Sentinel lymph-node biopsy-based prediction of further breast cancer metastases in the axilla

doi:10.1053/ejso.2001.1138

European Journal of Surgical Oncology (EJSO)

Volume 27, Issue 6, September 2001, Pages 532-538

https://doi.org/10.1053/ejso.2001.1138 Get rights and content

Abstract

Background: Histopathological factors may help identifying a subgroup of breast cancer patients with metastases confined to the sentinel lymph nodes (SLNs). Methods: A retrospective analysis was carried out on 111 tumours successfully mapped with Patent blue, 69 of which had SLN metastases. Results: Multivariate analysis revealed that SLN metastases situated in the sinuses and a small tumour size are the two most important predictors of involvement of only one SLN. The metastasis size and a small tumour size were found important in the model discriminating between tumours with metastases to SLNs only and those with non-SLN involvement. Classification of tumours with only one SLN metastasis and those with a multinodal involvement resulted in a smaller error rate, falsely classified as lesser nodal involvement. Patients with tumours <1.8 cm and metastatic to the sinuses of a single SLN had a low probability of non-SLN metastasis, and might be candidates for axillary sparing after a positive SLN biopsy. Conclusions: Further investigations are required to assess the validity of such predictive models for the identification of patients with no metastases beyond the SLN. Axillary treatment must remain the rule until predictive models of non-SLN involvement are fully validated.

References (38)

PJ Borgstein et al.
Sentinel lymph node biopsy in breast cancer: guidelines and pitfalls of lymphoscintigraphy and gamma probe detection
J Am Coll Surg
(1998)
N Beechey-Newman
Sentinel node biopsy: a revolution in the surgical management of breast cancer?
Cancer Treat Rev
(1998)
SS Bass et al.
The role of sentinel lymph node biopsy in breast cancer
J Am Coll Surg
(1999)
RJ Cote et al.
Role of immunohistochemical detection of lymph-node metastases in management of breast cancer
Lancet
(1999)
MR Shetty et al.
Tumor size and axillary metastasis, a correlative occurence in 1244 cases of breast cancer between 1980 and 1995
Eur J Surg Oncol
(1997)
B Cutuli et al.
Évaluation du risque d»envahissement ganglionnaire axillaire dans les cancers du sein inférieurs a 3 centimetres. Analyse d»un modele pr&eactue;dictif a partir de 893 cas
Chirurgie
(1998)
AE Giuliano et al.
Sentinel lymphadenectomy in breast cancer
J Clin Oncol
(1997)
JM Guenther et al.
Sentinel lymphadenectomy for breast cancer in a community managed care setting
Cancer J Sci Am
(1997)
D Krag et al.
The sentinel node in breast cancer. A multicenter validation study
N Engl J Med
(1998)
U Veronesi et al.
Sentinel lymph node biopsy and axillary dissection in breast cancer: results in a large series
J Natl Cancer Inst
(1999)

AE Giuliano et al.

Improved axillary staging of breast cancer with sentinel lymphadenectomt

Ann Surg

(1995)

I Jannink et al.

Serial sectioning of sentinel nodes in patients with breast cancer: a pilot study

Ann Surg Oncol

(1998)

BJ Czerniecki et al.

Immunohistochemistry with pancytokeratins improves the sensitivity of sentinel lymph node biopsy in patients with breast carcinoma

Cancer

(1999)

K Dowlatshahi et al.

Occult metastases in the sentinel lymph nodes of patients with early stage breast carcinoma. A preliminary study

Cancer

(1999)

G Cserni

Metastases in axillary sentinel lymph nodes in breast cancer as detected by intensive histopathological work up

J Clin Pathol

(1999)

MM Flett et al.

Sentinel node localization in patients with breast cancer

Br J Surg

(1998)

G Cserni et al.

The value of axillary sentinel nodal status in breast cancer

World J Surg

(2000)

Elston, CW, Ellis, IO, Assessment of histological grade, In Elston CW, Ellis IO (eds). The Breast, Systemic Pathology,...

AE Giuliano et al.

Lymphatic mapping and sentinel lymphadenectomy for breast cancer

Ann Surg

(1994)

Cited by (61)

Update on sentinel node pathology in breast cancer
2022, Seminars in Diagnostic Pathology
Pathologic examination of the sentinel lymph nodes (SLNs) in patients with breast cancer has been impacted by the publication of practicing changing trials over the last decade. With evidence from the ACOSOG Z0011 trial to suggest that there is no significant benefit to axillary lymph node dissection (ALND) in early-stage breast cancer patients with up to 2 positive SLNs, the rate of ALND, and in turn, intraoperative evaluation of SLNs has significantly decreased. It is of limited clinical significance to pursue multiple levels and cytokeratin immunohistochemistry to detect occult small metastases, such as isolated tumor cells and micrometastases, in this setting. Patients treated with neoadjuvant therapy, who represent a population with more extensive disease and aggressive tumor biology, were not included in Z0011 and similar trials, and thus, the evidence cannot be extrapolated to them. Recent trials have supported the safety and accuracy of sentinel lymph node biopsy (SLNB) in these patients when clinically node negative at the time of surgery. ALND remains the standard of care for any amount of residual disease in the SLNs and intraoperative evaluation of SLNs is still of value for real time surgical decision making. Given the potential prognostic significance of residual small metastases in treated lymph nodes, as well as the decreased false negative rate with the use of cytokeratin immunohistochemistry (IHC), it may be reasonable to maintain a low threshold for the use of cytokeratin IHC in post-neoadjuvant cases. Further recommendations for patients treated with neoadjuvant therapy await outcomes data from ongoing clinical trials. This review will provide an evidence-based discussion of best practices in SLN evaluation.
Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: A systematic review and an exploratory meta-analysis
2016, European Journal of Surgical Oncology
Citation Excerpt :
The incidence of ENE in SLN ranges from 24% to 40%.20,26,30 Due to its high incidence, due to its association with non-SLN metastasis, as even highlighted by Cserni and Stitzenberg et al. in a multivariate analysis,25,26 and by van la Parra et al. in a meta-analsysis,12 and also due to the results of this meta-analysis, it seems advisable to offer completion of the axillary lymph node dissection, rather than not. When considering the therapeutic in other cancer types (e.g. pancreatic ductal adenocarcinoma), ENE+ patients seem to benefit from adjuvant chemo-radiation, but not from chemotherapy alone.8,31
Invasive breast cancer is the most common malignancy in women. Its most common site of metastasis is represented by the lymph nodes of axilla, and the sentinel lymph node (SLN) is the first station of nodal metastasis. Axillary SLN biopsy accurately predicts axillary lymph node status and has been accepted as standard of care for nodal staging in breast cancer. To date, the morphologic aspects of SLN metastasis have not been considered by the oncologic staging system. Extranodal extension (ENE) of nodal metastasis, defined as extension of neoplastic cells through the nodal capsule into the peri-nodal adipose tissue, has recently emerged as an important prognostic factor in several types of malignancies. It has also been considered as a possible predictor of non-sentinel node tumor burden in SLN-positive breast cancer patients. We sought out to clarify the prognostic role of ENE in SLN-positive breast cancer patients in terms of overall and disease-free survival by conducting a systematic review and meta-analysis. Among 172 screened articles, 5 were eligible for the meta-analysis; they globally include 624 patients (163 ENE+ and 461 ENE−) with a median follow-up of 58 months. ENE was associated with a higher risk of both mortality (RR = 2.51; 95% CI: 1.66–3.79, p < 0.0001, I² = 0%) and recurrence of disease (RR = 2.07, 95% CI: 1.38–3.10, p < 0.0001, I² = 0%). These findings recommend the consideration of ENE from the gross sampling to the histopathological evaluation, in perspectives to be validated and included in the oncologic staging.
The use of onestep nucleic acid amplification (OSNA) and tumour related factors in the treatment of axillary breast cancer: A predictive model
2016, European Journal of Surgical Oncology
We aimed to determine the effectiveness of CK19 mRNA copy number and tumour related factors in predicting non-sentinel axillary nodal involvement, in order to facilitate the formulation of local treatment guidelines for axillary clearance (ANC) following intra-operative analysis of the sentinel node biopsy (SNB) using one-step nucleic acid amplification (OSNA).
Patients due to have (SNB) at our institution for breast cancer as well as patients with high grade ductal carcinoma in situ with pre-operative negative assessment of the axilla were included. Alternate slices of each node were sent for assessment by either OSNA or histopathology. Immediate ANC was performed if OSNA was positive. The CK19 mRNA nodal copy number, the total tumour load (TTL) measured by summation of mRNA copy numbers of all positive nodes, the nodal status at ANC and tumour characteristics for each patient were recorded. A model of risk probability was constructed using TTL and tumour related factors.
664 nodes were analysed from 425 patients who had SNB performed between 2011 and 2014. ANC was performed on 105 of these patients. The concordance between OSNA and histology was 91.4% and negative predictive value (NPV) was 97%.
TTL (p = 0.003) and LVI (p = 0.04) were identified as risk factors for non-sentinel nodal involvement. The risk probability model identified all patients with pN2 disease for ANC.
In the future a decision to perform ANC will be based on a risk stratification model based on TTL and tumour related factors.
Prediction of non-sentinel lymph node involvement in breast cancer patients with a positive sentinel lymph node
2014, Breast
Completion axillary lymph node dissection (cALND) is the golden standard if breast cancer involves the sentinel lymph node (SLN). However, most non-sentinel lymph nodes (NSLN) are not involved, cALND has a considerable complication rate and does not improve outcome. We here present and validate our predictive model for positive NSLNs in the cALND if the SLN is positive.
Consecutive early breast cancer patients from one center undergoing cALND for a positive SLN were included. We assessed demographic and clinicopathological variables for NSLN involvement. Uni- and multivariate analysis was performed. A predictive model was built and validated in two external centers.
21.9% of 470 patients had at least one involved NSLN. In univariate analysis, seven variables were significantly correlated with NSLN involvement: tumor size, grade, lymphovascular invasion (LVI), number of positive and negative SLNs, size of SLN metastasis and intraoperative positive SLN. In multivariate analysis, LVI, number of negative SLNs, size of SLN metastasis and intraoperative positive pathological evaluation were independent predictors for NSLN involvement. The calculated risk resulted in an AUC of 0.76. Applied to the external data, the model was accurate and discriminating for one (AUC = 0.75) and less for the other center (AUC = 0.58).
A discriminative predictive model was constructed to calculate the risk of NSLN involvement in case of a positive SLN. External validation of our model reveals differences in performance when applied to data from other institutions concluding that such a predictive model requires validation prior to use.
Quantitation of sentinel node metastatic burden and Her-2/neu over-expression accurately predicts residual axillary nodal involvement and extranodal disease in breast cancer
2013, European Journal of Surgical Oncology
Recent literature has suggested that completion axillary lymph node dissection (ALND) in breast carcinoma patients with positive SLN may not be necessary. However, a method for determining the risk of non-SLN or extranodal disease remains to be established.
To determine if pathological variables from primary tumors and sentinel lymph node (SLN) metastases could predict the probability of non-sentinel lymph node (NSLN) metastases and extranodal disease in patients with breast carcinoma and SLN metastases.
84 women with T1-3 breast cancer and clinically-negative axillae underwent completion ALND. Maximum diameter and width of SLN metastases were measured to calculate metastatic area. When multiple SLNs contained metastases, areas were summed to calculate the Total Metastatic Area (TMA). Multiple linear regression models were used to identify predictive factors.
Her-2/neu over-expression increased the odds of NSLN metastases (OR 4.3, p = 0.01) and extranodal disease (OR 7.9, p < 0.001). Independent SLN predictors were ≥1 positive SLN (OR, 7.35), maximum diameter and area of SLN metastases (OR 2.26, 1.85 respectively) and TMA (OR, 2.12). Maximum metastatic diameter/SLN diameter (OR 3.71, p = 0.04) and the area of metastases/SLN area (OR 3.4, p = 0.04) were predictive. For every 1 mm increase in diameter of SLN metastases, the odds of NSLN extranodal disease increased by 8.5% (p = 0.02). TMA >0.40 cm² was an independent predictor for NSLN metastases and extranodal disease.
Her-2/neu over-expression and parameters assessing metastatic burden in the SLN, particularly TMA, predicted the presence of NSLN involvement and extranodal disease in patients with breast carcinoma and SLN metastases.
Prediction of metastatic breast cancer in non-sentinel lymph nodes based on metalloprotease-1 expression by the sentinel lymph node
2013, European Journal of Cancer
Citation Excerpt :
Several studies have investigated clinical parameters to estimate the probability of non-sentinel node metastasis in SLN-positive patients. These reports found that the incidence of non-SLNs metastasis increased as the metastases in the SLN increased in size,4,6–10 and also with increasing number of positive SLN,4,11,12 extracapsular extension of the SLN-metastasis13 or lymphovascular invasion of the primary tumour.8,9,14–16 In addition, several nomogram scores based on these factors have been defined to determine the risk of finding additional positive axillary nodes if axillary node dissection is performed.13,17–20
Sentinel lymph node (SLN) biopsy is the current standard axillary approach for patients with clinically node-negative breast cancer. If the SLN is positive, is still also standard in most centres to proceed with a complete axillary dissection to predict the remaining nodes affectation, despite of SLN is the only positive lymph node in 50–68% of cases. If we could identify them, these patients could be spared a complete axillary dissection.
Elevated expression of specific matrix metalloproteases (MMPs) and their inhibitors (TIMPs) by stromal mononuclear inflammatory cells (MICs) of primary tumours is significantly associated with distant metastasis development in breast cancer. In the present study we first identified candidate MMPs/TIMPs associated with axillary metastasis in a preliminary group (n = 50), and subsequently examined the potential of their expression in the SLN for predicting the status of the remaining nodes, in 105 patients with intraoperative SLN-assessment.
MMP-1 expression by MICs from SLNs was significantly associated with metastatic spread to non-SLNs. Moreover, in all cases with negative MMP-1 expression by MICs from SLNs, the remaining non-SLNs were not affected (p < 0.0001). Therefore, we demonstrate that MMP-1 expression by MICs from SLNs had 100% sensitivity, 100% negative-predictive value and 61.5% specificity to predict non-SLNs status.
This is the first time that tumour spread to the remaining axillary nodes has been predicted from molecular features of the SLN(s). If confirmed in larger studies, patients could be spared the morbidity associated with an unnecessary complete lymphadenectomy.

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^☆: Correspondence to: Gábor Cserni, Bács-Kiskun County Teaching Hospital affiliated to the University of Szeged Medical School, H-6000 Kecskemét, Nyı́ri út 38.-POB 149, Hungary. Fax: 36-76-481219;E-mail: [email protected]

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Regular ArticlesSentinel lymph-node biopsy-based prediction of further breast cancer metastases in the axilla☆

Abstract

J Am Coll Surg

Cancer Treat Rev

J Am Coll Surg

Lancet

Eur J Surg Oncol

Chirurgie

Sentinel lymphadenectomy in breast cancer

J Clin Oncol

Sentinel lymphadenectomy for breast cancer in a community managed care setting

Cancer J Sci Am

The sentinel node in breast cancer. A multicenter validation study

N Engl J Med

Sentinel lymph node biopsy and axillary dissection in breast cancer: results in a large series

J Natl Cancer Inst

Improved axillary staging of breast cancer with sentinel lymphadenectomt

Ann Surg

Serial sectioning of sentinel nodes in patients with breast cancer: a pilot study

Ann Surg Oncol

Immunohistochemistry with pancytokeratins improves the sensitivity of sentinel lymph node biopsy in patients with breast carcinoma

Cancer

Occult metastases in the sentinel lymph nodes of patients with early stage breast carcinoma. A preliminary study

Cancer

Metastases in axillary sentinel lymph nodes in breast cancer as detected by intensive histopathological work up

J Clin Pathol

Sentinel node localization in patients with breast cancer

Br J Surg

The value of axillary sentinel nodal status in breast cancer

World J Surg

Lymphatic mapping and sentinel lymphadenectomy for breast cancer

Ann Surg

Regular Articles
Sentinel lymph-node biopsy-based prediction of further breast cancer metastases in the axilla☆