Positive Axillary Lymph Node Dissection Research Articles

A New Possible Cut-Off of Cytokeratin 19 mRNA Copy Number by OSNA in the Sentinel Node of Breast Cancer Patients to Avoid Unnecessary Axillary Dissection: A 10-Year Experience in a Tertiary Breast Unit.

Simple SummaryThis manuscript aims to investigate the features of patients with metastatic sentinel lymph node (SLN), evaluated by OSNA, and to predict which patients have a high risk of positive ALND. The finding of the present study suggests a new cut-off of CK19 mRNA copy number in the sentinel lymph node useful to personalize surgical treatments and avoid unnecessary axillary surgical treatments.(1) Background: The main discriminant in breast cancer prognosis is axillary lymph node status. In a select cohort of patients, axillary lymph node dissection (ALND) may be safely spared. This study aimed to determine a new possible cut-off of cytokeratin (CK) 19 mRNA copy number in the SLN to predict cases at high risk of positive ALND. (2) Methods: Clinical records of 1339 patients were retrospectively reviewed and were separated into two groups according to the axillary status (negative: ALNs− and positive ALNs+). Receiver operative characteristic (ROC) curves were used to identify a new optimal cut-off of CK19 mRNA copy number in SLN; (3) Results: Large tumor size and high grade were found mostly in ALNs+. Results from the ROC analyses, with an AUC of 82.1%, identified a new cut-off (9150 CK19 mRNA copies) showing 94% sensitivity, 67.3% specificity, 61.2% positive, and 95.3% negative predictive values; (4) OSNA remains the most-important intra-operative tool to identify patients who can benefit from ALND but with the traditional cut-off, many patients undergo needless ALND. The results of the present study suggest a new cut-off helpful to personalize surgical treatment and avoid unnecessary invasive procedures.

Indications and results of sentinel lymph node biopsy in breast cancer: Changes observed in 2018 compared to 2012

Background and objectiveOver the last 15 years, breast cancer (BC) treatment has undergone numerous changes, which have also affected the indications for Sentinel Lymph Node Biopsy (SLNB) as well as the procedures depending on its outcome. The aim of this study is to compare the results of the SLNB carried out at our Center during 2012, when we stopped performing an axillary lymph node dissection (ALND) after the finding of a micrometastasis, with those conducted in 2018, when we started applying Z011 criteria. Materials and methodsWe have performed a comparative retrospective observational study, including cN0 BC patients that underwent a SLNB in 2012 versus those that underwent this procedure in 2018. Results174 patients from 2012 and 165 from 2018 were studied. We found significant differences between the two groups: in 2018 there were fewer lobular invasive cancers (14 vs 28) (P < .05), a smaller mean pathological size (P < .001), a higher proportion of HER2 and triple negative tumors (28 vs 49) (P < .01) and, finally, an increase in use of neoadjuvant treatments (42.0% vs 6.7%). Regarding axillary involvement, we observed a decrease in both the presence of a positive sentinel node (24.1% in 2018 vs 42.4% in 2012) (P < .0001) as well as in the proportion of ALND performed (12.6% in 2018 vs 21.2% in 2012) and the presence of positive non sentinel nodes after a ALND (59.1% vs74.3%) (ns) ConclusionAlthough the 2018 cohort that underwent SLNB had more aggressive tumors, there were fewer positive SN and ALND performed. This is probably due to a more accurate radiological diagnosis with ultrasound, that enables to detect cN1 cases before surgery, and to the increasing use of neoadjuvant treatments that may downstage the axilla

Indicaciones y resultados de la biopsia del ganglio centinela en el cáncer de mama: cambios observados en el año 2018 respecto al año 2012

Background and objectiveOver the last 15 years, breast cancer (BC) treatment has undergone numerous changes, which have also affected the indications for sentinel lymph node biopsy (SLNB) as well as the procedures depending on its outcome. The aim of this study is to compare the results of the SLNB carried out at our center during 2012, when we stopped performing an axillary lymph node dissection (ALND) after the finding of a micrometastasis, with those conducted in 2018, when we started applying Z011 criteria. Materials and methodsWe have performed a comparative retrospective observational study, including cN0 BC patients that underwent a SLNB in 2012 versus those that underwent this procedure in 2018. ResultsA total of 174 patients from 2012 and 165 from 2018 were studied. We found significant differences between the 2groups: in 2018 there were fewer lobular invasive cancers (14 vs. 28) (P<0.05), a smaller mean pathological size(P<0.001), a higher proportion of HER2 and triple negative tumors (28 vs. 49; P<0.01) and, finally, an increase in use of neoadjuvant treatments (42.0 vs. 6.7%). Regarding axillary involvement, we observed a decrease in both the presence of a positive sentinel node (24.1% in 2018 vs. 42.4% in 2012; P<0.0001) as well as in the proportion of ALND performed (12.6% in 2018 vs. 21.2% in 2012) and the presence of positive non sentinel nodes after a ALND (59.1% vs. 74.3%; P=ns). ConclusionAlthough the 2018 cohort that underwent SLNB had more aggressive tumors, there were fewer positive SN and ALND performed. This is probably due to a more accurate radiological diagnosis with ultrasound, that enables to detect cN1 cases before surgery, and to the increasing use of neoadjuvant treatments that may downstage the axilla.

Development of a predictive score of axillary lymph node dissection based on targeted axillary dissection in patients with breast cancer diagnosis, affected lymph nodes, and neoadjuvant treatment

AimTo determine predictive factors of axillary lymph node dissection (ALND) results in breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NACT), and subsequent staging using Targeted Axillary Dissection (TAD). Material and methodCase-control study between January 2016 and August 2019. Patients with BC, cN1 staging, marked with a metallic clip prior to NACT, and subsequently staged with TAD and ALND were included. They were divided into 2 groups: ALND patients with or without metastatic involvement (group 1 and group 2, respectively). We carried out a univariate analysis comparing clinical, radiological, surgical and pathological variables, and a logistic regression, (dependent variable: positive result of ALND; independent variables: number of suspicious lymph nodes in diagnostic ultrasound, positive hormone receptors, HER2 positive, complete clinical-radiological response to NACT, positive TAD, and biopsy of ≤2 nodes in TAD). A score for prediction of a metastatic ALND was proposed, with an internal validation study. Results60 patients were included: Group 1: 33 (55.0%); Group 2: 27 (45.0%). Tumor size (Odds Ratio (OR) = 1.67; 95%CI 1.02–2.74), number of suspected nodes in ultrasound (OR = 2.20; 95%CI 1.01–4, 77), HER2 positive (OR 0.04; 95%CI 0.003–0.54), clinical-radiological response to NACT (OR = 0.07; 95%CI 0.01–0.75), and positive TAD (OR 15.48; 95%CI 1.68–142.78) were independent predictors of a positive result in ALND. We developed a “positive ALND predictive score”, with good calibration (Hosmer-Lemeshow test: p = 0.65), and discrimination (AUC = 0.93; 95% CI 0, 87–0.99), with highest Youden index (0.7) at cut-off point of 17% risk of positive ALND (sensitivity = 100%; specificity = 70%). ConclusionTumor size, number of suspected nodes, positive HER2, response to NACT, and metastatic TAD are independent predictors of ALND. The predictive score for positive ALND would be a good indicator to safely omit ALND.

Utilidad del SPECT-CT en la biopsia del ganglio centinela tras quimioterapia neoadyuvante en cáncer de mama y axila positiva

ObjectiveTo evaluate the usefulness of SPECT-CT hybrid studies in the biopsy of sentinel lymph node (SLNB) after neoadjuvant chemotherapy (NAC) in patients with axillary metastatic disease (N+). MethodsCross-sectional study of 25 patients treated in the HUGTIP Breast Functional Unit from March 2018 to September 2020. All patients included in the study were submitted to: (1)axillary ultrasound (US) and US visible marker placement in the affected node before starting the NAC; (2)placement of a ferromagnetic marker in the previously marked lymph node (MLN) after NAC; (3)assessment of axillary status after NAC: it includes SPECT-CT lymphoscintigraphy; SLNB and excision of the MLN whether different from the sentinel lymph node (SLN); and axillary lymph node dissection (ALND). ResultsIn 14 patients (56%) the MLN corresponded with the SLN. In 3 cases it was not possible identify the SLN and in 8 cases the MLN was not a SLN. The biopsy of MLN and SLN was negative for metastasis in 12 patients (2 of them had a positive ALND) and was positive for metastasis in 13 patients (4 of them had a positive ALND). ConclusionThe SPECT-CT study provided additional information about the identification and the concordance of the MLN and the SLN improving the surgical planning.

Abstract GS1-10: Radioactive Iodine Seed placement in the Axilla with Sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer: Results of the prospective multicenter RISAS trial

Abstract Rationale and research objective: As a result of neoadjuvant chemotherapy (NAC), approximately 1/3 of clinically node positive (cN+) breast cancer patients convert to a pathologic complete response (pCR) of the axilla. Targeted Axillary Dissection appears to be most accurate to evaluate axillary treatment-response, but evidence to support this is limited. The RISAS trial was set up to determine the accuracy of sentinel lymph node biopsy (SLNB) combined with excision of the pretreatment marked positive lymph node for axillary staging after NAC in cN+ patients. Methods: This prospective, multicenter trial included cT1-4N1,2,3b patients treated with NAC. Prior to NAC, an iodine seed was placed in the pathologically confirmed positive lymph node. After NAC, all patients underwent SLNB together with excision of the marked lymph node (RISAS-procedure) followed by axillary lymph node dissection (ALND). The identification rate and the accuracy (i.e. false negative rate (FNR) and negative predictive value (NPV)) were calculated for the RISAS procedure. Assuming an FNR of 2%, a prevalence of a positive ALND of 64% and a 10% drop-out rate, a sample size of 248 patients was needed to determine non-inferiority. The NULL hypothesis of inferiority would be rejected at a significance level of 5% if the upper bound of the two-sided 90% Clopper-Pearson confidence interval of the observed FNR would be below the non-inferiority margin of 6.25%. Secondary objectives included the accuracy of the SLNB and excision of the marked lymph node separately. Results: A total of 252 pathologically proven cN+ patients provided informed consent of whom 227 underwent the RISAS procedure/Targeted Axillary Dissection (SLNB combined with excision of the marked positive lymph node). The identification rate of the RISAS procedure is 98% (223/227). Preliminary analysis shows a false negative rate of approximately 5% and a negative predictive value of approximately 91%. Furthermore, by combining SLNB with excision of the marked lymph node, both the identification rate and the accuracy are improved compared to either the SLNB alone or the excision of the marked lymph node alone. Conclusion: This prospective multicenter validation trial shows that the RISAS procedure/Targeted Axillary Dissection is most suitable in terms of identification rate and accuracy to replace ALND for axillary staging after NAC in cN+ patients. The trial was funded by the Dutch Cancer Society (KWF, grant number 2015-8023). Citation Format: Janine Simons, Thiemo JA v Nijnatten, Linetta B Koppert, Carmen C van der Pol, Paul J v Diest, Agnes Jager, David v Klaveren, Boen LR Kam, Marc BI Lobbes, Maaike de Boer, Cees Verhoef, Paul RA Sars, Harold J Heijmans, Els RM van Haaren, Wouter J Vles, Caroline ME Contant, Marian BE Menke, Leonie HM Smit, Wendy Kelder, Marike Boskamp, Ingeborg Mares-Engelberts, Ernest JT Luiten, Marjolein L Smidt. Radioactive Iodine Seed placement in the Axilla with Sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer: Results of the prospective multicenter RISAS trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS1-10.

Utility of regional nodal irradiation in Japanese patients with breast cancer with 1-3 positive nodes after breast-conserving surgery and axillary lymph-node dissection.

The utility of regional nodal irradiation (RNI) is being considered in cases of 1-3 axillary node metastases after breast-conserving surgery (BCS) with axillary lymph-node dissection (ALND). Therefore, we examined the necessity of RNI by examining the sites of recurrences in cases at our institution. We retrospectively analyzed 5,164 cases of primary breast cancer between January 2000 and December 2014 at the Aichi Cancer Centre, identifying local and distant recurrences in 152 patients with primary breast cancer treated with BCS and ALND and who had 1-3 positive axillary nodes. All patients received whole-breast irradiation (WBI) and adjuvant systemic therapy with either chemotherapy or anti-endocrine therapy with or without anti-human epidermal growth factor receptor 2 therapy. The present study excluded patients with ipsilateral breast tumor recurrence, contralateral breast cancer, neoadjuvant chemotherapy, T4 tumors or N2-3 nodes and distant metastasis. From the database of our institution, we identified 152 cases that met the defined criteria. The median follow-up period was 71 months (1-176). Isolated locoregional recurrences were found in three patients (2.0%) and were recurrent only in the breast. Only one patient had local lymph node recurrence with distant recurrence. The 10-year rates of isolated regional disease-free survival (DFS), DFS, and overall survival were 95.41, 89.50 and 96.75%, respectively, which was better compared with previous studies. We conclude that the addition of RNI to WBI is not necessary for Japanese patients who have 1-3 positive axillary nodes and ALND.

Variability in lymph node irradiation in patients with breast cancer-results from amulti-center survey in German-speaking countries.

Lymph node irradiation in breast cancer has gained complexity due to recently published studies and technical innovations which then led to changes in international guidelines. We sought to determine real-time variability in lymph node irradiation in clinical practice in German-speaking countries. The Department of Radiation Oncology, Technical University of Munich (TUM), developed an online-based questionnaire focusing on the indication, target definition, and treatment technique of lymph node irradiation in patients with breast cancer. The invitation to participate in the survey was sent to members of the German Society of Radiation Oncology (DEGRO) by e‑mail. The results of the survey were exported from the online platform into SPSS for adetailed analysis. In total, 100physicians completed the questionnaire between 05/2019 and 06/2019. Despite the existence of several treatment and contouring guidelines, we observed large variability of lymph node irradiation: The guideline recommendation for internal mammary irradiation is not consistently implemented in clinical practice and irradiation of the axilla after positive SLNB (sentinel lymph node biopsy) or ALND (axillary lymph node dissection) is handled very differently. Furthermore, in most clinics, the ESTRO (European Society for Therapeutic Radiology and Oncology) contouring consensus is not used, and PTV (planning target volume) definitions and margins vary considerably. Further clinical studies should be performed with aparticular focus on radiotherapy for lymphatic drainage to support and amend the existing guidelines. These studies should establish amore standardized treatment of the lymph node regions in clinical practice. Quality assurance should enforce broad implementation of consensus recommendations.

The diameter of metastasis in positive sentinel lymph node biopsy affects axillary tumor load in early breast cancer

Omission of axillary lymph node dissection (ALND) after positive sentinel lymph biopsy (SLNB) has become a standard procedure for breast cancer patients with one or two metastatic lymph nodes. Here the aim was model development for selection for ALND. We analyzed 323 positive SLNB breast cancer patients, who afterwards underwent ALND. In 126 (39%), there were positive additional axillary lymph nodes. Specimens of resected lymph nodes were scanned and the volumes of tumors (expressed as diameter in mm) were calculated. The maximal diameter of metastasis in the sentinel lymph nodes (SLNDmax ) and axillary lymph nodes (ALNDsum ) indicated tumor load in the resected lymph nodes. ALNDsum higher or equal to 5mm was defined as high and present in 62 patients (21%). Risk factors for high ALNDsum were primary tumor diameter (P=0.0092), histopathological type (P=0.0173), number of positive SLNs (P=0.0012), type of metastasis (P=0.0025), molecular type (P=0.0037), SLNDmax (P=0.0001), and Her-2 status (P=0.0093). Independent variables for high ALNDsum were SLNDmax (P<0.0001), number of positive SLNs (P=0.0237) and primary tumor diameter (P=0.0296). Twenty-one percent patients with positive SLNB are at risk of high ALNDsum . SLNDmax is the strong predictive factor for high ALNDsum after positive ALND.

A cut-off of 2150 cytokeratin 19 mRNA copy number in sentinel lymph node may be a powerful predictor of non-sentinel lymph node status in breast cancer patients.

Since 2007, one-step nucleic acid amplification (OSNA) has been used as a diagnostic system for sentinel lymph node (SLN) examination in patients with breast cancer. This study aimed to define a new clinical cut-off of CK19 mRNA copy number based on the calculation of the risk that an axillary lymph node dissection (ALND) will be positive. We analyzed 1529 SLNs from 1140 patients with the OSNA assay and 318 patients with positive SLNs for micrometastasis (250 copies) and macrometastasis (5000 copies) underwent ALND. Axillary non–SLNs were routinely examined. ROC curves and Youden’s index were performed in order to identify a new cut-off value. Logistic regression models were performed in order to compare OSNA categorical variables created on the basis of our and traditional cut-off to better identify patients who really need an axillary dissection. 69% and 31% of OSNA positive patients had a negative and positive ALND, respectively. ROC analysis identified a cut-off of 2150 CK19 mRNA copies with 95% sensitivity and 51% specificity. Positive and negative predictive values of this new cut-off were 47% and 96%, respectively. Logistic regression models indicated that the cut-off of 2150 copies better discriminates patients with node negative or positive in comparison with the conventional OSNA cut-off (p<0.0001). This cut-off identifies false positive and false negative cases and true-positive and true negative cases very efficiently, and therefore better identifies which patients really need an ALND and which patients can avoid one. This is why we suggest that the negative cut-off should be raised from 250 to 2150. Furthermore, we propose that for patients with a copy number that ranges between 2150 and 5000, there should be a multidisciplinary discussion concerning the clinical and bio-morphological features of primary breast cancer before any decision is taken on whether to perform an ALND or not.

Outcomes of Post Mastectomy Radiation Therapy in Patients Receiving Axillary Lymph Node Dissection After Positive Sentinel Lymph Node Biopsy

We sought to determine the rate of postmastectomy radiation therapy (PMRT) among women treated with axillary lymph node dissection (ALND) after positive sentinel lymph node (SLN) biopsy results and to establish the effect of negative ALND results and PMRT on locoregional recurrence (LRR) and overall survival (OS). All patients were treated with mastectomy and ALND after positive SLN biopsy results. All patients had clinical N0 or NX disease at the time of mastectomy and received no neoadjuvant therapy. The presence of lymphovascular space invasion, presence of multifocality, number of positive SLNs and non-SLNs, clinical and pathologic stage, extranodal extension, age, and use of PMRT were evaluated for significance regarding the rates of OS and LRR. A total of 345 patients were analyzed. ALND after positive SLN biopsy results was negative in 235 patients (68.1%), and a total of 112 patients (32.5%) received radiation therapy.On multivariate analysis, only pathologic stage III predicted for lower OS (hazard ratio, 3.32; P<.001).The rate of 10-year freedom from LRR was 87.9% and 95.3% in patients with positive ALND results and patients with negative ALND results, respectively. In patients with negative ALND results with ≥3 positive SLNs, the rate of freedom from LRR was 74.7% compared with 96.7% in those with <3 positive SLNs (P=.009). In patients with negative ALND results, ≥3 positive SLNs predicted for an increase in LRR on multivariate analysis (hazard ratio, 10.10; P=.034). A low proportion of cT1-2, N0 patients with positive SLNs who undergo mastectomy receive PMRT after ALND. Even in this low-risk cohort, patients with ≥3 positive SLNs and negative ALND results are at increased risk of LRR and may benefit from PMRT.

Sentinel Lymph Node Biopsy is a Reliable Method for Lymph Node Evaluation in Neoadjuvant Chemotherapy-treated Patients with Breast Cancer

Sentinel lymph node (SLN) mapping in patients with breast cancer treated with neoadjuvant chemotherapy has been debated by surgeons as a result of potential compromise of lymphatic drainage. Whether clinicopathologic variables traditionally associated with SLN positivity differ in patients who have been treated with neoadjuvant chemotherapy has not been well studied. Patients diagnosed with breast carcinoma who underwent neoadjuvant chemotherapy, definitive breast surgery, sentinel node biopsy (SNB), and axillary lymph node dissection (ALND) were retrospectively identified over a 75-month period. Clinicopathologic parameters including age, clinical tumor and node stage, neoadjuvant chemotherapy regimen, pathological tumor and node stage, lymphovascular invasion (LVI), SLN and non-SLN involvement, and extranodal extension were recorded. Ninety-seven patients met inclusion criteria. Ninety-eight per cent had successful SLN mapping. Eight patients with negative SLNs had positive ALND (false-negative rate, 8.3%). Clinicopathological variables associated with SLN status included clinical axillary status (P = 0.038), pathologic tumor size, and nodal status and LVI (P < 0.001). Extranodal extension was significantly associated with non-SLN status (P = 0.004). In patients achieving a pathologic complete response (PCR), SNB remained feasible and accurate (false-negative rate, 11.6%). Successful SLN mapping in patients who have undergone neoadjuvant chemotherapy is highly accurate with a low false-negative rate even in patients who have a PCR.

Letter to the Editor regarding manuscript entitled: Completion axillary dissection can safely be omitted in screen detected breast cancer patients with micrometastases. A decade's experience from a single institution. Grabau D, Dihge L, Ferno M, Ingvar C, Ryden L. Eur J Surg Oncol. 2013 Jun;39(6):601–7

Grabau et al. tackle the very topical subject of identifying breast cancer patients where completion axillary lymph node dissection (ALND) can be omitted in the presence of positive findings at sentinel node biopsy. 1 Grabau D. Dihge L. Ferno M. Ingvar C. Ryden L. Completion axillary dissection can safely be omitted in screen detected breast cancer patients with micrometastases. A decade's experience from a single institution. Eur J Surg Oncol. 2013 Jun; 39: 601-607 Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar In a retrospective review of 1458 patients undergoing sentinel node biopsy for primary, unilateral breast cancer, they identify 62 (of 757) screen-detected and 81 (of 701) symptomatic patients with micrometastases. Only 3 of 62 (5%) screen-detected patients with micrometastases had further metastases on completion ALND compared to 18 of 81 (22%) symptomatic patients (p = 0.01). They conclude that ‘completion ALND can safely be omitted in screen-detected breast cancer patients with micrometastases in the sentinel nodes’. Letter to the Editor regarding response to manuscript entitled: Completion axillary dissection can safely be omitted in screen detected breast cancer patients with micrometastases. A decade's experience from a single institution. Grabau D, Dihge L, Ferno M, Ingvar C, Ryden L. Eur J Surg Oncol. 2013 Jun;39(6):601–7European Journal of Surgical OncologyVol. 39Issue 11PreviewThank you very much for your interest in our article. You report results from your own department where you do not find any significant difference in positive completion axillary dissection (ALND) in patients with micrometastases in sentinel nodes as a function of the mode of presentation (screen-detected vs. symptomatic). On the contrary you find a tendency to more positive completion ALND specimens in screen-detected patients with micrometastases in sentinel nodes. Full-Text PDF

Quantitative Molecular Analysis of Sentinel Lymph Node May Be Predictive of Axillary Node Status in Breast Cancer Classified by Molecular Subtypes

To determine the performance of intraoperative one-step nucleic acid amplification (OSNA) assay in detecting sentinel lymph node metastases compared to postoperative histology taking into account breast cancer molecular classification and to evaluate whether the level of cytokeratin 19 mRNA copy number may be useful in predicting the likelihood of a positive axillary lymph node dissection. OSNA assay was performed in a prospective series of 903 consecutive sentinel lymph nodes from 709 breast cancer patients using 2 alternate slices of each sentinel lymph node. The remaining 2 slices were investigated by histology. Cytokeratin 19 mRNA copy number, which distinguishes negative cases (<250 copies), micrometastases (+, ≥250≤5000 copies) and macrometastases (++, >5000 copies), was compared to axillary lymph node dissection status and to the biological tumor profile. Concordance between OSNA and histopathology was 95%, specificity 95% and sensitivity 93%. Multiple Corresponce Analysis and logistic regression evidenced that positive axillary lymph node dissection was significantly associated with a higher cytokeratin 19 mRNA copy number (>5000; p<0.0001), HER2 subtype (p = 0.007) and lymphovascular invasion (p<0.0001). Conversely, breast cancer patients with cytokeratin 19 mRNA copy number <2000 mostly presented a luminal subtype and a negative axillary lymph node dissection. We confirmed that OSNA assay can provide standardized and reproducible results and that it represents a fast and quantitative tool for intraoperative evaluation of sentinel lymph node. Omission of axillary lymph node dissection could be proposed in patients presenting a sentinel lymph node with a cytokeratin 19 mRNA copy number <2000 and a Luminal tumor phenotype.

Trade-offs associated with axillary lymph node dissection with breast irradiation versus breast irradiation alone in patients with a positive sentinel node in relation to the risk of non-sentinel node involvement: implications of ACOSOG Z0011

Recent data suggest that axillary lymph node dissection (ALND) may be unnecessary for patients with positive sentinel lymph node biopsy (SLNB) receiving whole-breast irradiation (ACOSOG Z0011). The purpose of this study was to use decision analysis with simulated patients to determine subgroups with positive SLNB who may still benefit from ALND. We performed a decision analysis simulating axillary recurrence (ALR) risk, lymphedema, and quality of life following breast-conserving surgery (BCS) with positive SLNB and either completion ALND and whole-breast radiation (ALND + BRT) or breast radiation (BRT) alone. Simulated patients were divided into two risk groups based on the likelihood of disease in non-sentinel axillary nodes after positive SLNB: those with risk 30-60 % ("high-risk") and those with risk under 30 % ("low-risk," similar to average Z0011 patients). In simulated patients aged 55, BRT alone resulted in 1 month of additional QALE in the low-risk group versus ALND + BRT, while ALND + BRT resulted in 9.7 months of additional QALE in the high-risk group versus BRT alone. Overall survival was similar at 5 years in this simulation with either treatment in both groups, but ALND + BRT was superior to BRT alone at 20 years in the high-risk group (42 vs. 38 %). In the low-risk group, BRT alone is preferable unless ALR risk with BRT is greater than 1.6 % or lymphedema risk with ALND is under 10 %. Patients eligible for Z0011 but at a higher risk of residual nodal disease following BCS and positive SLNB may benefit from ALND + BRT, rather than BRT alone.

15. How frequently is breast conservation possible after neoadjuvant chemotherapy in women with breast cancer – Overview of our surgical practice

15. How frequently is breast conservation possible after neoadjuvant chemotherapy in women with breast cancer – Overview of our surgical practice

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.

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 (&gt;2000) of CK19 mRNA together with HER2 subtype. Otherwise none of the luminal A patients with a positive SLN but presenting a copy number &lt;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.

Predictions for positive nodes in breast cancer using computerized modeling.

16 Background: The accuracy and consistency of sentinel lymph node (SLN) biopsy for axillary staging in breast cancer has been well established by multiple studies. Although the standard of care has been to perform a completion axillary lymph node dissection (ALND) on patients who have a positive sentinel node, recent data (ACOSG Z0010, Z0011 and NSABP B-32) suggests that an ALND may be avoided in certain subsets of patients. To further study this question, we used a Bayesian model to predict the probability of finding disease in the ALND for breast cancer. Methods: All SLN procedures performed by a single surgeon, for clinical T1-T2 N0 disease between September 2000 and March 2009 were retrospectively reviewed under an IRB approved protocol. Demographic, disease and surgical procedural variables were collected. Values are reported as mean ± standard deviation. A Bayesian model, a standard statistical model frequently used in medicine, was used to identify variables that could predict a positive ALND. Results: A total number of 235 SLN procedures were reviewed. The mean patient age was 58.6 ± 11.8 (range 28-88), tumor size was 1.8 ± 1.3 cm (range 0.2-7.4), and BMI was 28 ± 6.1. The number of SLN found was 3.6 ± 1.9 (range 0-10), and in 2 cases no SLN were found, for an overall failure rate of 0.85%. A total of 73 ALND were performed in this group; 27 cases had ALND as national study participants randomized to ALND, 44 cases for positive SLN, and 2 cases in which no SLN could be identified. The mean number of axillary lymph nodes removed was 14.8 ± 7 and the mean number of positive axillary nodes was 2.7 ± 4.1. Tumor size, tumor grade, number of positive SLN by hematoxylin and eosin staining, and a low technetium count of the first SLN were found to be significant predictors of positive axillary nodes during a completion ALND. There was also a trend for progesterone receptor expression as a predictor of axillary disease. Conclusions: A model to predict a positive ALND for breast cancer is presented. We found tumor characteristics, number of positive SLN and low technetium count for first SLN to be predictors for finding axillary disease. Further studies are needed to validate our model as a means of sparing women an ALND who have a low probability of finding additional breast disease.

Distant Metastasis Free Survival (DMFS) in Breast Cancer Patients with Micrometastases (pN1mi) in the Sentinel Lymph Node (SLN): Results in 582 Positive-SLN Patients in a Single Institution.

Abstract Background:The risk of developing distant metastases (DM) in pN1mi and isolated tumor cells (pN0i+) patients remains under question. Does occult axillary node metastases is an additional factor for using an adjuvant systemic therapy (AST) in early breast cancer ?Patients and Methods:Among 2695 patients operated on from 2000 to 2006 for SLN, 582 patients had a positive SNB: 307 were pN1, 154 pN1mi and 121 pN0i+ (6th AJCC-classification). All patients underwent an immediate or delayed Axillary Lymph Node Dissection (ALND). We report the results for DMFS [median follow-up of 56 months (2-105)].We used Kaplan-Meier method and Cox regression for multivariate analysis.Results:ALND were positive in pN1, pN1mi and pN0i+ patients respectively in 127 (41,3%), 20 (13%) and 14 (11.6%) of these patients. On univariate and multivariate analysis, positive ALND, mitotic index, pathologic tumor size were significantly related to the DMFS; on multivariate analysis, the type of axillary lymph node metastases was an additional significative factor. There was not relationship between pN0i+ and the development of DM. Surprisingly, patients with pN1mi had a 2.8 higher risk for developing DM than pN1 patients. pN1 patients receive more AST than pN1mi (75% and 22%), however AST was not prognostic (p=0.49).Conclusion:In our series, patients with pN1mi were associated with a worse prognosis related to DMFS compared to pN1. Use of AST and/or biological primary tumor characteristics could explain this paradoxical result. Longer follow-up and larger series are needed to determine the prognostic significance of axillary occult metastases. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 308.

Sentinel node biopsy performed in the neoadjuvant setting for breast cancer: results from the I-SPY TRIAL (CALGB 150007/150012 &amp; ACRIN 6657).

Abstract Abstract #202 Introduction: Controversy remains over whether to perform sentinel node biopsy (SNB) before or after neoadjuvant chemotherapy (NAC). We examined the practice patterns, feasibility, and accuracy of this procedure in high risk breast cancer patients treated with NAC in a multi-institutional correlative science study.&amp;#x2028; Methods: Patients with biopsy-proven breast cancer &amp;gt;3 cm enrolled into the I-SPY TRIAL to undergo 4 weeks of anthracycline-based NAC, 4 weeks of taxane treatment, then surgical intervention. Study protocol did not dictate axillary treatment. Timing of SNB was dictated by the surgeon. Practice patterns, outcome of SNB and axillary lymph node dissection (ALND), locoregional recurrence and distant metastases were recorded with a mean follow-up of 2.9 years.&amp;#x2028; Results: 237 patients enrolled, 221 completed the trial, 210 had complete data at the time of analysis; Table 1 shows axillary practice patterns.&amp;#x2028; &amp;#x2028; Overall, 43% had a positive SNB and/or ALND after NAC. 129 (61% of 210) patients presented with clinically positive nodes, 39 of which had a post-NAC SNB. 5/39 had no ALND (all SNB negative). Table 2 shows results for those who had a post-NAC SNB and ALND. For this subset of patients, sentinel node ID, accuracy, and false negative (FN) rates were 80%, 91% and 15% respectively. If SNB was negative, 20% of patients still had a positive ALND. 81 (39% of 210) patients presented with clinically negative nodes, 22 of which had a post-NAC SNB. 8/22 post-NAC SNB patients had no ALND (6 negative, 2 positive for 1mm disease). Table 2 shows results for those who had a post-NAC SNB and ALND. For this subset of patients, sentinel node ID, accuracy, and FN rates were 100%, 100% and 0%.&amp;#x2028; &amp;#x2028; Overall, there were 26 deaths; 96% occurred in those who presented with clinically positive nodes, 77% had positive post-NAC nodes. A negative axilla post-NAC was predictive of longer DFS over those with axillary disease post-NAC (p&amp;lt;0.05).&amp;#x2028; Conclusions: In clinically node negative patients, post-NAC SNB is feasible and accurate before or after NAC. Our data suggests that a post-NAC SNB is sufficient; this avoids an additional operation and allows us to gain information on post-NAC axillary status which is of prognostic significance. In clinically positive patients, SNB does not adequately reflect axillary disease; even when SNB was negative, 20% still had axillary disease. At this time, we recommend that ALND be performed on all clinically node positive patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 202.