PET—C畛断乳腺癌及其腋窝淋巴结转移的价值

目的探讨PET—CT对诊断乳腺癌及腋窝淋巴结转移情况的临床价值。方法选取行PET—CT检查的乳腺肿瘤患者40例，根据术后病理检查结果评价PET—CT对原发病灶定性和判断腋窝淋巴结转移情况的准确性并与腋窝淋巴结清扫情况进行比较；检验原发肿瘤病灶病理直径大小与超声、PET—CT诊断的一致性及其与标准化摄取值（SUV）值的相关性。结果PET—CT对乳腺癌的定性诊断准确率95％、灵敏度94％、特异度100％；根据腋窝淋巴结清扫术情况，PET—CT诊断腋窝淋巴结转移准确率88．2％、灵敏度89．2％、特异度83．3％；肿瘤病灶病理直径大小与PET-CT诊断相关性最高（P〈0．05），与SUV则无相关性（P〉0．05）。结论PET—CT对乳腺癌及腋窝淋巴结转移的诊断与病理诊断基本相符，灵敏度、特异度较高，两者诊断原发病灶大小的一致性最佳，可为取舍腋窝淋巴结清扫术和选择合理治疗方案提供有益参考。     

Ultrasound detection of axillary lymph node metastases in breast cancer

Presence or absence of lymph node metastases is the most accurate prognostic indicator in breast cancer. Clinical examination is unreliable in detecting involved nodes. Preoperative ultrasound scan of the axilla has been performed in 140 consecutive women with breast cancer. The sensitivity for involved nodes was 66% which was significantly higher than clinical examination (42%) (P = less than 0.01). However ultrasound gave more false positives than clinical examination and thus no overall improvement in prognostic information was achieved.     

Basal breast cancer molecular subtype predicts for lower incidence of axillary lymph node metastases in primary breast cancer

BACKGROUND: Axillary lymph node involvement remains the most important prognostic factor in early-stage breast cancer. We hypothesized that molecular classification based on breast cancer biology would predict the presence of nodal involvement at diagnosis, which might aid treatment decisions regarding the axilla. PATIENTS AND METHODS: From a clinically annotated tissue microarray of 4444 early-stage breast cancers, expression of estrogen receptor (ER), progesterone receptor (PgR), HER2, epidermal growth factor receptor, and cytokeratin 5/6 was determined by immunohistochemistry. Cases were classified by published criteria into molecular subtypes of luminal, luminal/HER2 positive, HER2 positive/ER negative/PgR negative, and basal. Risk of axillary nodal involvement at diagnosis was determined in 2 multivariable logistic regression models: a "core biopsy model" including molecular subtype, age, grade, and tumor size and a "lumpectomy model," which also included lymphovascular invasion. Luminal was used as the reference group. After internal validation of findings in 2 independent sets, we conducted combined analysis of both. RESULTS: In the core biopsy model, the molecular subtypes had a predictive effect for nodal involvement (P= .000001), with the basal subtype having an odds ratio for axillary lymph node involvement of 0.53 (95% CI, 0.41-0.69). Tumor grade (P=5.43 x 10(-12)) and size (P=8.52 x 10(-35)) were also predictive for nodal involvement. Similar results were found in the lumpectomy model, where lymphovascular invasion was also predictive (P=2.74 x 10(-115)). CONCLUSION: These results indicate that the basal breast cancer molecular subtype predicts a lower incidence of axillary nodal involvement, and including biomarker profiles to predict nodal status at diagnosis could help stratification for decisions regarding axillary surgery and locoregional radiation.     

Diagnosis of axillary lymph node metastases in patients with breast cancer

Summary The diagnosis of axillary (AX) metastases remains a challenge in the management of breast cancer and is a subject of controversy. Clinical node staging clearly is limited in the assessment of AX lymph nodes. AX mammography, ultrasonography, and computed tomography (CT) do not provide histologic information. Although nuclear magnetic resonance imaging may have considerable value in the diagnosis of AX metastases, it does not detect micrometastases. The use of biologic markers in the assessment of AX metastases remains a subject of investigation. On the other hand, biopsy of selected AX nodes or tissue with examination of histology or cytology generally would not identify a significant percentage of patients with AX node involvement. Sentinel lymph node biopsy, however, might be potentially useful for assessing AX metastases, although it remains investigational. In order to simplify diagnosis and reduce morbidity and mortality, alternatives to AX dissection must be sought and imaging and staging modalities refined. We present a review of the literature pertaining to the diagnosis of AX metastases in patients with breast cancer and a discussion of some current areas of controversy.     

Intraoperative assessment of axillary lymph node metastases in operable breast cancer

The diagnostic value of intraoperative histologic examination of frozen sections of axillary lymph nodes was investigated in 243 patients with operable breast cancer. One to six hard or enlarged axillary nodes were sampled from the axillary pad which was derived from a partial axillary dissection (including level 1 and 2 nodes). Half of these nodes were histologically examined using frozen sections during surgery. After a total axillary dissection, both the axillary nodes in the partial axillary dissection and the nodes dissected at level 3 were histologically examined on permanent section. A mean of four nodes were sampled (range: 1 to 6). Axillary dissection yielded a mean of 22 nodes (range: 6 to 60). Axillary sampling detected the presence of metastases in 65 of 84 (77%) patients with positive axillary lymph nodes. In the patients in whom the axillary involvement was not identified by axillary sampling, however, the extent of axillary involvement was limited to levels 1 and 2. Therefore, a partial axillary dissection may be justified for patients in whom axillary involvement is not found on frozen section of nodes from axillary sampling, whereas a total axillary dissection should be performed for patients in whom axillary involvement is found by these procedures.     

乳腺癌腋窝淋巴结声像图联合免疫组织化学与淋巴结转移的相关性研究

背景与目的：乳腺癌腋窝淋巴结转移对于乳腺癌患者的预后及治疗方案的选择有重要的指导意义。本研究旨在探讨乳腺癌腋窝淋巴结声像图表现联合免疫组织化学与腋窝淋巴结转移的相关性。方法：回顾性分析应用超声检出的366例乳腺癌患者共计728枚腋窝淋巴结的声像图表现,采用单因素分析、多因素logistic回归及受试者工作特征(receiver operating characteristic,ROC)曲线分析的方法,分别检验乳腺癌腋窝淋巴结皮质最大厚度、长短径之比、皮髓质之比和淋巴结血流特征,联合乳腺癌术后免疫组织化学结果,研究其与病理学腋窝淋巴结转移的相关性。结果：依据单因素分析,腋窝淋巴结皮质最大厚度、长短径之比、血流特征以及乳腺癌病灶p53的阳性表达率与淋巴结转移有关(P<0.05)。依据多因素分析及ROC分析,腋窝淋巴结皮质最大厚度是判定腋窝淋巴结转移的最佳指标。腋窝淋巴结皮质最大厚度大于3 mm的患者,其乳腺癌病灶的p53阳性表达率(42.78%)明显高于皮质最大厚度小于等于3 mm的患者(25.82%),差异有统计学意义(P<0.01)。结论：乳腺癌腋窝淋巴结声像图表现联合免疫组织化学评价腋窝淋巴结转移,对乳腺癌的临床诊疗方法选择具有重要价值。     

Oestrogen receptor concentration in primary breast cancer and axillary node metastases

Summary The primary tumour and 1–3 invaded, axillary nodes from each of 24 patients were examined both histologically for the proportion of the specimen constituted by malignant epithelial cells (cellularity index) and biochemically for oestrogen receptor concentration. Both malignant epithelial cell content and oestrogen receptor concentration were significantly higher in the nodal metastases than in the primary tumours, malignant cells constituting approximately half of the former tissue and three quarters of the latter. On average, receptor concentrations were 1.6 × (protein basis) to 2.3 × (wet weight basis) higher in nodes than in the primary tumours, probably due at least in part to the difference in cellularity. When, to eliminate the effect of the latter, receptor concentration in each tumour deposit was corrected using the appropriate cellularity index, the difference in receptor concentration between primary and node was significantly diminished, but not quite eliminated. In one patient, progestogen receptor concentrations were also studied and found to be higher in the nodes than in the primary tumour. If the actual quantity of receptor is to be used for predictive/prognostic purposes, then either a different cut-off point should be used for invaded nodes from that used for assessment on the primary tumour, or receptor concentrations should be corrected for differences in cellularity. Reprints: No reprints are supplied by this Department.     

Significance of axillary lymph node metastasis in primary breast cancer.

PURPOSE: Axillary lymph node status is the single most important prognostic variable in the management of patients with primary breast cancer. Yet, it is not known whether metastasis to the axillary nodes is simply a time-dependent variable or also a marker for a more aggressive tumor phenotype. The purpose of this study was to determine whether nodal status at initial diagnosis predicts outcome after relapse and therefore also serves as a marker of breast cancer phenotype. PATIENTS AND METHODS: Survival experience after first relapse in 1,696 primary breast cancer cases was analyzed using Cox proportional hazards regression. The following explanatory variables and their first-order interactions were considered: number of axillary lymph nodes involved (zero v one to three v four or more), hormone receptor status (any estrogen receptor [ER] negativity v ER negativity/progesterone receptor positivity v other ER positivity), primary tumor size (< 2 cm v 2 to 5 cm v > 5 cm), site of relapse (locoregional v distant), disease-free interval (< 1.5 years v 1.5 to 3 years v > 3 years), adjuvant endocrine therapy (none v any), adjuvant chemotherapy (none v any), and menopausal status (pre-, peri-, or postmenopausal). RESULTS: Axillary lymph node status, site of relapse, and hormone receptor status were all highly significant as main effects in the model. After adjustment for other variables, disease-free interval alone was only modestly significant but interacted with nodal status. After disease-free interval, hormone receptor status, and site of relapse were accounted for, survival after relapse was poorer in node-positive cases, when compared with node-negative cases. The hazard ratios for patients with one to three and four or more involved nodes were 1.2 (95% confidence interval [CI], 0.8 to 1.9) and 2.5 (95% CI, 1.8 to 3.4), respectively. CONCLUSION: Patients with four or more involved nodes at initial diagnosis have a significantly worse outcome after relapse than node-negative cases, regardless of the duration of the disease-free interval. We conclude that nodal metastasis is not only a marker of diagnosis at a later point in the natural history of breast cancer but also a marker of an aggressive phenotype.     

Proteomic profiling of primary breast cancer predicts axillary lymph node metastasis

To determine if protein expression in primary breast cancers can predict axillary lymph node (ALN) metastasis, we assessed differences in protein expression between primary breast cancers with and without ALN metastasis using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Laser capture microdissection was performed on invasive breast cancer frozen sections from 65 patients undergoing resection with sentinel lymph node (SLN) or level I and II ALN dissection. Isolated proteins from these tumors were applied to immobilized metal affinity capture (IMAC-3) ProteinChip arrays and analyzed by SELDI-TOF-MS to generate unique protein profiles. Correlations between unique protein peaks and histologically confirmed ALN status and other known clinicopathologic factors were examined using ANOVA and multivariate logistic regression. Two metal-binding polypeptides at 4,871 and 8,596 Da were identified as significant risk factors for nodal metastasis (P = 0.034 and 0.015, respectively) in a multivariate analysis. Lymphovascular invasion (LVI) was the only clinicopathologic factor predictive of ALN metastasis (P = 0.0038). In a logistic regression model combining the 4,871 and 8,596 Da peaks with LVI, the area under the receiver operating characteristic curve was 0.87. Compared with patients with negative ALN, those with > or =2 positive ALN or non-SLN metastases were significantly more likely to have an increased peak at 4,871 Da (P = 0.016 and 0.0083, respectively). ProteinChip array analysis identified differential protein peaks in primary breast cancers that predict the presence and number of ALN metastases and non-SLN status.     

Predicting axillary lymph node metastases in breast carcinoma patients

Routine axillary dissection is primarily used as a means of assessing prognosis to establish appropriate treatment plans for patients with primary breast carcinoma. However, axillary dissection offers no therapeutic benefit to node negative patients and patients may incur unnecessary morbidity, including mild to severe impairment of arm motion and lymphedema, as a result. This paper outlines a method of evaluating the probability of harbouring lymph node metastases at the time of initial surgery by assessment of tumour based parameters, in order to provide an objective basis for further selection of patients for treatment or investigation. The novel aspect of this study is the use of Maximum Entropy Estimation (MEE) to construct probabilistic models of the relationship between the risk factors and the outcome. Two hundred and seventeen patients with invasive breast carcinoma were studied. Surgical treatment included axillary clearance in all cases, so that the pathologic status of the nodes was known. Tumour size was found to be significantly correlated (P < 0.001) to the axillary lymph node status in the multivariate analysis with age (P = 0.089) and vascular invasion (P = 0.08) marginally correlated. Using the multivariate model constructed, 38 patients were predicted to have risk of nodal metastases lower than 20%, of these only 4 (10%) patients had lymph node metastases. A comparison with the Multivariate Logistic Regression (MLR) was carried out. It was found that the predictive quality of the MEE model was better than that of the MLR model. In view of the small sample size, further verification of this model is required in assessing its practical application to a larger population.     

腋淋巴结阳性乳腺癌结外侵犯的临床意义

目的 探讨乳腺癌患者淋巴结外侵犯(ECE)的临床意义.方法 回顾性分析1230例腋窝淋巴结阳性乳腺癌,观察ECE与临床病理指标之间关系及对患者预后的影响.结果 腋窝淋巴结阳性乳腺癌患者中,ECE阳性率为39.5%.绝经前和绝经后患者ECE的发生率分别为35.5%和47.5%(P＜0.001).ECE阳性组和阴性组的肿瘤直径分别为5.11±2.53 cm和3.90±1.80 cm(P＜0.001),肿瘤直径越大,ECE阳性比例越高(P＜0.001).ECE阳性患者和ECE阴性患者的阳性淋巴结数目分别为16.96±12.16和5.24±6.60(P＜0.001),随腋窝阳性淋巴结数目增多,ECE阳性率明显增加(P＜0.001).ECE的发生与ER、PR状态无显著相关(P=0.706).ECE足乳腺癌患者局部或区域复发的危险因素(P＜0.001),复发时间差异无统计学意义(P=0.559).ECE阳性组和ECE阴性组的远处转移时问分别为30.0个月和37.5个月(P=0.006).首发骨、皮肤和远隔淋巴结组及内脏转移组的ECE阳性率分别为60.4%和42.0%(P=0.001).ECE阳性患者的无转移生存时间、无局部或区域复发生存时间及总生存时间均小于ECE阴性患者.预后单因素和多因素分析显示,ECE是影响乳腺癌患者无转移生存时间、无局部或区域复发生存时间及总生存时间的独立危险因素.结论 乳腺癌患者ECE的发生与肿瘤直径和受累淋巴结数日呈正相关;ECE是乳腺癌局部或区域复发和远处转移的危险因素;ECE是影响乳腺癌患者无转移生存时间、无局部或区域复发生存时间及总生存时间的危险因素.     

Occult axillary lymph node metastases are of no prognostic significance in breast cancer

The significance of occult metastases in axillary lymph nodes in patients with carcinoma of the breast is controversial. Additional sections were cut from the axillary lymph nodes of 477 women with invasive carcinoma of the breast, in whom no metastases were seen on initial assessment of haematoxylin and eosin stained sections of the nodes. One section was stained with haematoxylin and eosin, and one using immunohistochemistry with two anti-epithelial antibodies (CAM5.2 and HMFG2). Occult metastases were found in 60 patients (13%). The median follow-up was 18.9 years with 153 breast cancer related deaths. There was no difference in survival between those with and those without occult metastases. Multivariate analysis, however, showed that survival was related to tumour size and histological grade. This node-negative group was compared with a second group of 202 patients who had one involved axillary node found on initial assessment of the haematoxylin and eosin sections; survival was worse in the patients in whom a nodal metastasis was found at the time of surgery. Survival was not related to the size of nodal metastases in the occult metastases and single node positive groups. Some previous studies have found a worse prognosis associated with occult metastases on univariate analysis, but the evidence that it is an independent prognostic factor on multivariate analysis is weak. We believe that the current evidence does not support the routine use of serial sections or immunohistochemistry for the detection of occult metastases in the management of lymph node negative patients, but that the traditional factors of histological grade and tumour size are useful.     

The importance of extracapsular extension of axillary lymph node metastases in breast cancer

PURPOSE: To evaluate the prognostic value of extracapsular extension (ECE) of axillary lymph node metastases in 221 patients with axillary lymph node-positive, T1-T2 breast cancer treated at Dokuz Eylul University Hospital, Department of Radiation Oncology. PATIENTS AND METHODS: The clinical records of patients with axillary node-positive, pathological stage II-III breast cancer examined at Dokuz Eylul University Hospital, Department of Radiation Oncology, between 1991-1999 were reviewed. All patients underwent modified radical mastectomy (MRM) or wide excision with axillary node dissection. Axillary surgery consisted of level I-II dissection. The number of lymph nodes dissected from the axilla was equal to or more than 10 in 92% of the patients. All 221 patients had pathological T1-T2 tumors. The number of involved lymph nodes was four or more in 112 51% patients and less than four in the remaining 109 (49%). In 127 (57.5%) patients, extracapsular extension was detected in axillary lymph nodes. Tangential radiotherapy fields were used to treat the breast or chest wall. Lymphatic irradiation was performed in 215 (97%) patients with fields covering both the supraclavicular and axillary regions. Median radiotherapy dose for lymph nodes was 5000 cGy in 25 fractions. The following factors were evaluated: age, menopausal status, histological tumor type, pathological stage, number of involved axillary lymph nodes, and extracapsular extension. The chi-square test was used to compare proportions of categorical covariates between groups of patients with and without ECE. Survival analyses were estimated with the Kaplan-Meier method. The Cox regression model was used for the analysis of prognostic factors. RESULTS: The median follow-up for the survivors was 55 months (range, 19-23). The median age was 52 years (range, 28-75). In patients with extracapsular extension the percentages of pathological stage III (22% vs 4.3%, P < 0.0001 and involvement of four or more axillary nodes (25.5% vs 69.3%, p < 0.0000) were higher. Multivariate analysis revealed a significant correlation between the presence of ECE and disease-free survival (DFS) (P = 0.04) as well as distant metastases-free survival (DMFS) (P = 0.002), but there was no significant correlation between ECE and overall survival (OS). Only an elevated number of involved axillary lymph nodes significantly reduced the overall survival (P = 0.001). CONCLUSION: The rate of extracapsular extension was found to be directly proportional to the number of axillary lymph nodes involved and the stage of disease. Extracapsular extension had significant prognostic value in both univariate and multivariate analysis for DFS and DMFS but not OS. The reason for ECE not affecting OS might be related to the much more dominant prognostic effect of the involvement of four or more axillary nodes on OS. Studies with more patients are needed to demonstrate that ECE is a likely independent prognostic factor for OS.     

Population‐based analysis of occult primary breast cancer with axillary lymph node metastasis

BACKGROUND:

Single‐institution data suggest that treatment with radiation and axillary lymph node dissection (ALND) may be an appropriate alternative to mastectomy for T0N+ breast cancer. Population‐based multi‐institutional data supporting this approach are lacking.

METHODS:

The cause‐specific survival (CSS) and overall survival (OS) of women with T0N+M0 ductal, lobular, or mixed breast cancer in the Surveillance, Epidemiology, and End Results database from 1983 to 2006 were analyzed. Groups were defined as: 1) no ALND, mastectomy, or RT (observation); 2) ALND only; 3) mastectomy plus ALND with or without postmastectomy radiation (Mast); and 4) breast‐conserving therapy (BCT) with ALND and radiation (BCT).

RESULTS:

In total, 750 of 770,030 patients with breast cancer had T0N+M0 disease (incidence, 0.10%), and 596 of those patients underwent ALND (79.5%). Patients who underwent Mast or BCT (n = 470) had a 10‐year OS rate of 64.9% compared with 58.5% for patients who underwent ALND only (n = 126; P = .02) and 47.5% for patients who underwent observation only (n = 94; P = .04). The 10‐year CSS rate was 75.7% for patients who underwent BCT versus 73.9% for patients who underwent Mast (P = .55). In multivariate analysis of CSS for patients who underwent Mast or BCT, the following factors were correlated with an unfavorable outcome: positive estrogen receptor status (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.24‐0.96; P = .04), ≥10 positive lymph nodes (HR, 5.7; 95%CI, 2.4‐13.4; P ≤ .01), and <10 resected lymph nodes (HR, 42.9; 95%CI, 1.2‐7.1; P = .02). Mast did not improve CSS compared with BCT (HR, 1.09; 95%CI, 0.57‐2.1; P = .79).

CONCLUSIONS:

Definitive locoregional treatment with either Mast or BCT improved the outcome of patients with T0N+breast cancer, and no difference in survival was observed between the treatments. Cancer 2010. © 2010 American Cancer Society.     

乳腺癌腋窝淋巴结转移的多因素分析

目的:研究乳腺癌腋窝淋巴结转移与年龄、民族、初潮年龄、第一胎生育年龄、绝经、绝经年龄、病程、哺乳时间、妊娠次数、肿瘤部位、肿瘤大小（B超、钼靶、MRI分别测值）、病理分型、雌激素受体（ER）、孕激素受体（PR）、C-erbB-2基因表达之间的关系及规律,为乳腺癌手术中腋窝淋巴结清扫术的指征提供理论依据。方法:回顾性分析356例乳腺癌患者的临床资料。结果:腋窝淋巴结转移228例（64%）,无转移128例（36%）;腋窝淋巴结转移与第一胎生育年龄、妊娠次数、哺乳时间、病程、肿瘤大小(B超、钼靶、MRI)、肿瘤部位、病理类型相关（P<0.05）,P值分别为0.007、0.005、0.006、0.022、（0.001、0.000、0.020）、0.009、0.000。结论:腋窝淋巴结的转移受多种因素影响。     

Prognostic significance of occult axillary lymph node metastases after chemotherapy‐induced pathologic complete response of cytologically proven axillary lymph node metastases from breast cancer

BACKGROUND:

Primary systemic chemotherapy has been a standard of care for the management of locally advanced breast cancer (LABC) patients and has increasingly been used for patients with large operable breast cancer. Pathologic complete response (pCR) of axillary lymph node metastases predicted an excellent probability of long‐term disease‐free and overall survival. Although the clinical significance of occult lymph node metastases in patients with breast cancer was extensively studied, their prognostic value in patients with LABC after primary chemotherapy was not known. This study evaluated the detection rate and clinical significance of occult lymph node metastases in lymph nodes that contained metastatic carcinoma at the time of initial diagnosis and converted to negative based on routine pathologic examination after primary systemic chemotherapy.

METHODS:

Fifty‐one patients with LABC and cytologically involved axillary lymph nodes that converted to negative after preoperative chemotherapy were identified from 2 prospective clinical trials. All lymph node sections were reviewed, 1 deeper level hematoxylin and eosin‐stained section of each lymph node was obtained and immunohistochemical staining for cytokeratin (CK) was performed. A total of 762 lymph nodes were evaluated for occult metastases. Kaplan‐Meier survival curves were used for calculating disease‐free and overall survival times.

RESULTS:

Occult axillary lymph node metastases were identified in 8 of 51 (16%) patients. In 6 patients, occult metastases were found in only 1 lymph node. In 7 patients, only isolated CK‐positive cells were identified. In all cases, occult carcinoma cells were embedded within areas of fibrosis, foreign body giant cell reaction, and extensive histiocytosis. Patients with occult lymph node metastases tended to have a higher frequency of residual primary breast tumors than those without occult metastases (4 of 8 vs 7 of 43, respectively). There was no statistically significant difference in disease‐free or overall survival times between patients with and without occult metastases after a median follow‐up 63 months.

CONCLUSIONS:

Persistent occult axillary lymph node metastases were not uncommon in patients with axillary lymph node‐positive LABC who experienced a pCR in involved lymph nodes after preoperative chemotherapy. However, such occult metastases did not adversely affect the good prognosis associated with axillary lymph node pCR. Therefore, routine lymph node CK evaluation was not recommended after primary chemotherapy. Cancer 2009. © 2009 American Cancer Society.     

Lack of efficacy of lymphoscintigraphy in detecting axillary lymph node metastases from breast cancer

Preoperative detection of metastases in regional lymph nodes should constitute a fundamental step towards a better management of breast cancer. The National Cancer Institute of Milan has traditionally been engaed in this particular problem, that is, the search for a new imaging technique for detecting lymph nodal metastases from breast cancer. In 1984 axillary lymphoscintigraphy was performed on 26 patients with operable breast cancer by periareolar injection of 100 μCi of ^99mTc sulphur microcolloid. The regional lymph nodes were identified as spot areas and a comparison was made between the number of primary draining axillary lymph nodes and their pathological examination. In only 2 of the 26 patients have more than 3 spot areas been revealed by axillary scintiscan, but this finding did not correspond to metastatic invasion. The lymphoscintigraphy pattern of the other 24 patients did not suggest any pathological condition. From our experience the method does not appear to help either a precise diagnosis of breast disease or the definition of the extent of mammary cancer.     

The significance of extracapsular extension of axillary lymph node metastases in early-stage breast cancer

PURPOSE: To investigate if extracapsular extension (ECE) of axillary lymph node metastases predicts for a decreased rate of disease-free survival or an increased rate of regional recurrence of breast carcinoma. METHODS: The study population consisted of 368 patients with T1 or T2 breast cancer and pathologically-positive lymph nodes treated with breast-conserving therapy between 1968 and 1986. The median number of sampled lymph nodes was 10. Median follow-up time for the surviving patients was 139 months (range 70-244). Twenty percent of the patients were treated with supraclavicular RT, and 64% received both axillary and supraclavicular RT, with a median dose to the nodes of 45 Gy. The following factors were evaluated: presence of ECE, number of sampled lymph nodes (LN), number of involved LN, size of primary tumor, histologic grade of tumor, presence of lymphatic vessel invasion (LVI), presence of an extensive intraductal component (EIC), radiation dose, use of adjuvant chemotherapy, and age of patient. Recurrences were reported as the 5-year crude sites of first failure, and were divided into breast recurrences (LR), regional nodal failure (RNF, defined as isolated axillary, supraclavicular, or internal mammary recurrence), and distant metastases (DM). RESULTS: One hundred twenty-two patients (33%) had ECE and 246 patients did not. The median number of LN with ECE was 1 (range 1-10) and 20% of patients had ECE in > or =4 LN. Patients with ECE tended to be older (median age 51 vs. 47, p = 0.01), and had a higher number of involved LN (median 3 vs. 2, p = 0.005) than patients without ECE. Forty-three percent of patients with ECE had > or =4 involved LN compared to 15% of patients without ECE (p<0.0001). Models of ECE and the above factors revealed no significant correlation between ECE and either disease-free or overall survival. There was no statistically significant increase in local, regional nodal, or distant failures in patients with ECE as compared to patients without ECE. CONCLUSION: In this population of patients with nodal involvement, the presence of ECE correlates with the number of involved LN but does not appear to add predictive power to models of local, regional, or distant recurrence when the number of positive LN is included.     

Induction of lymphangiogenesis in and around axillary lymph node metastases of patients with breast cancer

We studied the presence of lymphangiogenesis in lymph node (LN) metastases of breast cancer. Lymph vessels were present in 52 of 61 (85.2%) metastatically involved LNs vs 26 of 104 (25.0%) uninvolved LNs (P<0.001). Furthermore, median intra- and perinodal lymphatic endothelial cell proliferation fractions were higher in metastatically involved LNs (P<0.001). This is the first report demonstrating lymphangiogenesis in LN metastases of cancer in general and breast cancer in particular.