Martin Espinosa-Bravo

Prediction of non-sentinel lymph node metastasis in early breast cancer by assessing total tumoral load in the sentinel lymph node by molecular assay

INTRODUCTION The one-step nucleic acid amplification (OSNA) is a molecular procedure that yields a semiquantitative result for detection of nodal metastasis. Size of metastasis in the sentinel lymph node (SLN) by conventional histology has been described as a predictive factor for additional axillary metastasis. The objective of this study is to quantify intraoperatively the total tumoral load (TTL) in the positive SLNs assessed by OSNA and to determine whether this TTL predicts non-SLN metastasis in patients with clinically node negative early stage breast cancer. METHODS 306 patients with cT1-3N0 invasive breast cancer who had undergone intraoperative SLN evaluation by OSNA were included. TTL was defined as the addition of CK19 mRNA copies of each positive SLN (copies/μL). RESULTS TTL was a predictive factor of additional non-SLN metastasis in the complete axillary lymph node dissection (cALND) (OR, 1.67; 95% CI, 1.18-2.35). In the multivariate analysis, the TTL was a predictor of non-SLN metastasis in HR positive patients (OR, 1.69; 95% CI, 1.19-2.41). In our cohort of patients, with a TTL ≤1.2 × 10(5) copies/μL, there was a specificity of 85.3% and negative predictive value (NPV) of 80%. If we consider only the HR positive patients, with a TTL ≤5 × 10(5) copies/μL there was a specificity of 86.7% and NPV of 83.7%. CONCLUSIONS TTL assessed by OSNA assay predicts for additional non-SLN metastasis and this intraoperative tool can help guiding decisions on performing a cALND in breast cancer patients.

Electrothermal bipolar vessel sealing system in axillary dissection: A prospective randomized clinical study

We assessed whether axillary dissection using the electrothermal bipolar vessel sealing system (LigaSure) improved perioperative outcome when compared with conventional axillary dissection, in a prospective randomized study of 100 women with breast cancer. Those needing axillary dissection were randomized to the use of LigaSure or to conventional axillary dissection (with 50 patients in each group, all of whom had a closed suction drain in the axilla). The LigaSure patients had less intraoperative blood loss (exceeding 199 mL in 30.8% vs. 69.2%, P < 0.001), quicker axillary dissection (mean 48 vs. 63.2 min, P = 0.004), fewer days of suction drainage (4.3 vs. 5.7 days, P = 0.012), and shorter hospitalization (5.1 vs. 6.5 days, P = 0.021). No difference was found in the rate of hematomas, reoperations or infection. The use of LigaSure in axillary surgery reduced the surgical time and length of hospital stay, favoring early drain removal without increasing postoperative complications.

Extensive nodal involvement increases the positivity of blue nodes in the axillary reverse mapping procedure in patients with breast cancer.

The axillary reverse mapping (ARM) technique has been proposed to prevent arm lymphedema. We conducted this study to assess the feasibility of the technique and the outcomes of patients with neoadjuvant chemotherapy (NAC).

Detection of sentinel lymph node in breast cancer recurrence may change adjuvant treatment decision in patients with breast cancer recurrence and previous axillary surgery.

Use of sentinel lymph node dissection in patients with ipsilateral breast cancer recurrence is still controversial. The objective of this study is to evaluate the feasibility of the sentinel lymph node in breast cancer recurrence (SLNBR) and whether the positivity had impact in the adjuvant treatment. Between 2008 and 2012 we performed SLNBR in patients with ipsilateral breast tumor recurrence. We included 53 patients in a prospective study. Forty-three patients (81%) had a previous axillary lymph node dissection (ALND) and ten (19%) had a previous sentinel lymph node biopsy (SLNB). Identification rate after SLNB was 50% and after ALND was 60.5% (p = 0.4). Nine patients (26%) had a positive SLNBR. Adjuvant systemic treatment was given to all the patients with a positive SLNBR and to 23 (85%) with a negative SLNBR (p = 0.29). Six patients (66%) with positive SLNBR and 4 patients (14%) with negative SLNBR underwent radiation therapy (p < 0.01). As conclusions of our study we conclude that sentinel lymph node biopsy in breast tumor recurrence is feasible and significant differences were found in the use of radiation therapy in patients with a positive SLNBR.

Intraoperative Ultrasound-Guided Excision of Axillary Clip in Patients with Node-Positive Breast Cancer Treated with Neoadjuvant Therapy (ILINA Trial)

BackgroundThe accuracy of sentinel lymph node biopsy (SLNB) after neoadjuvant therapy (NAT) has been improved with the placement of a clip in the positive node prior to treatment. Several methods have been described for clipped node excision during SLNB after NAT. We assessed the feasibility of intraoperative ultrasound (IOUS)-guided excision of the clipped node during SLNB and investigated whether the accuracy of SLNB is improved.MethodsAfter approval by the Institutional Ethics Committee, all breast cancer patients undergoing NAT had an US-visible clip placed in the positive node. The ILINA trial consisted of IOUS-guided excision of the clipped node along with SLNB and axillary lymph node dissection (ALND).ResultsForty-six patients had a clip placed in the positive node. In two (4.3%) cases, the clip could not be seen prior to surgery and the patient underwent ALND; however, the clipped node was successfully removed by IOUS-guided excision in 44 patients. Thirty-five patients (79.5%) underwent SLNB along with IOUS-guided excision of the clipped node and ALND, and were subsequently included in the ILINA trial. Nine patients were not included (five patients with SLNB only and four patients with ALND without SLNB). SLNB matched the clipped node in 27 (77%) patients. The false negative rate for the ILINA protocol was 4.1% (95% confidence interval 0.1–21.1%).ConclusionsIOUS-guided excision of the axillary clipped node after NAT was feasible, safe, and successful in 100% of cases. The ILINA trial is accurate in predicting axillary nodal status after NAT.

Intraoperative ultrasound guided breast surgery: paving the way for personalized surgery

Since the first publication in 1988 about intraoperative ultrasound (IOUS) guided surgery, where Schwartz and colleagues (1) found that ultrasound (US) was an accurate and effective tool for localizing breast masses visualized by US and thus facilitating the surgical excision, multiple manuscripts have reported the use of IOUS to guide BCS in non-palpable breast cancer (2-4).

Increased detection of sentinel nodes in breast cancer patients with the use of superparamagnetic iron oxide tracer.

100 Background: The use of superparamagnetic iron oxide (SPIO) tracer for sentinel node biopsy (SLN) has shown non inferiority compared with the radioisotope technique in early breast cancer. False negative rates of SLN biopsy after neoadjuvant treatment (NAC) have decreased with dual tracer (radioisotope/dye) and with the excision of > 2 SLNs. This study was designed to evaluate the outcome of SLN after NAC using a dual tracer (SPIO-Tc99) and to compare it with the SLN by same dual tracer in the adjuvant setting. METHODS Between July 2013 and March 2014, 30 patients with invasive breast cancer (IBC) and SLN biopsy after NAC (NAC- SLN), and 118 patients with IBC not treated with NAC (adjuvant SLN), whose SLN was traced by Tc99 and SPIO were included in the study. Patients were injected subareolar with Tc99 the day before surgery and with the SPIO intraoperatively. SLN was excised if it was radioactive, magnetic or palpable. Patients signed an inform consent. RESULTS Detection rate by Tc 99 was successful in 113 (95.7%) patients and by SPIO in 116 (98.3%) in the adjuvant SLN (P= 0.0833) while in the NAC-SLN group detection rate by Tc-99 was successful in 28 patients (93.3%) and by SPIO in 30 patients (100%) (P =0.1573). Concordance rates per patient in the adjuvant SLN between techniques was 98.2%, while in the NAC-SLN was 100%. (p = 0.4762) Mean number of SLNs excised by 99Tc and SPIO were 1.9 and 2.21 respectively in the adjuvant SLN, (p=0.001) while 1.533 and 2.60 respectively in the NAC-SLN group. (p=0.0016) In the adjuvant SLN, the SLN was positive in 36 patients (30%), and in the NAC-SLN in 9 patients (30%). In the adjuvant SLN, both techniques detected same number of positive nodes but in the NAC-SLN, 9 patients had a positive SLN by SPIO (> 2 SLNs by SPIO and 1 SLN by Tc99) and 7 patients had a positive SLN by Tc99. CONCLUSIONS Detection of SLNs with SPIO allows for easy identification of axillary nodes and can be used to reliably identify SLNs in breast cancer. Even though the small sample size in the NAC-SLN, the higher number of SLNs excised by the SPIO may optimize the success of SLN after NAC.

Percutaneous ultrasound guided vacuum-assisted excision of benign breast lesions: A learning curve to assess outcomes

OBJECTIVE: To evaluate the efficacy and learning curve of ultrasoundguided vacuum-assisted excision (US-VAE) of benign breast lesions, and to assess characteristics associated with residual lesion. METHODS: This was a retrospective study with institutional review board-approval. Sonographic and clinical follow-up were performed 6 months after intervention. Effectiveness and safety of the technique were analyzed. The cumulative summation (CUSUM) graphs were used to evaluate learning curves concerning complete excision and hematoma. RESULTS: 152 ultrasound-VAEs in 143 patients were included. Initial complete resection was achieved in 90.8 % (138 of 152). 6-month follow-up was completed for 143 (94%) of cases and complete resection was observed in 72 % (100 of 143). Mean maximum size without residual tumor was 16.9 mm, while with residual lesion it was 21.9 mm (p = < 0.001), with a volume of 1.53 and 3.39 cm3, respectively (p = < 0.001). Increase in lesion size and volume was associated with less effectiveness (p = 0.05), clinical control (p = 0.05), and higher risk of clinically significant hematoma (p = 0.05). Receiver operating characteristic analysis demonstrate a volume threshold of 2.6 cm3 (r = 0.71, specificity 84.5%) for leaving no residual lesion. Cumulative summation graphs demonstrate that, on average, 11 excisions were required to acquire skills to perform complete excision in more than 80% at the end of the ultrasound-VAE and 18 excisions at 6 months. CONCLUSION: Ultrasound-VAE is an effective treatment for benign breast lesions. Breast lesion volume should be considered when assessing for percutaneous treatment. ADVANCES IN KNOWLEDGE: A follow-up of the learning process of ultrasound-VAE will be a valuable tool to assess the efectiveness and safety of the technique i.

Abstract P3-01-04: Improved sentinel lymph node detection with the use of superparamagnetic iron oxide tracer after neoadjuvant treatment in breast cancer patients

Background. The use of superparamagnetic iron oxide (SPIO) tracer for sentinel node biopsy (SLN) has shown non inferiority compared with the radioisotope technique in early breast cancer. In the neoadjuvant setting (NAC) identification rates with dual technique (blue dye and Tc 99) have been reported to be from 80% to 95%. SLN biopsy false negative (FN) rates after NAC have decreased with the use of dual tracer (radioisotope/ blue dye) and the excision of > 2 SLNs. This study was designed to evaluate the outcome of SLN after NAC using a dual tracer (SPIO and Tc99) versus SLN after NAC with radioisotope (Tc 99) alone. Material and Methods. After NAC, 188 patients underwent SLN with Tc99 (group Tc99) and 92 patients underwent a SLN with dual technique (group SPIO/Tc99). Inclusion criteria were patients T1-3 N0-1 before NAC and all patients had clinically and /or ultrasound negative axilla before the SLN procedure. Patients were injected subareolar with Tc99 the day before surgery and with the SPIO intraoperatively. SLN was excised if it was radioactive, magnetic or palpable. Patients signed an inform consent. Patients who were N0 pre and postNAC did not undergo an axillary lymph node dissection (ALND) (except for the initial validation patients) , while patients who were N1 pre NAC and N0 post NAC underwent SLN and ALND as part of the protocol. Results. Mean age of patients between groups were similar, 53.18 (range, 24-90 years old) in the Tc99 group and 52.53 (range, 23-82 years old) in the SPIO/Tc99. Identification rates were 95.72% and 97.8 % in the Tc99 and the SPIO/Tc99 group respectively (p = 0.21). In the Tc99 group, 58 (30.8%) patients were cN1 pre NAC while 13 (14%) in the SPIO/Tc99 (p =0.01). Rates of positive SLN after NAC were 32% in the Tc99 group while 20% in the SPIO/Tc99 group. False negative rates were 4.19% in the Tc99 group (1/50) and 8.3% in the SPIO/Tc99 group (1/13) (p=0.62). There was a statistically significant difference in the median number of SLNs between techniques, being 2.04 in the Tc99 and 2.60 in the SPIO/Tc99 group (p = 0.001). When the mean number of SLNs and the identification rates were differentiated between cN1 and cN0, the statistically significant differences remained unchanged. Conclusions. The use of dual technique (SPIO and Tc99) for the detection of SLN after NAC increases the identification rates over 97%, better than the reported studies in the NAC setting with Tc99 and blue dye. Although in our study increasing the number of SLNs excised has not decreased the false negative rates, rates of FN are below 10% in both groups. Larger number of cN1 patients is needed in the SPIO/Tc99 technique to validate these initial results. The dual technique with SPIO and Tc99 may optimize the success of SLN after NAC in breast cancer patients. Citation Format: Rubio IT, Esgueva-Colmenarejo A, Diaz-Botero S, Peg V, Espinosa-Bravo M. Improved sentinel lymph node detection with the use of superparamagnetic iron oxide tracer after neoadjuvant treatment in breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-01-04.

Abstract P2-01-17: Total tumoral load as a prediction tool of non-sentinel node metastases in patients with early breast cancer and positive sentinel lymph node assesed by OSNA

Background: Total tumoral load (TTL) in the sentinel lymph nodes (SLN) assessed by the OSNA assay is a new variable that is able to predict the likelihood of more axillary metastasis. Compared with the number of positive SLNs, the TTL is independent of the number of metastatic SLNs and a better predictor of further nodal metastasis. Although establishing specific cutoff-points of the TTL can be questionable because they may change in the future and increasingly become more patient specific, we have seen that TTL Methods: This is a retrospective cohort study of 145 consecutive patients with cT1-T2 invasive breast cancer with ultrasonographically node-negative treated between April 2010 to April 2013, where there is at least one positive SLN assesed by OSNA. We design a prediction tool based on the TTL results determined by OSNA to calculate the likelihood of not finding more positive non-SLN (http://www.vhebron.net/es/calculadora-risc-metastasi-2). Our group have demonstrated that TTL=15.000 could be a good cut off by its high NPV and sensitivity, 85.5% and 76.7%, respectively. Results: A total 325 SLNs were removed with a mean of 2.24. The type of SLN metastasis were macrometastasis in 85 patients (58.6%) and micrometastasis in 60 patients (41.4%). When considering patients with number of positive SLNs, of 109 patients with ≤2 positives SLNs and an cALND, 17 patients (22%) had non-SLN metastasis; and of 5 patients with ≥3 SLN, four (80%) had non-SLN metastasis. Taking the TTL results, of 51 patients with TTL Of 55 patients with TTL ≥15.000 copies/µL (with 1 or 2 positives SLNs) with cALND, 20 patients (36%) had non-SLN metastasis and there were a media of 2.5 non-SLN metastasis (range 1-8). Of 34 patients (62%) with one positive SLN with TTL ≥15.000 copies/µL, 12 patients (35%) had non-SLN metastasis; and of 21 patients with two positive SLN with TTL ≥15.000 copies/µL, eight patients (38%) had non-SLN metastasis. Conclusion: The total tumor load obtained by OSNA predicts non-SLN metastasis independent of the number of positive SLNs. The assess of the TTL in our cohort of patients show that patients with one or two positives SLNs with high TTL had high likelihood of non-SLN metastasis greater than 27% of Z0011 criteria. Prospective studies are needed to determine the clinical impact of this variable in patients outcome in the management of patients with SLN assesed by OSNA. Citation Format: Martin Espinosa-Bravo, Francesc Perez-Ceresuela, Sebastian Diaz-Botero, Vicente Peg, Isabel T Rubio. Total tumoral load as a prediction tool of non-sentinel node metastases in patients with early breast cancer and positive sentinel lymph node assesed by OSNA [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-17.