Do bone marrow micrometastases correlate with sentinel lymph node metastases in breast cancer patients?

BACKGROUND: Sentinel lymph node biopsies (SLNB) are used to detect axillary metastases as an important prognostic indicator for breast cancer patients. Bone marrow micrometastases (BMM) have also been shown to predict prognosis. This study examines whether SLNB and BMM are associated. STUDY DESIGN: A retrospective analysis was performed on 124 stages I to III breast cancer patients treated with mastectomy or lumpectomy, SLNB, and bone marrow aspiration between 1997 and 2003. SLNB were examined for the presence of metastases by hematoxylin and eosin (H&E) stains and also by immunohistochemistry (IHC) for lymph nodes negative by H&E. The kappa statistic was used to evaluate the association (agreement) between SLNB and BMM. RESULTS: In this study population, 36 patients (29%) had micrometastases detected in their bone marrow, and 51 patients (41%) had positive sentinel lymph nodes. Of the patients with positive BMM (n = 36), 53% (19 of 36) had positive SLNB (14 of 19 by H&E and 5 of 19 by IHC). In patients with negative BMM (n = 88), 36% (32 of 88) had a positive SLNB (27 of 32 by H&E and 5 of 32 by IHC). The kappa statistic and associated 95% confidence interval indicated poor agreement between SLNB and BMM (kappa = 0.15; 95% CI = -0.03, 0.32). CONCLUSIONS: There was poor agreement between axillary metastases and micrometastases detected in the bone marrow. This study suggests that BMM and axillary metastases are not concordant findings in most patients.     

Axillary lymph node dissection in breast cancer: an evolving question?

Axillary lymph node dissection (ALND) is performed for staging purposes. Sentinel lymph node biopsy may decrease the cost and morbidity of ALND. Are there patients that the procedure is not indicated avoiding cost and morbidity? We retrospectively studied the incidence of lymph node metastasis in 423 patients with T1 breast cancer. Thirty-one T1a, 146 T1b, and 246 T1c tumors were seen. The mean age was 61 years. Ten per cent were premenopausal, and 84 per cent were postmenopausal. Tumor size averaged 1.29 cm. Eighty-one per cent of the tumors were node negative and 19 per cent were node positive. One T1a patient (3 per cent) had an axillary metastasis, 19 T1b patients (13%), and 61 T1c patients (25%) were node positive, respectively. Seventy-three per cent were ER positive. Thirty-three patients (8%) died from cancer. Eighty-seven per cent received surgery with axillary lymph node dissection (ALND), and three per cent had surgery without ALND. Younger age, increased tumor size, premenopausal status, and ER negativity affected node positivity rates (P < 0.05). Death from breast cancer was more common among node-positive patients (P < 0.05). No difference was found regarding the performance of ALND and survival (P > 0.05). We feel that ALND can be safely omitted in T1a to reduce the morbidity and the expense of breast cancer treatment. In T1b and T1c tumors, the use of ALND is necessary, but morbidity and cost can be reduced by the use of sentinel lymph node biopsy.     

Is axillary lymph node dissection always necessary in breast cancer patients with a positive sentinel node?

Axillary lymph node dissection (ALND) is recommended for patients with breast cancer metastasis to a sentinel lymph node (SLN). However in 40-70% of cases, the SLN may be the only area of metastasis in the dissected axillary contents. In patients with a positive SLN, independently predictive factors for non-SLN metastasis include size of the primary tumor, the size of the SLN metastases, extracapsular extension, and the proportion of positive SLN's among all identified SLNs. Some authors have developed scores and nomograms to estimate a patient's risk for non-SLN metastases. These scores and nomograms should be applied prospectively to a large numper of SLN positive patients who thereafter undergo completion ALND. It is necessary to verify the predictive validity of these scores before we recommend the abandonment of ALND in patients with a very low likelihood of non-SLN metastasis. In this article we review the various predictive factors of non-SLN involvement and the scores or nomograms which have been developed to predict the likelihood of a positive ALND after a positive SLN biopsy.     

Do cytokeratin-positive-only sentinel lymph nodes warrant complete axillary lymph node dissection in patients with invasive breast cancer?

The small number of nodes harvested with lymphatic mapping and sentinel lymph node (SLN) biopsy has allowed a more detailed pathologic examination of those nodes. Immunohistochemical stains for cytokeratin (CK-IHC) have been used in an attempt to minimize the false negative rate for SLN mapping. This study examines the value of CK-IHC positivity in predicting further lymph node involvement in the axillary basin. From April 1998 through May 1999, 519 lymphatic mappings and SLN biopsies were performed for invasive breast cancer. SLNs were examined by imprint cytology, hematoxylin and eosin (H&E), and CK-IHC. Patients with evidence of metastatic disease by any of the above techniques were eligible for complete axillary node dissection (CAND). The frequency with which these modalities predicted further lymph node involvement in the axillary basin was compared. Of the 519 lymphatic mappings, 39 patients (7.5%) had a CK-IHC-positive-only SLN. Five (12.8%) of these 39 patients had at least 2 SLNs positive by CK-IHC. Twenty-six of the CK-IHC-positive-only patients underwent CAND. Three of these 26 patients (11.5%) had additional metastases identified after CAND. The sensitivity levels with which each modality detected further axillary lymph node involvement were as follows: CK-IHC, 98 per cent; H&E, 94 per cent; and imprint cytology, 87 per cent. A logistic regression to compare the prognostic value of the three modalities was performed. All were significant, with odds ratios of 19.1 for CK-IHC (P = 0.015), 5.3 for H&E (P = 0.033), and 3.86 for imprint cytology (P = 0.0059). These data validate the enhanced detection of CK-IHC for the evaluation of SLNs. Detection of CK-IHC-positive SLNs appears to warrant CAND in patients with invasive breast cancer. However, the therapeutic value of CAND or adjuvant therapies based on CK-IHC-positive SLNs would be best answered by prospective randomized trials.     

Is complete axillary lymph node dissection neccessary in T1 stage invasive pure tubular carcinomas of the breast?

The purpose of this study was to evaluate the frequency of axillary lymph node metastasis in invasive pure (not mixed) tubular carcinomas of the breast and to compare our results to other series published in the literature. We analyzed 16 cases of pure tubular carcinoma measuring 2 cm or less in diameter from our database from 1988 to 2004 diagnosed in lumpectomy and mastectomy specimens with associated axillary lymph node dissection. Histopathologic features were reviewed in all patients. In all cases, no axillary lymph node metastasis was observed (0%). These data slightly differ from the results of some studies recently published in the literature, in which the overall nodal involvement in pure tubular carcinomas ranges from 0% to 20%. We conclude that in invasive pure tubular carcinomas of the breast measuring less than 2 cm in diameter, complete axillary lymph node dissection should be avoided, and we propose a sentinel lymph node analysis instead.     

Critical analysis of the 2010 TNM classification in patients with lymph node–positive bladder cancer: Influence of lymph node disease burden

ObjectivesIn 2010, a new TNM staging system was published by American Joint Committee on Cancer, changing the nodal classification to include the presence of common iliac lymph node (LN) involvement as N3 category. The objective of this study was to define the capability of the current TNM nodal classification to separate patients with different prognostic stages and to evaluate the effect of LN disease burden.Methods and materialsA total of 93 patients with metastatic LNs after radical cystectomy and extended LN dissection for urothelial carcinoma of the bladder between 1999 and 2012 were included. The median follow-up was 21.5 months. The correlation between N3 and indicators of LN disease burden was analyzed using the Spearman correlation coefficient. Recurrence-free survival (RFS) and overall survival (OS) analysis was performed using the Kaplan-Meier and Cox proportional hazards methods.ResultsThe presence of N3 disease was associated with higher number of metastatic LNs (7 vs. 2, P<0.01); however, this was highly variable and correlation coefficients between common iliac metastatic LNs and other lymphatic disease burden indicators demonstrated weak association (0.39–0.63). Patients with N1 lesions were found to have a distinct RFS and OS (P<0.01 and P = 0.01, respectively). A trend toward worse RFS (P = 0.07) and OS (P = 0.08) was observed in patients with N3 lesions. However, no difference in RFS or OS was found between patients with N2 and N3 lesions (P = 0.83 and 0.50, respectively).ConclusionsThe N3 category in the current TNM classification defines a group of patients with high but heterogeneous disease burden. This may be the explanation for its lack of prognostic stratification when compared with N2 category bladder cancer.     

Sentinel lymph node BIOPSY after neoadjuvant therapy in breast cancer patients with lymph node involvement at diagnosis. Could wire localization of clipped node improve our results?

IntroductionSentinel lymph node biopsy (SLNB) after neoadjuvant therapy (NAT) in node-positive (N+) breast cancer patients at diagnosis remains a controversial issue, with no consensus on implementation or safety.ObjectivesWe sought to assess the accuracy of SLNB after NAT in biopsy-proven N+ cases at diagnosis and the efficacy and accuracy of wire localization of the clipped node to improve results.Material and methodsA cross-sectional diagnostic technique validation study in N+ patients following NAT was performed. The biopsy-proven affected lymph node was clipped at diagnosis. SLNB and axillary lymph node dissection (ALND) were performed in cases of clinical-radiological lymph node response after NAT. For the purposes of our study we added wire localization of the clipped node.Results103 patients were included (mean age, 54.4 years [± 12.7]). Wire marking was performed in 28 cases. The overall identification rate (IR) of SLN was 81.6%. The median number of nodes removed was 2 (range 2). The overall false negative rate (FNR) was 6.1%. Sensitivity and overall accuracy were 93.9% and 95.2%, respectively (area under curve 0.97). In the double-marked (clip and wire) group the FNR decreased to 0% and accuracy was 100%. Axillary pathologic complete response was observed in 24.3% of cases.ConclusionsSLNB is useful in node-positive patients at diagnosis who respond to NAT. Combining this with preoperative wire localization of the biopsied lymph node reduces the FNR without increasing the number of complications.     

Is sentinel lymph node biopsy more accurate than axillary dissection for staging nodal involvement in breast cancer patients?

Today evaluation of axillary involvement can be routinely performed with the technique of sentinel lymph node biopsy (SLNB). One of the greatest advantages of SLNB is the nearly total absence of local postoperative complications. It is important to understand whether SLNB is better than axillary lymph-node dissection (ALND) for staging axillary nodal involvement. The aim of the study was to evaluate the axillary staging accuracy comparing three different methods: axillary dissection, sentinel node biopsy with the traditional 4-6 sections and sentinel node biopsy with complete analysis of the lymph node. 527 consecutive patients (525 females and 2 males) with invasive breast cancer < or = 3 cm and clinically negative axillary nodes were divided into 3 different groups: group A treated with axillary dissection, group B treated with sentinel nodal biopsy analysed with 4-6 sections, and group C treated with sentinel node biopsy with analysis of the entire node. All patients underwent a quadrantectomy to treat the tumor. Group differences and statistical significance were assessed by ANOVA. The percentages of N+ in group A and group B were 25.80% and 28% respectively, while in the third group it rose to 45%, or almost half the patients. The differences among the three groups were statistically significant (p = 0.02). From our analysis of the data it emerges that axillary dissection and sentinel node biopsy with analysis of 4-6 sections have the same accuracy in staging the nodal status of the axilla; analysis of the entire sentinel lymph node revealed an increased number of patients with axillary nodal involvement, proving more powerful in predicting nodal stage. SLNB with complete examination of the SLN removed can be considered the best method for axillary staging in breast cancer patients with clinical negative nodes. In our study, the percentage of metastases encountered after complete examination of SLN was 45% compared to the accuracy of axillary dissection that was only 25.8%. Moreover, this approach avoids the useless axillary cleaning in about 55-60% of cases, decreasing postoperative morbidity and mortality.     

Extended lymph node dissection in robot-assisted radical prostatectomy： lymph node yield and distribution of metastases

In this study, we reported our experience performing robotic extended lymph node dissection （eLND） in patients with prostate cancer. A total of 147 patients with intermediate and high-risk prostate cancer who underwent robotic eLND from May 2008 to December 2011 were included in this analysis. The dissection template extended to the ureter crossing the iliac vessels. We assessed lymph node yield, lymph node positivity, and perioperative outcomes. Lymph node positivity was also evaluated according to the number of lymph nodes （LNs） removed （〈22 vs 〉22）. The median number of LNs removed was 22 （11-51）, and 97 positive LNs were found in 24 patients （16.3%）. While the obturator fossa was the most common site for LN metastases （42.3%, 41/97）, the internal iliac area was the most common area for a single positive LN packet （20.8%, 5/24）. Eight patients （33.3%, 8/24） had positive LNs at the common iliac area. The incidence of positive LNs did not differ according to the number of LNs removed. Complications associated with eLND occurred in 21 patients （14.3%） and symptomatic lymphocele was found in five patients （3.4%）. In conclusion, robotic eLND can be performed with minimal morbidity. Furthermore, LN yield and the node positive rate achieved using this robotic technique are comparable to those of open series. In addition, the extent of dissection is more important than the absolute number of LNs removed in eLND, and the robotic technique is not a prohibitive factor for performing eLND.     

Lower lymph node yield in axillary lymph node dissection specimens in breast cancer patients receiving neoadjuvant chemotherapy: Quality concern or treatment effect?

Axillary lymph node dissection (ALND) specimens should have at least ten-lymph nodes for examination according to established guidelines. Nonetheless, recent evidence suggests that neoadjuvant chemotherapy (NAC) results in fewer nodes in the specimen. We sought to examine if NAC patients have lower lymph node yield from ALND specimens and whether the number of lymph nodes in the specimen is correlated with pathologic complete response (pCR). Using the National Cancer Database (NCDB), a study cohort of female patients with node-positive, non-metastatic invasive breast cancer diagnosed from 2012 to 2015 was identified. The axillary lymph node retrieval count was compared in NAC and non-NAC patients and then correlated with pCR. A multivariable analysis was performed to identify factors that were associated with less than ten-lymph nodes in the ALND pathologic specimen. Of 56,976 patients identified, 27,197 (48%) received neoadjuvant chemotherapy; 29,779 (52%) did not. NAC patients failed to meet the ten-lymph node minimum in the ALND specimen more often than non-NAC patients (35% vs. 27%, p < 0.001). NAC patients with fewer than ten-lymph nodes were more likely to have a pCR than those with ten or more (22% vs. 16%, p < 0.001). On multivariable analysis, pCR of the primary tumor and receptor status were found to be independent predictors of having fewer than ten-lymph nodes in the ALND specimen. Node-positive breast cancer patients that underwent NAC were more likely to not meet the ten-lymph node standard. However, NAC patients who did not meet the minimum were also more likely to have a pCR compared to NAC patients who did. This suggests lower lymph node yield may not truly be a marker of lower quality surgery but rather a potential marker of NAC treatment effect.     

Sentinel lymph node biopsy or detection of micrometastasis in bone marrow: which might be an alternative to axillary lymph node dissection in breast cancer patients?

Axillary lymph node status has limited prognostic significance in breast cancer patients and much improvement can be made. Sentinel lymph node biopsy is emerging as an alternative to axillary lymph node dissection for staging, but its prognostic relevance is still uncertain. Detection of micrometastases in sentinel nodes and bone marrow may provide more information, but the clinical significance still needs to be confirmed by ongoing large trials. In this review, we focus on the possibility of sentinel lymph node biopsy or detection of bone marrow micrometastasis replacing traditional axillary lymph node dissection.     

Can axillary lymph node dissection be omitted in patients with breast cancer and positive sentinel nodes?

Sentinel lymph node biopsy has evolved as the surgical procedure of choice for women with clinically negative axillae, as part of an effort to move toward the less invasive surgical management of breast cancer. Axillary lymph node dissection remains the standard of care for patients with a positive axillary node and was previously performed on all patients with breast cancer prior to the implementation of the sentinel lymph node biopsy. There is, however, controversy regarding whether or not all patients with a positive sentinel lymph node need to undergo completion axillary dissection for either prognostic or therapeutic purposes. This article reviews the literature related to this controversial and evolving topic.     

Does the presence of sentinel lymph node macrometastases in breast cancer patients require axillary lymph node dissection?—Single‐center analysis

According to the current guidelines on treatment of breast cancer patients, identification of metastases in the sentinel lymph node (SLN (+)) is not an absolute indication for necessary axillary lymph node dissection (ALND). In our study, we present long‐term outcomes of treatment among SLN(+) patients referred for conservative treatment, for example, no further ALND. A total of 3145 breast cancer patients subjected to sentinel lymph node biopsy (SLNB) between November 2008 and June 2015. SLN metastases were identified in 719 patients (22.9%). Locoregional recurrences and distant metastases as endpoints were distinquished. The mean follow‐up time for patients after ALND was 36.2 months (6‐74 months); 18.8 months (6‐38 months) for patients with SLN macrometastases without ALND; and 34.0 months (6‐74 months) for patients with micrometastases. Adjuvant ALND was performed in 626 of SLN(+) patients. Conservative treatment was applied in the remaining 93 cases. Among SLN(+) patients without adjuvant ALND, there was one case of recurrence (1.07%). In the group of patients without SLN, metastases recurrence was noted in 32 patients (1.32%). Among SLN(+) patients diagnosed with macrometastases, recurrence concerned 2.01% of analyzed cases (all subjected to ALND). Lack of radical surgical treatment in SLN(+) breast cancer patients did not lead to worsening long‐term outcomes. In the occurrence of macrometastases to the sentinel lymph node, abandoning completion axillary lymph node dissection might be a reasonable option. However, it would require continuation of current research, preferably involving a clinical trial.     

Sentinel lymph node biopsy in early-stage breast cancer patients: improved survival through better staging?

Purpose

The objective of this review is to summarize the evidence demonstrating that the sentinel lymph node (SLN) procedure is not only associated with significantly less morbidity compared to the axillary dissection, but may also result in better staging and improved patient outcomes.

Methods

A search of MedLine and PubMed articles using the terms “sentinel lymph node biopsy”, “breast cancer”, “staging”, “morbidity”, “survival”, and “outcomes” was conducted.

Results

Breast cancer staging includes axillary evaluation as an integral component. Over the past two decades, sentinel lymph node biopsy has evolved as a technique that has an improved morbidity over traditional axillary dissection. The sentinel node(s) undergo a more intensive pathologic examination than traditional axillary contents. In the node-negative group of patients, this may have led to stage migration and potentially improved disease-free and overall survival.

Conclusion

The SLN procedure is not only associated with significantly less morbidity compared to the axillary lymph node dissection, it may also result in more accurate staging, better axillary tumor control and improved survival.