough, and based on the most relevant scientific evidence in this content area and that they present options acceptable to patients. According to the SSO/ASTRO guideline, the use of no ink on tumor (ie, no cancer cells adjacent to any inked edge/surface of specimen) as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of ipsilateral breast tumor recurrence and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. CONCLUSION: The ASCO review panel endorses the SSO/ASTRO recommendations with qualifications, as follows. The panel reinforces and amplifies the guideline authors' call for the monitoring of outcomes of the guideline at the institutional level, as institutions transition to adopting the SSO/ASTRO recommendations; would place greater emphasis on the importance of postlumpectomy mammography for cases involving microcalcifications; and calls for flexibility in the application of the guideline in light of the generally weak evidence supporting the recommendations.

Factors influencing the number of sentinel lymph nodes identified in patients with breast cancer.

BACKGROUND: Although the sentinel lymph node (SLN) is defined as the first node draining a tumor, multiple nodes are often identified. Few SLNs are required for adequate staging; removal of more may be unnecessary. The objective of this study was to determine factors influencing the number of SLN identified. METHODS: The University of Louisville Breast Sentinel Lymph Node Study was used to determine correlates of identifying greater than 4 SLNs by using univariate and multivariate analyses. RESULTS: An SLN was identified in 3,882 of 4,131 patients (94%). The median number of SLN identified was 2 (range 1-18); 90% had < or = 4 SLNs identified. Palpable tumors, surgeon inexperience, and dermal injection were associated with greater than 4 SLNs identified. All 3 of these factors remained significant on multivariate analysis. CONCLUSIONS: Palpable tumors often have greater than 4 SLNs identified, and the use of intradermal injection increases this probability.

Factors determining adequacy of axillary node dissection in breast cancer patients.

With increased focus on quality assurance, a complete axillary lymph node dissection (ALND) has been defined as the removal of 10 or more lymph nodes (LN). The objective of this study was to determine which patient, physician, and geographic factors predict the adequacy of ALND in breast cancer patients. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a multicenter, prospective study of 4,131 patients, all of whom had a sentinel node biopsy and completion ALND. Univariate and multivariate analyses were performed to determine which factors were independently associated with the removal of 10 or more LN. Of the 4,131 patients in this study, the median number of LN removed was 11 (range; 3-45). Ten or more LN were removed in 3,213 (77.8%) patients. The median patient age in this study was 60 (range; 27-100), with a median tumor size of 1.5 cm (range; 0.1-11.0 cm). On univariate analysis, patient age, tumor size, and palpability were correlated with adequacy of ALND. Academic affiliation and percentage of breast practice were significant physician factors predictive of adequacy of ALND. Both geographic region and community size were significantly correlated with adequacy of ALND. On multivariate analysis, patient age (p = 0.024), surgeon academic affiliation (p < 0.001), percentage breast practice (p < 0.001), and community size (p = 0.003) were significant determinants of adequacy of ALND. Younger patients were more likely to have an adequate ALND. Surgeons in academic practice had a higher rate of adequate ALND, as did those practicing in larger communities. Surgeons with a more breast experience had a lower rate of adequate ALND. Patient age, surgeon academic affiliation, and breast experience, as well as community size are all significant factors predictive of adequacy of ALND.

Predicting patients at low probability of requiring postmastectomy radiation therapy.

BACKGROUND: Postmastectomy radiation therapy (PMRT) is recommended for patients with four or more positive lymph nodes (LN+). Given the ramifications of PMRT for immediate reconstruction, we sought to create a model using preoperative and intraoperative factors to predict which patients with a positive sentinel lymph node will have less than four LN+. METHODS: The database from a prospective multicenter study of 4,131 patients was used for this analysis. Patients with one to three positive sentinel lymph nodes (SLN) and tumors < 5 cm (n = 1,133) in size were randomly divided into a training set (n = 580) and a test set (n = 553). Multivariate logistic regression was used on the training set to create a prediction rule that was subsequently validated in the test set. RESULTS: Median patient age was 57 (range, 27-100) years, and median tumor size was 2.0 (range, 0.2-4.8) cm. In the training set, factors associated with having four or more LN+ on multivariate analysis were: tumor size [odds ratio (OR) = 2.087; 95% confidence interval (CI): 1.307-3.333, P = 0.002), number of positive SLN (P < 0.0005), and proportion of positive SLN (OR = 3.602; 95% CI: 2.100-6.179, P < 0.005). A predictive model was established with a point assigned to each positive SLN, T2 (vs. T1), and if proportion of positive SLN was > 50%, for a maximum of five points. In both the training and test sets, patients with one point had a low probability of having four or more LN+ (3.8% and 3.3%, respectively). CONCLUSION: Tumor size, number of positive SLN, and the proportion of positive SLN influence whether patients will have four or more LN+. A simple model can predict the probability of requiring PMRT.

Prediction of sentinel lymph node-only disease in women with invasive breast cancer.

BACKGROUND: The purpose of this study was to create a model that predicts which breast cancer patients will have sentinel lymph node (SLN)-only metastasis. METHODS: SLN-positive breast cancer patients (N = 1,253) were analyzed. Multivariate analysis was performed to identify factors predicting SLN-only disease; a prediction rule was created. RESULTS: Median tumor size was 2 cm. The median number of SLNs removed was 2; the median number of positive SLNs was 1. Multivariate analysis found tumor size, number of positive SLN, and proportion of SLN positive were significant predictors of SLN-only disease (P < .001). A prediction rule with 1 point being given for >1 positive SLN, 1 point for >50% of SLN positive, and up to 4 points for tumor size (T1a = 1, T1b or T1c = 2, T2 = 3, and T3 = 4) was established. Ninety-five percent of patients with 1 point had SLN-only disease (P < .0001). CONCLUSION: An integer-based model may predict SLN-only disease and may be useful in determining whether completion axillary lymph node dissection is required.

Factors associated with surgical options for breast carcinoma.

BACKGROUND: Breast conservation surgery (BCS) and mastectomy have equivalent survival outcomes for women with breast carcinoma, but treatment decisions are affected by many factors. The current study evaluated the impact of patient and physician factors on surgical decision-making. METHODS: Statistical analyses were performed on a prospective multicenter study of patients with invasive breast carcinoma. Patient, physician, and geographic factors were considered. RESULTS: Of 4086 patients, BCS was performed in 2762 (67.6%) and mastectomy was performed in 1324 (32.4%). The median tumor size was 1.5 cm (range, < 0.1-9.0 cm) in patients undergoing BCS and 1.9 cm (range, 0.1-11.0 cm) in patients undergoing mastectomy (P < 0.00001). The median age of patients undergoing BCS was 59 years (range, 27-100 yrs), whereas patients who underwent mastectomy were older (median age of 63 yrs, range, 27-96 yrs [P < 0.00001]). Physicians in academic practices performed more lumpectomies than those who were not in an academic practice (70.9% vs. 65.7%; P = 0.001). More breast conservation procedures were performed by surgeons with a higher percentage of breast practice (P = 0.012). Geographic location was found to be significant, with the Northeast having the highest rate of breast conservation (70.8%) and the Southeast having the lowest (63.2%; P = 0.002). On multivariate analysis, patient age (odds ratio [OR]: 1.455; 95% confidence interval [95% CI], 1.247-1.699 [P < 0.001]), tumor size (P < 0.001), tumor palpability (OR: 0.613; 95% CI, 0.524-0.716 [P < 0.001]), histologic subtype (P = 0.018), tumor location in the breast (P < 0.001), physician academic affiliation (OR: 1.193; 95% CI: 1.021-1.393 [P = 0.026]), and geographic location (P = 0.045) were found to be significant. CONCLUSIONS: Treatment decisions were found to be related to patient clinicopathologic features, surgeon academic affiliation, and geographic location. Future studies will elucidate the communication and psychosocial factors that may influence patient decision-making.