Prognostic significance of the number of axillary lymph nodes removed in patients with node-negative breast cancer.

PURPOSE: The objective of the study was to evaluate the association between the number of lymph nodes removed at axillary dissection and recurrence and survival for patients with node-negative invasive breast cancer. PATIENTS AND METHODS: Subjects were 2,278 women with pathologically node-negative invasive breast cancer, diagnosed from 1989 to 1993 in British Columbia, Canada. Women aged > or = 90 years, with pure in-situ, bilateral invasive breast cancer or T4, N1, N2, or M1 stage, or who had axillary radiation were excluded. Two groups were defined for analysis: node-negative with no systemic therapy (n = 1,468) and node-negative with systemic therapy (n = 810). Median follow-up was 7.5 years. Prognostic variables assessed were age at diagnosis, tumor size, tumor grade, invasion of lymphatics, veins, or nerves, estrogen receptor status, and number of nodes removed. RESULTS: For patients not receiving systemic therapy, regional relapse was significantly increased with smaller numbers of nodes removed (P =.03). There was a trend toward shorter overall survival with fewer nodes removed (P =.06). Node-negative patients who received systemic therapy did not have a higher regional relapse rate or shorter overall survival when fewer nodes were recovered. CONCLUSION: Recovery of a small number of negative lymph nodes at axillary dissection likely understages patients and leads to undertreatment, resulting in an increased regional relapse rate and poorer survival. The use of systemic therapy may overcome this effect. The number of nodes removed, in conjunction with other prognostic factors, may be useful in selecting node-negative patients for systemic therapy.     

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.     

腋窝淋巴结清扫总数在预测淋巴结阴性乳腺癌患者预后中的价值

目的探讨腋窝淋巴结清扫总数在预测淋巴结阴性乳腺癌患者预后中的价值。方法采用Kaplan-Meier法和多因素回归分析方法,对138例有完整随访资料的淋巴结阴性乳腺癌患者的生存情况及影响因素进行分析。结果本组患者随访时间为33-96月,中位随访时间89月。5年总生存率为93.5%,无瘤生存率为80.1%。单因素分析显示,腋窝淋巴结清扫总数影响淋巴结阴性乳腺癌患者的预后(χ2=6.24,P<0.05),多因素回归分析发现腋窝淋巴结清扫总数是影响淋巴结阴性乳腺癌患者预后的独立因素之一(P=0.025)。结论手术清扫腋窝淋巴结数目可反映区域淋巴结清扫的彻底性以及评价术后病理分期的准确性,是影响淋巴结阴性乳腺癌患者预后的独立预后因素之一。     

Axillary lymph node ratio and total number of removed lymph nodes: predictors of survival in stage I and II breast cancer.

AIMS: Presence of axillary lymph node metastases is considered the most important prognostic factor for breast cancer survival. In a period of increasing popularity for the sentinel node procedure, clarity about the possible relation between axillary dissection and survival is essential. This study investigated whether the total number of removed lymph nodes and the ratio of invaded/removed lymph nodes (lymph node ratio (LNR) would prove to be independent prognostic factors for survival. METHODS: Data from 453 consecutive patients with stage I or II breast cancer were studied retrospectively. The total number of removed lymph nodes and the LNR were analysed for their prognostic value in comparison with known prognostic factors. RESULTS: Node-negative patients with < 14 lymph nodes removed had a 10 year survival of 79% compared with 89% in patients with > or = 14 lymph nodes removed (P=0.005). The 10 year survival for patients with an LNR > or = 0.2 was 52%, compared with 73% for patients with an LNR < 0.2 (P<0.0001). A Cox proportional hazards model showed that, for node-negative patients, only age and total number of removed lymph nodes were significant prognostic factors. For node-positive patients, age, total number of removed lymph nodes and the LNR were significant risk factors for survival outcome. The LNR was also significantly associated with the presence of distant metastases during follow-up (hazard ratio 3.56, range 1.63-7.77). CONCLUSIONS: In stage I and II breast cancer, a favourable prognosis was found for node-negative patients with > or = 14 removed lymph nodes. Before axillary lymph node dissection with its well-defined survival prognosis is replaced by less invasive staging methods, long-term survival using new staging techniques needs to be defined. For node-positive patients, the LNR proved to be an excellent predictor for survival outcome or development of metastatic disease. Selection of lymph node-positive patients based on the LNR may guide specific adjuvant treatment choices.     

Outcomes of a population-based series of early breast cancer patients with micrometastases and isolated tumour cells in axillary lymph nodes

BackgroundAxillary lymph node staging is traditionally important to provide prognostic information to guide further treatment. However, the relevance of isolated tumour cells (ITC) or micrometastases in axillary nodes and the need for adjuvant treatment remain uncertain.Patients and methodsData from 18 370 patients with pT1–2 breast cancer with pN0, pN0i+ or pN1mi were analysed. The primary end point was 5-year disease-free survival (locoregional recurrence, distant metastases or contralateral breast cancer).ResultsFive-year disease-free survival was 89.9% [95% confidence interval 89.5% to 90.4%]; and did not differ significantly between groups. After adjusting for prognostic factors (including treatment), patients with ITC had a comparable risk (hazard ratio = 1.12) as patients with node-negative disease, while patients with micrometastases had a 38% higher risk of recurrence.Conclusion(s)Patients with ITC and node-negative breast cancer appear to have similar prognosis, and those with micrometastases have a 38% higher risk of tumour recurrence. However, considering that disease-free survival is already high, we are reluctant to advise chemotherapy in all patients with ITC or micrometastases. In future, genomic tumour characteristics might predict the propensity of dissemination from the primary cancer better than the status of the axillary lymph nodes.     

Prognostic significance of the number of lymph nodes examined in patients with lymph node-negative breast carcinoma.

BACKGROUND: A recent report suggested that the number of lymph nodes examined was a strong predictor of survival in patients with lymph node-negative breast carcinoma. Among women who had >or= 20 lymph nodes examined, the risk of dying from breast carcinoma within 5 years was increased nearly 4-fold compared with women who had fewer lymph nodes examined. Because these findings were based on a relatively small cohort of patients, corroborative studies with larger patient populations were needed. METHODS: The authors studied the relation between the number of lymph nodes examined and breast carcinoma survival among 911 women with lymph node-negative breast carcinoma with a median length of follow-up of 84 months. The association between other prognostic indicators and survival and the number of lymph nodes examined also was investigated. RESULTS: The number of lymph nodes examined was not found to be associated with either 5-year or long-term survival. The proportion of women dying from breast carcinoma was the same (8%) in both groups (those patients with >or= 20 lymph nodes examined vs. those in whom < 20 lymph nodes were examined) and the hazard ratio was 0.98 (95% confidence interval, 0.58-1.64). CONCLUSIONS: In this larger study population, the authors failed to confirm the findings of an earlier investigation in which having a larger number of lymph nodes examined was associated with poorer survival. This finding suggests that it is unlikely the number of lymph nodes examined is an important prognostic indicator in patients with lymph node-negative breast carcinoma.     

Prognostic significance of axillary node and infraclavicular lymph node status after mastectomy

AIMS: The American Joint Committee on Cancer staging system for breast carcinomas has been revised. According to this revised staging system, metastasis to infraclavicular lymph nodes and number of positive axillary nodes have prognostic significance and a new stage, stage IIIC, has been introduced. The aim of this study is to investigate the association of positive axillary nodes by level and number with survival and stage migration between the old and the new stages in a large series of mastectomy patients. METHODS: Data from 1277 consecutive breast cancer patients treated by mastectomy were studied, retrospectively. Prognostic value of number of positive axillary nodes and entirely invasion of apex axillary nodes were analysed. Survival curves were generated by Kaplan-Meier method, and multivariate analysis was performed by Cox proportional hazard model. RESULTS: Five-year survival rates for metastasis to axillary level III and for stage IIIC breast cancer were 35.4 and 38.2%, respectively. Metastases to apex axillary nodes, 4-9 and 10 or more positive lymph nodes were found to be adverse and independent prognostic factors for survival in lymph node positive patients. CONCLUSION: Invasion of infraclavicular nodes and 4-9 and > or =10 positive axillary lymph nodes were independent predictors for survival in node positive breast carcinomas in this series. Patients with the new stage IIIC had the worst survival among breast cancer patients.     

Simultaneous immunohistochemical detection of tumor cells in lymph nodes and bone marrow aspirates in breast cancer and its correlation with other prognostic factors.

PURPOSE: We studied the prognostic and predictive value of immunohistochemically detected occult tumor cells (OTCs) in lymph nodes and bone marrow aspirates obtained from node-negative breast cancer patients. All were classified as distant metastases-free using conventional staging methods. PATIENTS AND METHODS: A total of 484 patients with pT1-2N0M0 breast cancer and 70 with pT1-2N1M0 breast cancer and a single affected lymph node participated in our trial. Ipsilateral axillary lymph nodes and intraoperatively aspirated bone marrow were examined. All samples were examined for OTCs using monoclonal antibodies to cytokeratins 8, 18, 19. Immunohistological findings were correlated with other prognostic factors. The mean follow-up was 54 +/- 24 months. RESULTS: OTCs were detected in 180 (37.2%) of 484 pT1-2N0M0 patients: in the bone marrow of 126 patients (26.0%), in the lymph nodes of 31 patients (6.4%), and in bone marrow and lymph nodes of 23 (4.8%) patients. Of the 70 patients with pT1-2N1MO breast cancer and a single involved lymph node, OTCs were identified in the bone marrow of 26 (37.1%). The ability to detect tumor cells increased with the following tumor features: larger size, poor differentiation, and higher proliferation. Tumors of patients with OTCs more frequently demonstrated lymph node invasion, blood vessel invasion, higher urokinase-type plasminogen activator levels, and increased PAI-1 concentrations. Patients with detected OTCs showed reduced disease-free survival (DFS) and overall survival (OAS) rates that were comparable to those observed in patients who had one positive lymph node. Multivariate analysis of prognostic factors revealed that OTCs, histological grading, and tumor size are significant predictors of DFS; OTCs and grading of OAS. CONCLUSION: OTCs detected by simultaneous immunohistochemical analysis of axillary lymph nodes and bone marrow demonstrate independent metastatic pathways. Although OTCs were significantly more frequent in patients with other unfavorable prognostic factors, they were confirmed as an independent prognostic factor for pT1-2N0M0, R0 breast cancer patients.     

Does the number of lymph nodes examined in patients with lymph node-negative breast carcinoma have prognostic significance?

BACKGROUND: There are conflicting data on the prognostic significance of the number of lymph nodes examined in patients with lymph node-negative breast carcinoma. Therefore, the authors analyzed the impact of the number of tumor-free axillary lymph nodes on disease-free survival (DFS) in two distinct patient populations. METHODS: Eight hundred thirty-three consecutive patients with breast carcinoma who underwent mastectomy between 1927 and 1987 and 1094 consecutive patients with breast carcinoma who underwent with breast-conservation therapy between 1984 and 2001 were diagnosed pathologically with negative axillary lymph node status. Patients were stratified into 4 groups according to the number of lymph nodes examined: Group 1 had 1-3 lymph nodes examined, Group 2 had 4-9 lymph nodes examined, Group 3 had 10-20 lymph nodes examined, and Group 4 had >20 lymph nodes examined. RESULTS: In the mastectomy cohort, with a median follow-up of 153 months, the 10-year DFS rate was 70%, 65%, 79%, and 81% for Groups 1-4, respectively. On multivariate analysis, pathologic tumor size (P<0.001) and the number of lymph nodes examined (P=0.010) were significant predictors for long-term DFS. In the breast-conservation cohort, with a median follow-up of 53 months, the 5-year DFS rate was 90%, 91%, 92%, and 95% for Groups 1-4, respectively. On multivariate analysis, the only predictors of DFS were method of detection (clinically vs. mammographically) (P=0.003) and tumor size (P=0.035). CONCLUSIONS: The recovery of <10 lymph nodes in lymph node-negative patients who underwent mastectomy resulted in a 10-15% decreased long-term DFS rate compared with patients who had a more extensive axillary assessment. However, the number of lymph nodes examined did not have an impact on the DFS rate in a contemporary cohort of patients who underwent breast-conservation therapy, which included radiation.     

Prognostic factors affecting survival and disease-free survival in lymph node-negative breast carcinomas

BACKGROUND AND OBJECTIVES: The objective of this study was to identify the patients who are at low or high-risk by defining the prognostic factors in node-negative breast carcinomas. METHODS: Medical records of 384 consecutive breast cancer patients with negative axillary lymph nodes who had been operated on between January 1994 and January 1997 at our hospital were retrospectively reviewed. Several clinical and pathological characteristics of patients were categorized. Univariate analyses of survival and disease-free survival (DFS) were performed by the Kaplan-Meier method and the log-rank test. Independent prognostic and predictive factors affecting survival and DFS were assessed by Cox proportional hazard method. RESULTS: 5-year survival and DFS were 91.4 and 85.7%, respectively. Size, grade, age, and lymphovascular invasion (LVI) were the prognostic factors that independently affected survival and DFS. Tamoxifen improved survival and DFS. While age younger than 35 was an adverse factor for both survival and DFS, age older than 49 was a detrimental factor for DFS. CONCLUSIONS: Patients who have a tumor with size greater than 2 cm, with histologic grade 3, with LVI, and patients with age under 35 or older than 49 have poorer prognosis among node-negative breast carcinomas, and are candidates for adjuvant therapy.     

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.     

Comparative analysis of micrometastasis to the bone marrow and lymph nodes of node-negative breast cancer patients receiving no adjuvant therapy.

PURPOSE: In node-negative patients, of whom up to 30% will recur within 5 years after diagnosis, markers are still needed that identify patients at high enough risk to warrant further adjuvant treatment. In the present study we analyzed whether a correlation exists between microscopic tumor cell spread to bone marrow and to lymph nodes and attempted to determine which route is clinically more important. PATIENTS AND METHODS: According to a prospective design, bone marrow aspirates and axillary lymph nodes of level I (n = 1,590) from 150 node-negative patients with stage I or II breast cancer were analyzed immunocytochemically with monoclonal anticytokeratin (CK) antibodies. We investigated associations with prognostic factors and the effect of micrometastasis on patients' prognosis. RESULTS: CK-positive cells in bone marrow aspirates were present in 44 (29%) of 150 breast cancer patients, whereas only 13 patients (9%) had such positive findings in lymph nodes; simultaneous microdissemination to bone marrow and lymph nodes was seen in merely two patients. No correlation of bone marrow micrometastases with other risk factors was assessed. Reduced 4-year distant disease-free and overall survival were each associated with a positive bone marrow finding (P =.032 and P =.014, respectively) but not with lymph node micrometastasis. Multivariate analysis revealed an independent prognostic effect of bone marrow micrometastasis on survival, with a hazards ratio of 6.1 (95% confidence interval, 1.2 to 31.3) for cancer-related death (P =.031) in our series. CONCLUSION: Immunocytochemical detection of micrometastatic cells in bone marrow but not in lymph nodes is an independent prognostic risk factor in node-negative breast cancer that may have implications for surgery and stratification into adjuvant therapy trials.     

Survival after negative sentinel lymph node biopsy in breast cancer at least equivalent to after negative extensive axillary dissection.

AIM: Sentinel lymph node biopsy (SLNB) without completion axillary lymph node dissection (ALND) is replacing ALND as the axillary staging procedure of choice in breast cancer patients with a clinically negative axilla even though it is unclear whether this influences patient survival. Our aim was to compare the survival of breast cancer patients with a negative SLNB without completion ALND to that of extensive ALND-negative patients. METHODS: Eindhoven Cancer Registry data on breast cancer patients diagnosed between 1989 and 2002 with follow-up to 1 January 2005 was used. Survival was compared between 880 SLNB-negative women (median follow-up 3.6years) without completion ALND and 1681 ALND-negative women (median follow-up 7.7years) with at least 10 axillary nodes removed. Conclusions were made after correcting for age, tumour size, tumour location, tumour histology, tumour grade, mitotic activity index (MAI), hormone receptor status, and local and systemic treatment in uni- and multivariate analyses. RESULTS: Crude 5-year survival rates were 85% for ALND-negative and 89% for SLNB-negative breast cancer patients (p=0.026). After correction for potential confounders in a multivariate Cox regression analyses, the hazard ratio for overall mortality of ALND-negative compared to SLNB-negative patients without completion ALND was 1.23 (95% confidence interval: 0.93-1.64). CONCLUSION: Survival after a SLNB without completion ALND is at least equivalent to after an extensive ALND in node-negative breast cancer patients. This means that the SLNB only can safely replace ALND as the procedure of choice for axillary staging in breast cancer patients with a clinically negative axilla.     

The correlation of extranodal invasion with other prognostic parameters in lymph node positive breast cancer

BACKGROUND: The presence of extranodal invasion (ENI) in the metastatic lymph nodes is reported to increase the risk of locoregional recurrence while shortening disease-free and overall survival in patients with breast cancer. In this study the relationship between ENI and other prognostic parameters and survival is investigated. METHODS: Of 650 patients with breast cancer who were treated in Ankara Oncology Teaching and Research Hospital from 1996 to 2003, 368 (56.6%) had lymph node metastasis. The patients with axillary metastasis were separated into two groups as with and without invasion to lymph node capsule and the surrounding adipose tissue. Clinicopathologic features were analyzed by univariate and multivariate logistic regression. RESULTS: Of 368 patients with axillary metastasis, 135 (36.7%) had ENI. Based on multivariate analysis; the number of metastatic lymph nodes, lymphatic invasion, and tumor necrosis were found to be related with ENI. In the group with ENI, 5-year overall survival rate was 74.8%, compared to 82.3% for patients without ENI which was significantly lower (P = 0.04). CONCLUSIONS: In lymph node positive breast cancer with presence of ENI, adverse prognostic parameters are more frequently encountered and has a worse overall survival compared to group without ENI.     

Determinants of axillary recurrence after axillary lymph node dissection for invasive breast cancer.

AIM: This study was undertaken to gain insight into the risk factors for axillary recurrence among patients with invasive breast cancer who underwent breast-conserving treatment or mastectomy and axillary lymph node dissection. METHODS: In a matched case-control design, 59 patients with axillary recurrence and 295 randomly selected control patients without axillary recurrence were compared. Matching factors included age, year of incidence of the primary tumour and postsurgical axillary nodal status. RESULTS: For patients with negative axillary lymph nodes, those with a tumour in the medial part of the breast had a 73% (95% CI: 4-92%) lower risk of axillary recurrence compared to those with a tumour in the lateral part of the breast. For the patients with positive axillary lymph nodes the risk of axillary recurrence was 65% (95% CI: 16-86%) lower for those who had received axillary irradiation compared to those without axillary irradiation. Within the age group <50 years, the risk or axillary recurrence was 82% lower (95% CI: 45-94%) for patients with more than six lymph nodes found in the axillary specimen compared to those with six or less than six lymph nodes. CONCLUSIONS: Although based on a small number of patients, this study indicates that axillary irradiation is effective in reducing the risk of axillary recurrence for patients with positive lymph nodes. This favourable effect only applies to the subgroup with extranodal extension or nodal involvement in the apex of the axilla, as these were the only patients receiving axillary radiation during the study period. Copyright Harcourt Publishers Limited.     

Risk factors for regional nodal failure after breast-conserving therapy: regional nodal irradiation reduces rate of axillary failure in patients with four or more positive lymph nodes

PURPOSE: To determine the incidence of, and risk factors for, regional nodal failure (RNF) and to evaluate the effectiveness of, and indications for, regional nodal irradiation (RNI) in patients with Stage I-II breast cancer treated with breast-conserving therapy. METHOD AND MATERIALS: A total of 1500 cases of Stage I-II breast cancer were treated with breast-conserving therapy between February 1980 and December 2000. All patients underwent excisional biopsy, and 925 (62%) underwent re-excision. Level I-II axillary lymph node dissection was done in 94% of patients. The lymph nodes were pathologically involved in 335 patients (22%); 255 with 1-3 nodes and 80 with >/=4 nodes involved. All patients received whole breast irradiation to a median dose of 45 Gy, and 97% received a tumor bed boost to a median dose of 61 Gy. Treatment included the breast only in 1309 patients (87%), and the breast and regional lymphatics in 191 (13%). RESULTS: With a median follow-up of 8.1 years, 35 patients had failure within the regional nodes: 12 patients (6%) who received RNI and 23 patients (2%) who did not. The 5- and 10-year rate for any RNF was 1.9% and 2.8%, respectively. The 5 and 10-year rates of axillary failure and supraclavicular failure were 0.6% and 1.0% and 0.9% and 1.6%, respectively. In patients with >/=4 positive lymph nodes, RNI reduced the 10-year rate of any RNF from 11% to 2% (p = 0.024), the rate of axillary failure from 5% to 0% (p = 0.019), and the rate of supraclavicular failure from 11% to 2% (p = 0.114). RNI did not affect the rate of axillary failure or supraclavicular failure in patients with 1-3 positive nodes. In node-negative patients, the rate of RNF was significantly greater if <6 nodes were removed at the time of axillary dissection. Multiple clinical, pathologic, and treatment-related factors were analyzed for association with RNF. On univariate analysis, RNF was associated with the number of nodes excised, number of positive nodes, percentage of positive nodes, size of nodal metastasis, presence of angiolymphatic invasion, estrogen receptor status, age, systemic chemotherapy, and RNI. Three subsets of patients had unusually high rates of RNF, those with >/=67% nodes positive (16%), nodal metastasis >/=2.0 cm (44%), or age 10 nodes excised, respectively (p = 0.05). CONCLUSION: Failure within the regional lymph nodes as an isolated site of first relapse is uncommon in patients with Stage I-II breast cancer treated with breast-conserving therapy. RNI can significantly reduce the rate of RNF (axillary failure) in patients with >/=4 positive lymph nodes. The maximal size of the lymph node metastasis was found to be the only significant independent predictor of RNF, with nodal metastases >/=2.0 cm associated with extremely high regional failure rates. Despite this, young age and the extent of axillary dissection (particularly as related to the number of positive nodes) also appear to be important and should be considered when evaluating patients for RNI. Inadequate axillary dissection was not only associated with increased regional failure, but also reduced survival.     

Prognostic value of lymph node ratio in poor prognosis node‐positive breast cancer patients in Saudi Arabia

Aim: Women in Saudi Arabia develop breast cancer at a young age with high prevalence of poor prognostic features. Because of such features, it is necessary to examine prognostic factors in this population. One such factor is the prognostic role of lymph node ratio (LNR). Methods: We performed retrospective analyses of patients with invasive non‐metastatic breast cancer who underwent axillary lymph node dissection and had one or more positive axillary lymph nodes. Results: Two hundred and seventeen patients were considered eligible for the analysis. The median age was 46 years. At a median follow‐up of 39.8 months, the median disease‐free survival (DFS) was 67.3 months (95% CI, 50.4 to 84.3 months). Neither the classification of patients based on positive lymph node (pN) staging system, nor the absolute number of pN prognosticated DFS. Conversely, age ≤ 35 years at diagnosis, grade 3 tumors and the intermediate (>0.20 to ≤0.65) and high (>0.65) LNR categories were the only variables that were independently associated with adverse DFS. Using these variables in a prognostic model allowed the classification of patients into three distinctive risk strata. The overall survival (OS) in this series was 92.5 months (95% CI, 92.1–92.6). Only ER negative tumor adversely influenced OS. Conclusion: Analysis of survival outcome of mostly young patients with early breast cancer identified adverse prognostic variables affecting DFS. If the utility of the derived model including LNR is proven in a larger patient population, it may replace the use of absolute number of positive axillary lymph nodes.     

Minimal axillary lymph node involvement in breast cancer has different prognostic implications according to the staging procedure

It is still controversial whether the identification of micrometastases and isolated tumor cells in the axillary lymph nodes of patients with breast cancer has any prognostic value. We evaluated the prognostic role of isolated tumor cells and micrometastases in the axillary lymph nodes in 3,158 consecutive patients pT1-2 pN0-N1mi (with a single involved lymph node) and M0, referred to the Division of Medical Oncology after surgery performed at the European Institute of Oncology from April 1997 to December 2002. Median follow-up was 6.3 years (range 0.1–11 years). Sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) were performed in 2,087 and 1,071 patients, respectively. A worse metastasis-free survival was observed for patients with micrometastatic disease compared to node-negative patients, if staged with ALND (log-rank P < .0001; HR: 3.17; 95% CI 1.72–5.83 at multivariate analysis), but not for patients who underwent SLNB (log-rank P = 0.36). The presence of a single micrometastatic lymph node is associated with a higher risk of distant recurrence as compared to node-negative disease only for patients undergoing ALND for staging purposes. Treatment recommendations for systemic therapy should not take into account the presence of a single micrometastatic lymph node identified during complete serial sectioning of sentinel node(s).     

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.     

Association between extent of axillary lymph node dissection and patient,tumor, surgeon,and hospital factors in patients with early breast cancer

BACKGROUND AND OBJECTIVES: Axillary lymph node dissection (ALND) in patients with breast cancer is crucial for accurate staging, provides excellent regional tumor control, and is included in the standard of care for the surgical treatment of breast cancer. However, the extent of ALND varies, and the extent of dissection and the number of lymph nodes that comprise an optimal axillary dissection are under debate. Despite conflicting evidence, several studies have shown that improved survival is correlated with more lymph nodes removed in both node-negative and node-positive patients. The purpose of this study is to determine which patient, tumor, surgeon, and hospital characteristics are associated with the number of nodes excised in early breast cancer patients. METHODS: A random sample of 938 women with node-negative breast cancer was drawn from the Ontario Cancer Registry and the data supplemented with chart reviews. The extent of axillary dissection was studied by examining the number of nodes examined in relation to the patient, tumor, surgeon, and hospital factors. RESULTS: The mean number of lymph nodes excised was 9.8 (SD = 4.8; range, 1-31), and 49% of patients had >/=10 nodes excised. Lower patient age was associated with the excision of more lymph nodes (>/=10 nodes: 63% of patients <40 years vs. 38% of patients >/=80 years). Surgeon academic affiliation and surgery in a teaching hospital were highly correlated with each other and were significantly associated with the excision of >/=10 nodes. The number of nodes excised was not associated with any tumor factors, nor with the breast operation performed. These results were confirmed with multivariable models. CONCLUSIONS: Even though the number of lymph nodes found in the pathologic specimen can be influenced by factors other than surgical technique (e.g., number of nodes present, specimen handling, and pathologic examination), this study shows significant variation of this variable and an association with several patient and surgeon/hospital factors. This variation and the association with survival warrant further study and effort at greater consistency.