Frequency and Predictors of Axillary Lymph Node Metastases in Iranian Women with Early Breast Cancer

Background: Axillary lymph node metastasis is the most important predictive factor for recurrence risk andsurvival in patients with invasive breast carcinoma. The aim of this study was to determine factors associated withmetastatic involvement of axillary lymph nodes in Iranian women with early breast cancer. Methods: This article reportsa retrospective study of 774 patients with T1-T2 breast cancer who underwent resection of the primary tumor and axillarystaging by SLNB and/or ALND between 2005 and 2015 at our institution. Results: Of the 774 patients included in thisstudy, 35.5% (275 cases) had axillary lymph node involvement at the time of diagnosis. Factors associated with nodalinvolvement in univariate analyses were tumor size, lymphovascular invasion (LVI), tumor grade, ER/PR status andHER2 expression. All factors identified with univariate analyses were entered into a multivariate logistic regressionmodel and tumor size (OR= 3.01, CI 2.01–4.49, P <0.001), ER/PR positivity (OR = 1.74, CI 1.1.16–2.62, P = 0.007)and presence of LVI (OR = 3.3.8, CI 2.31–4.95, P <0.001) remained as independent predictors of axillary lymph nodeinvolvement .Conclusions: In conclusion, the results of this study suggests that positive hormonal receptor status, LVIand tumor size are predictive factors for ALNM in Iranian women with early breast cancer.     

Sentinel lymphadenectomy without systematic axillary dissection in breast cancer patients: predictors of non-sentinel lymph node metastasis.

AIMS: To identify factors predicting metastatic involvement of non sentinel axillary lymph nodes in breast cancer patients who underwent sentinel lymph node (SLN) biopsy followed by complete axillary dissection only in case of metastatic sentinel lymph node. METHODS: A prospective database including 165 breast cancer patients who underwent SLN biopsy without further complete axillary dissection in case of non-metastatic SLN was reviewed. Primary tumor size, pathologic grade, lymphatic invasion in the primary tumor, estrogen receptor status, tumor size in the SLN and number of metastatic SLNs were tested as possible predictors of metastatic involvement of non-SLN. RESULTS: The sentinel lymph node detection rate was 97% (160/165 patients). The mean number of SLNs per patient was 1.8 (range: 1-5). Fifty patients (31.3%) had a metastatic axillary SLN: 10 of the 42 patients with T1a or T1b breast tumors and 40 of the 118 patients with T1c< or = 15mm tumors. Fifteen of the 50 patients with metastatic SLN had metastatic non-SLN. Primary tumor size, tumor size in the SLN, pathologic grade, estrogen receptor status and age were not significantly associated with metastatic involvement of non-SLN. Number of metastatic SLNs fell short of reaching statistical significance (P: NS). Lymphatic invasion in the primary tumor was the only factor significantly associated with the presence of tumor in the non SLN (P<0.01). CONCLUSION: In our series, only lymphatic invasion in the primary tumor was correlated with metastases detection in the non-SLN. We could not identify a subset of patients without metastatic non-SLN in patients with metastatic SLN.     

Histopathological predictors of axillary lymph node metastases in patients with Breast Cancer

Background  A tumor 30 mm or less in diameter is a standard candidate for breast conserving surgery (BCS) in Japan. Axillary lymph node metastases (ALNM) is the most important prognostic factor for survival in patients with breast cancer, but the role of axillary node dissection has been controversial. Histopathological predictive factors of axillary lymph node involvement have not been established. The purpose of this study was to determine the association between the incidence of ALNM and histopathological factors by univariate and multivariate analysis. Methods  Sixty-five patients with noninvasive ductal carcinoma, and 993 patients with tumors 30 mm or less in diameter who underwent axillary dissection between 1988 and 1997 at our institute were reviewed. The association between ALNM and 13 histopathological factors (size, age, histological subtype, histological invasiveness, lymphatic invasion, vascular invasion, macroscopic classification, histological daughter mass, ductal spread, ER, PgR, p-53, and c-erbB-2) were analyzed by univariate and, when significant, by multivariate analysis. Results  Only one patient with noninvasive ductal carcinoma had ALNM, and 33.1% of 993 patients with a tumor 30 mm or less in size had ALNM. Multivariate analysis identified six factors as independent predictors for ALNM: lymphatic invasion, size, histological invasiveness, macroscopic classification, age and histological daughter mass. Conclusions  Axillary lymph node dissection can be omitted in patients with noninvasive ductal carcinoma. Histopathological features of tumors 30 mm or less in diameter can be used to estimate the risk of ALNM, and routine axillary node dissection might be spared in selected patients at minimal risk of ALNM, if the treatment decision is not influenced by lymph node status, such as in elderly patients.     

Axillary node metastasis from T1N0M0 breast cancer: possible avoidance of dissection in a subgroup

BACKGROUND: Axillary lymph node dissection is now no longer considered to be the standard treatment in all patients with invasive breast cancer. We have attempted to identify a sub-group of patients with invasive breast carcinoma who may not need to undergo axillary lymph node dissection. METHODS: Patients (n = 823) with T1 N0M0 invasive breast cancer treated at our hospital between 1970 and 1994 were studied. We investigated the relationship between positive axillary lymph nodes and the following clinico-pathological factors: patient age, menopausal status, contralateral breast cancer (synchronous or asynchronous), tumor location, tumor size (T:cm), histopathology, histological grade, presence or absence of malignant microcalcification or spiculation on mammography and estrogen receptor status. RESULTS: The incidence of axillary lymph node metastases in patients with T1N0M0 invasive breast cancer was 25% (208/823). The node-negative group was significantly older than the node-positive group. Premenopausal patients had a higher rate of lymph node metastases although this was not significant. The frequency of nodal metastases when related to the tumor size was as follows: T< or =1.0 cm, 17%; T< or =1.5 cm, 25%; T< or =2.0 cm, 29%. Mammography revealed that patients with malignant calcification or spiculation had a significantly higher rate of nodal metastases than those without these findings. Certain tumor types (medullary, mucinous and tubular carcinomas) had lower positive rates for lymph node involvement. With regard to the histological grade, lymph node positivity increased significantly with high-grade tumors. No correlation was observed between any other factors and the presence or absence of lymph node metastases. CONCLUSIONS: It may be possible to avoid axillary lymph node dissection in postmenopausal patients (50 years or older) where the histological type is favorable when the tumor diameter is < or =1.0 cm and when microcalcification or spiculation is absent on mammography.      

T1 breast cancer: identification of patients at low risk of axillary lymph node metastases

Objective. The status of the axillary lymph nodes is one of the most important prognostic factors in patients with breast cancer. A panel of molecular markers of tumor aggressiveness in addition to conventional clinical and histopathologic features were analyzed in an attempt to identify a subgroup of patients with a low risk of axillary lymph node metastases. Material and methods. Data from 358 patients with T1 breast cancer who underwent level I/II axillary lymph node dissection (ALND) were investigated. Hormone receptor status, Ki-67, S-phase fraction, DNA ploidy, HER-2/neu, p53, epidermal growth factor receptor, urokinase type plasminogen activator, plasminogen activator inhibitor-1, bone marrow micrometastases as well as patient age, menopausal status, tumor site, tumor size, histologic type, tumor grade, carcinoma in situ, multifocality, and lymph vascular invasion (LVI) were studied to predict axillary lymph node status. Results. In a multivariate logistic regression analysis LVI (present v.s. not present), Ki-67 (18% v.s. <18%), tumor size (1.1–2 cm v.s. 1 cm), and histologic grade (G3 v.s. G1/2) were identified as independent predictive factors of axillary lymph node metastases. Approximately 13% of patients (n = 47) with well or moderately differentiated tumors less than or equal to 1 cm, no lymph vascular invasion, and a low Ki-67 staining were identified as having a low risk of axillary lymph node metastases of 4.3%. However, 20 patients with all four unfavorable predictive factors had a 75% incidence of axillary lymph node involvement. Conclusion. Primary tumor characteristics can be used to identify a subgroup of patients with a low risk of axillary lymph node metastases in T1 breast cancer. Preoperative risk assessment might be used to omit routine ALND in those patients at low risk of axillary lymph node metastases.     

2108例T1~2期乳腺癌患者腋窝淋巴结转移的相关因素分析

目的：探讨T1~2期乳腺癌患者临床与病理因素与腋窝淋巴结转移的关系,指导前哨淋巴结活检术（SL-NB）的应用,以避免腋窝清扫术（ALND）后并发症的发生。方法收集接受手术且经病理确诊的T1~2期乳腺癌病例,对其临床病理资料进行回顾性统计分析。通过单因素分析和多因素Logistic回归分析寻找乳腺癌发生腋窝淋巴结转移的影响因素。结果共2108例患者入组,其中1021例患者发生淋巴结转移（48.4%）。单因素分析显示年龄、肿瘤大小、病理类型、组织学分级、脉管瘤栓、ER、PR、Ki-67指数以及分子分型等因素与淋巴结转移有关（P﹤0.05）;而HER-2是否过表达与淋巴结转移无关。多因素Logistic回归分析显示,患者的腋窝淋巴结转移的独立影响因素为肿瘤大小、病理类型、组织学分级、脉管瘤栓、ER表达状况（P﹤0.05）;而年龄也可能是腋窝淋巴结有无转移的独立影响因素（P=0.053）。结论肿瘤越大、分化越差、伴脉管瘤栓、ER阳性表达以及病理类型为浸润性小叶癌的T1~2期乳腺癌患者的淋巴结转移风险更高,而年龄≤50岁也可能增加了腋窝淋巴结转移的风险。T1~2期乳腺癌患者是否直接行ALND应持谨慎的态度。     

Low number of examined lymph nodes in node-negative breast cancer patients is an adverse prognostic factor.

BACKGROUND: The aim of the study was to determine whether the number of lymph nodes removed at axillary dissection is associated with recurrence and survival in node-negative breast cancer (NNBC) patients. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 1606 women with pathologically node-negative T1-T3 invasive breast cancer. Median follow-up was 61 months (range 2-251). Potential prognostic factors assessed included: number of axillary lymph nodes examined, age, menopausal status, tumor size, histological type, tumor grade, estrogen receptor(ER), progesterone receptor (PR) and HER2. RESULTS: At 5 years, relapse-free survival (RFS) rate was 85% and breast cancer-specific survival (BCSS) rate was 94%. In univariate analysis, factors significantly associated with lower RFS and BCSS were: fewer than six lymph nodes examined (RFS, P = 0.01; BCSS, P = 0.007), tumor size >2 cm, grade III, negative ER or PR. Statistically significant factors for lower RFS and BCSS in multivariate analysis were: fewer than six lymph nodes examined [RFS, hazard ratio (HR) 1.36, P = 0.029; BCSS, HR 1.87, P = 0.005], tumor size >2 cm, tumor grade III and negative PR. CONCLUSIONS: Examination of fewer than six lymph nodes is an adverse prognostic factor in NNBC because it could lead to understaging. Six or more nodes need to be examined at axillary dissection to be confident of a node-negative status. This may be useful, in conjunction with other prognostic factors, in the assessment of NNBC patients for adjuvant systemic therapy.     

Plasma D-dimer levels in operable breast cancer patients correlate with clinical stage and axillary lymph node status.

PURPOSE: To investigate the relationship between preoperative plasma D-dimer levels and extent of tumor involvement in operable breast cancer patients. PATIENTS AND METHODS: A total of 140 preoperative plasma specimens were obtained from women scheduled to undergo diagnostic breast biopsies. Ninety-five patients in the initial group went on to undergo axillary lymph node dissection. Of the 140 patients from whom plasma samples were obtained, 102 were subsequently diagnosed with invasive breast carcinoma, nine were subsequently diagnosed with ductal carcinoma-in-situ, and 20 were subsequently diagnosed with benign breast disease. Plasma D-dimer levels were quantitated using a commercially available immunoassay kit (DIMERTEST; American Diagnostica, Greenwich, CT). The relationships between plasma D-dimer and other prognostic variables (tumor size, estrogen receptor, progesterone receptor, nuclear grade, histologic grade, lymphovascular invasion, and clinical stage grouping) were then examined using univariate and multivariate linear and logistic regression analyses. RESULTS: Median plasma D-dimer levels were significantly higher in patients with invasive carcinoma than those patients with either benign breast disease or carcinoma-in-situ (P =.0001). A significant relationship existed between the presence of elevated D-dimer (> 100 ng/mL) and involved axillary lymph nodes (chi(2) test; P =.001). Elevated D-dimer levels predicted positive lymph node involvement in both univariate regression (P =.0035) and multivariate linear regression (P =.012) models. In addition, elevated D-dimer levels predicted the presence of lymphovascular invasion in univariate logistic regression (P =. 0025) and multivariate logistic regression analysis (P =.0053). Quantitative D-dimer levels were highly correlated with clinical stage grouping (analysis of variance test; P =.002). CONCLUSION: Plasma D-dimer levels were markers of lymphovascular invasion, clinical stage, and lymph node involvement in operable breast cancer. This correlation suggests that detectable fibrin degradation, as measured by plasma D-dimer, is a clinically important marker for lymphovascular invasion and early tumor metastasis in operable breast cancer.     

The significance of nuclear morphometric variables as prognostic predictors in breast cancer.

The preoperative biopsies from primary breast carcinomas of 504 women were subjected to interactive morphometric analysis of a) the mean nuclear area (NA), b) standard deviation of nuclear area (SDNA), c) mean area of the 10 largest nuclei (NAl0), d) nuclear perimeter (PE), e) standard deviation of nuclear perimeter (SPDE), f) largest nuclear diameter (Dmax) and g) shortest nuclear diameter (Dmin), h) histological grade and i) classical prognostic variables. The above data were correlated with the disease outcome during the mean follow-up period of 11.2 years. Tumor size (p less than 0.0001), morphometric variables (p = 0.0001-0.005) and histological grade (p = 0.03) predicted axillary lymph node metastasis at the time of diagnosis. According to multivariate analysis, tumour size and NA predicted the axillary lymph node metastasis independently. Axillary lymph node status (p less than 0.0001) and histological grade (p = 0.01) predicted the tumour recurrence and recurrence-free survival, whereas the morphometric variables had no significant predictive value. Axillary lymph node status (p less than 0.0001), tumour size (p less than 0.0001), histological grade (p = 0.0012) and morphometric variables (p = 0.003-0.035) predicted the disease-related survival. Of the morphometric variables, NA and the Dmin were the two most important predictors of tumour-related survival in univariate analysis. Dmax had independent prognostic information in multivariate survival analysis. In the same analysis, tumour size and axillary lymph node status were more important predictors. In conclusion, the morphometric variables analysed have independent predictive value in female breast cancer. Their value is, however, inferior to that of the tumour size and axillary lymph node status, but equal to that of the histological grade.     

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.     

Reappraisal of internal mammary node metastases as a prognostic factor in patients with breast cancer.

Clinical, histologic, and biologic prognostic factors were examined in 144 patients with invasive breast cancer. It was determined whether variable prognostic factors, especially internal mammary lymph node metastases, would serve as a basis for the prognosis of breast cancer. In a univariate study, overall survival was significantly correlated with tumor size, axillary lymph node status, axillary and internal mammary lymph node metastases, and DNA ploidy status. Especially among patients with one to three positive axillary nodes, survival in case of internal mammary involvement were significantly lower than without internal mammary involvement. In a multivariate study, only axillary and internal mammary lymph node metastases were recognized as important, independent prognostic factors of survival, but neither axillary lymph node status nor DNA ploidy status appeared as important prognostic factors. It was concluded that internal mammary lymph node metastases is additional prognostic factor, especially in patients with one to three positive axillary nodes. Because axillary and internal mammary lymph node metastases could not be predicted from their clinical assessment, axillary lymph node dissection and biopsy of internal mammary nodes may be a useful staging procedure for these patients.     

Classical prognostic factors in node-negative breast cancer: the DBCG experience.

Classical prognostic factors were analyzed in patients with low-risk primary breast cancer, defined as absence of tumor-positive axillary lymph nodes, tumor size less than or equal to 5 cm in diameter, and no invasion into skin or deep fascia. The primary surgical treatment was total mastectomy and lower axillary dissection. None of the patients received adjuvant therapy. Between 1977 and 1990, 7315 patients entered the study, and at the time of this analysis (January 1, 1990), the median follow-up time is 5 years. In univariate analyses, the following variables were significantly related to recurrence-free survival: age in premenopausal patients; tumor size; number of negative nodes removed; histological grade; and in premenopausal patients, estrogen receptor and progesterone (PgR) status. In multivariate analyses, age in premenopausal patients was the most important factor, followed by tumor size and histological grade, whereas PgR status in premenopausal patients was just of borderline significance. These variables should be included in multivariate analyses testing the value of more recently introduced prognostic factors.     

Risk of internal mammary lymph node metastases and its prognostic value in breast cancer patients

The risk of an internal mammary lymph node (IMN) metastasis and its prognostic value for patients with invasive breast cancer were assessed by evaluating 142 patients who had either a mastectomy with lymph node dissection or a biopsy of the IMN. By univariate analysis, overall survival significantly correlated with the patient's age, clinical axillary node status, tumor size, and DNA ploidy, as well as histologically confirmed axillary and IMN metastases. By multivariate analysis, however, only the presence of axillary and IMN metastases appeared to be an important independent factor affecting survival. However, the incidence of IMN metastases was associated significantly with age, clinical tumor and axillary node status, tumor size, axillary lymph node metastases, and DNA ploidy. Accordingly, the patient's age, tumor size, DNA ploidy, and axillary lymph node metastases proved to be effective variable for discrimination. Consequently, in predicting the presence of IMN metastases, a diagnostic accuracy of 82%, a sensitivity of 84%, and a specificity of 82% can be achieved by a discriminant function. We conclude that the discriminant function with these four variables is effective in assessing the risk of IMN metastases. © 1993 Wiley-Liss, Inc.     

Patients with Recurrent Breast Cancer: Does the Primary Axillary Lymph node Status Predict more Aggressive Tumor Progression?

BACKGROUND: The extent of axillary lymph node involvement represents the foremost important prognostic parameter in primary breast cancer, and, thus, is one of the main determinants for subsequent systemic treatment. Nevertheless, the relevance of the initial axillary lymph node status on survival after disease recurrence is discussed controversially. Persisting prognostic impact after relapse would identify lymph node status as a marker for tumor biology, in contrast to a simply time-dependent phenomenon. METHOD: Retrospective analysis of 813 patients with locoregional or distant recurrence of primary breast cancer, who were primarily diagnosed with their disease at the I. Frauenklinik, Ludwig-Maximilians-University, Munich, and the University Hospital in Berlin-Charlottenburg, Germany, between 1963 and 2000. To be eligible, patients were required to have been treated for resectable breast cancer free of distant disease at the time of primary diagnosis, and must have undergone systematic axillary lymph node dissection. Patients with unknown tumor size or nodal status were excluded from the study. All data were gathered contemporaneously and compared with original patients files, as well as the local cancer registry, ensuring high quality of data. The median observation time was 60 (standard deviation 44) months. RESULTS: At time of primary diagnosis, 273 patients (33.6%) were node-negative, while axillary lymph node metastases were detected in 540 patients (66.4%). In univariate analysis tumor size, axillary lymph node status, histopathological grading, hormone receptor status, as well as peritumoral lymphangiosis and haemangiosis carcinomatosa were significantly correlated with survival after relapse (all, P < 0.0001). Kaplan-Meier analysis estimated the median survival time after relapse in node-negative patients to be 42 months (31-52 months, 95% CI), and 20 months in patients with 1-3 axillary lymph node metastases (16-24 months, 95% CI), compared to 13 months in patients with at least 4 involved axillary nodes (12-15 months, 95% CI). Multivariate logistic regression analysis, allowing for tumor size, axillary lymph node status, histopathological grading, presence of lymphangiosis carcinomatosa, relapse site and disease-free interval confirmed all parameters, except of histopathological grading (P = 0.14), as significant, independent risk factors for cancer associated death. Subgroup analyses, accounting for site of relapse and duration of disease-free interval, confirmed primary lymph node status as independent predictor for cancer-associated death after relapse. CONCLUSION: Lymph node involvement at primary diagnosis of breast cancer patients predicts an unfavorable outcome after first recurrence, independently of the site of relapse and disease-free interval. These observations support the hypothesis that primary lymph node involvement is not a merely time-dependent indicator for tumor progression, but indicates tumors with aggressive biological behavior.     

Predictive Factors for the Status of Non-sentinel Nodes in Breast Cancer Patients with Tumor Positive Sentinel Nodes

In patients with tumor positive sentinel nodes, axillary lymph node dissection is routinely performed while a majority of these patients have no tumor involvement in the non-sentinel nodes. The authors tried to identify a subgroup of patients with a tumor positive sentinel node without non-sentinel node tumor involvement. In 135 consecutive patients with tumor positive sentinel nodes and axillary lymph node dissection performed, the incidence of non-sentinel node involvement according to tumor and sentinel node related factors was examined. The size of the sentinel node metastasis, size of primary tumor and number of tumor positive sentinel nodes were the three factors significantly predicting the status of the non-sentinel nodes. The size of the sentinel node metastasis was the strongest predictive factor (P < 0.0001). In a subgroup of 41 patients with a stage T1 tumor and micrometastatic involvement in the sentinel node only 2 patients (5%) had non-sentinel node involvement. In patients with small primary tumors and micrometastatic involvement of the sentinel nodes, the chance of non-sentinel node involvement is small but cannot be discarded. Because the clinical relevance of micrometastases in lymph nodes is still unclear it is not advisable to omit axillary lymph node dissection even in these patients.     

Prediction of supraclavicular lymph node metastasis in breast carcinoma

PURPOSE: Supraclavicular lymph node metastasis in breast cancer patients has a poor prognosis, and aggressive local treatment has usually resulted in severe morbidity. The purpose of this study was to select high-risk neck metastasis patients for prophylactic radiotherapy. METHODS: Between 1990 and 1998, 2658 consecutive invasive breast cancer patients underwent surgery and adjuvant therapy in the hospital. The median age was 47 years (range 22-92). The median follow-up period was 39 months. The following factors were analyzed: age, tumor size, tumor location, histologic type, histologic grade, estrogen and progesterone receptor status, DNA flow cytometry study results, number of positive axillary lymph nodes, use of chemotherapy, radiotherapy, and/or hormonal therapy, and level of involved axillary nodes. RESULTS: Of the 2658 patients, 113 (4.3%) developed supraclavicular lymph node metastasis during this period. Young age (< or =40 years), tumor size >3 cm, high histologic grade, angiolymphatic invasion, negative estrogen receptor status, synthetic phase fraction >4%, >4 positive nodes, and level II or III involved nodes were all significant for predicting neck metastasis in the univariate analysis. Three predictive factors were significant after multivariate analysis: high histologic grade, >4 positive nodes, and axillary level II or III involved nodes. In patients with axillary level I involved nodes and < or =4 positive nodes, the incidence was 4.4%. If axillary level III was involved, the rate of supraclavicular lymph node metastasis was 15.1%. CONCLUSION: The incidence of supraclavicular lymph node metastasis was higher in the groups with >4 positive nodes and in those with axillary level II or III involved nodes. Selective use of comprehensive radiotherapy for these high-risk patients will achieve good locoregional control.     

Number of Metastatic Sentinel Nodes As Predictor of Axillary Involvement in Patients with Breast Cancer

BACKGROUND AND OBJECTIVES: More than half of patients with positive sentinel node (SN) have no metastases in non-sentinel nodes (NSNs) on axillary lymph node dissection (ALND). The aim of this study was to investigate factors predictive of NSNs involvement, in order to identify patients with metastatic disease confined to the SN which might avoid ALND. METHODS: ALND was performed in 167 patients with metastatic SN. Axillary NSNs status was correlated with the size of SN metastases, the size of the primary tumor and the occurrence of lymphovascular invasion. In 72 cases, the radiotracer (Tc-99m albumin colloid) marked multiple (in most cases 2 or 3) nodes. In this group, NSNs status was correlated with the number of metastatic radioactive nodes (1 or > 1), and with the above mentioned histopathologic factors. RESULTS: NSNs metastases were found in 57/167 cases (34.1%), the rate increasing proportionate to the size of both SN metastases (p < 0.0001) and primary tumor (p = 0.0075), while no significant correlation was found for lymphovascular invasion (p = 0.1769). At univariate and multivariate analysis of findings from the 72 cases with multiple probe-detected hot nodes, positivity in more than one hot node was the strongest predictor of NSN involvement (p = 0.0019). CONCLUSIONS: The identification and excision of multiple hot nodes can be useful in the prediction of NSNs involvement in patients with metastatic SN.     

C-erbB-2 overexpression in primary breast cancer: independent prognostic factor in patients at high risk

Summary The prognostic value of c-erbB-2 protein overexpression has been evaluated in 463 patients with operable breast cancer after a median follow-up of 66 months. Overexpression was observed in 99/463 (21%) of the breast tumors. It showed significant positive correlation to histological grade (p < 0.0001) and tumor size (p < 0.02). A relationship of borderline significance was observed between c-erbB-2 protein overexpression and negative or low estrogen receptor (ER) content. No significant correlation was found to lymph node involvement or proliferating tumor cell fraction as determined by the proliferating cell nuclear antigen (PCNA). After a median follow-up of 66 months (range 6 to 109 months), the overall survival of all patients amounted to 63%. Multivariate analysis revealed lymph node involvement, tumor size, histological grade, histological type, c-erbB-2 protein overexpression, progesterone receptor (PR) content, and oral contraceptive use as independent prognostic factors. In an univariate analysis, the overall survival amounted to 72% and 38% of tumor patients with negative and positive c-erbB-2 protein overexpression, respectively. The most significant finding is that c-erbB-2 overexpression has been recognized as an independent predictive factor in subsets of tumor patients who would be expected to have a generally poor prognosis, such as those indicating axillary lymph node involvement, large tumor size (> 2 cm), and PR negativity.     

前哨淋巴结阳性早期乳腺癌非前哨淋巴结的组织学检测及临床意义

目的：研究早期乳腺癌患者前哨淋巴结(SLN)阳性时非前哨淋巴结(NSN)转移的可能性及其临床意义。方法：对84例SLN阳性接受乳癌根治术的早期乳腺癌患者的NSN及HER-2免疫组化等进行检测，分析NSN转移的发生率及相关临床因素。结果：SLN阳性患者NSN转移的检出率是48．8％(41／84)，NSN转移与原发肿瘤的大小、SLN转移灶的大小及HER-2的表达状况有关，原发肿瘤直径小于1cm及SLN转移灶小于1mm时NSN无转移，NSN的阳性率随原发肿瘤及SLN转移灶直径的增大而提高，HER-2蛋白阳性者NSN转移率高。结论：原发肿瘤直径小于1cm且SLN转移灶小于1mm时的早期乳腺癌患者可免于腋窝清扫，反之亦然；HER-2阳性患者NSN转移率较高，应考虑腋窝清扫。     

Influence of tumor biological factors on tumor cell dissemination in primary breast cancer

BACKGROUND: The presence of disseminated tumor cells in the bone marrow (BM) of breast cancer patients is associated with poor prognosis and may therefore be related to aggressive breast cancer as indicated by tumor biological and clinicopathological factors. The aim of this study was to identify those features of the primary tumor related to the presence of disseminated tumor cells in the BM. PATIENTS AND METHODS: Clinical data from 508 primary breast cancer patients were analyzed. Tumor biological features of the primary tumor including HER2, p53, Ki-67, bcl-2 and hormone receptor status, as well as clinicopathological factors including histology, menopausal status, lymph node status, tumor size and grade, were studied for their association with BM involvement by univariate and multivariate analysis. RESULTS: Two-hundred and two out of 508 (40%) primary breast cancer patients had disseminated tumor cells in the BM. p53 expression, hormone receptor status, HER2 and Ki-67 were significantly related to BM involvement. The multivariate analysis revealed that p53 expression (OR: 1.9, 95% CI: 1.2 - 3.0) followed by progesterone receptor status (OR: 1.5, 95% CI: 1.0 - 2.2) were the only independent determinants for BM involvement. CONCLUSION: The presence of disseminated tumor cells in the BM was not influenced by tumor load as reflected by tumor size and lymph node involvement, whereas tumor biological factors were independently correlated to BM involvement. The results substantiate the important role of tumor biological factors of the primary tumor for tumor cell dissemination.