Primary tumour characteristics and axillary lymph node status in breast cancer.

This paper examines the correlation between axillary lymph node status and primary tumour characteristics in breast cancer and whether this can be used to select patients for axillary lymphadenectomy. The results are based on a retrospective analysis of 909 patients who underwent axillary dissection in our unit. Axillary lymph nodes containing metastases were found in 406 patients (44.7%), all with invasive carcinomas, but in none of the 37 carcinomas-in-situ. Nodal status was negative in all T1a tumours, but lymph node metastases were present in 16.3% and 35.7% of T1b and T1c tumours respectively. When histological grade was taken into account, positivity for grade I T1b and T1c tumours fell to 13.6% and 26.7% respectively. Lymph node metastases were found in 85% of patients with lymphovascular invasion in their tumours as compared to only 15.4% of those without and in 45.5% of oestrogen and progesterone receptor-positive tumours. When one or both hormone receptors were absent this figure was much higher. It appears that for T1a breast cancers axillary dissection is not necessary, whereas for T1b, T1c and grade I T2 tumours other histopathological parameters should be taken into consideration in deciding who should undergo axillary lymphadenectomy.     

The impact of axillary lymph nodes removed in staging of node-positive breast carcinoma

PURPOSE: Number of positive lymph nodes in the axilla and pathologic lymph node status (pN) have a great impact on staging according to the current American Joint Committee on Cancer staging system of breast carcinoma. Our aim was to define whether the total number of removed axillary lymph nodes influences the pN and thus the staging. METHODS AND MATERIALS: The records of 798 consecutive invasive breast cancer patients with T1-3 tumors and positive axillary lymph nodes who underwent modified radical mastectomy between 1999 and 2005 in our hospital were reviewed. The total number of removed nodes were grouped, and compared with the patient and tumor characteristics and the influence of the number of nodes removed on the staging was analyzed. RESULTS: The proportion of patients with > or =4 positive nodes (59%), and pN3 status (51%) were the highest in the group with 21-25 nodes removed. Compared with patients with 1-20 nodes removed, the proportion of patients with > or =4 positive nodes (52%), and pN3 status (46%) were significantly higher in those with more than 20 nodes removed. Although the proportion of Stage IIA and IIB decreased, the proportion of Stage IIIA and IIIC increased in patients with >20 nodes removed compared with those with 1-20 nodes removed. CONCLUSIONS: In patients with axillary node-positive breast carcinoma, staging is highly influenced by total number of removed nodes. Levels I-III axillary dissection with more than 20 axillary lymph nodes removed could lead to more effective adjuvant chemotherapy and increases substantially the proportion of patients to receive radiotherapy.     

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

BACKGROUND:

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

METHODS:

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

RESULTS:

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

CONCLUSIONS:

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

Unnecessary axillary node dissections in the sentinel lymph node era

In the sentinel lymph node era, axillary lymph node dissection (ALND) for uninvolved axillary lymph nodes should be considered unnecessary and inappropriate. Between January 2000 and August 2005, 3487 out of 10,031 invasive breast cancer patients consecutively operated at the European Institute of Oncology were considered not suitable for sentinel lymph node biopsy (SNB) and were directly submitted to ALND (‘direct ALND’). In 2875 cases (82%) a variable grade of axillary involvement was shown, while in 612 patients (18%) no evidence of metastatic spreading was documented in the axilla. In particular, the presence of suspicious nodes at pre-operative clinical evaluation of the axilla (191 patients), neoadjuvant treatment (188 patients), large tumour >2 cm (88 patients), multifocality of disease (76 patients), previous excisional biopsy (49 patients), were considered the most frequent contraindications to SNB and led to an ‘unnecessary ALND’. According to the wider extension of the indications for SNB over the time, the number of ‘unnecessary ALNDs’ progressively decreased from 26% (in 2000) to 9% of the ‘direct ALNDs’ (in 2005). As the clinical indications to SNB are progressively extending to encompass most breast cancer patients with non-metastatic disease who were previously excluded, great effort should be made to avoid ‘unnecessary ALNDs’.     

乳腺癌腋淋巴结转移超声诊断的多因素分析

目的：通过分析乳腺癌癌肿及其腋淋巴结的声像图表现,探讨癌肿及腋淋巴结声像图特征与病理学腋淋巴结转移的相关性。方法：回顾性分析应用超声检出的145例乳腺癌患者及其278枚腋淋巴结的声像图表现,采用单因素分析、多因素logistic回归及ROC曲线分析的方法,分别检验乳腺癌癌肿内血流特征及癌肿最大直径、腋淋巴结血流特征、径线比及最大皮质厚度与病理学腋淋巴结转移的相关性。结果：依据单因素分析,乳腺癌癌肿血流≥Ⅱ级者、癌肿直径较长者,对应病理学腋淋巴结转移率较高（P〈0．05）;周边型或混合型血流分布、径线比较小、皮质厚度较厚的腋淋巴结,其病理学淋巴结转移率较高（P〈0．05）。依据多因素分析,乳腺癌癌肿直径、淋巴结径线比和皮质最大厚度与病理学腋淋巴结转移明显相关。经ROC曲线分析,腋淋巴结最大皮质厚度是判定腋淋巴结转移的较佳指标。结论：依据乳腺癌癌肿及腋淋巴结超声影像学特征评价腋淋巴结转移,具有明显的临床实用价值。     

Malignant fibrous histiocytoma of the breast with axillary lymph node involvement

This case history describes a 70-year-old female patient with a malignant fibrous histiocytoma (MFH) of the breast with secondary involvement of the skin and axillary lymph node metastases. We think that in the case of a MFH of the breast a radical or modified radical mastectomy should be pursued instead of a simple mastectomy.     

200 Sentinel lymph node biopsies without axillary lymph node dissection -- no axillary recurrences after a 3-year follow-up

The aim of this study is to evaluate the rate of axillary recurrences in sentinel lymph node (SLN)-negative breast cancer patients after sentinel lymph node biopsy (SLNB) alone without further axillary lymph node dissection (ALND). Between May 1999 and February 2002, 333 consecutive patients with primary invasive breast cancer up to 4 cm and clinically negative axillae were entered into this prospective study. Sentinel lymph nodes were identified using the combined method with blue dye (Patent blue V) and technetium 99m-labelled albumin (Nanocoll). Sentinel lymph nodes were examined by frozen sections, standard haematoxylin and eosin staining and immunohistochemistry staining. In SLN-positive patients, ALND was performed. Sentinel lymph node-negative patients had no further ALND. The SLN identification rate was 98.5% (328 out of 333). In all, 128 out of 328 (39.0%) patients had positive SLNs and complete ALND. A total of 200 out of 328 (61.0%) patients were SLN negative and had no further ALND. The mean tumour size of SLN-negative patients was 16.5 mm. The mean number of SLNs removed was 2.1 per patient. There were no local or axillary recurrences at a median follow-up of 36 months. The absence of axillary recurrences after SLNB without ALND in SLN-negative breast cancer patients supports the hypothesis that SLNB is accurate and safe while providing less surgical morbidity than ALND. Short-term results are very promising that SLNB without ALND in SLN-negative patients is an excellent procedure for axillary staging in a cohort of breast cancer patients with small tumours.     

Relationship between body weight and the incidence of positive axillary nodes at mastectomy for breast cancer

The question, whether obesity is associated with an increased incidence of positive axillary nodes at mastectomy for breast cancer, was studied in two quite different hospital populations; one from a large urban teaching hospital (Montefiore) and one from a medium-sized Air Force medical center (Malcolm Grow). In the Montefiore population, the answer was "yes"; 67% of the node-positive patients, but only 31% of the node-negative patients were obese (20% or more above ideal weight) (p less than 0.05). In the Malcolm Grow population, the answer was "no"; 20% of the node-positive and 20% of the node-negative patients were obese. The different answers, we believe, are due to the biological differences between the populations; the Montefiore population was shorter (by an average of 1.7 inches), heavier (by an average of 20 lbs), and more obese. The incidence of obesity was about three times as high in the Montefiore population (52% versus 20%; p less than 0.02) and it contained a statistically distinct subpopulation of obese patients, while the few obese patients in the Malcolm Grow population constituted merely the upper tail of a unimodal log-normal distribution of weight in that population. We propose that it is possible to demonstrate a relationship of obesity to node-positivity in the Montefiore population but not in the Malcolm Grow population because obesity was highly prevalent in the former and almost nonexistent in the latter. It seems self-evident that it is not possible to demonstrate an effect of obesity in a population if that population manifests no significant obesity, statistically speaking, but disregarding this principle, we believe, may account for the controversy in the literature about whether obesity is a risk factor in breast cancer.     

Sentinel lymph node biopsy is feasible even after total mastectomy

BACKGROUND: Previous mastectomy is unanimously considered to represent an absolute technical contraindication to sentinel lymph node biopsy (SLNB). METHODS: Four patients who underwent total mastectomy and plastic reconstruction with prosthesis, developed, during the follow up, a unique invasive limited local subdermic recurrence amenable to surgical excision, with clinically negative axillary nodes. In all patients preoperative lymphoscintigraphy with subdermal injection of (99m)Tc-labeled colloidal particles correctly showed an axillary sentinel lymph node (SLN). RESULTS: Metastases in SLN were detected in two patients, and a complete axillary dissection followed. The remaining two patients had a negative SLN and no axillary clearance was performed. CONCLUSIONS: In selected cases, the subdermal injection of radioisotope permits the identification of an axillary SLN, even in mastectomized patients. Despite SLNB in mastectomized patients being technically feasible, only a larger population and longer patient follow up could confirm its true predictive value. However, there are no anatomical or physiological reasons to exclude "a priori" this diagnostic opportunity.     

乳腺癌新辅助化疗后前哨淋巴结活检意义的前瞻性研究

目的:探讨乳腺癌患者新辅助化疗(NAC)后腋窝前哨淋巴结活检的可行性.方法:采用99Tc硫胶体联合亚甲蓝示踪法对60例NAC后达到临床腋淋巴结阴性的乳腺癌患者和60例临床腋淋巴结阴性的早期乳腺癌患者进行腋窝前哨淋巴结活检术(SLNB),评估SLNB的检出率和准确性,比较两组患者SLNB的检出率和假阴性率,并分析NAC后SLNB检出率和假阴性率与患者及肿瘤特点的关系.结果:60例NAC后患者的前哨淋巴结(SLN)检出率为90%,SLNB的敏感度为90%,特异度为93.33%,准确性为91.67%,假阴性率为10%.其检出率和假阴性率与早期乳腺癌组比较,差异均无统计学意义(P=0.743,P=1.000).NAC组化疗前临床分期T3或N2以上者,腋淋巴结的检出率均显著下降,差异有统计学意义(P=0.030,P=0.000),分期N2以上者假阴性率显著增高,差异有统计学意义,P=0.001.结论:对NAC后达到临床淋巴结阴性的乳腺癌患者,腋窝SLN的检出率和假阴性率与早期乳腺癌SLNB差异无统计学意义,化疗前的TN分期是SLNB检出率和假阴性影响因素.     

Prognostic Significance of Axillary Lymph Node Micrometastases and Microvessel Count in Breast Cancer

Objective  To investigate the influence of axillary lymph node micrometastases and the microvessel count on the prognosis of patients with breast cancer. Methods  Forty-eight patients with breast cancer, who had no tumor cells in their regional lymph nodes based on conventional histopathologic examination, were re -examined with immunohistochemical LSAB techniques. H&E, anti-EMA, CK 19 and FVIII factor staining was used to identify tumor cells in both lymph nodes and tumor tissues and to count the mtcrovessels. A total of 882 lymph nodes were examined. Results  Immunostaining-positive tumor cells were found in 9.0 %( 79/882) of the dissected lymph nodes. The positive rates were not significantly different between a surviving group and a deceased group (P>0.05). The microvessel count was significantly higher in group that had died (P<0.001). Conclusion  The lymph node micrometastases did not show any correlation with patients’ survival, but the microvessel density had a negative correlation with the survival period in breast cancer patients who had negative axillary lymph nodes.     

Prognostic significance of axillary lymph node micrometastases and microvessel count in breast cancer

Objective To investigate the influence of axillary lymph node micrometastases and the microvessel count on the prognosis of patients with breast cancer. Methods Forty-eight patients with breast cancer, who had no tumor cells in their regional lymph nodes based on conventional histopathologic examination, were re -examined with immunohistochemical LSAB techniques. H&E, anti-EMA, CK 19 and FVIII factor staining was used to identify tumor cells in both lymph nodes and tumor tissues and to count the mtcrovessels. A total of 882 lymph nodes were examined. Results Immunostaining-positive tumor cells were found in 9.0 %( 79/882) of the dissected lymph nodes. The positive rates were not significantly different between a surviving group and a deceased group (P>0.05). The microvessel count was significantly higher in group that had died (P<0.001). Conclusion The lymph node micrometastases did not show any correlation with patients’ survival, but the microvessel density had a negative correlation with the survival period in breast cancer patients who had negative axillary lymph nodes.     

Long-term morbidity of patients with early breast cancer after sentinel lymph node biopsy compared to axillary lymph node dissection

BACKGROUND AND OBJECTIVES: Sentinel lymph node biopsy (SLNB) is widely accepted as an excellent method in the management of early breast cancer in patients with clinically negative axillary lymph nodes. Since SLNB requires less traumatic surgery to the axilla than axillary lymph node dissection (ALND), it was assumed to result in reduced shoulder/arm morbidity. However, data on long-term morbidity after SNLB are sparse. The present study was set up to compare long-term arm/shoulder morbidity as well as oncological outcome after SLNB versus ALND in patients with early breast cancer. METHODS: Oncological outcome, objective shoulder/arm morbidity, and subjective complaints after SLNB or ALND for T1 breast cancer were assessed after a minimum follow-up of 20 months. RESULTS: One hundred thirty four patients were included in the study. Thirty-one patients underwent SNLB only, 103 patients had SLNB followed by ALND or ALND only. Loss of strength and hypaesthesia were less frequent after SLNB. No lymph oedema occurred after SNLB without adjuvant radiotherapy. Subjective complaints concerning pain, hypaesthesia, and paresthesia were more common in the ALND group. No axillary recurrence developed in either group. CONCLUSIONS: Isolated SLNB in node-negative pT1 breast cancer patients is a highly efficient tool to reduce postoperative long-term morbidity without compromising the local control of the disease. The reported ameliorations should favour SLNB as staging and treatment modality in patients suffering from early breast cancer.     

Estimating the overlap between sentinel lymph nodes and axillary node samples in breast cancer

Management of the axilla in breast cancer patients is a controversial issue. Axillary sampling and sentinel lymphadenectomy are both conservative surgical approaches which aim to stage the disease. These procedures target selective treatment of node-positive patients and seem to allow the omission of axillary clearance in node-negative ones. In this way, they reduce the rate of complications in an otherwise overtreated subset of patients. Forty consecutive patients with palpable T1 and T2 breast carcinoma underwent sentinel lymphadenectomy following mapping with Patent blue dye, with subsequent axillary clearance and excision of the tumor or mastectomy. Then the largest/firmest 3,4,5 and 6 nodes were selected from all the lymph nodes in order to model an axillary sample. It was suggested that these are the nodes that are the most likely to be included in the specimen during sampling, because of their size and consistency. The probability of the sentinel lymph nodes falling into the sample of the 3-6 largest/firmest nodes was calculated. The sentinel nodes predicted the axillary nodal status in 95%, while the samples of the largest 3, 4, 5 and 6 nodes were predictive in 95, 96, 98 and 98%, respectively. The two methods of evaluation displayed a considerable overlap, as the sentinel node would have been included in the 3 6 largest/firmest nodes in 79 92% of the cases, depending on the number of largest nodes evaluated. The overlap was greater after fine needle aspiration of the primary tumor. Although the two alternative staging procedures of 3, 4, 5 or 6 node sampling and sentinel lymphadenectomy with the vital blue dye technique cannot be simultaneously done without one influencing the other, and the first method was only modeled, the results suggest that there is a considerable overlap between the two; axillary sampling may often remove the sentinel lymph nodes.     

Prognostic significance of total number of nodes removed, negative nodes removed, and ratio of positive nodes to removed nodes in node positive breast carcinoma

BACKGROUND: This study was undertaken to investigate whether total number of nodes (pNtot) removed, negative nodes removed (pNneg), and ratio of positive nodes to total nodes removed (pNratio) are predictors of survival in node positive patients. STUDY DESIGN: The records of 801 consecutive invasive breast cancer patients with T1-3 tumour and positive axillary lymph node who underwent modified radical mastectomy in our hospital were reviewed. pNtot and pNneg were categorized, and pNratio was computed. The influence of these probable prognostic factors on survival was investigated. Survival curves were generated by Kaplan-Meier method and log-rank test was used for comparisons. Multivariate analyses were performed by Cox proportional hazard model. RESULTS: Median pNtot, and pNneg are 19 (range 5-54), and 13 (range 0-53), respectively. pNtot>15, and pNneg>15 were independently associated with reduced hazard ratios (HRs) of 0.62 (CI 0.48-0.79), and 0.68 (CI 0.52-0.89), respectively. The highest ratio (>0.25) of pNratio is associated with the highest hazard ratio for death (HR 3.8, CI 2.74-5.50) compared to the lowest ratio for death (<0.001). CONCLUSIONS: pNtot, pNneg, and pNratio appear prognostic factors for survival in node positive breast cancers. Axillary lymph node dissection with more number of nodes removed (>15) or negative nodes (>15) are associated with increased survival.     

Characteristics of and therapeutic options for contralateral axillary lymph node metastasis in breast cancer

Aim

Contralateral axillary metastasis (CAM) from breast cancer is uncommon. This papers aims to identify the features of our patients with CAM, as well as clarify management options.

Methods

We reviewed all of our breast cancer patients during the period from 2004 to 2009. All patients with a proven pathological diagnosis of CAM were included. Patients were evaluated for demographics, tumor features and management modalities.

Results

A total of 21 patients were included, forming 1.9% of our breast cancer population. The median age was 51 years (range 29-71). Twelve patients had large central or diffuse tumors. Most of the tumors were of invasive ductal type (95%), of high grade (81%) and with lymphovascular invasion (81%). The majority of cases were locally advanced (stage III: 90%). Hormonal receptor positivity and HER-2 overexpression were seen in 48% and 42% of cases, respectively. Those pathological features were significantly worse than those of patients without CAM. Ten patients had synchronous and 11 patients had metachronous CAM. Treatment modalities included axillary dissection, chemotherapy and hormonal therapy. Four patients died from metastatic disease and 5 patients are still alive without evidence of metastasis.

Conclusion

CAM is associated with tumors with aggressive pathological features. Hormonal therapy is associated with an excellent response in patients whose tumors are hormone-receptor positive. Axillary dissection is indicated in patients with early-stage tumors, when there is no response to systemic therapy, or for palliation. It is associated with excellent local control.     

Variability in axillary lymph node dissection for breast cancer

BACKGROUND: The axillary nodal status may influence the prognosis and the choice of adjuvant treatment of individual breast cancer patients. The variation in number of reported axillary lymph nodes and its effect on the axillary nodal stage were studied and the implications are discussed. METHODS: Between 1994 and 1997, a total of 4,806 axillary dissections for invasive breast cancers in 4,715 patients were performed in hospitals in the North-Netherlands. The factors associated with the number of reported nodes and the relation of this number with the nodal status and the number of positive nodes were studied. RESULTS: The number of reported nodes varied significantly between pathology laboratories, the median number of nodes ranged from 9 to 15, respectively. The individual hospitals explained even more variability in the number of nodes than pathology laboratories (range in median number 8-15, P < 0.0001). The number of reported nodes increased gradually during the study period. A decreasing trend was observed with older patient age. A higher number of reported nodes was associated with a markedly increased chance of finding tumor positive nodes, especially more than three nodes. The frequency of node positivity increased from 28% if less than six nodes to 54% if >/=20 nodes were examined, the percentage of tumors with >/=4 positive nodes increased from 4 to 31%. Multivariate analysis confirmed these results. CONCLUSIONS: This population-based study showed a large variation in the number of reported lymph nodes between hospitals. A more extensive surgical dissection or histopathological examination of the specimen generally resulted in a higher number of positive nodes. Although the impact of misclassification on adjuvant treatment will have varied, the impact with regard to adjuvant regional radiotherapy may have been considerable.     

Cosmetic outcome of breast conserving therapy after sentinel node biopsy versus axillary lymph node dissection

INTRODUCTION: Next to locoregional control, good cosmetic outcome is one of the main goals of breast conserving treatment (BCT) for breast cancer surgery. Factors affecting cosmetic outcome are well known. The sentinel node (SN) procedure avoids lymphedema in the breast, which might influence cosmetic outcome. The aim of this study was to evaluate the cosmetic outcome of BCT after the SN procedure compared to that after axillary lymph node dissection (ALND).METHODS: The subjects were 20 patients who underwent ALND and 20 patients who underwent the SN procedure. After a minimum follow-up period of 43 months, we photographed each patient. Fifteen healthy women served as control subjects. We used the percentage breast retraction assessment index (pBRA=BRA/reference length x 100) to compare cosmetic outcome.RESULTS: The median pBRAs of the ALND group and SN group (14.3 and 6.71, respectively) significantly differed ( p=0.001). The pBRA of the SN group was comparable to the pBRA (6.1) of the control group ( p=0.317).CONCLUSION: Cosmetic outcome of BCT after the SN procedure was superior compared to the cosmetic outcome after ALND. This is an important additional reason to implement the SN procedure in routine daily practice.