Pathologic analysis of tumor size and lymph node status in multifocal/multicentric breast carcinoma

BACKGROUND: For unifocal invasive breast carcinoma, increasing tumor diameter predictably correlates with a greater frequency of lymph node involvement, thereby facilitating treatment decisions. In invasive breast tumors presenting with multiple nodules, however, it is unclear whether tumor size correlates with lymph node dissemination in a similar manner. METHODS: The authors analyzed a series of 101 invasive breast carcinomas presenting with multiple macroscopically apparent lesions (2 foci: n = 77; 3: n = 20; 4: n = 4). Two different assessments of the tumor size (diameter of largest focus and combined diameter of all the foci) were then correlated with the status of axillary lymph nodes. For comparison with unifocal tumors, the authors used both external and internal control series (the latter consisting of 469 patients from their institution). The associations between lymph node status, tumor size, and multifocality were modeled using univariate and multivariate logistic regression, for each modality of tumor size assessment. RESULTS: The logistic curves for multifocal and unifocal tumors were significantly different when the largest diameter was used as a tumor size estimate. Multifocal cases had higher frequencies of lymph node involvement than unifocal lesions of similar size category. In a multivariate logistic regression, the odds ratio of positive lymph node status in multifocal versus unifocal cases was 2.8 using largest diameter as a tumor size estimate (P < 0.0001). When the combined diameter assessment was used, however, the regression curve of multifocal cases was similar to that of unifocal cases, and the frequency of lymph node positivity was not significantly different in multifocal versus unifocal cases of the same size (odds ratio, 1.4; P = 0.13). CONCLUSIONS: The authors' results show that, if aggregate diameters are used, unifocal and multifocal breast carcinomas are similar with respect to frequency of regional lymph node metastasis. Currently used algorithms, which use the diameter of the largest nodule, result in understaging of multifocal breast carcinomas due to underestimation of actual tumor size.     

Multifocal and multicentric breast cancer: does each focus matter?

PURPOSE: The identification of multiple tumors in the breast is associated with increased nodal involvement when compared with similar staged unifocal disease. This study compares two methods of tumor size assessment to predict tumor behavior in the relationship between size and axillary node involvement for patients with multifocal and multicentric breast cancer. METHODS: The histologic reports of every patient with multifocal breast cancer treated in New South Wales between April 1995 and September 1995 were examined. Tumors were assessed using two size estimates: (1) largest tumor focus diameter and (2) the aggregate diameters of all tumor foci. The dimensions were compared with unifocal tumors and against node positivity. RESULTS: Ninety-four (11.1%) of 848 women had multifocal breast cancer and of these 49 women (52.1%) had axillary node involvement compared with 37.5% with unifocal breast cancer (P =.007). The use of aggregate dimension reclassified significant numbers of multifocal tumors at a more advanced stage. Use of this method to stage cancers, rather than the largest tumor size, removed the excess node positivity when compared with unifocal, stage-matched breast carcinomas. CONCLUSION: The tendency of breast tumors to metastasize is a reflection of the total tumor load. Failure to measure the additional tumor burden provided by multiple small foci may understage a woman's disease. This may deny patients the opportunity of adjuvant therapies if the contribution of the smaller foci to the incidence of node positivity and survival is ignored.     

乳腺癌腋窝淋巴结转移血管生成的免疫组化研究

目的　研究乳腺癌腋窝淋巴结转移的血管生成情况。方法　采用内皮细胞ⅧFRAg 免疫组化染色技术,对37 例乳腺癌根治术或改良根治术切除的乳腺癌组织和121 枚腋窝转移淋巴结进行免疫组化染色。在100 倍视野下通过显微电视系统计数微血管密度( MVD) ,并用显微测量器测量转移灶的直径。结果　在121 个淋巴结中找到13 处微转移灶,其平均直径为(210 ±37) μm ,无血管生成。腋窝淋巴结转移瘤的MVD 为89-3 ±18-4 ,与乳腺癌组织MVD(93-8 ±21-8) 差异无显著性,且微血管分布不均,周围高于中央。结论　淋巴结微转移灶无血管生成,转移瘤有血管生成。为抑制微转移灶发展成转移瘤,以及抑制转移瘤的生长,抑制血管生成可能是控制淋巴结转移的有效措施。     

Sentinel node biopsy in patients with multiple breast cancer

BACKGROUND: Multicentric or multifocal breast cancer is considered a limitation for sentinel lymph node biopsy (SLNB). Studies showing that all quadrants of the breast drain via common afferent lymphatic channels indicate that multiple tumors do not affect lymphatic drainage. We therefore assessed the accuracy of SLNB in patients with multiple breast tumors. METHODS: Of the 942 breast cancer patients who underwent SLNB using radioisotope at Asan Medical Center between January 2003 and December 2006, 803 had unifocal and 139 had multiple tumors. Axillary dissection after SLNB was performed on 884 patients, 757 with unifocal and 127 with multiple tumors. All patients underwent lymphatic scintigram for removal of sentinel lymph nodes (SLNs). The clinical characteristics and accuracy of SLNB was compared in patients with unifocal and multiple breast cancer. RESULTS: In the multiple tumor group, 2.68 +/- 0.84 SLNs were identified in 136 of 139 patients (identification rate, 97.84%); 81.5% of SLNs were identified by scintigram. The incidence of axillary metastases was 29.50% (41/139). SLNB accuracy was 97.63% (124/127), with a false negative (FN) rate of 7.89% (3/38). In the unifocal group, 2.67 +/- 0.96 SLNs were identified in 787 of 803 patients (identification rate, 98.00%); 84.8% of SLNs were identified by scintigram. The incidence of axillary metastasis was 22.04% (177/803). SLNB accuracy was 98.02% (742/757), with a FN rate of 8.62% (15/174). The accuracy and FN rate of SLNB did not differ significantly between unifocal and multiple breast cancer. CONCLUSION: The accuracy of SLNB in multiple breast cancer is comparable to its accuracy in unifocal cancer. These findings indicate that SLNB can be used an as alternative to complete axillary lymph node dissection in patients with multiple breast tumors.     

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.     

Emmunohistochemical study on angiogenesis of axillary lymph node metastasis in human invasive breast carcinoma

The axially lymph node is one of the earliest and most common metastatic positions of breast carcinoma. Hence, axillary lymph node status (metastasis or no) and the number of metastatic lymph nodes are considered to be important indicators which affect prognosis of breast cancer patients. It has been widely confirmed that malignant solid tumor growth must be dependent upon angiogenesis/neovascularization. Considerable evidence has shown that microvessel density (MVD) of breast cancer tissue c…     

Axillary lymph node dose with tangential breast irradiation

PURPOSE: The advent of sentinel lymph node mapping and biopsy in the staging of breast cancer has resulted in a significant decrease in the extent of axillary nodal surgery. As the extent of axillary surgery decreases, the radiation dose and distribution within the axilla becomes increasingly important for current therapy planning and future analysis of results. This analysis examined the radiation dose distribution delivered to the anatomically defined axillary level I and II lymph node volume and surgically placed axillary clips with conventional tangential breast fields and CT-based three-dimensional (3D) planning. METHODS AND MATERIALS: Fifty consecutive patients with early-stage breast cancer undergoing breast conservation therapy were evaluated. All patients underwent 3D CT-based planning with conventional breast tangential fields designed to encompass the entire breast parenchyma. Using CT-based 3D planning, the dose distribution of the standard tangential breast irradiation fields was examined in relationship to the axillary level I and II lymph node volumes. Axillary level I and II lymph node anatomic volumes were defined by CT and surgical clips placed during complete level I-II lymph node dissection. Axillary level I-II lymph node volume doses were examined on the basis of the prescribed breast radiation dose and 3D dose distribution. RESULTS: All defined breast volumes received > or =95% of the prescribed dose. By contrast, the 95% isodose line encompassed only an average of 55% (range, 23-87%) of the axillary level I-II lymph node anatomic volume. No patient had complete coverage of the axillary level I-II lymph node region by the 95% isodose line. The mean anatomic axillary level I-II volume was 146.3 cm(3) (range, 83.1-313.0 cm(3)). The mean anatomic axillary level I-II volume encompassed by the 95% isodose line was 84.9 cm(3) (range, 25.1-219.0 cm(3)). The mean 95% isodose coverage of the surgical clip volume was 80%, and the median value was 81% (range, 58-98%). The mean volume deficit between the axillary level I-II volume and the surgical clip volume was 41.7 cm(3) (median, 30.0 cc). CONCLUSION: In this study, standard tangential breast radiation fields failed to deliver a therapeutic dose adequately to the axillary level I-II lymph node anatomic volume. No patient received complete coverage of the axillary level I-II lymph node volume. Surgically placed axillary clips also failed to delineate the level I-II axilla adequately. Definitive irradiation of the level I and II axillary lymph node region requires significant modification of standard tangential fields, best accomplished with 3D treatment planning, with specific targeting of anatomically defined axillary lymph node volumes as described, in addition to the breast parenchymal volumes.     

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.     

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.      

Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases

Two of the most important prognostic indicators for breast cancer are tumor size and extent of axillary lymph node involvement. Data on 24,740 cases recorded in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were used to evaluate the breast cancer survival experience in a representative sample of women from the United States. Actuarial (life table) methods were used to investigate the 5-year relative survival rates in cases with known operative/pathologic axillary lymph node status and primary tumor diameter. Survival rates varied from 45.5% for tumor diameters equal to or greater than 5 cm with positive axillary nodes to 96.3% for tumors less than 2 cm and with no involved nodes. The relation between tumor size and lymph node status was investigated in detail. Tumor diameter and lymph node status were found to act as independent but additive prognostic indicators. As tumor size increased, survival decreased regardless of lymph node status; and as lymph node involvement increased, survival status also decreased regardless of tumor size. A linear relation was found between tumor diameter and the percent of cases with positive lymph node involvement. The results of our analyses suggest that disease progression to distant sites does not occur exclusively via the axillary lymph nodes, but rather that lymph node status serves as an indicator of the tumor's ability to spread.     

Clinical relevance of the distribution of the lesions in 500 consecutive breast cancer cases documented in large-format histologic sections

BACKGROUND: Breast carcinoma is a heterogeneous group of diseases deviating from each other not only in their clinical manifestations and outcome but also in their histologic appearance. The submacroscopic morphology of breast carcinomas, the distribution of the lesions, and the extent of the disease are seldom studied. Even more infrequently are these parameters included in surgical pathology reports. Conversely, the routine use of large-format histologic sections in workup of operated breast specimens provides better insight into the significance of these parameters. The aim of the study was to identify breast carcinoma growth patterns indicating increased metastatic potential of the tumor and a need for more aggressive therapy. METHODS: In all, 500 consecutive breast cancer cases, all of which were documented on large-format histologic sections, were retrospectively analyzed. The distribution of both in situ and invasive components of the tumors (unifocal/multifocal/diffuse) was defined, determined, and compared with the type of surgical intervention performed and the frequency of ipsilateral lymph node metastasis as endpoints. The extent of the disease, the size of the tumor, the presence or absence of lymphovascular invasion (LVI), and the proportion of invasive lobular carcinomas in the categories with different distributions were also analyzed. RESULTS: Only 34% of the analyzed cases could be categorized as unifocal. This kind of tumor distribution was associated with lymph node metastasis in 28% of the cases, with LVI in 18%, with breast-conserving surgery in 67%, and with a proportion of 4% invasive lobular carcinomas. Tumors with a unifocal invasive component upgraded to multifocal or diffuse because of the distribution of the associated in situ component had similar characteristics. With their larger extent, tumors with a diffuse in situ component required mastectomy in 43% of cases. Multifocal distribution of the invasive component in the tumors was associated with higher frequency of LVI (42%) and lymph node metastases (48%), with a substantially lower number of cases undergoing breast-conserving surgery (33%) and with a higher proportion of lobular carcinomas (25%). If the multifocal invasive foci were associated with a diffuse in situ component, the proportion of invasive lobular carcinomas was only 5%. The extent of the lesions (defined as the area of breast tissue involved by in situ, invasive, and/or intravascular tumor foci) was >or=2 cm in >90% of multifocal cases and >or=4 cm in >70%. Diffusely growing invasive carcinomas were rare (only 20 cases), but were associated with lymph node metastasis in 60% of cases and resulted in mastectomy in 85% of the cases. Approximately two-thirds (65%) of these tumors belonged to invasive lobular carcinomas. The extent of diffusely growing invasive carcinomas was >or=4 cm in 75% of the cases. Although LVI was detected in only 10% of tumors with a diffusely growing invasive component, such tumors were found to have lymph node metastasis significantly more often (odds ratio of 2.33) and required mastectomy much more frequently (odds ratio of 2.58) compared with purely unifocal breast carcinomas. CONCLUSIONS: These results indicate that the distribution of invasive and in situ tumor structures in breast carcinomas as defined in the current study, together with the extent of disease, are important morphologic parameters which determine the required surgical intervention and are related to biologic factors such as metastatic capacity. The method of large-section histology allows the examiner to properly document and demonstrate these important parameters, thus facilitating understanding of their clinical relevance.     

Obesity and body fat distribution and breast cancer prognosis

This study addresses the effect of obesity and body fat distribution on axillary lymph node involvement, tumor size, and estrogen receptor (ER) level in breast cancer patients. Anthropometric measurements were prospectively obtained on 248 consecutively and newly diagnosed women with invasive breast cancer. The anthropometric measurements evaluated were abdomen, thigh, subscapular, and midaxillary skinfolds; weight; and height. Weight and Quetelet Index (kg/m2) were significantly (P = 0.001) associated with lymph node involvement in postmenopausal patients. The abdomen:thigh skinfold ratio was significantly higher in premenopausal patients (P = 0.004) and postmenopausal (P = 0.03) without axillary node involvement compared with women with 4+ axillary node involvement. The abdomen:thigh skinfold was higher (P = 0.05) in women with smaller breast cancers (less than 2.0 cm) and higher ER levels. Weight and Quetelet Index did not affect tumor size or ER level. This study demonstrated that obese postmenopausal women who developed breast cancer tend to have more axillary node involvement than their leaner counterparts. Generalized obesity did not affect tumor size or ER level. Premenopausal and postmenopausal women with upper body fat distribution appear to be a subset of women who have a more favorable prognosis as measured by less lymph node involvement, smaller tumors, and higher levels of ER in their tumors.     

超声判断乳腺癌患者腋淋巴结转移的多因素分析

目的 观察乳腺癌患者原发灶及腋下淋巴结（LN）的超声诊断图像和彩色Doppler特点,分析淋巴结转移（LNM）的相关因素,以获得超声诊断乳腺癌患者腋下LNM的较佳组合指标。方法 超声观察113例乳腺癌患者的原发灶和腋LN。观察原发灶的位置、最大径、数量、内部钙化灶边带回声、边界、肿瘤内部的血流丰富程度分级（0-Ⅲ级）、最高流速和阻力指数;观察患侧腋LN目最大径、纵横比、纵切面皮质厚度与淋巴门厚度比值（皮／门比）、皮质局部最大厚径、淋巴结的血流分布类型、最高流速和阻力指数。全部患者均进行乳房改良根治术,以腋LN清扫的病理结果作为金标准,对与LNM相关的影像及临床因素进行单因素及多因素分析（Logistic回归）,并利用受试者工作率性（ROC）曲线评价诊断指标。结果 113例乳腺癌患者的超声观察指标单因素分析结果显示,原发灶的最大径、多发或弥漫、血流丰富度,对腋LNM有影响,差异有统计学意义（P=0．029-0．005）腋LN的纵横比、皮／门比、皮质局部最大厚径、血流分布类型与腋LNM有关,差异有统计学意义（P=0．000）。将单因素分析有意义的指标进行多因素分析,与腋LNM有关的影响因素为：LN的皮／门比LN的纵横比以及原发灶的最大径,利用ROC曲线评价各单项指标及其不同组合指标的诊断价值结果显示,LN皮／门比＋LN纵横比＋原发灶最大径这一组合指标最优,其ROC曲线的线下面积最大,即灵敏度和特异度之和最大。结论 对乳腺癌患者进行腋LN超声扫查,综合考虑原发灶大小LN的纵横比、皮质厚度及其与淋巴门厚度的比例关系,将有助于提高超声诊断腋LNM的正确率,较为准确地判断腋LN的状态。     

Subareolar injection of 99m-Tc sulfur colloid for sentinel nodes identification in multifocal invasive breast cancer

The objective were to study the relevance of the subareolar injection for sentinel node [SN] detection in multiple foci breast cancer. Seventy-nine patients with infiltrative breast carcinoma (diagnosed pre-operatively by core biopsy) and a mean age of 55 (31-78) years were enrolled. All patients were free of previous homolateral surgery, chemotherapy, locoregional radiotherapy or prevalent axillary lymph node. Using four 0.1 ml injections of 1.8 MBq, the technetium-99m 100 nm filtered sulfur colloid was injected by subareolar way (group I) in 16 cases of radiologically cancer with multiple invasive foci and 31 cases of radiologically unifocal cancer, and by peritumoral way (group II) in 32 cases of radiologically unifocal cancer. Scintigrams were obtained 2 to 4 hours after the injections and radioactive nodes were detected peroperatively 18 hours after the injection by intraoperative detection probe. Individual removal of all radioactive nodes was followed by axillary dissection at levels I and II of Berg including Rotter area control. All sentinel nodes were submitted to standard histopathological analysis on serial sections at 500 mu intervals completed by immunohistochemistry for cytokeratin on negative SN. SN were detected by scintigrams in 85% and 88% of the cases of group I and group II respectively, but in 98% and 97% of the cases of respectively both groups by intraoperative probe. Group I was composed of 69% ductal, 22% lobular and 9% tubular carcinomas, and group II of 87% ductal, 10% lobular and 3% tubular carcinomas. Seven and 5 radiologically unifocal tumors were in fact with multiple invasive foci at histology in groups I and II respectively. The complete scintigraphic procedure permitted the detection of a mean number of 2.7 (1-7) SN in group I and 2.3 (1-4) in group II (NS). In group I, the SN were metastatic in 22 patients (48%), 15 of them with the metastases being restricted to the SN, whereas in group II, the SN were metastatic in 9 patients (28%), 5 of them with the positivity restricted to the SN. No false negative result (SN negative and other axillary nodes positive) was observed in group I and only one false negative result in group II which was related to a cancer with histological multiple invasive foci. Sensitivities were 100% and 90%, and negative predictive values were 100% and 95%, for groups I and II respectively. Subareolar injection of radiocolloid allows identification of SN in cases of unifocal and multiple cancer. The mean number of SN detected by the subareolar method is not significantly different, although higher, to that detected by peritumoral injection.     

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.     

Infiltrating breast carcinoma smaller than 0.5 centimeters. Is lymph node dissection necessary?

BACKGROUND: The incidence of axillary lymph node metastases from infiltrating breast carcinomas measuring 1.0 cm or smaller reported in the literature varies from 0% (for tumors measuring < or =0.5 cm) to 27.1% (for all tumors < or =1 cm). METHODS: The authors examined all infiltrating breast carcinomas measuring 1.0 cm or smaller with axillary lymph node dissections in patients seen at their institution between January 1990 and March 1997 (117 cases) to determine the incidence of axillary lymph node metastases. All tumors were evaluated for patient age, histologic type of tumor, modified Bloom-Richardson grade, estrogen and progesterone receptor status, ploidy, S-phase fraction, and angiolymphatic vessel invasion, to determine whether there was a relation between the indicators and axillary lymph node metastases. The authors also performed immunohistochemical stains for the basement membrane components laminin and Type IV collagen on the tumors demonstrating metastases and on an equal number of size- and date-matched tumors not demonstrating metastases. RESULTS: Twelve cases of infiltrating carcinoma with axillary lymph node metastases were identified (a 10.3% overall incidence of metastases). Lymph node metastases were not identified in any of the cases with tumors measuring < or =0.5 cm (24 cases). The incidence of axillary lymph node metastases for carcinomas 0.6-1.0 cm was 12.9% (12 of 93 cases). High nuclear grade was found to correlate with the presence of lymph node metastases (P = 0.007). No statistically significant correlation was found between the other indicators examined and axillary lymph node metastases or between basement membrane staining and axillary lymph node metastases. CONCLUSIONS: The authors concluded that infiltrating breast carcinomas measuring < or =0.5 cm are unlikely to have demonstrable axillary lymph node metastases. Lymph node dissections in these women may be unnecessary. Nuclear grade may be the best predictor of lymph node metastases in T1b tumors.     

乳腺导管原位癌伴微浸润发生腋窝淋巴结转移的相关因素分析

目的探讨乳腺导管原位癌伴微浸润(breast ductal carcinoma in situ withmicroinvasion,DCIS-Mi)患者发生腋窝淋巴结转移的危险因素。方法应用回顾性调查方法收集2000年1月至2008年10月可手术乳腺DCIS-Mi病例共174例,分析有无腋窝淋巴结转移患者的不同分子病理特征,并通过χ2检验、Spearman检验以及Logistic回归分析筛选腋窝淋巴结转移的危险因素。结果 174例DCIS-Mi患者中,有腋窝淋巴结转移者9例(5.17%)。DCIS-Mi病灶中,DCIS级别与腋窝淋巴结转移呈正相关(r=0.262,P=0.000),激素受体状态与腋窝淋巴结转移呈负相关(r=-0.192,P=0.011)。经Logistic回归分析各因素相互调整后,DCIS高级别(OR=37.191,P=0.005)和肿瘤直径≥4.0cm(OR=29.634,P=0.023)是DCIS-Mi病灶发生转移的高危因素。结论在DCIS-Mi患者中,DCIS级别高和肿瘤直径≥4.0cm者容易发生腋窝淋巴结转移,对此类患者进行个体化治疗是必要的。     

Loss of FHIT expression in breast cancer is correlated with poor prognostic markers.

OBJECTIVE: The fragile histidine triad (FHIT) gene is a putative tumor suppressor gene that is thought to be involved in the carcinogenesis of breast cancer. Loss of FHIT expression has been observed in up to 72% of breast cancers and has been associated with increased p53, a high proliferation index, and increased tumor size and grade. However, loss of FHIT expression has not been investigated in association with apoptosis and cyclooxygenase-2 (COX-2) expression in breast cancer. Furthermore, expression of FHIT in primary breast tumors and their metastatic axillary lymph nodes has also not been previously described. The purpose of this study was to evaluate the expression of FHIT, COX-2, bcl-2, and p53 in primary breast tumor tissue; correlate their expression with known clinical and pathologic markers; and in cases when tissue was available, evaluate the expression of FHIT and COX-2 in the corresponding metastatic axillary lymph node in the same patient. METHODS: Primary breast tumor specimens from 80 patients were examined for the presence of FHIT, COX-2, bcl-2, and p53 expression by immunohistochemistry using standard methods. When tissue was available, the expression of FHIT and COX-2 was also evaluated in the corresponding metastatic axillary lymph node specimen. RESULTS: FHIT expression in primary breast tumors was 56%. There was a significant correlation between FHIT expression in primary breast tumor and bcl-2 expression (P = 0.017). We also observed a significant inverse correlation between FHIT expression in primary breast tumor tissue and p53 expression (P = 0.023) in lymph node-negative cases. A significant inverse correlation between FHIT expression in the primary tumor and Ki-67 (P = 0.009) was also observed in lymph node-negative cases. FHIT expression in primary tumors correlated with FHIT expression in the metastatic lymph node (52.5%; P = 0.001). FHIT expression in primary tumors did not correlate with COX-2 expression. CONCLUSION: Our results suggest that loss of FHIT expression in breast cancer is associated with poor prognostic features. Furthermore, loss of FHIT expression is also seen in metastatic axillary lymph node. The prognostic and predictive value of these findings needs to be further evaluated in larger trials with longer follow-up.     

PET-CT-based auto-contouring in non-small-cell lung cancer correlates with pathology and reduces interobserver variability in the delineation of the primary tumor and involved nodal volumes

PURPOSE: To compare source-to-background ratio (SBR)-based PET-CT auto-delineation with pathology in non-small-cell lung cancer (NSCLC) and to investigate whether auto-delineation reduces the interobserver variability compared with manual PET-CT-based gross tumor volume (GTV) delineation. METHODS AND MATERIALS: Source-to-background ratio-based auto-delineation was compared with macroscopic tumor dimensions to assess its validity in 23 tumors. Thereafter, GTVs were delineated manually on 33 PET-CT scans by five observers for the primary tumor (GTV-1) and the involved lymph nodes (GTV-2). The delineation was repeated after 6 months with the auto-contour provided. This contour was edited by the observers. For comparison, the concordance index (CI) was calculated, defined as the ratio of intersection and the union of two volumes (A intersection B)/(A union or logical sum B). RESULTS: The maximal tumor diameter of the SBR-based auto-contour correlated strongly with the macroscopic diameter of primary tumors (correlation coefficient = 0.90) and was shown to be accurate for involved lymph nodes (sensitivity 67%, specificity 95%). The median auto-contour-based target volumes were smaller than those defined by manual delineation for GTV-1 (31.8 and 34.6 cm(3), respectively; p = 0.001) and GTV-2 (16.3 and 21.8 cm(3), respectively; p = 0.02). The auto-contour-based method showed higher CIs than the manual method for GTV-1 (0.74 and 0.70 cm(3), respectively; p < 0.001) and GTV-2 (0.60 and 0.51 cm(3), respectively; p = 0.11). CONCLUSION: Source-to-background ratio-based auto-delineation showed a good correlation with pathology, decreased the delineated volumes of the GTVs, and reduced the interobserver variability. Auto-contouring may further improve the quality of target delineation in NSCLC patients.     

Progesterone Receptor Status and Tumor Size as Possible Indicators of Axillary Lymph Node Involvement in T1 Carcinoma of the Breast

Disagreement persists on the necessity of axillary lymph node dissection for small T1 stage unilateral breast cancers. In this study of 120 women with T1 primary tumors who underwent extensive dissection, better definition of pathological factors that can predict axillary node metastases might have spared 88 (73.3%) who were node negative. We assessed age, tumor size, histology, grade and hormone receptor status as possible indicators of lymph node involvement. As expected, tumor size was a strong predictor of the likelihood of node involvement (p = 0.026 in univariate and p = 0.0024 in multivariate analyses). Progesterone receptor status also correlated significantly (p = 0.0008 in univariate and p = 0.017 in multivariate analyses) with axillary positivity. Tumor grade was found to be significant (p = 0.018) only in univariate analysis. These findings contribute to the ongoing search for confident selection of subgroups of patients who will undergo lumpectomy but can safely be spared axillary node dissection.