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.     

Validation of the Tenon breast cancer score for predicting non-sentinel lymph node status in breast cancer patients with sentinel lymph node metastasis: a prospective multicenter study

Background Axillary lymph node dissection (ALND) is the standard treatment for patients with sentinel node (SN) metastasis, but most of these patients have negative non-sentinel nodes (non-SN). We have developed a scoring system (the Tenon score) to help identify a subgroup of patients who have a low risk of having non-SN metastases and who may thus forgo ALND. Here we validated the Tenon score in an independent cohort of SN-positive patients. Patients and methods We tested the accuracy of the Tenon score for predicting non-SN status in a prospective multicenter study of 226 SN-positive breast cancer patients. We calculated the false-negative rate, sensitivity, specificity, and positive (PPV) and negative predictive values (NPV). Receiver operating characteristics (ROC) curves were constructed and the areas under the curve (AUC) were calculated as a measure of discriminatory capacity. Results At least one non-SN was positive in 63 patients (27.9%). One hundred and twenty (53.1%) of the 226 patients had a Tenon score of 3.5 or less. Among these 120 patients, five had at least one positive non-SN. With a score cut-off of 3.5, the negative predictive value was 95.8% and the false-negative rate was 4.2%. Overall, the Tenon score accurately predicted non-SN status, with an AUC of 0.82 (95% confidence interval, 0.77–0.88). Conclusion In this multicenter study of an independent patient population, the Tenon score was accurate and reproducible for predicting non-SN status in breast cancer patients. The simplicity and reliability of the variables on which the Tenon score is based may be an advantage over other scoring systems.     

Pure tubular carcinoma of the breast and sentinel lymph node biopsy: A retrospective multi-institutional study of 234 cases

Background

Pure Tubular Carcinoma (PTC) of the breast is a rare histological subtype of invasive breast cancer characterized by a low rate of lymph node involvement. Currently there is no consensus on less surgical axillary node staging according to this histological subtype.

Methods

We performed a retrospective multi-institutional study. Inclusion criteria were PTC, sentinel lymph node detection (SLND) and conservative breast surgery.

Results

From January 1999 to December 2006, 234 patients were included in the study from 9 institutions. The median pathological tumor size was 9.59 (1–22) mm. SLN were successfully detected in 98% (229/234) of patients. Among the 234 patients, a macrometastasis was found in 6 cases (2.5%), micrometastasis in 15 cases (6.4%), and isolated cells in 2 cases (0.8%). In the case of patients with SLND macrometastasis, half of them had macrometastasis in the complementary axillary lymphadenectomy, and none in the case of SLN only micrometastasis or isolated cells. Of the 122 patients with a pathological tumor size <10 mm, none had sentinel node macrometastasis. According to a multivariate analysis, pathological tumor size (>10 mm) was the only parameter significatively linked to the risk of lymph node involvement (p = 0.007).

Conclusion

In a large multi-institutional series with SLND, we have shown that the risk of axillary lymph node involvement in PTC is very low. In the case of PTC <10 mm, we suggest that surgical axillary evaluation, even with SLND, may not be warranted.     

Impact of completion axillary lymph node dissection in patients with breast cancer and isolated tumour cells or micrometastases in sentinel nodes

BackgroundOmission of completion axillary lymph node dissection (ALND) is a standard practice in patients with breast cancer (BC) and negative sentinel nodes (SNs) but has shown insufficient evidence to be recommended in those with SN invasion.MethodsA retrospective analysis of a cohort of patients with BC and micrometastases (Mic) or isolated tumour cells (ITCs) in SN. Factors associated with ALND were identified, and patients with ALND were matched to patients without ALND. Overall survival (OS) and recurrence-free survival (RFS) were estimated in the overall population, in Mic and in ITC cohorts.FindingsAmong 2009 patients analysed, 1390 and 619 had Mic and ITC in SN, respectively. Factors significantly associated with ALND were SN status, histological type, age, number of SN harvested and absence of adjuvant chemotherapy. After a median follow-up of 60.4 months, ALND omission was independently associated with reduced OS (hazard ratio [HR] 2.41, 90 confidence interval [CI] 1.36–4.27, p = 0.0102), but not with increased RFS (HR 1.21, 90 CI 0.74–2.0, p = 0.52) in the overall population. In matched patients, the increased risk of death in case of ALND omission was found only in the Mic cohort (HR 2.88, 90 CI 1.46–5.69), not in the ITC cohort. The risk of recurrence was also significantly increased in the subgroup of matched Mic patients (HR 1.56, 90 CI 0.90–2.73).InterpretationA separate analysis of Mic and ITC groups, matched for the determinants of ALND, suggested that patients with Mic had increased recurrence rates and shorter OS when ALND was not performed. Our results are consistent with those of previous studies for patients with ITC but not for those with Mic. Randomised controlled clinical trials are still warranted to show with a high level of evidence if ALND can be safely omitted in patients with micrometastatic disease in SN.     

Pathologic examination of sentinel lymph nodes in breast cancer by a single haematoxylin-eosin slide versus serial sectioning and immunocytokeratin staining: clinical implications

BACKGROUND: The objective was to determine the additional value of pathologic examination using three-level sectioning and immunocytokeratin (ICK) staining of sentinel lymph node (SN) biopsies in cT1-2N0M0 breast carcinoma patients regarding lymph node staging and eligibility of systemic therapy taking primary tumor characteristics in account. METHODS: SN slides of 277 patients out of a total group of 961 patients known to have tumor-positive SNs detected by three-level sectioning and ICK staining were re-examined. Haematoxylin-eosin (HE) slide level three was scanned for tumor deposits, and when present, extra capsular extension, maximum tumor diameter and number of positive SNs was noted. In addition, slides of the axillary dissection of non-SNs were reviewed, with determination of metastasis size and number of positive non-SNs. Primary tumor characteristics (grade, diameter, estrogen receptor) were recorded. RESULTS: In the single-HE examination, 26 cases SN micrometastasis and 6 macrometastasis were missed, 3 cases of micrometastasis were incorrectly classified as isolated tumor cells, and 9 patients with macrometastasis were misclassified as micrometastasis. In addition, in the tumor-negative single-HE examination, additional axillary lymph node dissection (ALND) revealed 6 cases of non-SN metastasis. Taking primary tumor factors into account for adjuvant systemic therapy, 21 patients would have been denied the choice for systemic therapy if single-HE examination was carried out only. CONCLUSIONS: Single-HE examination of SN may result in a reduction of locoregional and systemic treatment according to treatment guidelines then current in the Netherlands.     

A nomogram predictive of non-sentinel lymph node involvement in breast cancer patients with a sentinel lymph node micrometastasis

Purpose

Predictive factors of non-sentinel lymph node (NSN) involvement at axillary lymph node dissection (ALND) have been studied in the case of sentinel node (SN) involvement, with validation of a nomogram. This nomogram is not accurate for SN micrometastasis. The purpose of our study was to determine a nomogram for predicting the likelihood of NSN involvement in breast cancer patients with a SN micrometastasis.

Methods

We collated 909 observations of SN micrometastases with additional ALND. Characteristics of the patients, tumours and SN were analysed.

Results

Involvement of SN was diagnosed 490 times (53.9%) with standard staining (HES) and 419 times solely on immunohistochemical analysis (IHC) (46.1%). NSN invasion was observed in 114 patients (12.5%), whereas 62.3% (71) had only one NSN involved and 37.7% (43) two or more NSN involved. In multivariate analysis, significant predictive factors were: tumour size (pT stage ≤10 mm or >11 and ≤20 or >20 mm [odds ratio (OR) 2.1 and 3.43], micrometastases detected by HES or IHC [OR 1.64], presence or absence of lymphovascular invasion (LVI) [OR 1.76], tumour histological type mixed or not [OR 2.64]. The rate and probability of NSN involvement with the model are given for 24 groups, with a representation by a nomogram.

Conclusion

One group, corresponding to 10.1% of the patients, was associated with a risk of NSN involvement of less than 5%, and five groups, corresponding to 29.8% of the patients, were associated with a risk ≤10%. Omission of ALND could be proposed with minimal risk for a low probability of NSN involvement.     

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   

Multicentre validation of different predictive tools of non-sentinel lymph node involvement in breast cancer

Sentinel lymph node (SN) biopsy offers the possibility of selective axillary treatment for breast cancer patients, but there are only limited means for the selective treatment of SN-positive patients. Eight predictive models assessing the risk of non-SN involvement in patients with SN metastasis were tested in a multi-institutional setting. Data of 200 consecutive patients with metastatic SNs and axillary lymph node dissection from each of the 5 participating centres were entered into the selected non-SN metastasis predictive tools. There were significant differences between centres in the distribution of most parameters used in the predictive models, including tumour size, type, grade, oestrogen receptor positivity, rate of lymphovascular invasion, proportion of micrometastatic cases and the presence of extracapsular extension of SN metastasis. There were also significant differences in the proportion of cases classified as having low risk of non-SN metastasis. Despite these differences, there were practically no such differences in the sensitivities, specificities and false reassurance rates of the predictive tools. Each predictive tool used in clinical practice for patient and physician decision on further axillary treatment of SN-positive patients may require individual institutional validation; such validation may reveal different predictive tools to be the best in different institutions.     

International multicenter tool to predict the risk of four or more tumor-positive axillary lymph nodes in breast cancer patients with sentinel node macrometastases

Recently, many centers have omitted routine axillary lymph node dissection (ALND) after metastatic sentinel node biopsy in breast cancer due to a growing body of literature. However, existing guidelines of adjuvant treatment planning are strongly based on axillary nodal stage. In this study, we aim to develop a novel international multicenter predictive tool to estimate a patient-specific risk of having four or more tumor-positive axillary lymph nodes (ALN) in patients with macrometastatic sentinel node(s) (SN). A series of 675 patients with macrometastatic SN and completion ALND from five European centers were analyzed by logistic regression analysis. A multivariate predictive model was created and validated internally by 367 additional patients and then externally by 760 additional patients from eight different centers. All statistical tests were two-sided. Prevalence of four or more tumor-positive ALN in each center’s series (P = 0.010), number of metastatic SNs (P < 0.0001), number of negative SNs (P = 0.003), histological size of the primary tumor (P = 0.020), and extra-capsular extension of SN metastasis (P < 0.0001) were included in the predictive model. The model’s area under the receiver operating characteristics curve was 0.766 in the internal validation and 0.774 in external validation. Our novel international multicenter-based predictive tool reliably estimates the risk of four or more axillary metastases after identifying macrometastatic SN(s) in breast cancer. Our tool performs well in internal and external validation, but needs to be further validated in each center before application to clinical use.     

Completion axillary dissection can safely be omitted in screen detected breast cancer patients with micrometastases. A decade's experience from a single institution

Background

The need for completion axillary lymph node dissection (ALND) in breast cancer patients with micrometastases in the sentinel nodes (SNs) is controversial. The aim of this retrospective observational study is to determine if the method of detection of early breast cancer is predictive for additional positive nodes in patients with micrometastases in the SNs.

Methods

Between 2001 and 2011 a total of 1993 women with primary unilateral breast cancer had surgery at Skåne University Hospital, Lund. Of 1993 patients, 1458 had an SN biopsy and nearly all patients with micro- and macrometastases had ALND.

Results

Micrometastases defined as >0.2 mm/>200 cells and ≤2.0 mm were found in 62 of 757 screen-detected patients and in 81 of 701 patients with symptomatic breast cancer. Only 3 of the screen-detected patients with micrometastases, all with tumour size >15 mm (range 18–39 mm), had metastases in the completion ALND whereas this was found in 18 of the symptomatic patients with micrometastases (p = 0.01), (tumour size, range 10–30 mm). Logistic regression analysis adjusted for method of detection, tumour size and histological grade showed 5 times higher odds for further metastases in ALND in patients with symptomatic presentation vs. screen-detected breast cancer.

Conclusion

Despite the small number of patients with micrometastases in this large cohort of breast cancer patients, these results support the contention that completion ALND can safely be omitted in screen-detected breast cancer patients with micrometastases in the SNs.     

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.     

Sentinel node biopsy as a practical alternative to axillary lymph node dissection in breast cancer patients: An approach to its validity

Background:Sentinel node biopsy (SNB) has been proposed as analternative to axillary lymph-node dissection (ALND) in breast cancer. Beforeimplementing SNB in our practice, we wished to test its validity by comparingit to the standard ALND, both in our hands and with other reported series. Patients and methods:One hundred thirty-two patients wereincluded prospectively. SNB and immediate ALND were performed. For SNB, atechnetium-colloid was used to produce preoperative lymphoscintigraphy andintraoperative gamma-probe search for the SN. Serial sectioning andimmunostains were used on the SN. A comprehensive review of the literature wasdone in order to run a meta-analysis of diagnostic tests using a summaryreceiver operating characteristic curve (SROC) to calculate the pooledparameters of sensitivity and associated 95% confidence interval(95% CI), including our own data. Results:Our technical success rate was 96%. Localsensitivity was 96%, with a 95% CI from85%–99%. Seven patients were upstaged by the SNB. Aliterature search identified 18 studies published from 1996–1999.Estimates of sensitivity ranged from 83%–100%. The pooleddata meta-analysis gave a global sensitivity of 91%, with a 95%CI from 89%–93%. The area under the global SROC curve was0.9967. Conclusions:The minimally invasive SNB was shown to be apractical alternative to ALND. We propose to use local as well as globalsensitivity and associated 95% CI to test the validity of SNB in theclinical setting. Due to limitations of ALND as the golden standard, SNB canin fact be considered a more accurate method for nodal staging.     

The role of preoperative axillary ultrasound and fine-needle aspiration cytology in identifying patients with extensive axillary lymph node involvement

Introduction

In the recent past, both clinically node-positive and node-negative but sentinel node-positive patients underwent axillary lymph node dissection (ALND), although the two groups seem to have substantially different degree of nodal involvement.

More tumor‐affected lymph nodes because of the sentinel lymph node procedure but no stage migration,because the 2002 TNM classifies small tumor deposits as pathologic N0 breast cancer

BACKGROUND:

Intensified examination of the sentinel lymph node (SN) may result in increased detection of tumor‐affected lymph nodes. The authors of this report hypothesized that the introduction of the SN procedure has led to stage migration because of the intensified workup of SNs by pathologists.

METHODS:

After the introduction of the SN procedure, 360 patients with operable breast cancer were included prospectively from 2 large hospitals (Hospital A and Hospital B). The prospectively included patients (the “SN era” group) were compared with 88 historic controls from the year 1994 who were diagnosed with primary breast cancer before introduction of the SN procedure.

RESULTS:

After correcting for classic clinical and pathologic prognostic factors in a multiple logistic regression analysis, the detection frequency of lymph node involvement was significantly higher in the SN era group compared with historic controls (P = .04). However, when using the 2002 TNM classification, in which isolated tumor cells (≤0.2 mm) were categorized as lymph node‐negative disease, no stage migration was observed (P = .98). Also, when analyzing both hospitals (Hospital A vs Hospital B) separately with respect to lymph node involvement, there was no difference, between the SN era and the historic controls (P = .79 and P = .69, respectively). This remained nonsignificant after the analysis was corrected for patient and primary tumor characteristics (P = .85 and P = .66, respectively).

CONCLUSIONS:

Introduction of the SN procedure has led to the detection of more tumor‐affected lymph nodes because of the intensified workup of SNs by pathologists. However, stage migration did not occur when tumor deposits of ≤0.2 mm were categorized as lymph node‐negative disease, according to the 2002 TNM classification. Cancer 2009. © 2009 American Cancer Society.     

乳腺癌前哨淋巴结活检研究进展

近年来,乳腺癌的发病率越来越高,乳腺癌治疗方式也在不断改进,但手术仍然是早期乳腺癌治疗的主要手段。对于早期乳腺癌,前哨淋巴结活检术（sentinel lymph node biopsy,SLNB）是一种安全、精确的手术方式,已逐渐替代腋窝淋巴结清扫术（axillary lymph node dissection,ALND）成为早期乳腺癌治疗的标准术式。随着研究的深入,SLNB的应用范围更广,术后生活质量显著改善,但其操作尚需要进一步统一规范。在前哨淋巴结微转移、宏转移、前哨淋巴结活检阳性的老年患者以及新辅助化疗的前哨淋巴结活检等方面尚未达成共识,还需要更多大型多中心前瞻性的随机试验来进一步论证。     

Sentinel lymph node biopsy is associated with improved survival compared to level I & II axillary lymph node dissection in node negative breast cancer patients

Objective

The few long-term follow-up data for sentinel lymph node (SLN) negative breast cancer patients demonstrate a 5-year disease-free survival of 96–98%. It remains to be elucidated whether the more accurate SLN staging defines a more selective node negative patient group and whether this is associated with better overall and disease-free survival compared with level I & II axillary lymph node dissection (ALND).

Methods

Three-hundred and fifty-five consecutive node negative patients with early stage breast cancer (pT1 and pT2 ≤ 3 cm, pN0/pN_SN0) were assessed from our prospective database. Patients underwent either ALND (n = 178) in 1990–1997 or SLN biopsy (n = 177) in 1998–2004. All SLN were examined by step sectioning, stained with H&E and immunohistochemistry. Lymph nodes from ALND specimens were examined by standard H&E only. Neither immunohistochemistry nor step sections were performed in the analysis of ALND specimen.

Results

The median follow-up was 49 months in the SLN and 133 months in the ALND group. Patients in the SLN group had a significantly better disease-free (p = 0.008) and overall survival (p = 0.034). After adjusting for other prognostic factors in Cox proportional hazard regression analysis, SLN procedure was an independent predictor for improved disease-free (HR: 0.28, 95% CI: 0.10–0.73, p = 0.009) and overall survival (HR: 0.34, 95% CI: 0.14–0.84, p = 0.019).

Conclusions

This is the first prospective analysis providing evidence that early stage breast cancer patients with a negative SLN have an improved disease-free and overall survival compared with node negative ALND patients. This is most likely due to a more accurate axillary staging in the SLN group.     

Ratio of marked and excised sentinel lymph nodes and scintigraphic appearance time in melanoma patients with negative sentinel lymph node

Aim

Metastases can occur in up to 15% of all melanoma patients with negative sentinel lymph node examination (SN –). We retrospectively investigated the number of preoperatively marked sentinel lymph nodes (SNs) with lymphoscintigraphy and effectively surgically removed SNs in SN – patients with cutaneous melanoma ≥0.5 mm. Ratio of these parameters was calculated and impact of this ratio as well as impact of scintigraphic appearance time (SAT) on disease progression was studied.

Materials and methods

Data on 122 SN – patients — 70 women (58%), mean age 56.5 years — were analyzed. Mean follow-up time was 58 months.

Results

Mean tumour thickness of all patients was 2.3 mm. In 51 patients (42%) the number of SNs marked in lymphoscintigraphy was higher than excised in surgery, in 47 patients (38%) the same number as marked was excised and in 24 patients (20%) a lower number was marked than excised. Metastases occurred in 17 patients (14%) after a mean time of 24.8 months. Mean tumour thickness (5.4 mm) was significantly higher in these patients than in the other patients (p = 0.000). Ratio of marked and excised SNs had no influence on disease progression; the only parameter influencing outcome was tumour thickness (p = 0.000). Short SAT was significantly associated with higher tumour thickness (p = 0.004).

Conclusion

Our study indicates that, in routine clinical practice, it suffices to harvest the first SN, as the ratio of marked and excised SNs has no impact on disease progression.     

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.     

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.     

T1 breast cancer: identification of patients at low risk of axillary lymph node metastases

Objective. The status of the axillary lymph nodes is one of the most important prognostic factors in patients with breast cancer. A panel of molecular markers of tumor aggressiveness in addition to conventional clinical and histopathologic features were analyzed in an attempt to identify a subgroup of patients with a low risk of axillary lymph node metastases. Material and methods. Data from 358 patients with T1 breast cancer who underwent level I/II axillary lymph node dissection (ALND) were investigated. Hormone receptor status, Ki-67, S-phase fraction, DNA ploidy, HER-2/neu, p53, epidermal growth factor receptor, urokinase type plasminogen activator, plasminogen activator inhibitor-1, bone marrow micrometastases as well as patient age, menopausal status, tumor site, tumor size, histologic type, tumor grade, carcinoma in situ, multifocality, and lymph vascular invasion (LVI) were studied to predict axillary lymph node status. Results. In a multivariate logistic regression analysis LVI (present v.s. not present), Ki-67 (18% v.s. <18%), tumor size (1.1–2 cm v.s. 1 cm), and histologic grade (G3 v.s. G1/2) were identified as independent predictive factors of axillary lymph node metastases. Approximately 13% of patients (n = 47) with well or moderately differentiated tumors less than or equal to 1 cm, no lymph vascular invasion, and a low Ki-67 staining were identified as having a low risk of axillary lymph node metastases of 4.3%. However, 20 patients with all four unfavorable predictive factors had a 75% incidence of axillary lymph node involvement. Conclusion. Primary tumor characteristics can be used to identify a subgroup of patients with a low risk of axillary lymph node metastases in T1 breast cancer. Preoperative risk assessment might be used to omit routine ALND in those patients at low risk of axillary lymph node metastases.