99mTc-labelled SM3 in the preoperative evaluation of axillary lymph nodes and primary breast cancer with change detection statistical processing as an aid to tumour detection.

The extent of primary surgery for breast cancer could be tailored to the patient if previous information on the presence or absence of lymph node involvement could be reliably determined. Prospective radioimmunoscintigraphy in 29 patients with primary breast cancer that was found on screening has been undertaken with 555 MBq (15 mCi) 99mTc SM3, an Imperial Cancer Research Fund (ICRF) murine monoclonal antibody, 0.5 mg with images at 10 min and 22 h, and analysis using a change detection algorithm. Sites of significant change between the early and later images were displayed as a map of probabilities. Image-positive and -negative axillary lymph nodes were compared by histology in the 28 evaluable patients. The correct identification of the presence or absence of node involvement, even if impalpable, has been shown in 24 out of 28 patients (29 lymph node groups). Sensitivity was 90% (nine out of ten), specificity 84% (16 out of 19) and accuracy 86%. These results encourage further assessment of this technique.     

Sentinel lymph node concept in patients with esophageal cancer

It is not uncommon that first lymph node involvement appears at a distant lymph node not at a nearest node from the primary lesion in patients with esophageal cancer. Identification of the sentinel node, which permits the detection of the first draining node from a primary lesion, is expected to individualize the treatment of esophageal cancer. From our study in 23 patients with esophageal cancer using Tc-99 m tin colloids, the sentinel node concept seemed to be applicable to patients with esophageal cancer (-pT2). However, injection techniques and intraoperative probe searching for hot nodes are more difficult and uncertain in esophageal cancer compared to superficial cancers such as breast cancer and malignant melanoma. Further studies are necessary to reliably apply the sentinel node biopsy technique to patients with esophageal cancer.     

Predicting axillary lymph node metastases in breast cancer patients with tumors under 2 cm in size

Background  To assess whether lymph nodes are consistently negative below a certain tumor size, we investigated the incidence and predictors of lymph node metastasis in breast cancer patients with tumors under 2 cm in size. Methods  A total of 238 breast cancer patients with tumors under 2 cm in size were retrospectively reviewed. Results  Preoperatively, 219 tumors were palpable while 19 were not. There was no lymph node metastasis in the nonpalpable tumors (n=19) or those 5 mm or less in size (n=1) tumors, but 17% of those greater than 5 mm but less than 10 mm (n=30) and 29% of those greater than 10 mm but 20 mm or less (n=188) tumors had nodal involvement. Conclusions  Our sample size was too small to determine a specific tumor size that would warrant omission of axillary lymph node dissection. However, axillary lymph node dissection may be avoided in breast cancer patients with clinically nonpalpable tumors.     

Sentinel lymph node biopsy and axillary dissection in breast cancer: results in a large series

BACKGROUND: Axillary lymph node dissection is an established component of the surgical treatment of breast cancer, and is an important procedure in cancer staging; however, it is associated with unpleasant side effects. We have investigated a radioactive tracer-guided procedure that facilitates identification, removal, and pathologic examination of the sentinel lymph node (i.e., the lymph node first receiving lymphatic fluid from the area of the breast containing the tumor) to predict the status of the axilla and to assess the safety of foregoing axillary dissection if the sentinel lymph node shows no involvement. METHODS: We injected 5-10 MBq of 99mTc-labeled colloidal particles of human albumin peritumorally in 376 consecutive patients with breast cancer who were enrolled at the European Institute of Oncology during the period from March 1996 through March 1998. The sentinel lymph node in each case was visualized by lymphoscintigraphy, and its general location was marked on the overlying skin. During breast surgery, the sentinel lymph node was identified for removal by monitoring the acoustic signal from a hand-held gamma ray-detecting probe. Total axillary dissection was then carried out. The pathologic status of the sentinel lymph node was compared with that of the whole axilla. RESULTS: The sentinel lymph node was identified in 371 (98.7%) of the 376 patients and accurately predicted the state of the axilla in 359 (95.5%) of the patients, with 12 false-negative findings (6.7%; 95% confidence interval = 3.5%-11.4%) among a total of 180 patients with positive axillary lymph nodes. CONCLUSIONS: Sentinel lymph node biopsy using a gamma ray-detecting probe allows staging of the axilla with high accuracy in patients with primary breast cancer. A randomized trial is necessary to determine whether axillary dissection may be avoided in those patients with an uninvolved sentinel lymph node.     

Clinicopathologic Features Predicting Involvement of Nonsentinel Axillary Lymph Nodes in Iranian Women with Breast Cancer

Background: Almost half of the breast cancer patients with positive sentinel lymph nodes have no additional disease in the remaining axillary lymph nodes. This group of patients do not benefit from complete axillary lymph node dissection. This study was designed to assess the clinicopathologic factors that predict non-sentinel lymph node metastasis in Iranian breast cancer patients with positive sentinel lymph nodes. Materials and Methods: The records of patients who underwent sentinel lymph node biopsy, between 2003 and 2012, were reviewed. Patients with at least one positive sentinel lymph node who underwent completion axillary lymph node dissection were enrolled in the present study. Demographic and clinicopathologic characteristics including age, primary tumor size, histological and nuclear grade, lymphovascular invasion, perineural invasion, extracapsular invasion, and number of harvested lymph nodes, were evaluated. Results: The data of 167 patients were analyzed. A total of 92 (55.1%) had non-sentinel lymph node metastasis. Univariate analysis of data revealed that age, primary tumor size, histological grade, lymphovascular invasion, perineural invasion, extracapsular invasion, and the number of positive sentinel lymph nodes to the total number of harvested sentinel lymph nodes ratio, wereassociated with non-sentinel lymph node metastasis. After logistic regression analysis, age (OR=0.13; 95% CI, 0.02-0.8), primary tumor size (OR=7.7; 95% CI, 1.4-42.2), lymphovascular invasion (OR=19.4; 95% CI, 1.4-268.6), extracapsular invasion (OR=13.3; 95% CI, 2.3-76), and the number of positive sentinel lymph nodes to the total number of harvested sentinel lymph nodes ratio (OR=20.2; 95% CI, 3.4-121.9), were significantly associated with non-sentinel lymph node metastasis. Conclusions: According to this study, age, primary tumor size, lymphovascular invasion, extracapsular invasion, and the ratio of positive sentinel lymph nodes to the total number of harvested sentinel lymph nodes, were found to be independent predictors of non-sentinel lymph node metastasis.     

Detection of extra-axillary lymph node involvement with FDG PET/CT in patients with stage II–III breast cancer

PurposeThe aim of this prospective study was to assess the incidence of extra-axillary lymph node involvement on baseline FDG PET/CT in patients with stage II–III breast cancer scheduled for neo-adjuvant chemotherapy.MethodsPatients with invasive breast cancer of >3 cm and/or proven axillary lymph node metastasis were included for before neo-adjuvant chemotherapy. Baseline ultrasound of the infra- and supraclavicular regions was performed with fine-needle biopsy as needed. Subsequently FDG PET/CT was performed. All visually FDG-positive nodes were regarded as metastatic based on the previously reported high specificity of the technique.ResultsSixty patients were included. In 17 patients (28%) extra-axillary lymph nodes were detected by FDG PET/CT, localised in an intra-mammary node (1 lymph node in 1 patient), mediastinal (2 lymph nodes in 2 patients), internal mammary chain (9 lymph nodes in 8 patients), intra- and interpectoral (6 lymph nodes in 4 patients), infraclavicular (5 lymph nodes in 4 patients) and in the contralateral axilla (3 lymph nodes in 2 patients). Ultrasound-guided cytology had detected extra-axillary lymph node involvement in seven of these patients, but was unable to detect extra-axillary nodes in the other 10 patients with positive extra-axillary lymph nodes on FDG PET/CT. Radiotherapy treatment was altered in 7 patients with extra-axillary involvement (12% of the total group).ConclusionsFDG PET/CT detected extra-axillary lymph node involvement in almost one-third of the patients with stage II–III breast cancer, including regions not evaluable with ultrasound. FDG PET/CT may be useful as an additional imaging tool to assess extra-axillary lymph node metastasis, with an impact on the adjuvant radiotherapy management.     

Predictors of positive axillary lymph nodes in breast cancer patients with metastatic sentinel lymph node

INTRODUCTION: Breast cancer with metastatic sentinel lymph nodes (SLN) may have clinico-pathologic factors associated with the presence of positive non-sentinel axillary nodes (NSLN). The aim of the present study was to determine factors that predict involvement of NSLN in breast cancer patients with positive SLN. MATERIAL AND METHODS: A prospective database search identified 80 patients who underwent SLN biopsy for invasive breast cancer between January 1999 and August 2002. Clinico-pathologic data was analyzed to determine factors that predicted additional positive axillary nodes. RESULTS: A total of 23 patients had positive SLN and underwent conventional axillary lymph node dissection. Statistical analysis revealed that lympho-vascular invasion (p~0.00000), SLN metastasis >2 mm (p=0.002), and the presence of extra-nodal involvement (p=0.002), were positive predictors of the metastatic involvement of NSLN. CONCLUSIONS: The likelihood of positive NSLN correlates with pathologic parameters such as the presence of lympho-vascular invasion, size of the SLN metastasis, and extra-nodal involvement. These data may be helpful with the regard to the decision to undertake axillary dissection in breast cancer patients with metastatic sentinel lymph nodes.     

Carcinoembryonic antigen expression and patient survival in carcinoma of the breast

Immunoperoxidase staining was used to examine carcinoembryonic antigen (CEA) expression in 167 breast cancer cases. Patients with histological evidence of regional or localized breast cancer who lived less than 3 years or greater than 10 years were assessed. Overall expression of CEA was 65%. There was no significant correlation in CEA expression and survival in either regional or localized breast cancer cases. There was no association between CEA expression and number of lymph nodes involved, size of tumor, parity, gravidity, blood type, or menopausal status of the patients in either group. When the lymph nodes of cases with regional breast cancer were examined, there was a statistically significant number of short survivors whose primary tumor was negative for CEA, but whose metastatic tumor expressed the marker when compared to long survivors with regional lymph node involvement.     

Additional axillary metastases and stage migration in breast cancer patients with micrometastases or submicrometastases in sentinel lymph nodes

BACKGROUND: In patients with breast cancer, micrometastases and submicrometastases are increasingly found in sentinel nodes when step sectioning and/or immunohistochemical staining are applied. The aims of the current study were to investigate the incidence of micro- and submicrometastases in the sentinel node, to estimate the risk of additional metastases in the remaining axillary lymph nodes, and to consider implications for staging and treatment. METHODS: A total of 2150 breast cancer patients who had undergone axillary sentinel node biopsy between 1999 and 2004 were retrospectively evaluated. RESULTS: In all, 649 patients (30%) had a tumor-positive axillary sentinel node. Of these 649 patients, 148 had (23%) micrometastases and 105 (16%) submicrometastases. Of the 148 patients with micrometastases, 106 underwent axillary lymph node dissection (ALND) and additional metastases were found in 20 patients (19%). Sixteen (15%) had macrometastases and were upstaged. The other 4 patients had additional micrometastases. Seven of the 106 patients (7%) received additional systemic treatment based on the findings in the axillary lymph nodes. Fifty-four of the 105 patients with submicrometastases underwent ALND. Two (4%) of them had additional macrometastases and were upstaged and 2 had additional micrometastases. None received additional treatment based on the ALND findings. CONCLUSIONS: Of the involved sentinel nodes, 23% contained micrometastases and 16% submicrometastases. Additional macrometastases were found in 15% and 4%, respectively, and treatment was altered in 7%. Based on these findings, offering additional treatment of the axilla is suggested in patients with micrometastases, but refraining from ALND in patients with submicrometastases in their sentinel node.     

乳腺癌腋淋巴结微小转移与癌组织c-erbB-2、nm23基因表达关系的研究

目的 探讨乳腺癌腋淋巴结微小转移与c-erbB-2、nm23基因表达的关系。方法 采用免疫组织化学S-P法对70例淋巴结常规HE染色无癌转移的乳腺癌腋淋巴结1141枚进行上皮细胞角蛋白19（CK-19）表达和原发癌组织进行c-erbB-2、nm23基因表达的检测。结果 淋巴结CK-19阳性率为4.21%（48/1141）,其病例阳性率为27.14%（19/70）。c-erbB-2阳性率为44.29%（31/70）,nm23阳性率为80.00%（56/70）.CK-19阳性组的c-erbB-2阳性率明显高于CK-19阴性组﹙P＜0.05﹚,CK-19阳性组的nm23阳性率明显低于CK-19阴性组﹙P＜0.05﹚。CK-19阳性率与病人月经状况、病理类型、临床分期、激素受体状况无关（P＞0.05）。结论 乳腺癌腋淋巴结CK-19表达与癌组织c-erbB-2基因表达呈正相关,与癌组织nm23基因表达呈负相关,与病人月经状况、临床分期、病理类型、激素受体状况无关。     

Sentinel node biopsy in breast cancer: the experience of Brescia Civic Hospital

The accuracy of the sentinel node technique in the evaluation of axillary node involvement in breast cancer was evaluated in 83 consecutive patients with monofocal T1-2 carcinoma, who were clinically N0 and who underwent lymphoscintigraphy with 99mTc-colloid integrated with intraoperative sentinel node detection by a portable probe. Lymphoscintigraphy revealed at least one sentinel node in 75 patients (90.4%), always identified by the probe. In eight patients (9.6%) the sentinel node was detected neither by lymphoscintigraphy nor by the probe. All removed lymph nodes were analyzed by hematoxylin-eosin histology and the sentinel node by immunostaining. In 28/75 patients (37.3%) at least one metastatic axillary lymph node was detected; in 16 of the 28 N+ subjects (57%) only the sentinel node was positive. The false negative rate (sentinel node negative/other axillary lymph nodes positive) was 17.85% (5/28 patients). In 9/23 patients (39%) micrometastases were found in the sentinel node only. In conclusion, specific sentinel node positivity in 57% of cases supports the validity of the sentinel node concept. Moreover, nine patients would have been considered N0 by standard hematoxylin-eosin histology without sentinel node-aided immunostaining. A 17.8% false negative rate calls for caution in patients with negative sentinel nodes.     

Radiotherapy of MRI-detected involved internal mammary lymph nodes in breast cancer

Background

The internal mammary (IM) lymph node chain, along with the axillary nodal basin, is a first-echelon breast lymphatic draining site. A growing body of evidence supports irradiation of this region in node-positive breast cancer. This study evaluated the effectiveness of radiotherapy in treating magnetic resonance imaging (MRI)-detected abnormal IM lymph nodes in newly-diagnosed non-metastatic breast cancer.

Methods

A structured query was performed on an electronic institutional database to identify women with radiographic evidence of abnormal IM node(s) on breast MRI from 2005 to 2013. Manual review narrowed inclusion to patients with a primary diagnosis of non-metastatic breast cancer with abnormal IM node(s) based on pathologic size criteria and/or abnormal enhancement.

Results

Of the 7070 women who underwent pre-treatment MRI, 19 (0.3%) were identified on imaging to have a total of 25 abnormal pre-treatment IM lymph nodes, of which 96% were located in the first two intercostal spaces and 4% in the third space. A majority of the primary tumors were high-grade (94.7%) and hormone-receptor negative (73.7%), while 47.4% overexpressed HER-2/neu receptor. Axillary nodal disease was present in 89.5% of patients, while one patient had supraclavicular involvement. At a median follow-up of 38 months, 31.6% of patients had developed metastatic disease and 21.1% had died from their disease. Of the patients who received IM coverage, none had progressive disease within the IM lymph node chain.

Conclusions

Radiologic evidence of pre-treatment abnormal IM chain lymph nodes was associated with advanced stage, high grade, and negative estrogen receptor status. The majority of positive lymph nodes were located within the first two intercostal spaces, while none were below the third. Radiation of the IM chain in combination with modern systemic therapy was effective in achieving locoregional control without surgical resection in this cohort of patients.

     

Expression of the breast cancer metastasis suppressor gene, BRMS1, in human breast carcinoma: lack of correlation with metastasis to axillary lymph nodes.

The BRMS1 (breast cancer metastasis suppressor 1) gene has been found to suppress metastasis in animal models without inhibiting primary tumor growth. The aim of this study was to measure expression of BRMS1 mRNA in a panel of human breast carcinomas and compare its expression with parameters of local dissemination such as tumor size and lymph node metastasis. We also compared expression of BRMS1 mRNA in normal breast tissue, fibroadenomas, primary breast cancers and axillary nodal metastases from primary breast cancers. BRMS1 mRNA was detected in 10/11 (90%) specimens of normal breast tissue, 12/16 (75%) fibroadenomas, 64/82 (78%) primary breast cancer and 11/15 (64%) lymph node metastases (p, NS). In the primary cancer, expression was independent of tumor size, tumor grade, metastasis to axillary nodes and hormone receptor status. Furthermore, similar levels of BRMS1 were found in normal breast tissue, primary breast carcinomas and lymph node metastases from primary breast cancer. Our results do not suggest a role for BRMS1 in suppressing metastasis to local lymph nodes in patients with breast cancer.     

The “Sentinel Chain”: a new concept for prediction of axillary node status in breast cancer patients

SummaryBackground and objectives More than half the breast cancer patients with positive sentinel lymph nodes (SLN) do not harbor additional metastases in non-sentinel nodes (NSN). The aim of this study was to identify a subgroup of patients with positive SLNs and negative NSNs, on the basis of tumor involvement patterns in multiple radioactive nodes.Methods Between 2000 and 2004, 290 patients with primary invasive breast cancer and clinically negative axillary nodes had a SLN biopsy in our breast unit. Radiotracer was identified intraoperatively in the axilla. All radioactive nodes were removed and radioactivity was measured in each node extracorporeally. Nodes were ranked according to radioactivity, constituting a “Sentinel Chain”, and the histopathological status of each node was reported. The different metastatic involvement patterns of the Sentinel Chain were correlated with the metastatic status of the NSNs after axillary dissection. Information was charted in a prospective database.Results Of 290 patients, 216 (74.5%) had multiple radioactive nodes. Ninety patients (31%) had SLN metastases. Fifty patients had multiple ranked radioactive nodes and positive SLNs. Twenty-five of these patients had a sequential involvement pattern, with tumor-bearing high radioactivity nodes, and uninvolved low-radioactivity nodes. In the 23 of these 25 patients who had axillary dissection, NSN involvement was detected in only one patient (4.3%), whereas in 24 patients with other involvement patterns of the Sentinel Chain, NSN involvement reached 54.2% (p<0.001).Conclusion Tumor-free status of NSN may be predicted using the Sentinel Chain concept in some breast cancer patients with positive SLNs.     

Incidence and prognostic significance of complete axillary downstaging after primary chemotherapy in breast cancer patients with T1 to T3 tumors and cytologically proven axillary metastatic lymph nodes.

PURPOSE: To determine the incidence and prognostic significance of eradication of cytologically proven axillary lymph node metastases in breast cancer patients treated with primary chemotherapy. PATIENTS AND METHODS: Between January 1985 and December 1994, 152 breast cancer patients with invasive T1 to T3 tumors and axillary metastases cytologically proven by fine-needle sampling underwent primary chemotherapy followed by lumpectomy or mastectomy, level I and II axillary lymph node dissection, and irradiation. We studied pathologic complete responses (pCRs) of axillary nodes and breast tumors, as well as predictors of distant metastases. RESULTS: Thirty-five patients (23%) had axillary pCRs, and 20 patients (13.2%) had pCRs of primary breast tumors. Scarff-Bloom-Richardson grade 3 tumors (P =.04) and a clinical response to chemotherapy > or = 50% (P =.003) were associated with negative axillary status at dissection. An initial tumor size < or = 3 cm (63 patients) was associated with pCR of the primary tumor (P =.02) but not with complete histologic clearance of axillary lymph nodes. The median length of follow-up was 75 months. In the univariate analysis, age greater than 40 years (P =.003), absence of residual nodal disease (P =.01), and pCR of the tumor (P =.05) were associated with better distant disease-free survival. Five-year distant disease-free survival rates were 73.5% +/- 14.9% among patients with no involved nodes at the time of surgery and 48.7% +/- 9.2% among patients with residual nodal disease. In the multivariate Cox regression analysis, parameters associated with poor distant disease-free survival were age < or = 40 years (P =.002), persistence of nodal involvement (P =.03), and S-phase fraction greater than 4% (P =.02). CONCLUSION: Our results suggest that axillary status is a better prognostic factor than response of the primary tumor to primary chemotherapy.