Elisabeth L. Dupont

Significance of Sentinel Lymph Node Micrometastases in Human Breast Cancer

BACKGROUND The significance of micrometastatic disease in the sentinel lymph nodes (SLN) of patients with invasive breast cancer has been questioned. The objective of our study was to review the impact of micrometastatic carcinoma detected by SLN biopsy. STUDY DESIGN Between January 1997 and May 2004, 2,408 patients with invasive breast cancer and an SLN with micrometastatic (N0[i+], N1mi) or no metastatic (N0[i-]) disease were identified through our breast database. Slide review was performed and reclassified by the 6(th) edition of the American Joint Committee on Cancer Staging Manual. Of these, 27 were excluded from analysis because of evidence of macrometastatic disease on slide review or enrollment in the American College of Surgeons Oncology Group Z10 study. RESULTS Of 2,381 patients, 2,108 were N0(i-), 151 were N0(i+), and 122 were N1mi. Overall and disease-free survivals of patients with an N1mi SLN were substantially worse than those in patients with an N0(i-) SLN (p < 0.001 and p=0.006, respectively). Additional positive non-SLNs were identified in 15.5% (15 of 97) of N1mi patients and 9.3% (10 of 107) of N0(i+) patients undergoing completion axillary lymph node dissection. Overall survival of the N0(i+) SLN patients not undergoing axillary dissection was substantially less than those undergoing axillary dissection (p=0.02). CONCLUSIONS Detection of micrometastatic carcinoma (N1mi) in the SLNs of invasive breast cancer patients is a major indicator of poorer survival compared with N0(i-) patients. Although survival of patients with an N0(i+) SLN does not statistically differ from that of N0(i-) patients, 9.3% of these patients had additional axillary nodal disease on axillary dissection, and N0(i+) patients had a decreased survival when axillary dissection was omitted.

Age and Body Mass Index May Increase the Chance of Failure in Sentinel Lymph Node Biopsy for Women with Breast Cancer

Age and body mass index (BMI) have been shown to correlate with an increased incidence of failure in identifying a sentinel lymph node (SLN). Mapping senior, overweight adults is common; therefore, the relationship of patient age and BMI on SLN biopsy success is essential. This study examines the mapping failures as they relate to age and BMI. From April 1994 to May 1999, patients underwent an injection of radiocolloid (450 mci) and blue dye (5 cc) prior to SLN biopsy. SLN biopsy failure was defined as lymph nodes being unidentifiable by blue dye or having an in vivo node radiocolloid count of less than 3:1 over background count. BMI was measured as (weight in pounds)(703)/(height in inches) 2; 1,356 patients were attempted for SLN mapping, and 54 failed (3.98%). The radioactive node count was inversely proportional to age ( p < 0.0001). The radioactive node count decreased by a mean of 34 counts per node with each additional year ( p < 0.001). The estimated odds ratios for success were 0.945 for age and 0.946 for BMI. Therefore, every increase of 1 year of age or one unit of BMI decreased the odds of success by approximately 5%. The mean BMI was 29.54 in failed patients and was 26.42 in successful mapping patients ( p = 0.042). Surgeons should be aware that node counts will decrease with increasing age and that increased age and BMI are potential risk factors for SLN mapping failure. However, increased age and/or BMI alone do not appear to be contraindications for SLN biopsy in older or overweight patients.

Benign mechanical transport of breast epithelial cells to sentinel lymph nodes

The evaluation of sentinel lymph nodes (SLNs) for the presence of malignant epithelial cells is essential to the staging of breast cancer patients. Recently, increased attention has focused on the possibility that epithelial cells may reach SLNs by benign mechanical means, rather than by metastasis. The purpose of this study was to test the hypothesis that pre-SLN biopsy breast massage, which we currently use to facilitate the localization of SLNs, might represent a mode of benign mechanical transport. We studied 56 patients with invasive and/or in situ ductal carcinoma and axillary SLNs with only epithelial cells and/or cell clusters (≤0.2 mm in diameter and not associated with features of established metastases) detected predominantly in subcapsular sinuses of SLNs on hematoxylin and eosin- and/or anti-cytokeratin-stained sections. No patient had an SLN involved by either micro- or macro-metastatic carcinoma. Epithelial cells and cell clusters, ≤0.2 mm in size and without features of established metastases, occurred more frequently in the SLNs of patients who underwent pre-SLN biopsy breast massage (P < 0.001, χ2 test). The latter finding supports the hypothesis that pre-SLN biopsy breast massage is a mode of benign mechanical transport of epithelial cells to SLNs.

Pregnancy-Associated Breast Cancer Patients Can Safely Undergo Lymphatic Mapping

Abstract:  As more women put off pregnancy until their 30s and beyond, the possibility of pregnancy‐associated breast cancer (PABC) will rise. Treatment options for patients with PABC need to consider possible harm to the fetus. The goal of this study is to review our institution’s experience with sentinel lymph node (SLN) biopsies in patients with PABC. A prospectively accrued breast Institutional Review Board (IRB) approved data base was searched under separate IRB approval for cases of SLN biopsy in patients with PABC. Ten patients were identified between 1994 and 2006 out of 5,563 patients. A chart review was performed on all 10 patients. Ten patients with PABC and an average gestation age of 15.8 weeks underwent SLN biopsy. All patients successfully mapped. Positive SLN were identified in 5/10 patients (50%) while there was no evidence of metastases in 5/10 patients (50%). 9/10 (90%) of patients went on to deliver healthy children without any reported problems. One patient (10%) decided to terminate her pregnancy in the first trimester following surgery prior to the start of chemotherapy. SLN biopsy can safely be performed in patients with PABC with minimal risk to the fetus. By performing a SLN biopsy, a large proportion of patients with PABC may be spared the risk of a complete axillary lymph node dissection.

Sentinel node biopsy before neoadjuvant chemotherapy for determining axillary status and treatment prognosis in locally advanced breast cancer

BackgroundTreatment of locally advanced breast cancer with neoadjuvant chemotherapy assesses an in vivo tumor response while increasing breast conservation. Axillary clearance of nodal disease after treatment defines prognostic stratification. Our study objective was to show that sentinel node staging before treatment can optimize posttreatment prognostic stratification in clinically N0 patients.MethodsEighty-nine patients with locally advanced breast cancer were treated with neoadjuvant chemotherapy. Of these, 42 (47%) clinically palpable or image-detected nodes (cN+) were histologically confirmed before treatment (group 1), and 47 (53%) patients without palpable lymph nodes (cN0) had a sentinel lymph node (SLN) biopsy before treatment (group 2). Survival analysis was conducted with the Kaplan-Meier method.ResultsIn groups 1 and 2, 82 (92%) of 89 patients had node-positive disease before treatment. Seven (8%) of 89 had negative SLNs and no completion axillary lymph node dissection, 24 (27%) patients had a complete pathologic axillary response (pCRAX; 11 [26%] of 42 in group 1 and 13 [33%] of 40 in group 2), and 58 (65%) of 89 had residual disease in the axilla. Breast-conserving therapy was applied to 27 (30%) of 89 patients. The seven SLN-negative patients had no axillary recurrence at 25 months, and pCRAX patients had a significantly higher overall survival than patients with residual disease.ConclusionsThis study validates the prognostic stratification of patients with a complete pathologic axillary response to neoadjuvant chemotherapy. The addition of SLN biopsy to cN0 patients before treatment increased accurate nodal staging by 53%, eliminated completion axillary lymph node dissection in 15%, and demonstrated an improved prognosis in 28% of pCRAX patients. SLN biopsy before treatment provides accurate staging of cN0 patients; allows acquisition of standard treatment markers, prognostic biomarkers, and microarray analysis; and affords prognostic stratification after treatment.

Completion axillary lymph node dissection minimizes the likelihood of false negatives for patients with invasive breast carcinoma and cytokeratin positive only sentinel lymph nodes

OBJECTIVE To document the incidence of metastatic disease in complete axillary lymph node dissections (CALND) of patients with invasive carcinoma after a sentinel lymph node (SLN) biopsy, positive only by immunohistochemical staining for cytokeratin (CK-IHC). METHODS Sections of all SLNs, negative by routine histology, were immunostained and examined for cytokeratin positive cells. Sections of lymph nodes from CALND specimens were interpreted using routine hematoxylin and eosin (H&E) staining. RESULTS A total of 409 patients (29.6%) had metastatic disease in at least one sentinel lymph node on H&E examination. Of 971 H&E negative patients, 78 (8.0%) were positive only by CK-IHC. Sixty-two of the CK-IHC positive only patients underwent CALND. Nine of these 62 patients (14.5%) had metastases identified in the CALND specimen. CONCLUSIONS Because 14.5% of patients with invasive breast cancer and SLNs positive only by CK-IHC were found to have H&E positive lymph nodes on CALND, we conclude first, that CK-IHC should be used to evaluate SLNs, and second, that CALND should be considered when SLNs are positive by CK-IHC only. This approach will result in an absolute reduction of the false negative rate (absolute false negative rate reduced by 2.6% in our series).

Use of Reoperative Sentinel Lymph Node Biopsy in Breast Cancer Patients

BACKGROUND Ipsilateral breast recurrence or second primary breast cancer can develop in patients who have undergone breast conservation and sentinel lymph node biopsy (SLNB). This brings into question the necessity of complete axillary lymph node dissection (CALND) versus a second SLNB (remapping). Our objective is to determine the feasibility of a reoperative SLNB. STUDY DESIGN A review of patients receiving a reoperative SLNB between April 1994 and December 2006 was conducted with IRB approval. Fifty-six patients underwent a second SLNB on the ipsilateral side an average of 42.5 months after their first SLNB. RESULTS Sentinel lymph nodes were successfully remapped in 45 of 56 (80.4%) patients. Of 45 patients successfully remapped, 36 (80%) were node negative and were spared CALND. There was only 1 patient (2.2%) in whom a sentinel lymph node was identified outside of the ipsilateral axilla. At 26 months mean followup for the second SLNB, there have been no axillary recurrences and 1 death. CONCLUSIONS Our findings demonstrate that remapping sentinel nodes in patients with ipsilateral recurrence or new primary breast cancer after SLNB achieved success in 80.4% of patients. Overall, 80.0% (36 of 45) of the successfully remapped patients were spared a CALND.

Clinical relevance of internal mammary node mapping as a guide to radiation therapy

BACKGROUND The surgical management of breast cancer has changed markedly with the development of lymphatic mapping and sentinel lymph node (SLN) biopsy. Lymphatic mapping technique varies with respect to injection method, mapping agent, and surgical technique. The decision to pursue the internal mammary nodes (IMN) is another source of controversy. METHODS From April 1998 to November 2000, 1,470 patients underwent lymphatic mapping for breast cancer and were prospectively entered into the breast database. The combined technique method was used, consisting of both isosulfan blue dye and technetium-99 labeled sulfur colloid. Patients with inner quadrant lesions and suspicion for internal mammary metastasis had preoperative lymphoscintigraphy. Those with internal mammary radioactivity noted by either lymphoscintigraphy or gamma probe underwent removal of the internal mammary sentinel nodes. RESULTS Thirty-six of the 1,470 (2.4%) patients mapped had at least 1 internal mammary lymph node removed. Inner quadrant lesions were present in 24 of the 36 (67%) IMN mapped patients. Of the 36 patients mapping to the IM area, 5 (14%) had at least 1 IM node positive. Two of the 5 (40%) had only IM metastasis, with 1 of these patients having 5 of 5 IMN positive and no disease detected in her axilla. A total of 2 of the 5 (40%) IM positive patients had more than 1 IMN positive. Twenty-eight of the 36 (78%) IM node harvested patients had preoperative lymphoscintigraphy, with 18 (64%) IMN appearing on imaging. Complications occurred in 3 of the 36 (8%) IMN mapped patients, without clinical significance. CONCLUSIONS Mapping to the IMN basin with the finding of metastasis results in N3 disease by the current staging system. The consequence for these patients is radiation therapy to the IMN basin. It is significant to note that 14% (5 of 36) were upstaged as result of IMN detection and 40% (2 of 5) had multiple positive IMNs. Substantial disease was detected in these 5 patients necessitating additional radiation therapy while avoiding IM radiation and its attendant complications in 86% of patients mapping to the IM basin.

Breast cancer in patients with prior augmentation: Presentation, stage, and lymphatic mapping

The purpose of this study was to determine whether breast cancer patients who had prior breast augmentation presented at a more advanced stage than nonaugmented breast cancer patients, and to determine the mode of presentation and effectiveness of lymphatic mapping and sentinel lymph node biopsy in this same group of patients. A total of 4186 breast cancer patients from 1987 to 2002 were reviewed. Patients who had augmentation before their diagnosis of breast cancer were compared with a control group of nonaugmented breast cancer patients. The Wilcoxon rank sum test was used to compare tumor size, node positivity, and stage. The patient’s age at presentation was also compared by the two-sided pooled t test. Seventy-six patients who previously underwent augmentation were identified with 78 breast cancers. Seventy percent (48 of 69) were initially detected by palpation, whereas 30 percent (21 of 69) were initially identified mammographically. Fifty-three percent (n = 41) underwent mastectomy and 47 percent (n = 37) underwent a lumpectomy. This compares with a 63.6 percent (2615 of 4110) breast conservation rate in the nonaugmented population during the same time period. The two groups did not differ regarding (tumor) size (p = 0.77), nodal positivity (p = 0.32), or stage (p = 0.34). The mean time between implant placement and a diagnosis of breast cancer was 14 years. The average age of the patients who had previously undergone augmentation at breast cancer diagnosis was 49.5 years (SD, 9.0 years) versus 57.1 years (SD, 13.5 years) for the nonaugmented patients (p < 0.0001). Forty-nine of the patients underwent lymphatic mapping, with a 100 percent success rate in identifying the sentinel lymph node. There have been no clinically detected axillary recurrences in the patients who had a negative sentinel lymph node biopsy. Breast cancer patients who have undergone previous augmentation are more likely to present with a palpable mass. This initial mode of detection does not appear to translate into a larger tumor size or worse prognosis. Breast conservation and lymphatic mapping can be performed successfully in previously augmented patients.

Survival Outcomes in Node-Negative Breast Cancer Patients Evaluated With Complete Axillary Node Dissection Versus Sentinel Lymph Node Biopsy

BackgroundSentinel lymph node (SLN) biopsy combined with microstaging-associated immunohistochemical staining for cytokeratin more accurately assigns patients to their corresponding diagnostic stage. The purpose of this study was to compare the survival outcomes of node-negative patients who received an SLN biopsy with historical control data of node-negative patients who received routine complete axillary lymph node dissection (CALND) in the pre-SLN biopsy era.MethodsUnder institutional review board approval, 2458 node-negative invasive breast cancer patients between the ages of 25 and 94 years (mean, 60 years) were treated at our institution from January 1986 to May 2004. Of these 2458 patients, 604 (25%) were evaluated with CALND, whereas 1854 (75%) were evaluated with SLN biopsy. All were treated according to the current stage-specific guidelines. Kaplan-Meier graphs of overall survival and disease-free survival were constructed for each group of patients, and the two groups were compared by using the log-rank test.ResultsOverall survival and disease-free survival for the CALND and SLN biopsy groups did not differ significantly (P = .98). The average number of lymph nodes extracted in the pre-SLN biopsy group was 18, whereas the average number of SLNs extracted in the post-SLN biopsy group was 3.ConclusionsThe survival rate among node-negative breast cancer patients who received an SLN biopsy alone has proven to have no significant difference (P = .98) from the survival rate among node-negative patients who received a CALND. SLN biopsy alone should replace CALND as the primary tool for axillary staging of breast cancer in node-negative patients.