Jane Fey

A Nomogram for Predicting the Likelihood of Additional Nodal Metastases in Breast Cancer Patients With a Positive Sentinel Node Biopsy

AbstractBackground:The standard of care for breast cancer patients with sentinel lymph node (SLN) metastases includes complete axillary lymph node dissection (ALND). However, many question the need for complete ALND in every patient with detectable SLN metastases, particularly those perceived to have a low risk of non-SLN metastases. Accurate estimates of the likelihood of additional disease in the axilla could assist greatly in decision-making regarding further treatment. Methods:Pathological features of the primary tumor and SLN metastases of 702 patients who underwent complete ALND were assessed with multivariable logistic regression to predict the presence of additional disease in the non-SLNs of these patients. A nomogram was created using pathological size, tumor type and nuclear grade, lymphovascular invasion, multifocality, and estrogen-receptor status of the primary tumor; method of detection of SLN metastases; number of positive SLNs; and number of negative SLNs. The model was subsequently applied prospectively to 373 patients. Results:The nomogram for the retrospective population was accurate and discriminating, with an area under the receiver operating characteristic (ROC) curve of 0.76. When applied to the prospective group, the model accurately predicted likelihood of non-SLN disease (ROC, 0.77). Conclusions:We have developed a user-friendly nomogram that uses information commonly available to the surgeon to easily and accurately calculate the likelihood of having additional, non-SLN metastases for an individual patient.

The Risk of Axillary Relapse After Sentinel Lymph Node Biopsy for Breast Cancer Is Comparable With That of Axillary Lymph Node Dissection: A Follow-up Study of 4008 Procedures

Objective:We sought to identify the rate of axillary recurrence after sentinel lymph node (SLN) biopsy for breast cancer. Summary Background Data:SLN biopsy is a new standard of care for axillary lymph node staging in breast cancer. Nevertheless, most validated series of SLN biopsy confirm that the SLN is falsely negative in 5–10% of node-positive cases, and few studies report the rate of axillary local recurrence (LR) for that subset of patients staged by SLN biopsy alone. Methods:Through December of 2002, 4008 consecutive SLN biopsy procedures were performed at Memorial Sloan-Kettering Cancer Center for unilateral invasive breast cancer. Patients were categorized in 4 groups: SLN-negative with axillary lymph node dissection (ALND; n = 326), SLN-negative without ALND (n = 2340), SLN-positive with ALND (n = 1132), and SLN-positive without ALND (n = 210). Clinical and pathologic characteristics and follow-up data for each of the 4 cohorts were evaluated with emphasis on patterns of axillary LR. Results:With a median follow-up of 31 months (range, 1–75), axillary LR occurred in 10/4008 (0.25%) patients overall. In 3 cases (0.07%) the axillary LR was the first site of treatment failure, in 4 (0.1%) it was coincident with breast LR, and in 3 (0.07%) it was coincident with distant metastases. Axillary LR was more frequent among the unconventionally treated SLN-positive/no ALND patients than in the other 3 conventionally treated cohorts (1.4% versus 0.18%, P = 0.013). Conclusions:Axillary LR after SLN biopsy, with or without ALND, is a rare event, and this low relapse rate supports wider use of SLN biopsy for breast cancer staging. There is a low-risk subset of SLN-positive patients in whom completion ALND may not be required.

Sentinel lymph node biopsy: is it indicated in patients with high-risk ductal carcinoma-in-situ and ductal carcinoma-in-situ with microinvasion?

Background: Axillary lymph node status is the strongest prognostic indicator of survival for women with breast cancer. The purpose of this study was to determine the incidence of sentinel node metastases in patients with high-risk ductal carcinoma-in-situ (DCIS) and DCIS with microinvasion (DCISM).Methods: From November 1997 to November 1999, all patients who underwent sentinel node biopsy for high-risk DCIS (n = 76) or DCISM (n = 31) were enrolled prospectively in our database. Patients with DCIS were considered high risk and were selected for sentinel lymph node biopsy if there was concern that an invasive component would be identified in the specimen obtained during the definitive surgery. Patients underwent intraoperative mapping that used both blue dye and radionuclide. Excised sentinel nodes were serially sectioned and were examined by hematoxylin and eosin and by immunohistochemistry.Results: Of 76 patients with high-risk DCIS, 9 (12%) had positive sentinel nodes; 7 of 9 patients were positive for micrometastases only. Of 31 patients with DCISM, 3 (10%) had positive sentinel nodes; 2 of 3 were positive for micrometastases only. Six of nine patients with DCIS and three of three with DCISM and positive sentinel nodes had completion axillary dissection; one patient with DCIS had an additional positive node detected by conventional histological analysis.Conclusions: This study documents a high incidence of lymph node micrometastases as detected by sentinel node biopsy in patients with high-risk DCIS and DCISM. Although the biological significance of breast cancer micrometastases remains unclear at this time, these findings suggest that sentinel node biopsy should be considered in patients with high-risk DCIS and DCISM.

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 ≤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 ≤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 ≤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 ≤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.

Isosulfan blue dye reactions during sentinel lymph node mapping for breast cancer

UNLABELLED In the United States, identification of the sentinel lymph node (SLN) requires the use of (99m)Tc-labeled colloid, 1% isosulfan blue dye, or both to trace the lymphatic drainage of a given neoplasm. We report our experience with adverse reactions to isosulfan blue dye during SLN mapping in breast cancer. A chart review of the breast cancer SLN database was performed; it included 2392 sequential patients who underwent SLN biopsy involving isosulfan blue dye at Memorial Sloan-Kettering Cancer Center from September 12, 1996, to August 17, 2000. Thirty-nine of 2392 patients (1.6%) had a documented allergic reaction during the mapping procedure. Most reactions (69%) produced urticaria, blue hives, a generalized rash, or pruritus. The incidence of hypotensive reactions was 0.5%. Although anaphylaxis after the injection of isosulfan blue dye is rare, this article highlights the need to suspect anaphylaxis when hemodynamic instability occurs after the injection of this compound. Our experience indicates that bronchospasm and respiratory compromise are unusual and that most patients do not require emergent intubation and can be managed with short-term pressor support. In addition, our data indicate that patients with a sulfa allergy do not display a cross-sensitivity to isosulfan blue dye. IMPLICATIONS We report the largest single-institution review of adverse reactions to injection of isosulfan blue dye during sentinel lymph node mapping in breast cancer. Bronchospasm and respiratory compromise are unusual, and most patients can be treated with short-term pressor support. Patients with a sulfa allergy do not display a cross-sensitivity to isosulfan blue dye.

Predicting Nonsentinel Node Status After Positive Sentinel Lymph Biopsy for Breast Cancer: Clinicians Versus Nomogram

BackgroundWith increasing frequency, breast cancer patients and clinicians are questioning the need for completion axillary lymph node dissection (ALND) in the setting of a positive sentinel lymph node (SLN). We previously developed a nomogram to estimate the likelihood of residual disease in the axilla after a positive SLN biopsy result. In this study, we compared the predictions of clinical experts with those generated by the nomogram and evaluated the ability of the nomogram to change clinicians’ behavior.MethodsPathologic features of the primary tumor and SLN metastases of 33 patients who underwent completion ALND were presented to 17 breast cancer specialists. Their predictions for each patient were recorded and compared with results from our nomogram. Subsequently, clinicians were presented with clinical information for eight patients and asked whether they would perform a completion ALND before and after being presented with the nomogram prediction.ResultsThe predictive model achieved an area under the receiver operating characteristic curve of .72 when applied to the test data set of 33 patients. In comparison, the clinicians as a group were associated with an area under the receiver operating characteristic curve of .54 (P < .01 vs. nomogram). With regard to performing a completion ALND, providing nomogram results did not alter surgical planning.ConclusionsOur predictive model seemed to substantially outperform clinical experts. Despite this, clinicians were unlikely to change their surgical plan based on nomogram results. It seems that most clinicians can improve their predictive ability by using the nomogram to predict the likelihood of additional non-SLN metastases in a woman with a positive SLN biopsy result.

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.

The accuracy of sentinel lymph node biopsy in multicentric and multifocal invasive breast cancers

BACKGROUND Sentinel lymph node biopsy (SLNB) has proved to be an accurate alternative to complete axillary lymph node dissection (ALND) in clinically node-negative breast cancer patients. Multicentric (MC) and multifocal (MF) invasive breast cancers are considered to be relative contraindications to SLNB. We examine the accuracy of SLNB in patients with MC and MF invasive breast cancers. STUDY DESIGN From September 1996 to August 2001, a total of 3,501 patients with clinically node-negative breast cancer underwent SLNB using both blue dye and radioisotope at our institution. A total of 70 patients had MC or MF invasive breast cancer, a successful SLNB, and mastectomy for local control. All had >/=10 axillary nodes excised (including the SLN) in a planned ALND. Exclusion criteria included MC and MF in situ carcinoma; breast conservation; previous breast irradiation, ALND, or SLNB; recurrent breast cancer; neoadjuvant chemotherapy; or ALND based solely on SLNB pathologic examination. RESULTS; The incidence of axillary metastases was 54% (38 of 70). SLNB accuracy was 96% (67 of 70), sensitivity 92% (35 of 38), and false-negative rate 8% (3 of 38). All patients with an inaccurate SLNB had a dominant invasive tumor >5 cm and one patient had palpable axillary disease intraoperatively. The SLN was the only site of axillary metastasis in 37% (14 of 38). Results were compared with those of published SLNB validation studies, most of which reflect experience with single-site invasive breast cancers. No statistically significant difference was noted for accuracy, sensitivity, or false-negative rate. CONCLUSIONS SLNB accuracy in MC and MF disease is comparable with that of published validation studies. MC and MF patients with a dominant T3 tumor (>5 cm) or axillary disease palpable intraoperatively should have a concurrent formal ALND. Our retrospective data suggest SLNB may be used as a reliable alternative to conventional ALND in selected patients with MC or MF disease. Further studies in this patient population are warranted.

A declining rate of completion axillary dissection in sentinel lymph node-positive breast cancer patients is associated with the use of a multivariate nomogram.

Objective:To compare sentinel lymph node (SLN)-positive breast cancer patients who had completion axillary dissection (ALND) with those who did not, with particular attention to clinicopathologic features, nomogram scores, rates of axillary local recurrence (LR), and changes in treatment pattern over time. Background:While conventional treatment of SLN-positive patients is to perform ALND, there may be a low-risk subgroup of SLN-positive patients in whom ALND is not required. A multivariate nomogram that predicts the likelihood of residual axillary disease may assist in identifying this group. Methods:Among 1960 consecutive SLN-positive patients (1997–2004), 1673 (85%) had ALND (“SLN+/ALND”) and 287 (15%) did not (“SLN+/no ALND”). We compare in detail the clinicopathologic features, nomogram scores, and rates of axillary LR between groups. Results:Compared with the SLN+/ALND group, patients with SLN+/no ALND were older, had more favorable tumors, were more likely to have breast conservation, had a lower median predicted risk of residual axillary node metastases (9% vs. 37%, P < 0.001), and had a marginally higher rate of axillary LR (2% vs. 0.4%, P = 0.004) at 23 to 30 months’ follow-up; half of all axillary LR in SLN+/no ALND patients were coincident with other local or distant sites. For patients in whom intraoperative frozen section was either negative or not done, the rate of completion ALND declined from 79% in 1997 to 62% in 2003 to 2004 but varied widely by surgeon, ranging from 37% to 100%. For 10 of 10 evaluable surgeons, the median nomogram scores in the SLN+/no ALND group were ≤10.5. Conclusions:SLN+/no ALND breast cancer patients, a selected group with relatively favorable disease characteristics, had a 9% predicted likelihood of residual axillary disease by nomogram but an observed axillary LR of 2%. A gradual and significant decline over time in the rate of completion ALND is associated with, but not entirely explained by, the institution of a predictive nomogram. It is reasonable to omit ALND for a low-risk subset of SLN-positive patients.

Sensory morbidity after sentinel lymph node biopsy and axillary dissection: a prospective study of 233 women.

BackgroundWe prospectively compared the sensory morbidity and lymphedema experienced after sentinel node biopsy (SLNB) and axillary dissection (ALND) over a 12-month period by using a validated instrument.MethodsPatients undergoing breast-conserving therapy completed the Breast Sensation Assessment Scale (BSAS) at baseline and 3, 6, and 12 months after surgery. Repeated-measures analysis of variance was used to compare ALND and SLNB over the 12-month period. Upper- and lower-arm circumference measurements at baseline and 12 months were used to assess lymphedema.ResultsSLNB was associated with substantial sensory morbidity, although significantly less than ALND, over time on all four subscales and the summary score. A statistically significant improvement in sensory morbidity occurred for both groups in the first 3 months, with no further change thereafter. For both types of axillary surgery, younger patients had significantly higher BSAS scores than older patients. There was no significant difference in arm circumference between patients with SLNB and ALND at 12 months.ConclusionsAmong women undergoing breast-conserving therapy, SLNB has significant sensory morbidity, although approximately half that of ALND. Sensory morbidity improves in the first 3 months after surgery, but patients continue to report sensory morbidity at 1 year. Longitudinal follow-up is required to further assess lymphedema.