Sentinel node tumour burden quantified based on cytokeratin 19 mRNA copy number predicts non-sentinel node metastases in breast cancer: Molecular whole-node analysis of all removed nodes

ObjectiveThe one-step nucleic acid amplification (OSNA) assay can assess an entire lymph node and detect clinically relevant metastases quantified based on cytokeratin 19 (CK19) mRNA copy number. The OSNA assay of all sentinel lymph nodes (SNs) and non-sentinel nodes (non-SNs) allows for the accurate measurement of tumour burden in either situation. We aim to reveal the usefulness of the OSNA assay regarding the prediction of non-SN metastasis.MethodsThe subjects consisted of 185 breast cancer patients who underwent axillary dissection after a metastatic SN biopsy and whose SNs and non-SNs were examined using the OSNA whole-node assay between 2009 and 2011. The non-SN tumour burden was classified as macrometastasis (CK19 mRNA ?5000 copies/μl) or micrometastasis (250–5000 copies/μl). The relationship between SN and non-SN tumour burdens and predictors of non-SN metastasis were investigated.ResultsAmong these 185 patients, 38 patients (20.5%) had macrometastasis and 58 (31.4%) had micrometastasis only in the non-SNs. Non-SN macrometastasis rates increased in direct proportion to the SN copy number: approximately 5% in patients with SNs with 250–500 copies; 20%, 500–5000 copies and 30%, ?5000 copies. However, non-SN micrometastasis rates were approximately 30% regardless of the SN copy number. In multivariate analyses, the mean SN copy number, number of macrometastatic SN and lymphovascular invasion were significant for identifying non-SN macrometastases.ConclusionsThe SN tumour burden quantified using the OSNA assay predicts non-SN metastases. A novel mathematical model to predict the non-SN tumour burden can be generated using the results of the OSNA assay.     

Axillary lymph-node dissection for positive sentinel nodes in breast cancer patients.

AIM: The aim was to identify a subset of breast cancer patient with positive sentinel nodes (SNs) for whom secondary axillary clearance would be unnecessary.METHODS: Between March 1999 and May 2001, 288 patients with T0-T2 breast cancer less than 3cm in diameter had SN detection either by a colorimetric method or using a combined technique. SNs were stained with haematoxylin and eosin (H&E). For all negative SNs, serial sections and immunochemistry (IHC) were performed. All patients with positive SNs underwent a complete axillary lymph node dissection. One hundred and twenty patients were SN positve.RESULTS: Non-sentinel node positivity (NSNP) was closely associated with the size of the tumour (14.3%, 54.1% and 51.8% for pT1a-b, pT1c and pT2 tumours respectively) and with the size of the SN metastasis: 15.9% IHC detected micrometastasis, 33.3% and 78.8% micro- and macrometastasis detected with H&E staining respectively. NSNP was found in 24.0% and 42.8% of patients with pT1c breast cancer and with micrometastasis detected by IHC and H&E staining. The node positivity rate reached 81.1% for pT1c lesions with macrometastasis in the SN. For the patients with pT2 breast cancer, these rates were 12.5% (IHC), 28.5% (H&E) 91.1% (macrometastasis).CONCLUSIONS: We are unable to isolate precisely a subset of patients for whom total axillary lymph node dissection would be unnecessary. A subset of 14 small tumours (<1cm diameter) demonstrated micrometastases in the SN without NSNP.     

Pathologic features associated with nonsentinel lymph node metastases in patients with metastatic breast carcinoma in a sentinel lymph node

BACKGROUND: To the authors' knowledge it has not yet been determined which patients with primary breast carcinoma and an axillary sentinel lymph node (SN) metastasis have additional metastases in nonsentinel lymph nodes. METHODS: Pathologic features of the primary breast carcinoma and its SN metastasis were examined in 194 patients and correlated with the tumor status of the non-SNs in the same axillary basin. Two-level cytokeratin immunohistochemistry was applied to the SNs and to non-SNs of cases that were negative by standard hematoxylin and eosin examination. RESULTS: Lymph node staging based on SN findings, size of the primary tumor, and presence of peritumoral lymphatic vascular invasion (LVI) were associated with non-SN metastasis. The majority (63%) of the 101 patients with SN macrometastases had non-SN metastases. Extranodal hilar tissue invasion in conjunction with SN involvement also was strongly associated with non-SN metastasis (P = 0.0001) but was present in only 65% of patients (35 of 54 patients) with non-SN macrometastases. Approximately 26% of patients (24 of 93 patients) with SN micrometastases (相似文献   

Intraoperative assessment of sentinel lymph nodes in patients with breast carcinoma: accuracy of rapid imprint cytology compared with definitive histologic workup

BACKGROUND: As sentinel lymph node biopsy (SNB) becomes a new surgical standard in the treatment of patients with breast carcinoma, there is an emergent need for a fast and accurate method with which to assess the SN intraoperatively, so a decision can be made regarding whether to perform axillary lymph node dissection during primary surgery. In the current study, the authors performed a prospective investigation of the relative merits of imprint cytology for that purpose.METHODS: Seventy-six patients with T1-T2 breast carcinoma were included after undergoing successful SNB. SNs were freshly sectioned at 2-mm intervals and imprint smears were obtained from all cut surfaces. The smears were examined using a rapid May-Grünwald-Giemsa stain variation, and the SNs were judged to be positive or negative for metastases. SNs later were submitted for paraffin embedding and serial sectioning. Both hematoxylin and eosin stained and cytokeratin (CK) immunostained sections were examined. The postoperative evaluation of the SNs was taken as the gold standard.RESULTS: Intraoperative cytology showed a sensitivity of 67.7%, a specificity of 100%, an accuracy of 86.8%, and a negative predictive value of 81.8%. The majority of false-negative cases (8 of 10 cases) were due to micrometastasis in the SNs that were discovered only after exhaustive examination with serial sectioning and CK immunostaining.CONCLUSIONS: The results of the current study demonstrate that the accuracy of imprint cytology is high enough to warrant its use for intraoperative SN assessment. If the findings are negative, axillary lymph node dissection can be omitted. Only a few patients with SN micrometastasis may require reoperation.     

Sentinel node micrometastasis and distant failure in breast cancer patients

BACKGROUND: Lymphatic mapping and sentinel lymph node (SN) biopsy has rapidly replaced axillary lymph node dissection for clinically node-negative breast cancers. Because of a short follow-up period when the procedure was new, there were few reports of the clinical recurrence rate in breast cancer patients treated with SN biopsy. The present study attempts to clarify the occurrence of distant failure after SN biopsy, especially in breast cancer patients with SN micrometastasis. METHODS: The subjects consisted of 375 cases with clinically node-negative breast cancer, who had undergone SN biopsies. Chemotherapy and/or hormonal therapy was recommended based on the pathological primary tumor characteristics. The patients with SN micrometastasis also received adjuvant therapy equal to node-positive patients. RESULTS: Examinations of lymph nodes indicated metastases in 73 cases. Among the invasive cancers, 54 cases had macrometastasis, 19 cases had micrometastasis and 241 cases had a tumor free SN. The median follow-up period ws 30 months (range 6 to 66 months). Distant relapse rates per person-years were 0.3% in the cases with tumor free SN and 3.3% among the macrometastatic cases. However, systemic disease was not observed in the cases with SN micrometastasis. CONCLUSIONS: These results may show that upstaging due to SN investigation increases the number of cases who should receive anti-cancer drugs, and consequently reduces the distant relapse rate. Further studies in a large number of cases as well as longer follow-up are needed to determine the prognostic significance of SN micrometastasis.     

The sentinel node concept in endometrial cancer: histopathologic validation by serial section and immunohistochemistry.

BACKGROUND: The sentinel node (SN) is defined as the first node in the lymphatic system that drains a tumor site. If the SN is not metastatic, then all other nodes should also be disease-free. We used serial sections and immunohistochemical (IHC) staining to examine both SN and non-sentinel nodes (non-SNs). PATIENTS AND METHODS: Twenty-three patients (median age 69 years) with early endometrial cancer underwent a laparoscopic SN procedure based on a combined detection method, followed by complete laparoscopic pelvic lymphadenectomy. If the SN was free of metastasis by both hematoxylin and eosin (H&E) and IHC staining, all non-SNs were also examined by the combined staining method. RESULTS: SNs were identified in 19 patients (82.6%). A total of 47 SNs were removed (mean 2.5). Ten SNs (21.3%) from five patients (26.3%) were found to be metastatic at the final histologic assessment. In 14 patients, no metastatic SN involvement was detected by H&E and IHC staining. In these 14 patients, 120 non-SNs were examined by serial sectioning and IHC, and none were found to be metastatic. CONCLUSION: The SN procedure appears to reliably predict the metastatic status of the regional lymphatic basin in patients with early endometrial cancer.     

Improved Detection of Metastases by Step Sectioning and Immuno-Histochemical Staining of Axillary Sentinel Nodes in Patients with Breast Carcinoma

Background: The object of this study was to examine whether a new protocol including step-sectioningand immunohistochemistry (IHC) staining of axillary sentinel nodes (SN) would lead to detection of moremetastases in patients with breast cancer. Materials and Methods: Sixty-nine tumor free sentinel lymph nodeswere examined. Step frozen sectioning was performed on formalin fixed SN and stained both by hematoxylinand eosin (H and E) and cytokeratin markers using IHC. Any tumoral cell in IHC stained slides were consideredas a positive result. Metastases up to 0.2 mm were considered as isolated tumor cells and 0.2 up to 2 mm asmicrometastasis. Results: Mean age of the patients was 48.7±12.2 years. Step sectioning of the SN revealed 11involved by metastasis which was statistically significant (p<0.001). Furthermore, 15 (21.7%) of the patientsrevealed positive results in IHC staining for pan-CK marker and this was also statistically significant (p=0.001).Ten patients had tumoral involvement in lymph nodes harvested from axillary dissection and 4 out of 15 lymphnodes with positive result for CK marker were isolated tumor cells. However, 4 of 10 patients with tumor positivelymph nodes in axillary dissection were negative for CK marker and in contrast 6 of the pan-CK positive SNwere in patients with tumor-free axillary lymph nodes. Conclusions: Both IHC and step sectioning improve thedetection rate of metastases. Considering the similar power of these two methods, we recommend using eitherIHC staining or step sectioning for better evaluation of harvested SNs.     

Detection of sentinel lymph nodes in gastric cancers based on immunohistochemical analysis of micrometastases

BACKGROUND AND OBJECTIVES: The sentinel lymph node (SN) theory has the potential to change the trend of surgery for gastric cancer that is based on wide resection of the stomach with dissection of regional lymph nodes. However, feasibility tests of SN mapping procedures in gastric cancers with analysis of micrometastasis are rare. This study aimed to estimate the clinical usefulness of SN mapping using a dual procedure with dye- and gamma probe-guided techniques for gastric cancers, based on immunohistochemical staining (IHC) analysis. METHODS: SN mapping procedures were performed on 41 patients with T1-T2 gastric cancer, and gastrectomy with D2 lymphadenectomy followed. All SNs and non-SNs obtained from the patients were tested by IHC analysis using anti-cytokeratin antibodies. RESULTS: Using the dual mapping procedure, SNs were detected in all patients (100%). SN was positive in all patients with lymph node metastasis except in one with non-solid type poorly differentiated adenocarcinoma with marked lymphatic permeation, thus achieving an accuracy rate of 98%. CONCLUSIONS: The method was accurate in predicting nodal status and could be an indicator for less invasive treatment in patients with gastric cancer.     

Omitting axillary lymph node dissection in sentinel node negative breast cancer patients is safe: a long term follow-up analysis

PURPOSE: To evaluate the rate of axillary recurrences in sentinel node (SN) negative breast cancer patients without further axillary lymph node dissection (ALND). PATIENTS AND METHODS: Between October 1994 and November 1999, all SN negative breast cancer patients who did not underwent complete ALND were enrolled in this prospective study. SN biopsy was performed by using the triple technique which combines preoperative lymphoscintigraphy, intraoperative use of blue dye, and a handheld gamma probe to visualize and localize the SN. SNs were examined by standard hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC). During the first year after surgery all patients underwent clinical examination at 3 monthly intervals. This follow-up interval was prolonged to 6 month after the first year. RESULTS: From the 104 patients, 93 (89%) underwent breast-conserving therapy; all remaining patients were treated by modified radical mastectomy. In 91 cases a ductal carcinoma and in 13 cases a lobular carcinoma was diagnosed. One SN was removed in 80, two SNs in 18, and three SNs in 2 patients. Twenty patients received systemic therapy based on age and primary tumor characteristics. After a median follow-up of 57 month only one axillary recurrence was observed. During follow-up three patients developed distant metastases. One of these patient with metastases to the bone is alive with evidence of disease. The remaining two patients died 9 and 19 month after surgery. CONCLUSIONS: Our long term follow-up results indicate that survival is excellent (98%) and local axillary control is adequate (99%) after omitting ALND in a group of 104 SN negative breast cancer patients.     

Histopathological validation of the sentinel node concept in cervical cancer.

BACKGROUND: The sentinel node (SN) is defined as the first node in the lymphatic system that drains a tumor site. If the SN is not metastatic, then all other nodes should also be disease-free. We used serial sections and immunohistochemical (IHC) staining to examine both sentinel and non-sentinel nodes (non-SNs). MATERIALS AND METHODS: From July 2001 to March 2003, 18 patients (median age, 48 years) with cervical cancer (stage IA2, one patient; stage IB1, nine patients; stage IB2, three patients; stage IIA, three patients; and stage IIB, two patients) underwent a laparoscopic SN procedure based on a combined detection method, followed by complete laparoscopic pelvic lymphadenectomy. If the SN was free of metastasis by both hematoxylin and eosin (H&E) and IHC staining, all non-SNs were also examined by the combined staining method. RESULTS: A mean of 2.4 SNs (range 1-5) and 8 non-SNs (range 4-14) were excised per patient. Eight SNs (18.2%) from five patients (27.8%) were found to be metastatic at the final histological assessment, including two macrometastatic SNs, three micrometastatic SNs and isolated tumor cells in three SNs. In 13 patients, no metastatic SN involvement was detected by H&E and IHC staining. In these 13 patients, 106 non-SNs were examined by serial sectioning and IHC, and none was found to be metastatic. CONCLUSIONS: The SN procedure appears to reliably predict the metastatic status of the regional lymphatic basin in patients with cervical cancer.     

The significance of one positive axillary node.

AIMS: The aim of this study was to identify a subgroup of patients with breast cancer that can safely avoid axillary dissection. METHODS: Using data collected by the Eindhoven Cancer Registry, we compared the clinico-pathological features of 489 patients with only one positive lymph node to those of 817 patients with more than one positive lymph node in the axilla. All patients underwent complete axillary dissection, not preceded by a sentinel node biopsy. RESULTS: Tumour size greater than 1cm, harvesting more than 15 axillary lymph nodes at histopathological examination, metastasis size larger than 2mm, extranodal extension, and nodal involvement of the axillary apex are independently associated with the occurrence of more than one metastatic axillary lymph node. CONCLUSION: No subgroup could be identified in which axillary dissection can always be omitted. However, tumour size<1cm, finding a micrometastasis rather than a macrometastasis, and especially not finding extranodal extension were independently associated with finding only one positive axillary lymph node.     

Implications of the sentinel lymph node procedure for local and systemic adjuvant treatment

PURPOSE OF REVIEW: The objective of the sentinel lymph node procedure in breast cancer is to perform an accurate axillary staging and provide good local control, while sparing the patients the morbidity of an axillary lymph node dissection. Since its routine clinical use, questions were raised concerning the implications for local and systemic adjuvant treatment. This review provides an update of the recent literature. RECENT FINDINGS: As a result of a more detailed histopathologic work-up of the sentinel lymph node, higher rates of lymph node metastases are detected. This leads to an upstaging of a subset of node-negative patients and an increase in the overall percentage of node-positive patients. However, the clinical implications of micrometastases and isolated tumor cells remain unclear. Furthermore, sentinel lymph nodes may be found in the internal mammary lymph node chain but the treatment of these nodes is subject of debate. SUMMARY: Current guidelines recommend axillary lymph node dissection in patients with a positive sentinel node. The surgical removal of the internal mammary lymph node is only indicated in the context of a clinical trial. Radiation therapy of the axilla is an acceptable alternative for patients who refuse an axillary lymph node dissection (clinical trial). The value of radiotherapy to the internal mammary lymph node has never been established. Systemic treatment decisions in patients with a macrometastasis or micrometastasis in the sentinel lymph node follow the guidelines of node-positive patients, whereas in patients with isolated tumor cells only, guidelines for node-negative patients are followed. The results of ongoing clinical trials will be important for the development of further guidelines.     

Follow-up of cases with false-negative pathologic sentinel nodes in breast cancer

BACKGROUND: The clinical practice of sentinel lymph node biopsy for breast cancer patients started in 1999 in our hospital, to obviate unnecessary axillary lymph node dissection. The present study examines the pathological false-negative cases on intraoperative sentinel lymph node investigations and evaluates their outcomes. METHODS: The subjects consisted of 183 cases with clinically node-negative breast cancer who had undergone sentinel node biopsy. When the sentinel node was noted to contain malignant cells intraoperatively, a complete axillary lymph node dissection was performed subsequently. The patients with tumor free sentinel nodes underwent no further axillary surgery. The pathological false-negative cases in this series were defined as patients with lymph node involvement which was revealed postoperatively, despite negative intraoperative sentinel node examinations. After these surgeries and/or adjuvant therapies, interval clinical evaluations were performed for all patients. RESULTS: Intraoperative diagnosis of the sentinel node was 96.2% accurate compared with the results of permanent sections. There were six pathological false-negative cases, a false-negative rate of 4.1%, all of which had only micrometastasis. Five cases received systemic adjuvant therapy and have been disease-free, however, one patient who refused further therapy developed infraclavicular lymph node metastasis two years after surgery. CONCLUSIONS: In the management of the patients with postoperatively revealed sentinel node micrometastasis, systemic adjuvant therapies might reduce local relapse without secondary lymph node dissection.     

Optimal management of patients with a positive sentinel lymph node

Sentinel lymph node biopsy has revolutionized breast cancer surgery, obviating axillary lymph node dissection as a staging procedure in clinically node-negative patients. Concomitantly, improved pathologic assessment of the sentinel lymph node has led to the discovery of progressively smaller quantities of metastases, the clinical importance of which has not yet been established. Sentinel lymph node metastases can now be organized into three categories of decreasing size: macrometastases, micrometastases, and isolated tumor cells. Although the standard of care is to perform an axillary dissection for patients with macro- or micrometastases, certain subsets of patients may fare well without an axillary dissection. Axillary radiation in positive sentinel node management is also a subject of ongoing investigation, especially in light of long-term survival data equivalent to that of axillary lymph node dissection. Isolated tumor cells are of undetermined significance and do not require completion axillary dissection when discovered in the absence of other sentinel node findings. This article discusses management recommendations in the context of macrometastasis, micrometastasis, and isolated tumor cells.     

Carbon dye histologically confirms the identity of sentinel lymph nodes in cutaneous melanoma

BACKGROUND: False-negative results from lymphatic mapping and sentinel lymphadenectomy (LM/SL) are associated with technical failures in nuclear medicine and surgery or with erroneous histologic evaluation. Any method that can confirm sentinel lymph node (SN) identity might decrease the false-negative rate. Carbon dye has been used as an adjunct to assist lymphadenectomy for some tumors, and the authors hypothesized that it could be used for the histologic verification of SNs removed during LM/SL. The current study assessed the clinical utility of carbon dye as a histopathologic adjunct for the identification of SNs in patients with melanoma and correlated the presence of carbon particles with the histopathologic status of the SNs. METHODS: LM/SL was performed using carbon dye (India ink) combined with isosulfan blue dye and sulfur colloid. Blue-stained and/or radioactive lymph nodes (two times background) were defined as SNs. Lymph nodes were evaluated for the presence of carbon particles and melanoma cells. If an SN lacked carbon dye in the initial histologic sections, four additional levels were obtained with S-100 protein and HMB-45 immunohistochemistry. Completion lymph node dissection (CLND) was performed if any SN contained melanoma cells. RESULTS: One hundred patients underwent successful LM/SL in 120 lymph node regions. Carbon particles were identified in 199 SNs from 111 lymph node regions of 96 patients. Sixteen patients had tumor-positive SNs, all of which contained carbon particles. The anatomic location of the carbon particles within these tumor-positive SNs was found to be correlated with the location of tumor cells in the SNs. The presence of carbon particles appeared to be correlated with blue-black staining (P = 0.0001) and with tumor foci (P = 0.028). All 35 non-SNs that were removed during LM/SL were tumor-negative, and only 2 contained carbon particles. Of the 272 non-SNs removed during CLND, 5 contained metastases; 3 of these 5 were the only non-SNs that had carbon particles. The use of carbon particles during LM/SL was found to be safe and nontoxic. CONCLUSIONS: Carbon dye used in LM/SL for melanoma permits the histologic confirmation of SNs. Carbon particles facilitate histologic evaluation by directing the pathologist to the SNs most likely to contain tumor. The location of carbon particles within SNs may assist the pathologist in the detection of metastases, thereby decreasing the histopathologic false-negative rate of LM/SL and subsequently reducing the same-basin recurrence rate.     

Micro-metastases in axillary lymph nodes: an increasing classification and treatment dilemma in breast cancer due to the introduction of the sentinel lymph node procedure

BACKGROUND: Sentinel lymph node (SN) biopsy will increasingly replace axillary lymph node dissection (ALND) for staging in breast cancer. For daily practice, examination of the SN by serial sectioning (SS) and/or immunohistochemistry (IHC) is being promoted. Use of these techniques may result into stage migration due to the increased detection of micro-metastases. The consequence may be overshooting of patients with adjuvant therapy, as the prognostic relevance of (small) micro-metastases and isolated tumor cells is unclear. METHODS: The prognostic impact of micro-metastases is determined by reviewing ALND studies with a follow up of at least 5 years, including more than 100 patients, before the SN era. Furthermore, studies in which conventionally haematoxylin-eosin (H&E) negative SNs are investigated for occult metastases by SS and/or IHC are reviewed. RESULTS: In only one of eight studies, occult metastases were an independent risk factor for reduced survival. The outcome is dependent on the size of the nodal metastasis. IHC and SS as used in the SN procedure indeed induce a shift from pNO to pN1a (according to TNM). CONCLUSION: By the thorough pathologic examination of the SN, isolated tumor cells and micro-metastases are more frequently detected. We propose to classify small micro-metastases (<0.5 mm) in a separate pN1a(min) category (min for minimal) to prevent stage migration. As the prognostic relevance of isolated tumor cells and (small) micrometastases has not been proven, the value of adjuvant therapy can be questioned for patients with otherwise good prognostic factors.     

Symmetrization reduction mammaplasty combined with sentinel node biopsy in patients operated for contralateral breast cancer

BACKGROUND AND OBJECTIVES: Occult invasive cancer found in reduction mammaplasty specimen in the contralateral breast in breast cancer patients requires axillary lymph node dissection (ALND) to assess the lymph node status. Routine Sentinel node (SN) biopsy in these patients may avoid secondary ALND when an occult cancer is found and the SN is negative in the permanent histological examination. METHODS: One hundred sixty-nine breast cancer patients underwent contralateral reduction mammaplasty for symmetrization and with SN biopsy of the non-cancer breast. SN mapping was done using a vital blue dye alone (n = 136) or in combination with a radiocolloid (n = 33). RESULTS: A mean number of 1.4 SNs (range 1-3 SNs) was identified in 158 of 169 patients (identification rate 93.5%). One of 158 patients revealed a positive SN but no tumor was found in the reduction mammaplasty/mastectomy specimen, whereas the SN was negative in 157 patients. Histological examination of the 169 reduction mammaplasty specimen revealed 5 occult invasive cancers and 4 patients with high grade DCIS but due to a negative SN biopsy the patients were spared a secondary ALND. CONCLUSION: The small number of patients with occult contralateral cancers may not warrant routine SN mapping in patients scheduled for contralateral reduction mammaplasty.     

An axilla scoring system to predict non-sentinel lymph node status in breast cancer patients with sentinel lymph node involvement

Background. Axillary lymph node dissection (ALND) is the current standard of care for breast cancer patients with sentinel lymph node (SN) involvement. However, the SN is the only involved axillary node in a significant proportion of these patients. Here we examined factors predictive of non-SN involvement in patients with a metastatic SN, in order to develop a scoring system for predicting non-SN involvement.Materials and Methods. This study was based on a prospective database of 337 patients who underwent SN biopsy for breast cancer, of whom 81 (24) were SN-positive; we examined factors predictive of non SN involvement in the 71 of these 81 women who underwent complementary ALND. All clinical and histological criteria were recorded and analysed according to non-SN status, by using Chi-2 analysis, Students t-test, and multivariate logistic regression.Results. Univariate analysis showed a significant association between non-SN involvement and histological primary tumor size (p=0.0001), SN macrometastasis (p=0.01), the method used to detect SN metastasis (H&E versus immunohistochemistry) (p=0.03), the number of positive SNs (p=0.049), the proportion of involved SNs among all identified SNs (p=0.0001) and lymphovascular invasion (p=0.006). Histological primary tumor size (p=0.006), SN macrometastasis (p=0.02) and the proportion of involved SNs among all identified SNs (p=0.03) remained significantly associated with non-SN status in multivariate analysis. Based on the multivariate analysis, we developed an axilla scoring system (range 0–7) to predict the likelihood of non-SN metastasis in breast cancer patients with SN involvement.Conclusion. In patients with invasive breast cancer and a positive SN, histological primary tumor size, the size of SN metastases, and the proportion of involved SNs among all identified SNs were independently predictive of non-SN involvement.     

Clinical evidence of breast cancer micrometastasis in the era of sentinel node biopsy

Sentinel node biopsy for early-stage breast cancer has been established as an excellent surgical and staging procedure developed to enhance the detection of minimal lymph node involvement such as micrometastases. Multisection and the proper use of immunohistochemical staining have led to the increased detection of micrometastases, and this has given rise to new questions about the treatment to be employed concerning micrometastasis. That is whether complete axillary lymph node dissection (ALND) and adjuvant systemic therapy are really required for patients with micrometastasis because of the low prevalence of nonsentinel lymph node metastasis. Some currently published case studies report that selected patients with micrometastases without further ALND would not suffer from a high incidence of regional recurrence. However, the long-term prognostic risk of systemic recurrence and local failure associated with residual axillary disease in the sentinel lymph node-positive patient electing for no further axillary surgery has not been defined. Numerous studies have investigated the impact of occult metastases, which may be regarded as micrometastases or a small tumor deposit. Although data from randomized controlled trials are lacking, these studies suggest that the prognosis of breast cancer patients with micrometastases should not be considered the same as that in truly node-negative patients. Patients with micrometastases should have some adjuvant systemic therapy. Ongoing randomized trials will provide prospective answers to the question of the optimal treatment for micrometastasis.