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.     

C-erbB-2 oncoprotein expression versus internal mammary lymph node metastases as additional prognostic factors in patients with axillary lymph node-positive breast cancer.

The relationship was assessed between c-erbB-2 oncoprotein expression and other prognostic factors in breast cancer, such as axillary and internal mammary node metastases. The value of these indicators was analyzed in estimating prognosis, especially in patients with axillary node-positive breast cancer. These results showed that c-erbB-2 is significantly related to clinical stage and axillary node metastases. A univariate study revealed that disease-free and overall survival were correlated significantly with clinical stage, tumor size, axillary and internal mammary node metastases, and 21N status. Among the patients with axillary node involvement, however, 21N status did not appear to be a significant additional prognostic factor. Internal mammary node metastases were significant. In a multivariate study, only axillary and internal mammary node metastases were significant prognostic factors for either the entire group of patients or those with positive axillary nodes. Therefore, axillary node dissection and biopsy of the internal mammary nodes may provide important prognostic information for patients with breast cancer.     

Importance of the level of axillary involvement in relation to traditional variables in the prognosis of breast cancer.

Survival in breast cancer correlates with the presence of metastatic lymph nodes, so that removal and pathological examination of the axillary nodes provides the most important prognostic information and basis for planning subsequent therapy. However as the size of primary tumours at diagnosis is decreasing, the likelihood of axillary involvement is also declining, so that the indications for axillary dissection are undergoing radical revision. To definitively establish the value of removing all three axillary lymph node levels (as defined by Berg) in node positive breast cancer, retrospective analysis of a large series receiving complete dissection was carried out. consecutive breast cancer patients (n=1003) with positive axillary nodes were analyzed: all received identical axillary treatment and the three levels were tagged with metal disks to facilitate recognition and pathological examination. Follow-up (mean 97 months) was exceptionally complete. The length of disease-free and overall survival were taken as the primary endpoints. The variables considered in the statistical analysis were tumour size, number of metastatic nodes, axillary invasion by level (the three classic levels), perilymphnodal invasion and age. By univariate analysis, overall and disease-free survival decreased significantly as tumour diameter, number of involved lymph nodes, and involvement by axillary level increased. Multivariate analysis assessing the relative importance of these variables when all were considered together found that they were all important independent predictive factors for survival. This study confirms the importance of tumour size and number of metastatic axillary nodes as predictors of outcome in breast cancer. In addition, the level of axillary invasion as a third independent factor of equal importance to the established indicators was identified. When axillary dissection is performed it should be complete, and all three Berg levels tagged separately, so that involvement by level can be ascertained. This provides additional important prognostic information on which to base subsequent treatment decisions.     

Importance of nuclear morphology in breast cancer prognosis.

The purpose of this study is to define prognostic relationships between computer-derived nuclear morphological features, lymph node status, and tumor size in breast cancer. Computer-derived nuclear size, shape, and texture features were determined in fine-needle aspirates obtained at the time of diagnosis from 253 consecutive patients with invasive breast cancer. Tumor size and lymph node status were determined at the time of surgery. Median follow-up time was 61.5 months for patients without distant recurrence. In univariate analysis, tumor size, nuclear features, and the number of metastatic nodes were of decreasing significance for distant disease-free survival. Nuclear features, tumor size, and the number of metastatic nodes were of decreasing significance for overall survival. In multivariate analysis, the morphological size feature, largest perimeter, was more predictive of disease-free and overall survival than were either tumor size or the number of axillary lymph node metastases. This morphological feature, when combined with tumor size, identified more patients at both the good and poor ends of the prognostic spectrum than did the combination of tumor size and axillary lymph node status. Our data indicate that computer analysis of nuclear features has the potential to replace axillary lymph node status for staging of breast cancer. If confirmed by others, axillary dissection for breast cancer staging, estimating prognosis, and selecting patients for adjunctive therapy could be eliminated.     

Lymph node metastases versus DNA ploidy as prognostic factors for invasive ductal carcinoma of the breast

We evaluated the relationship between the DNA ploidy status and other variable prognostic factors, especially regional lymph node metastases, in 121 patients with invasive ductal carcinoma of breast, together with the value of these factors in estimating the prognostic of breast cancer. The ploidy status was diploid in 40% of the patients, and aneuploid in 60%. A significantly higher incidence of aneuploidy was found in patients with more than 4 positive axillary lymph nodes, positive internal mammary lymph nodes, or clinical stage 3 of malignancy. In a univariate study, overall survival and disease-free survival were significantly correlated with axillary and internal mammary lymph node metastases, tumor size, and clinical stage of malignancy. The disease-free survival rates for the diploid group tended to be somewhat higher than those for the aneuploid group of patients without axillary lymph node metastases. In the multivariate analysis, however, only axillary lymph node metastasis was significantly correlated with overall survival and disease-free survival. There was also a trend for the internal mammary lymph node metastases to be correlated with survival. As the DNA ploidy status was closely correlated with the axillary and internal mammary lymph node metastases, it did not appear to be an independent prognostic factor in this small series.     

Interest of periareolar injection for colorimetric detection of sentinel node in breast cancer

Most teams working on sentinel node biopsy in the treatment of breast cancer inject either radioactive colloid or vital blue dye around the primary tumour. Many anatomical studies and lymphoscintigraphical studies, some very old, have shown that the lymphatic drainage of the breast is collected first in the periareolar plexus of Sappey, then routed to the axilla in 95% of cases, via one or two primary collectors. In a series of 94 breast cancers measuring less than 3 cm, with any palpable axillary lymph node, 2 ml of patent blue was injected intradermally around the areola, at the two meridians around the tumor. The sentinel node was identified in 89 cases (94,7%), regardless of the location of the primary tumor. All the sentinel nodes were located in the lower axilla. An average of 1.6 nodes were found per patient. In 41 cases, axillary lymph node dissection was performed either immediately (5 technical failures, 9 positive frozen section) or delayed only if the sentinel node was positive, either on standard H&E staining or on immunohistochemistry (27 cases). Thus, axillary lymph node dissection was not performed in 48 patients (55%). In positive node patient, the sentinel node was the only positive lymph node in 20 patients (55%). For 5 positive node patients, axillary lymph node dissection was not performed: poor vital status (2 micro-metastatic nodes) or by decision of patient (3 IHC positive nodes). With this periareolar injection procedure, the rate of detection is highly satisfactory and is comparable to that usually published with peritumoral injection. This procedure seems appropriate in all cases, regardless of the topography, the size or the multifocality of breast cancer.     

男性乳腺癌的临床病理特征和预后分析

目的 分析男性乳腺癌(MBC)患者的临床病理特征,并探讨影响其预后的因素.方法 对23例MBC患者的病历资料进行回顾性分析.采用Kaplan-Meier法计算患者的生存率,并对影响患者预后的危险因素进行分析.结果 23例MBC患者的发病年龄为37~82岁,中位年龄61.6岁;肿瘤平均直径为3.8 cm.全组患者的3年、5年、10年总生存率分别为84.0%、61.6%、54.8%;3年、5年、10年无病生存率分别为63.1%、51.6%、51.6%.单因素分析结果显示,TNM分期、原发肿瘤大小、腋窝淋巴结是否转移对MBC患者的5年总生存率和无病生存率均有影响(P﹤0.05);激素受体状态对MBC患者的5年生存率有影响(P﹤0.05),对MBC患者的5年无病生存率无影响(P﹥0.05).结论 TNM分期、原发肿瘤大小、腋窝淋巴结是否转移是影响MBC患者5年总生存率和无病生存率的预后因素;激素受体状态是影响MBC患者5年生存率的预后因素.早期诊断及综合治疗是延长MBC患者生存期的关键.     

The correlation between the spread of metastases by level in the axillary nodes and disease-free survival in breast cancer. A multifactorial analysis

Axillary lymph nodes were separated from 492 radical or modified radical mastectomies for primary breast cancer and examined according to their anatomical level corresponding to their position along the theoretical pathway of lymph drainage from the breast. The patterns of metastasis and the relationship between metastatized levels and disease-free survival were investigated to see whether complete axillary dissection is necessary for the staging and the planning of adjuvant therapy in breast cancer.Progressive involvement from level I (proximal) to level III (distal) was found in 206 specimens (80.8% of tumors with axillary metastases), while discontinuous or “skip” metastases were present in 49 (19.2%), including 38 (14.9%) with positive nodes at level II or III but not at level I. “Skip” metastasis was more frequent when fewer than four nodes were positive, and not related to either the size and the primary tumor or its location.The effect of age, menopausal status, tumor size, node status, number of positive nodes, anatomic level of axillary node involvement, estrogen and progesterone receptors, and adjuvant therapies on disease-free survival was evaluated using a multivariate proportional hazard model and life table analysis. This showed that disease-free survival was strongly related to the number of positive nodes (P < 0.001), tumor size (P = 0.001) and level of node involvement (P = 0.01) as independent prognostic factors. Moreover, the subset of patients with four or more positive nodes and involvements of level III had a higher risk of recurrence (25% recurrence-free patients 5 years after mastectomy).The high frequency of “skip” mestastases and the prognostic value of both the level of involvement and the number of metastatic nodes suggest that a complete axillary dissection is needed in the surgical management of breast cancer to obtain all the data useful in the planning of adjuvant therapy.     

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.     

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.     

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.      

Treatment results and prognostic factors of early breast cancer treated with a breast conserving operation and radiotherapy

BACKGROUND: The purpose of this study was to analyze the prognostic factors affecting local control and survival rates for patients with early breast cancer who received breast conserving treatment (BCT) and to find out the optimal treatment according to their risk factors. METHODS: From October 1994 to December 2001, 605 patients with 611 stage I and II breast cancers received BCT, and the results were analyzed retrospectively. BCT consists of breast conserving surgery and whole breast irradiation. All the patients underwent lumpectomy or quadrantectomy. Axillary lymph node dissection or sentinel lymph node biopsy was performed in 608 cases (99.5%). The radiation dose to the whole breast was 50.4 Gy over 5 weeks with a 1.8 Gy daily fraction and with boost doses of 9-14.4 Gy administered to the tumor bed. Adjuvant chemotherapy was performed in most of the patients with axillary lymph node metastasis or tumors larger than 1 cm. The median follow-up period was 47 months. RESULTS: Local relapse, regional relapse and distant metastasis occurred in 15 (2.5%), 16 (2.6%) and 43 patients (7.1%), respectively. The 5-year overall survival, local-relapse-free survival, distant-metastasis-free survival and disease-free survival rates were 95.3%, 97.2%, 91.3% and 88.5%, respectively. On multivariate analysis, age (P = 0.02), number of involved axillary lymph nodes (P = 0.01) and nuclear grade (P = 0.01) affected the local-relapse-free survival. The factors associated with disease-free survival were the T stage (P = 0.05), number of involved axillary lymph nodes (P = 0.01) and nuclear grade (P = 0.001). Overall survival was associated with the T stage (P = 0.02), number of involved axillary lymph nodes (P = 0.01) and c-erb B2 overexpression (P = 0.05). Patients with more than two factors among (i) age 1 cm, (ii) positive lymph node metastasis and (iii) high nuclear grade showed an inferior 5-year disease-free survival rate compared with others (P = 0.0005). CONCLUSIONS: The most important prognostic factor affecting local control, disease-free survival and overall survival was axillary lymph node metastasis. The nuclear grade influenced local control and disease relapse. Patients with multiple unfavorable risk factors such as positive axillary lymph nodes, high nuclear grade, young age and large tumor showed poorer local control and disease-free survival than patients without any risk factors, and so more aggressive treatment is required for these patients.     

The benefits and limitations of sentinel lymph node biopsy

Opinion statement The status of the axilla is the single most important prognostic indicator of overall survival in patients with breast cancer. Staging is based on tumor size and on the presence of lymph node metastases. The number of lymph nodes, although prognostic, no longer impacts treatment options. Sentinel lymph node (SLN) mapping and dissection is a more sensitive and accurate technique for nodal evaluation and has been applied to staging of axillary lymph nodes in patients with breast cancer, providing prognostic information, with less surgical morbidity than with axillary lymph node dissection (ALND). When analyzed by an experienced pathologist with serial sectioning and immunohistochemical evaluation, SLN is the most accurate detection tool used in staging of breast cancer. In many centers that use these staging principles, ALND is no longer performed for histologically negative axillary SLNs. In addition, this technique may also be therapeutic because in most patients, the SLN is the only positive axillary node. SLN biopsy is justified in women with ductal carcinoma in situ who have a high risk of invasive carcinoma, such as those with large tumors, a mass, or high-grade lesions. SLN biopsy is performed in the setting of neoadjuvant chemotherapy and demonstrates accurate evaluation of the axilla in 90% of the cases. Women with locally advanced breast cancer may derive great benefit from a minimally invasive approach to the axilla because the extent of nodal involvement is unlikely to change further treatment. For clinically palpable nodes, ALND should be performed for therapeutic and local control. The use of sentinel node mapping in pregnancy is controversial. Vital blue dye is contraindicated in pregnant patients, although some have used radioactive colloid alone to map this subgroup of patients.     

Identifying good prognosis group of breast cancer patients with 1-3 positive axillary nodes for adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy

OBJECTIVE: We conducted a retrospective analysis of prognosis factors for survival in breast cancer patients with 1-3 axillary lymph node metastases and tried to identify a subset of patients with good prognosis suitable for cyclophosphamide, methotrexate and 5-fluorouracil (CMF) adjuvant chemotherapy. METHODS: A cohort of 446 breast cancer patients received definite surgery and adjuvant chemotherapy with CMF at Chang Gung Memorial Hospital from 1990 to 1998. They were enrolled in the study. The median follow-up time was 69 months. Prognostic factors including age, tumor size, number of involved nodes, steroid receptor status, tumor ploidy, synthetic-phase fraction, histologic grade and administration of tamoxifen were analysed for disease-free survival (DFS) and overall survival (OS) by Cox regression model. RESULTS: The estimated 5 year OS and DFS for all patients were 85.4 and 71.5%, respectively. Multivariate analysis revealed that tumor size, age and estrogen receptor (ER) status were independent prognostic factors for OS, and tumor size, age, ER status and number of involved nodes were independent prognostic factors for DFS. The 5 year OS rates of the low-risk group (age >40, tumor < or =3 cm and positive ER) and average-risk group (either age < or =40, tumor >3 cm or negative ER) were 98.8 and 82.4%, respectively (P = 0.0001). The 5 year DFS of the low-risk and high-risk group were 88.2 and 67.7%, respectively (P = 0.0001). CONCLUSION: Among breast cancer patients with 1-3 positive lymph nodes excellent survival rate was found in those who had favorable prognostic factors, including age >40, tumor size < or =3 cm and positive ER. Adjuvant chemotherapy with CMF regimen is optimal for these low-risk patients.     

Prognostic indicators for breast cancer patients with one to three regional lymph node metastases, with special reference to alterations in expression levels of bcl-2, p53 and c-erbB-2 proteins

Patients with primary breast carcinoma with one to three axillary lymph node metastases but without distant metastases (n1-3) in Japan have been shown to have a 10-year disease-free survival rate of > 60%. It would be reasonable to divide n1-3 Japanese breast cancer patients into groups with high- or low-risk for recurrence and to consider post-operative adjuvant therapy. In the present study, we analyzed 228 consecutive Japanese patients with n1-3 breast cancer who underwent radical mastectomy and were followed up for a median time of 11.0 years. The expression of bcl-2, p53 and c-erbB-2 proteins in the primary tumors was examined immunohistochemically and their prognostic roles were also analyzed along with conventional clinicopathologic indicators. bcl-2 expression was correlated with positive estrogen receptor status and inversely correlated with p53, c-erbB-2 and histologic grade. Univariate analysis showed that bcl-2, p53 and c-erbB-2 expression were prognostic indicators of the patient's group as well as node status, histologic grade, tumor size, age at diagnosis, menopausal status and estrogen receptor status. Cox's regression analysis demonstrated that the number of nodes involved, menopausal status, p53 and bcl-2 were independent predictors for overall survival and that histologic grade and the number of nodes involved were independent predictors for disease-free survival. These results suggest that bcl-2 expression in combination with p53 and c-erbB-2 expression, the number of lymph node metastases, histologic grade and menopausal status are useful in selecting subgroups of n1-3 breast cancer patients with good or poor prognoses.      

157例35岁以下女性乳腺癌的预后分析

目的 分析青年期乳腺的临床和病理学特点以及这些因素对生存期的影响。方法 对1962－1993年间157例青年期乳腺癌作回顾性总结,分析病理类型、肿瘤大小、腋淋巴结情况、TNM分期与生存率的关系,以及妊娠乳腺癌的预预后。结果 发病率占同期乳癌人群的8．9％,十年 生存率45．9％。肿瘤＞3cm,腋淋巴结转移82．5％。十年生存率22．4％;肿瘤≤3cm,腋淋巴结转移45．9％,十年生存率59．6％（P＜0．001）。腋淋巴结转移数量≥4枚,5年内死亡率高达61．8％。Ⅱb期以早的病人五年生存率83．0％,Ⅲa期以后的病人五年生存率31．1％。妊娠或产后1年内乳腺癌十年总生存率51％。结论 青年期乳腺癌与年长内乳腺癌十年总生存率51％。结论 青年期乳腺癌与年长组相比不更差的预后、肿瘤大小与腋淋巴结转移以及数量呈正相关,肿瘤大小、腋淋巴结转移数量与生存率负相关。Ⅱb基以早病人显示良好预后。妊娠或产后1年内乳腺癌预后并不差。手术范围扩大不体现生存优势。     

Indications for sentinel lymph node biopsy in patients with breast cancer: retrospective and simulation analyses

BACKGROUND: The disease status of axillary lymph nodes at diagnosis is the most powerful predictor of prognosis for patients with breast cancer. Axillary lymph node dissection (ALND) has been the standard treatment. Recently, lymphatic mapping and sentinel lymph node biopsy (SNB) have been suggested as alternatives to ALND. However, a clear indication for SNB has not yet been established. The goal of this study was to determine which patients might best benefit from the SNB method. METHODS: A retrospective study compared the relationship of age, menopausal status, tumor size group, histology and clinical evaluation of nodes to histological axillary lymph node status in 5892 consecutive Japanese breast cancer patients who underwent ALND. A simulation analysis with reported SNB sensitivity and specificity was carried out. RESULTS: Clinical lymph node evaluation was the most relevant factor to predict axillary nodal status. However, even patients with no clinical nodal involvement (N0) showed only 71% axillary nodal negativity. Tumor group based on tumor size and histology also related to axillary nodal status. The simulation analysis revealed that of patients with negative lymph node probability, more than 66% were good candidates for SNB. CONCLUSION: The clinically negative node (N0) is the most important indication for SNB. Therefore, the candidates for SNB should be picked from the patients with N0. When no histological information is available, patients whose tumor is 20 mm or smaller are candidates for SNB. When histological information is available, the SNB indication extends to patients whose type of tumor has histologically good prognosis or a low probability of having nodal involvement, regardless of tumor size.     

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.     

乳腺癌临床特征与预后分析

目的：总结经综合治疗的233例乳腺癌患者的临床病理特征及生存情况,探讨影响乳腺癌预后的因素。方法：建立乳腺癌患者的临床资料库,采用SPSS8.0统计软件对临床数据进行单因素及多因素生存分析,以发现影响乳腺癌长期生存的因素。结果：所有患者1、2、3、5和8年生存率分别为95.71%（223/233）、82.83%（193/233）、61.37%（143/233）、37.34%（87/233）和6.87%（16/233）。单因素分析显示腋淋巴结转移数目;原发肿瘤大小与生存呈负相关（P均〈0.001）;TNM晚期患者复发转移的患者中位生存明显缩短（P均〈0.0001）;术后辅助化疗方案选择含有蒽环类的方案组生存期优于不含有蒽环类的方案组（P〈0.05,X^2=9.99）;病理类型治疗方式与生存时间相关（P均〈0.01）。COX比例风险模型分析显示治疗方式、术后辅助性化疗方案和复发转移具有独立预后意义（P〈0.05）。Logistic分析结果显示,原发肿瘤大小、腋窝淋巴结转移状态、病理类型、综合治疗方式是影响乳腺癌复发转移的主要因素,其影响程度的排序依次是腋窝淋巴结转移、原发肿瘤大小、病理类型、综合治疗方式（P〈0.0001）。结论：乳腺癌患者的远期生存及复发转移与原发肿瘤大小、腋窝淋巴结转移状态、病理类型、术后化疗方案的选择及个体化综合治疗方式密切相关。     

The prognosis of small primary breast cancers

The Nottingham Prognostic Index (NPI) is an integrated prognostic index used to predict patient survival for women with invasive breast cancer. The index is based on invasive tumour size, histological lymph node stage and tumour grade. The value of such an index has been questioned in small invasive breast cancers and it has been suggested that size is the only necessary prognostic determinant. The aims of this study were to determine the extent of regional lymph node involvement and survival in women with small invasive breast cancers and to assess the value of the NPI. Between 1976 and 1994, 2684 women aged ≤70 years were treated for primary operable invasive breast cancers of ≤5 cm in maximum diameter, of which 318 measured ≤1 cm. Follow-up data were evaluated to determine histological factors important in predicting survival outcomes in women with cancers ≤1 cm in diameter and comparing their survival according to the NPI with all women treated for primary operable breast cancers ≤5 cm in maximum diameter. Histological lymph node involvement was demonstrated in 56/318 (18%) of cancers of ≤1 cm in diameter. Significant survival differences were demonstrated for small breast cancers according to lymph node stage, vascular invasion and histological tumour grade. Only lymph node stage and histological tumour grade were independent prognostic indicators using a multivariate Cox model. The survival curves for small tumours stratified by the NPI were similar to those of cancers up to 5 cm in diameter. The results indicate that lymph node staging and histological grading are still important prognostic determinants for breast cancers ≤1 cm in diameter. An axillary node staging procedure should be performed for all invasive breast cancers ≤1 cm in diameter. The NPI remains relevant for small breast cancers.