The role for sentinel lymph node dissection after neoadjuvant chemotherapy in patients who present with node-positive breast cancer.

BACKGROUND: Sentinel lymph node (SLN) dissection has been investigated after neoadjuvant chemotherapy and has shown mixed results. Our objective was to evaluate SLN dissection in node-positive patients and to determine whether postchemotherapy ultrasound could select patients for this technique. METHODS: Between 1994 and 2010, 150 patients with biopsy proven axillary metastasis underwent SLN dissection after chemotherapy and 121 underwent axillary lymph node dissection (ALND). Clinicopathologic characteristics were analyzed before and after chemotherapy. Statistical analyses included Fisher's exact test for nodal response and multivariate logistic regression for factors associated with false-negative events. RESULTS: Median age was 52 years. Median tumor size at presentation was 2 cm. The SLN was identified in 93 % (139/150). In 111 patients in whom a SLN was identified and ALND performed, 15 patients had a false-negative SLN (20.8 %). In the 52 patients with normalized nodes on ultrasound, the false-negative rate decreased to 16.1 %. Multivariate analysis revealed smaller initial tumor size and fewer SLNs removed (<2) were associated with a false-negative SLN. There were 63 (42 %) patients with a pathologic complete response (pCR) in the nodes. Of those with normalized nodes on ultrasound, 38 (51 %) of 75 had a pCR. Only 25 (33 %) of 75 with persistent suspicious/malignant-appearing nodes had a pCR (p = 0.047). CONCLUSIONS: Approximately 42 % of patients have a pCR in the nodes after chemotherapy. Normalized morphology on ultrasound correlates with a higher pCR rate. SLN dissection in these patients is associated with a false-negative rate of 20.8 %. Removing fewer than two SLNs is associated with a higher false-negative rate.

How many sentinel lymph nodes are enough during sentinel lymph node dissection for breast cancer?

BACKGROUND: : It remains unclear how many sentinel lymph nodes (SLNs) must be removed to accurately predict lymph node status during SLN dissection in breast cancer. The objective of this study was to determine how many SLNs need to be removed for accurate lymph node staging and which patient and tumor characteristics influence this number. METHODS: : The authors reviewed data for all patients in their prospective database with clinical tumor, lymph node, metastasis (TNM) T1 through T3, N0, M0 breast cancer who underwent lymphatic mapping at their institution during the years 1994 through 2006. There were 777 patients who had at least 1 SLN that was positive for cancer. Simple and multiple quantile regression analyses were used to determine which patient and tumor characteristics were associated with the number of positive SLNs. The baseline number of SLNs that needed to be dissected for detection of 99% of positive SLNs in the total group of patients also was determined. RESULTS: : The mean number of SLNs removed in the 777 lymph node-positive patients was 2.9 (range, 1-13 SLNs). Greater than 99% of positive SLNs were identified in the first 5 lymph nodes removed. On univariate analysis, tumor histology, patient race, tumor location, and tumor size significantly affected the number of SLNs that needed to be removed to identify 99% of all positive SLNs. On multivariate analysis, mixed ductal and lobular histology, Caucasian race, inner quadrant tumor location, and T1 tumor classification significantly increased the number of SLNs that needed to be removed to achieve 99% recovery of all positive SLNs. CONCLUSIONS: : In general, the removal of a maximum of 5 SLNs at surgery allowed for the recovery of >99% of positive SLNs in patients with breast cancer. The current findings indicated that tumor histology, patient race, and tumor size and location may influence this number.

Long-term outcomes in patients with mucinous, medullary, tubular, and invasive ductal carcinomas after lumpectomy.

BACKGROUND: Mucinous, medullary, and tubular carcinomas are uncommon types of breast cancer whose rarity does not permit large single-institution studies or randomized trials to define optimal treatments. In this study, we evaluated the long-term outcomes of breast-conserving therapy (BCT) for these subtypes of breast cancer and compared them with those for invasive ductal carcinoma. METHODS: In our institutional database of patients who received BCT from 1965 to 1999, 1,643 patients with stage I to II mucinous (61), medullary (37), tubular (60), and invasive ductal (1,485) histologies were identified. The clinical and pathologic features of the 4 groups were evaluated and compared with respect to local-regional recurrence rates, disease-free survival, and overall survival (OS). RESULTS: No statistically significant differences were found in the local-regional failure rate among the 4 groups (10.6-year median follow-up). Only patients with tubular carcinoma had better 5- and 10-year OS rates (P = .013). In multivariable analysis, factors associated with improved OS included age at or below 50 years, negative nodal status, use of chemotherapy or hormonal therapy, and tubular histology. CONCLUSIONS: BCT for mucinous, medullary, or tubular carcinoma resulted in similar local-regional failure rates to that for invasive ductal carcinoma. Tubular carcinoma patients had the most favorable OS. BCT is an appropriate treatment strategy for early-stage mucinous, medullary, and tubular carcinomas.

Comparative analysis of sentinel lymph node operation in male and female breast cancer patients.

BACKGROUND: Male breast cancer accounts for < 1% of breast cancers. Sentinel lymph node (SLN) operation is commonly used in the evaluation of female breast cancer patients. The purpose of this study was to determine whether SLN operation is as feasible and accurate in male patients compared with female patients. STUDY DESIGN: Between 1999 and 2005, 30 men and 2,784 women underwent SLN operation. Clinical and pathologic data were reviewed and statistical analysis performed. RESULTS: Men presented at an older age (p = 0.005) and with larger tumors than women (p = 0.04). The SLN was identified in 100% of men and in 98.3% of women (p = NS). The mean number of SLNs harvested was 3.5 in men and 3.0 in women (p = NS). The incidence of positive SLNs was higher in men (37.0% versus 22.3%), although this did not reach statistical significance (p = 0.1). In patients with a positive SLN there were additional non-SLNs positive in 62.5% of men, compared with 20.7% in women (p = 0.01). The median size of the largest lymph node metastasis was 10 mm in men and 3 mm in women (p = 0.03). CONCLUSIONS: SLN operation in clinically node-negative men is feasible and accurate. Male breast cancer patients present at an older age and with larger tumors than female breast cancer patients. Male patients have higher nodal tumor burden reflected in a larger size of nodal metastasis and increased risk of harboring additional disease in axillary lymph nodes when the SLN is positive. Intraoperative SLN evaluation should be considered in the surgical management of male breast cancer.

Use of lymphoscintigraphy defines lymphatic drainage patterns before sentinel lymph node biopsy for breast cancer.

BACKGROUND: Lymphoscintigraphy (LSG) can identify lymphatic drainage patterns before sentinel lymph node (SLN) biopsy is performed in patients with early-stage breast cancer, but the importance of extraaxillary SLNs seen on LSG is unknown. We assessed whether drainage patterns seen on LSG were associated with histologic findings in axillary SLNs recovered at SLN biopsy. STUDY DESIGN: From a prospectively maintained database, we identified 1,201 clinically node-negative patients with invasive breast cancer who underwent preoperative LSG and axillary SLN biopsy. Patient and tumor characteristics, LSG results, and final SLN pathology results were examined. RESULTS: LSG showed drainage to internal mammary (IM) nodes in 1.6% of patients, axillary nodes in 68.1%, both IM and axillary nodes in 19.8%, and no drainage in 10.3%. Drainage to IM nodes was observed for tumors in all quadrants of the breast. Patients with IM drainage had a younger median age than patients without IM drainage (51.8 versus 58.3 years, respectively; p < 0.001). The intraoperative axillary SLN identification rate was higher when axillary drainage was observed on LSG than when it was not observed (98.7% versus 93.0%, respectively; p < 0.001), but the LSG drainage pattern was not associated with pathologic status of the SLN or number of metastatic SLNs. At a median followup of 32 months, 4 patients had regional nodal recurrence. CONCLUSIONS: Almost one-fourth of patients had lymphatic drainage to the extraaxillary lymph nodes, particularly the IM nodes, seen on LSG. Extraaxillary drainage seen on LSG did not preclude identification of axillary SLNs at operation. Longterm followup of patients with lymphoscintigraphic evidence of extraaxillary drainage is needed to determine whether regional and systemic recurrence patterns differ in these patients.

Incidence of anaphylactoid reactions to isosulfan blue dye during breast carcinoma lymphatic mapping in patients treated with preoperative prophylaxis: results of a surgical prospective clinical practice protocol.

BACKGROUND: Severe anaphylactoid reactions to isosulfan blue dye requiring resuscitation are reported to occur in 1.1% of patients with breast carcinoma undergoing sentinel lymphadenectomy. In December 2001, the authors began administering a prophylactic regimen before dye injection to determine whether prophylaxis reduced the incidence of life-threatening reactions. METHODS: All patients were mapped with technetium-99m-labeled sulfur colloid. Those also receiving isosulfan blue dye were administered a glucocorticoid, diphenhydramine, and famotidine intravenously just before or at induction of anesthesia. Adverse reactions at the time of surgery were analyzed. RESULTS: Between December 2001 and July 2003, 1013 consecutive patients underwent sentinel lymphadenectomy for breast carcinoma. Six hundred sixty-seven patients (65.8%) received prophylaxis and isosulfan blue dye, 33 (3.3%) received prophylaxis but no dye, 12 (1.2%) received dye but no prophylaxis, and 301 (29.7%) received no prophylaxis or dye. Blue urticaria and facial edema were observed in 3 (0.5%) of 667 patients receiving prophylaxis and dye and in 1 (8.3%) of 12 patients receiving dye but no prophylaxis. There were no episodes of hypotension, and no patients required vasopressors, ventilatory support, or intensive care observation. Adverse reactions to agents other than blue dye were observed in 2 (0.3%) of 667 patients receiving prophylaxis and dye and in 3 (1.0%) of 301 receiving no prophylaxis and no dye (P = 0.1773). CONCLUSIONS: Preoperative prophylaxis was found to reduce the severity, but not the overall incidence, of adverse reactions to isosulfan blue dye. No life-threatening reactions were noted in patients treated with preoperative prophylaxis. Based on these results, the authors now routinely recommend administration of prophylaxis to patients receiving isosulfan blue for lymphatic mapping and sentinel lymph node biopsy.

Lower and central tumor location correlates with lymphoscintigraphy drainage to the internal mammary lymph nodes in breast carcinoma.

BACKGROUND: Radiation to the internal mammary chain (IMC) may be indicated for breast carcinoma patients with positive axillary sentinel lymph nodes (SLNs) and lymphoscintigraphic evidence of drainage to the IMC. The purpose of this study was to identify predictors of IMC drainage in patients with positive axillary SLNs. METHODS: The records of 297 breast carcinoma patients with positive axillary SLNs and preoperative lymphoscintigraphy were reviewed between 1995 and 2002. Radiolabeled colloid was injected peritumorally with lymphoscintigraphy performed 30-60 minutes later. Drainage to the regional nodes of 279 patients was seen on lymphoscintigraphy. Associations among patient and tumor-related factors and drainage to the IMC were examined. RESULTS: Drainage to the IMC on lymphoscintigraphy was seen in 63 patients (21%). IMC drainage only occurred in 4 patients, and 59 patients had both axillary and IMC drainage. The only variable that correlated with IMC drainage was tumor location (P = 0.017). Rates of drainage to the IMC were 14.1% for upper outer quadrant (n = 128), 16.7% for upper inner quadrant (n = 30), 31.6% for lower outer quadrant (n = 19), 42.9% for lower inner quadrant (n = 14), and 28.4% for central tumors (n = 88). IMC drainage rates differed significantly between upper and lower tumors (lower 36.4% vs. central 28.4% vs. upper 14.6%, P = 0.003) but not between medial and lateral tumors (medial 25.0% vs. central 28.4% vs. lateral 16.3%, P = 0.077). CONCLUSIONS: Patients with tumors in the lower or central breast and positive axillary SLNs have increased incidence of drainage to the IMC. Preoperative lymphoscintigraphy can help to define the nodal basins at risk for harboring disease.

Impact of clinicopathological factors on sensitivity of axillary ultrasonography in the detection of axillary nodal metastases in patients with breast cancer.

BACKGROUND: Ultrasonography and fine-needle aspiration (FNA) are used to evaluate the breast and regional nodes in breast cancer patients. We sought to identify factors influencing the sensitivity of ultrasonography for detection of nodal metastasis. METHODS: Patients with a clinically negative axilla who underwent axillary ultrasonography and sentinel lymph node biopsy were included. RESULTS: Of 208 patients, axillary ultrasonography was negative in 180 (86%) and suspicious or indeterminate in 28 (14%). FNA was performed in 22 patients whose findings were indeterminate or suspicious, and 3 were positive for malignancy. Final pathological examinations revealed positive nodes in 53 patients: 39 (22%) of 180 with negative ultrasonographic findings and 14 (50%) of 28 with indeterminate or suspicious ultrasonographic findings (P =.001). Excisional biopsy was more common for patients with indeterminate or suspicious findings on preoperative ultrasonography (P =.038). There were no significant differences in tumor size, histological features, size of nodal metastasis, or number of positive nodes between patients whose ultrasonography findings were negative and those whose findings were indeterminate or suspicious. CONCLUSIONS: Ultrasonographically suggested nodal metastasis is associated with the finding of nodal disease on final pathological examination. No significant clinicopathologic criteria were found to impact sensitivity of ultrasonography; however, excisional biopsy for diagnosis may be a confounding variable in subsequent axillary ultrasonography.

Clinicopathologic factors predicting involvement of nonsentinel axillary nodes in women with breast cancer.

BACKGROUND: It is unclear which breast cancer patients with positive sentinel lymph nodes (SLNs) require a completion axillary lymph node dissection. Our aim was to determine factors that predict involvement of nonsentinel axillary nodes (NSLNs) in patients with positive SLNs. METHODS: We reviewed the records of all patients with invasive breast cancer who underwent SLN biopsy at our institution between 1993 and August 2001. Multivariate analysis was used to identify clinicopathologic features in SLN-positive patients that predict involvement of NSLNs. RESULTS: A total of 131 patients had a positive SLN and underwent completion axillary lymph node dissection. Multivariate analysis revealed that primary tumor >2 cm (P =.009), SLN metastasis >2 mm (P =.024), and lymphovascular invasion (P =.028) were independent predictors of positive NSLNs. The number of SLNs harvested was a significant negative predictor (P =.04). In our model, based on the presence of these factors, the positive predictive value was 100% for a score of 4. CONCLUSIONS: The likelihood of positive NSLNs correlates with primary tumor size, size of the largest SLN metastasis, and presence of lymphovascular invasion. A scoring system incorporating these factors may help determine which patients would benefit from additional axillary surgery.