A new clinical cut-off of cytokeratin 19 mRNA copy number in sentinel lymph node better identifies patients eligible for axillary lymph node dissection in breast cancer

AimsCytokeratin 19 (CK19) mRNA copy number predicts the probability of tumour load in axillary lymph nodes (ALN) and can help in decision-making regarding the axillary dissection. The purpose of this study was to define a new cut-off of CK19 mRNA copy number using the one-step nucleic acid amplification (OSNA) assay on metastatic sentinel lymph nodes (SLN) in order to identify cases at risk of having one or more positive ALN.Methods1296 SLN from 1080 patients were analysed with the OSNA assay. 194 patients with positive SLN underwent ALN dissection and the mean value of CK19 copy number (320 000) of their SLN was set as initial cut-off. Receiver operative characteristics curve identify a best cut-off of 7700 (sensitivity 78%, specificity 57%). A comparison between our and the traditional cut-off (5000) was performed.ResultsThe cut-off of 7700 successfully identifies patients with positive ALN (p=0.001, false- negative cases: 17%). In the range between 5000 and 7700, one patient with positive ALN would not undergo axillary dissection, whereas eight patients with negative ALN would be correctly identified.ConclusionsWe suggest that the level of CK19 mRNA copy number could be the only parameter to consider in the intraoperative management of the axilla.

Download Full-text

Evaluation of a multiparametric system able to predict nonsentinel lymph node status in breast cancer patients with a micrometastatic sentinel node assessed by the one step nucleic acidamplification (OSNA) assay.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1050 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1050-1050

Author(s):

Simonetta Buglioni ◽

Marcella Mottolese ◽

Beatrice Casini ◽

Enzo Gallo ◽

Irene Terrenato ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Molecular Diagnostic ◽

Lymph Node Status ◽

Cytokeratin 19 ◽

Axillary Lymph ◽

Ck19 Mrna ◽

Copy Numbers ◽

Number Of Patients ◽

Osna Assay

1050 Background: Axillary lymph node dissection (ALND) may not be necessary in women with breast cancer (BC) who have micrometastasis in a sentinel lymph node (SLN), owing to the low risk of non-SLN (NSLN) involvement. In our Institute we validated and adopted the molecular diagnostic tool OSNA based on the quantitative measurement of Cytokeratin 19 (CK19) mRNA.The aims of our work in a subgroup of women with micrometastatic SLN, were: 1) to correlate the copy numbers of CK19 mRNA with the risk of additional positive NSLNs; 2) to assess the relationships between the molecular subtype classification and the probability of a positive ALND; 3) to verify whether a combination of the new above mentioned parameters is able to identify a subgroup of patients with a micrometastatic SLN and a negligible risk of positive NSLNs in whom ALND may be avoided. Methods: The SLN lysates from 709 patients were analyzed by OSNA assay. We considered only patients with a micrometastatic SLN (copy numbers between 250 and 5000/μL) and the probability of having a positive ALND was calculated by the logistic regression model. This series of BC patients were divided into four main subtypes taking in account the BC classification as defined by a combination of estrogen, progesteron receptors and HER2 status. Results: OSNA positivity for micrometastasis was reported in 91/709 cases (12,8%).The number of patients with positive ALND was 20 (22%). The statistical analyses showed that the metastatic involvement of NSLNs is associated with SLNs with a high copy numbers (>2000) of CK19 mRNA together with HER2 subtype. Otherwise none of the luminal A patients with a positive SLN but presenting a copy number <1000, had a positive NSLNs. Conclusions: We showed that biologically-driven analyses may be able to build new models with higher performance in terms of breast cancer axillary status prediction after positive SLN biopsy for micrometastasis. The copy numbers of CK19 mRNA and the molecular subtypes are more advantageous than traditional parameters because they are not pathologist-dependent and therefore they are more reliable and reproducible.

Download Full-text

Does Neoadjuvant Chemotherapy for Breast Cancer Affect Lymph Node Harvest Rates?

The American Surgeon ◽

10.1177/000313481908500724 ◽

2019 ◽

Vol 85 (7) ◽

pp. 690-694

Author(s):

Richard L. White ◽

Pooja P. Palmer ◽

Sally J. Trufan ◽

Deba Sarma

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Neoadjuvant Chemotherapy ◽

Lymph Nodes ◽

Axillary Dissection ◽

Axillary Lymph ◽

Significant Difference ◽

Chi Squared ◽

Patient Groups ◽

Neo Adjuvant Chemotherapy

Some authors report that patients receiving neoadjuvant chemotherapy have fewer lymph nodes harvested during axillary dissection and more dissections with < 10 nodes compared with patients who undergo surgery initially. We sought to determine whether there was a difference between these patient groups in terms of number of nodes harvested and number of dissections with < 10 nodes. Retrospective review of 258 patients diagnosed with breast cancer who underwent an axillary lymph node dissection between July 1,2015, and December 31, 2017 was performed. Chi-squared test was used to assess differences between patient groups. Of 258 patients undergoing dissection, 48 per cent received neoadjuvant chemotherapy; 52 per cent underwent surgery as first therapeutic intervention. Mean number of nodes resected; 14.3 + 6.3 for patients with no prior chemotherapy versus 14.9 + 6.6 for patients with neoadjuvant chemotherapy ( P = 0.48). For patients undergoing surgery as first intervention, 21 per cent had < 10 nodes harvested. For patients receiving neo-adjuvant chemotherapy, 20 per cent had < 10 nodes harvested. Patients who received neoadjuvant chemotherapy showed no statistically significant difference in the number of lymph nodes harvested during axillary dissection compared with patients undergoing surgery as first intervention. Neoadjuvant chemotherapy does not reduce the node harvest at the time of axillary dissection.

Download Full-text

A prospective clinical study for molecular intra-operative detection of lymph node metastasis in breast cancer patients by one step nucleic acid amplification (OSNA) in comparison to intensive histological investigation

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.609 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 609-609

Author(s):

F. Di Filippo ◽

M. Mottolese ◽

C. Botti ◽

F. Marandino ◽

A. Psaila ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Cancer Patients ◽

Diagnostic Tool ◽

Diagnostic Delay ◽

Molecular Diagnostic ◽

Cytokeratin 19 ◽

Breast Cancer Patients ◽

Ck19 Mrna ◽

Osna Assay

609 Background: The aims of the study were 1) to assess the accuracy of a new intra-operative molecular diagnostic tool named OSNA, based on the measurement of cytokeratin 19 (CK19) mRNA, in the detection of axillary sentinel lymph node (SLN) metastases in patients with breast carcinoma 2) to determine the concordance of OSNA analysis with multilevel haematoxylin and eosin (H&E) and immunohistochemical (IHC) examination. Methods: A prospective series of 247 consecutive SLNs from 187 breast cancer patients was evaluated. The OSNA assay (Sysmex, Kobe - Japan) follows a short sample preparation step and subsequent rapid amplification of CK19 mRNA based on reverse transcription loop-mediated isothermal amplification. Each SLN was immediately divided into four slices. Two alternate slices were used for the intra-operative OSNA assay. The remaining two slices were investigated by six-level histopathology with 100 μm skip ribbons using routine H&E and CK19 IHC staining. The results of histology and OSNA were then compared. Results: Pts characteristics: infiltrating ductal/infiltrating lobular/mucinous/medullar/DCIS: 130/10/1/1/25. OSNA and histo-pathological methods identified 54 SLNs positive and 185 negative cases (2/3 contained isolated tumour cells). We found 8 discordant cases, 2 OSNA negative with micrometastasis found by IHC/H&E analysis, 5 OSNA positive for micrometastases but IHC/H&E negative and 1 case macrometastatic at OSNA, while negative at IHC/H&E analysis. The overall concordance of OSNA with histopathology was 96.7% with a specificity of 96.8% and sensitivity of 96.4%. These discordances could be due to sampling bias such that a micrometastasis was confined to the slices used for OSNA or the slices used for histology. Conclusions: The current study suggests that the performance provided by OSNA assay is comparable to intensive histopathological work-up even when using only half a lymph node. The method could be applied as a rapid and reliable intra-operative diagnostic tool thus preventing breast cancer patients from a diagnostic delay or second surgery due to a postoperatively diagnosed positive SLN. No significant financial relationships to disclose.

Download Full-text

Lymph Node Radiotherapy Instead of Extended Axillary Surgery - the New Standard

Breast Care ◽

10.1159/000489892 ◽

2018 ◽

Vol 13 (3) ◽

pp. 173-175 ◽

Cited By ~ 2

Author(s):

Peter Niehoff ◽

Silla Hey-Koch

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Axillary Dissection ◽

Early Stage ◽

Axillary Staging ◽

Lymph Node Staging ◽

Axillary Lymph ◽

Regional Lymph Nodes

Breast cancer treatment has undergone major changes in the last 20 years. Specifically, the role of axillary lymph node dissection has changed from radical axillary dissection with excision of a high number of lymph nodes to sentinel lymph node biopsy (SLNB). This paradigm shift is associated with a controversial debate regarding the significance of axillary staging, the need for surgery, and the role of radiotherapy. Looking ahead, lymph node staging and axillary treatment might shift from SLNB and/or axillary dissection to ultrasound-guided needle biopsy and irradiation of regional lymph nodes in order to reduce treatment-related sequelae in early-stage breast cancer.

Download Full-text

Evaluating the Effect of Axillary Lymph Node Involvement and Dissection in the Development of Post-Mastectomy Lymphedema

Iraqi National Journal of Medicine ◽

10.37319/iqnjm1.1.3 ◽

2019 ◽

Vol 1 (1) ◽

pp. 14-21

Author(s):

Ahmed Abdulnabi ◽

Issam Merdan

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Axillary Dissection ◽

Disease Process ◽

Radical Mastectomy ◽

Lymph Node Involvement ◽

Breast Cancer Surgery ◽

Axillary Lymph ◽

Node Involvement

Background: Lymphedema of the upper extremity is a serious consequence of breast cancer surgery. Postmastectomy lymphedema of the upper limb is usually related to many risk factors, like axillary surgery, radiotherapy, venous obstruction, obesity, and infection. In the current study, the objective was to identify the relationship between the extent of lymph node involvement and axillary dissection on the development of lymphedema. Patients and methods: One hundred and seventy patients managed by modified radical mastectomy with axillary dissection for mammary-invasive adenocarcinoma between January 2009 and December 2016 in Al-Fayhaa Teaching Hospital. The patients were divided into three groups according to the number of lymph nodes involvd, by pathology. The patients had been followed up for at least two years and assessed by standard lymphedema assessment, then categorized into three groups, according to the severity of lymphedema. Results: After the analysis of patient parameters, the highest age group was 36–45 years. More than 60% of the patients had 4–9 lymph nodes involved. Forty-one patients from the 170 developed lymphedema postoperatively. Forty patients had seroma and twenty-one patients had wound infection postoperatively. Conclusion: Post-mastectomy lymphedema is a sequelae of disease process related to the extent of lymph-node involvement and resection rather than operative fault. Key words: breast cancer, mastectomy, lymphedema.

Download Full-text

May axillary dissection be avoided after micro metastases in sentinel lymph node analyzed by OSNA method?

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.18 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 18-18

Author(s):

A. Velasco ◽

S. Morales ◽

M. J. Panades ◽

S. Gonzalez ◽

F. Vilardell ◽

...

Keyword(s):

Lymph Node ◽

Sentinel Lymph Node ◽

Sentinel Node ◽

Axillary Dissection ◽

Tumour Size ◽

Quantitative Measure ◽

Cytokeratin 19 ◽

Breast Cancer Patients ◽

Ck19 Mrna ◽

Osna Method

18 Background: The study of the sentinel node biopsy is a common method to assess axillary involvement before surgical resection. The OSNA assay based on reverse transcriptase loop mediated amplification (RT-LAMP) and quantification of cytokeratin 19 (CK19) mRNA allows a rapid intra-operative detection of the metastases in the sentinel lymph node in breast cancer patients. Pathologists considered micro metastases when the size of the node involvement was between 0.2 and 2 mm and the OSNA method assess micro metastases when the copy number of CK19 is between 250 and 5000. Methods: From a total of 341 patients in which sentinel node had been analyzed, we studied a series of 32 patients whose sentinel nodes had micro metastases assessed by OSNA and who underwent subsequent axillary dissection. Median breast tumour size was 1.6 cm, 10 patients (31%) had less than 1 cm in size and only 6 patients (19%) had >2 cm. 78% of patients shown positive oestrogen receptor and 14 patients (44%) had low Ki67 (<14%). The CK19 mRNA was quantified in all patients (32) resulting in a median value of 540 (210-4800). Results: The median value of the nodes removed by axillary dissection was 14 (9-19). We found tumor invasion in none of them by histopathological conventional study. Conclusions: Since we have found no axillary involvement when the sentinel node have micro metastases analyzed by the OSNA method it seems that quantitative measure of CK19 by OSNA may be a useful procedure in order to avoid axillary dissection, although it would be necessary to perform larger studies to demonstrate this effect.

Download Full-text

P011 A new clinical cut-off of cytokeratin 19 mRNA copy number in sentinel lymph node of breast cancer

The Breast ◽

10.1016/s0960-9776(15)70062-7 ◽

2015 ◽

Vol 24 ◽

pp. S29

Author(s):

S. Buglioni ◽

I. Terrenato ◽

B. Casini ◽

V. D'Alicandro ◽

F. Di Filippo ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Sentinel Lymph Node ◽

Copy Number ◽

Cytokeratin 19 ◽

Mrna Copy Number

Download Full-text

Axillary lymph nodes and breast cancer metastasis.

The Professional Medical Journal ◽

10.29309/tpmj/2021.28.07.5919 ◽

2021 ◽

Vol 28 (7) ◽

pp. 978-982

Author(s):

Shahid Hussain Soomro ◽

◽

Abdul Sattar Abro ◽

Vaqar-e-Sahar Shah ◽

Saima Ather Shaikh ◽

...

Keyword(s):

Lymph Node ◽

Lymph Nodes ◽

Axillary Dissection ◽

Cancer Metastasis ◽

Breast Cancer Metastasis ◽

Axillary Lymph Nodes ◽

Lymph Node Status ◽

Axillary Lymph ◽

Carcinoma Breast ◽

Female Patients

Objectives: The purpose of current study is to evaluate the correlation of axillary lymph node status with metastases in patients presented with carcinoma breast. Study Design: Prospective study. Setting: Surgical Unit 1, CMC Hospital Larkana. Period: March 2019 to January 2020. Material & Methods: Female patients presented with carcinoma breast were assessed clinically and by investigation then underwent a mastectomy and axillary dissection (sampling or clearance). Data was entered into pre-designed proforma. After proper staging, surgery was done in all patients accordingly. Lymph node involvement was confirmed histopathology. Then it was correlated with clinical findings. Results: Fifty-five female patients of proven carcinoma breast underwent a mastectomy and axillary dissection. The majority of the patients (76%) were between 30-60 years, the median age being 45 years. The left breast contained the tumor in 30 (55.5%) patients while the rest of the patients had the right breast involved. The size of the tumor varied from 2cm to 12cm. 33 (61%) patients were in the pre-menopausal state while 21 (38.88%) were in postmenopausal state. In 07 patients (13%) the axillary lymph nodes were not palpable while in the rest of the 47 patients (87%), the axillary lymph nodes were palpable to a variable extent. Most of the patients were in an advanced stages. Among seven patients (N0), histopathology revealed positive lymph nodes in 3/7 (42.85%) patients. Conclusion: Breast carcinoma is a serious type of carcinoma affecting the younger generation in our community, usually diagnosed at a late stage. Clinical examination is not an effective way for proper staging. Further investigations should be performed for accurate staging and management.

Download Full-text