De-escalation Of Axillary Surgery Research Articles

De-escalation of Axillary Surgery in the Neoadjuvant Chemotherapy (NACT) Setting for Breast Cancer: Is it Oncologically Safe?

The treatment of breast cancer has progressed considerably over the years, with a significant de-escalation from radical mastectomies to the current paradigm of breast conserving surgery (BCS) and neoadjuvant chemotherapy (NACT). We aimed to appraise the literature regarding the feasibility of de-escalation of treatment of axillary disease in the context of NACT. We appraised studies and guidelines published regarding this topic and discussed them in this mini-review. The SNB following NACT is oncologically safe in patients with clinically node negative disease and in patients with biopsy proven axillary node involvement at presentation provided that the dual technique is used and the clipped pathological node is harvested.

Axillary management for patients with breast cancer after neoadjuvant chemotherapy: Results of a survey amongBrazilian breast surgeons.

Currently, there are broadly differing patterns in the management of the axilla after neoadjuvant chemotherapy (NAC) and no consensus with clinically strong evidence onthe subject. A survey was performed to assess the current axillary management after NAC amongBrazilian breast cancer surgeons. The Brazilian Society of Mastology members were invited by email to complete an anonymous online survey and a total of 426 responses were collected. The majority of responders (67%) indicated performing routine axillary staging by physical exam, ultrasound, and fine needle biopsy in case of a suspicious node before NAC. Among breast surgeons working in the Brazilian Public Unified Health System, 11.3% answered that sentinel lymph node biopsy (SLNB) is not reasonable after NAC in their services. Seventy-seven responders (18.2%) reported performing SLNB instead of axillary lymph node dissection (ALND) only in patients who are clinically node-negative before NAC. Axillary complete pathologic response is necessary to omit ALND for 42.8% of responders. The molecular profile of a breast tumor is not considered when choosing axillary management after NAC for 73.7% of responders. Our survey highlighted the trend towards de-escalation of axillary surgery and observed high heterogeneity in axillary management after chemotherapy in a group of brazilian breast surgeons.

Neoadjuvant chemotherapy versus adjuvant chemotherapy in breast cancer patients: Analysis of breast conserving rate and de-escalation of axillary surgery in 5,141 Korean women.

e12531 Background: Neoadjuvant chemotherapy (NCT) in breast cancer has several advantages such as more breast conservation surgery (BCS) rate and de-escalation of extent of axillary surgery. Actual practice change in this area compared with adjuvant chemotherapy (ACT) is not well established. Methods: We retrospectively analyzed 5,141 women diagnosed with breast cancer from 2009 to 2013, treated with chemotherapy before or after definite surgery. BCS rate and axillary surgery categories (sentinel lymph node biopsy (SNB), axillary lymphnode dissection (ALND) or SNB followed by ALND) are compared between two groups. Results: Among 5,141 patients, 3930 (76.4%) women had ACT and 1211 (23.6%) had NCT. Median age at diagnosis was 48 (range 22-83). BCR rate was lower in T2 (57.1% vs 64.1%), T3 (12.6% vs 20.9%) group between ACT vs NCT ( p=0.03, 0.001), no difference was shown in T1 and T4 tumors. SNB try (SNB only or SNB followed by ALND) rate was still higher in ACT group with cN0 (98.4% vs 95.4%), cN1 (89.3% vs 73.5%), cN2 (77.9% vs 62.1%) tumors ( p=0.001, <0.001, 0.003, respectively). SNB only rate which means that patients spared ALND, was lower in ACT group with all cN stage (cN1; 17.5% vs 29.2%, cN2; 3.2% vs 5.9%, cN3; 5.1% vs 20.5%, all p=0.000) except cN0 (95.6% vs 81.4%, p<0.001). Axillary surgery rate analyzed with pathologic N stage showed more ALNDs attempted even after achieving pathologic complete nodal response or minimal residual N disease (ypN0: 4.4% vs 27.2%, ypN0(i) & ypN1mi; 26.2% vs 57.6%, p<0.001, =0.001 respectively). In contrast however, average of total axillary nodes retrieved by cN stage were statistically lower in NCT group in clinically positive tumors (N1; 15.3 vs 12.7, N2; 19.1 vs 14.6, N3; 25.1 vs 15.6, all p<0.001). Conclusions: NCT had shown advantage to perform more BCS than ACT in T2, T3 tumors. SNB attempts in NCT was comparable to ACT. Still, patients with NCT received more aggressive axillary surgery than ACT shown by axillary surgery category irrespective of negative SNB results.

Axillary management after neoadjuvant chemotherapy in breast cancer: A survey by Brazilian Society of Mastology.

e12609 Background: Several trials have been investigating the accuracy of sentinel lymph node biopsy (SLNB) in clinically node-positive breast cancer patients undergoing neoadjuvant chemotherapy (NAC). A survey of breast surgeons was performed to assess the current management of axilla after NAC in Brazilian clinical practice. Methods: Brazilian Society of Breast Surgeons members were invited by email to complete an anonymous online survey. From 2000 eligible members, 426 (21.3%) members responded the survey. Results were summarized as proportions based on the number of responses to each question. Results: The majority of responders, 43.4%, indicated performing routine axillary staging by physician exam, ultrasound and PAAF (if necessary) in patients who are to undergo neoadjuvant chemotherapy. Approximately 43% of responders perform SLNB instead of ALND in patients with N1 axillary involvement before neoadjuvant chemotherapy, however many breast surgeons also indicated SLNB for N2 (27.7%) and N3 (18.8%) patients. Axillary complete pathologic response (ypN0) is necessary to omit ALND for 42.8% of responders and 19.5% do not perform ALND in patients getting ypN1is+ (isolated tumoral cells). Considering the option with patients getting ypN1is+ (isolated tumoral cells) and ypN1mic (micrometastases), 24.5% reported not performing ALND after SLND. Fifty-eight participants, 13.8%, accepted only SLNB in patients getting ypN1is+ (isolated tumoral cells), ypN1mic (micrometastases) and ypN1. The molecular profiling of breast tumor is considered when choosing axillary management after neoadjuvant chemotherapy for 26.3% of responders and for 73.7% the molecular profiling is not influencing the decision. Conclusions: Our survey highlighted the trend toward de-escalation of axillary surgery in patients undergoing neoadjuvant treatment and a high heterogeneity in axillary management after chemotherapy in Brazilian practice.

Factors associated with axillary conversion after neoadjuvant chemotherapy in initially node positive breast cancer patients: A transSENTINA analysis.

567 Background: Current study concepts in early breast cancer after neoadjuvant chemotherapy (NAT) are aiming at reducing morbidity by omission of axillary surgery in selected patients. Selection criteria for this strategy have to include the probability of conversion from cN1 to ycN0. We analyzed the association of clinical/pathological parameters and axillary conversion with data from arms C and D of the SENTINA trial (Kühn T et al., Lancet Oncol 2013). Methods: Patients were recruited to Arms C/D of the SENTINA trial in case they presented with clinically positive nodes before NAT. Based on their response to NAT they were then assigned to either arm C (clinically conversion to ycN0) or arm D (no clinical conversion (ycN+). In both the pre- and post-NAT scenarios, clinically involved lymph nodes were defined as palpable and/or suspect by ultrasound. Univariate logistic regression analyses were carried out to evaluate the association between clinical/pathological parameters and axillary conversion after NAT. Results: Of the 892 patients in arms C and D of the SENTINA trial 716 were evaluable for this analysis. After NAT, 593 patients converted to ycN0 and were therefore assigned to arm C; in contrast, 123 patients still had involved lymph nodes after NAT (ycN+) and were assigned to Arm D. Arms C and D were compared regarding the clinical/pathological parameters tumor diameter by ultrasound before and after NAT, grading, multifocality, ER status, PR status, HER2 status, pathological complete remission in the breast (breast pCR), morphology, lymphovascular invasion (LVI) and hemangiosis. Only small tumor diameter after NAT (p = 0.0038), achievement of breast pCR (p = 0.0001) and lack of LVI (p = 0.0009) were positively associated with axillary conversion from cN1 to ycN0 after NAT. Conclusions: Because of the small patient number in arm D, we were not able to identify an association between parameters of tumor biology (ER, PR, HER2 and TN status) and axillary conversion. However, favorable response of the primary tumor (represented both clinically by tumor diameter after NAT and pathologically by pCR in the breast) were positively associated with conversion from cN1 to ycN0. These results justify including patients with clinical and pathological response of the primary tumor in trials investigating de-escalation of axillary surgery after NAT.

De-escalation of axillary surgery in breast cancer patients treated in the neoadjuvant setting: a Dutch population-based study

PurposeAn overall trend is observed towards de-escalation of axillary surgery in patients with breast cancer. The objective of this study was to evaluate this trend in patients treated with neoadjuvant systemic therapy (NST).MethodsPatients with cT1-4N0-3 breast cancer treated with NST (2006–2016) were selected from the Netherlands Cancer Registry. Patients were classified by clinical node status (cN) and type of axillary surgery. Uni- and multivariable logistic regression analyses were performed to determine the clinicopathological factors associated with performing ALND in cN+ patients.ResultsA total of 12,461 patients treated with NST were identified [5830 cN0 patients (46.8%), 6631 cN+ patients (53.2%)]. In cN0 patients, an overall increase in sentinel lymph node biopsy (SLNB) only (not followed by ALND) was seen from 11% in 2006 to 94% in 2016 (p < 0.001). SLNB performed post-NST increased from 33 to 62% (p < 0.001). In cN+ patients, an overall decrease in ALND was seen from 99% in 2006 to 53% in 2016 (p < 0.001). Age (OR 1.01, CI 1.00–1.02), year of diagnosis (OR 0.47, CI 0.44–0.50), HER2-positive disease (OR 0.62, CI 0.52–0.75), clinical tumor stage (T2 vs. T1 OR 1.32, CI 1.06–1.65, T3 vs. T1 OR 2.04, CI 1.58–2.63, T4 vs. T1 OR 6.37, CI 4.26–9.50), and clinical nodal stage (N3 vs. N1 OR 1.65, CI 1.28–2.12) were correlated with performing ALND in cN+ patients.ConclusionsALND decreased substantially over the past decade in patients treated with NST. Assessment of long-term prognosis of patients in whom ALND is omitted after NST is urgently needed.

Synchronous Sentinel Node Biopsy in Autologous Breast Reconstruction in Node Negative Axilla

Background: National Institute of Clinical Excellence guidelines recommends that all eligible patients with breast cancer who needs mastectomy should be offered immediate breast reconstruction. In Implant based reconstruction sentinel node biopsy (SLNB) is performed at the time of mastectomy in clinically node negative axilla but in autologous free flap reconstruction SLNB is routinely performed upfront. This helps to determine the sentinel node biopsy status prior to autologous reconstruction and allows the surgeons to perform axillary node clearance safely without any threat to the anastomosis when free flaps are anastomosed to thoracodorsal (TD) vessels in axilla. With a trend towards de escalation of axillary surgery in appropriate cases and the increasing use of Internal mammary Vessels (IMV) for vascular anastomosis we proposed that the impact of performing sentinel node biopsy synchronously with mastectomy and immediate DIEP reconstruction will be minimal.

Tumour infiltrating lymphocytes are a predictive factor for sentinel lymph nodes status in breast cancer

Background: In the era where the attitude towards breast cancer treatment changed into de-escalation of axillary surgery, it is important to find new predictive factors for lymph nodes status. Many items were studied including tumour size, lymphovascular invasion, histological grade and type of tumour, hormonal receptors, Ki67, etc. However none of them were validated for clinical use. Tumour infiltrating lymphocytes (TILs) have a good correlation with response to chemotherapy. Our objective was to investigate the predictive value of TILs for sentinel lymph nodes status in early breast cancer.

Abstract P3-03-43: Incorporation of MSKCC nomogram to guide the application of intra-operative sentinel lymph node frozen section evaluation in patients with early breast cancer

Abstract Background and Objectives: Although de-escalation of axillary surgery becomes more popular, axillary lymph node dissection (ALND) is still the standard care for sentinel lymph node(SLN) positive patients not meeting the criteria of ACOSOG Z0011 in many hospitals, and frozen section (FS) of SLN is one of the valuble intra-operative assesments to avoid axilla re-operation although it was controversial due to accuracy and efficiency concerns. This study was to assess the performance of selective use of frozen section evaluation guided by MSKCC lymph node metastasis risk prediction nomogram to optimize the proceudure to be more accurate and cost effective. Methods: Surgical pathology records of consecutive 2582 biopsies in 2552 patients breast cancer patients from 2011 to 2017 were reviewed, intra-operative frozen section diagnosis were compared to post-operative paraffin reports. We calculated the sensitivity, specificity, accuracy and FNR for different MSKCC risk, the axilla re-operation rate with or without FS and the number needed to treat (NNT) to avoid second ALND was also analyzed. Results: The sensitivity, specificity, and FNR of FS were 84.7%, 99.9%, and 15.3% respectively. The axilla re-operation rates were significantly decreased if FS was done(4.7%±0.4% with FS versus 35.8%±5.8% without FS, P&amp;lt;0.001). The estimated axilla re-operation rate without FS was positively correlated with MSKCC risk(r=0.99, P&amp;lt;0.001), while NNT to avoid second ALND by FS were negatively correlated with MSKCC risk(r=-0.98, P&amp;lt;0.001). When patients were divided into four groups according to quartile MSKCC risk, the axilla re-excisional rates were 18.4%, 25.1%, 38.7%, 58.7% without FS, while 4.8%, 3.2%, 5.6%, 3.2% with FS, and NNT correspondingly decreased from 7.3, 4.5, 3.0 to 1.8. An decision-making algorithm for application of FS was proposed. Conclusion: Stratified decision-making algorithm based on MSKCC prediction model improved the efficiency of FS to avoid axilla re-operatioin in patients undergoing sentinel lymph node biopsy. We recommend FS be restricted to patients with MSKCC risk higher than 0.5 who do not meet ACOSOG Z0011 criteria. Citation Format: Yang H, Wang S, Shen D, Cao Y, Tong F, Chen D, Liu P, Peng Y. Incorporation of MSKCC nomogram to guide the application of intra-operative sentinel lymph node frozen section evaluation in patients with early breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-43.

Diagnosing and Managing the Malignant Axilla in Breast Cancer

The management of the malignant axilla remains a controversial topic. Although many issues have been resolved with the results of randomised controlled trials, there are still areas where evidence is lacking. This review will focus on the current diagnostic methods used to detect lymph node (LN) metastases as well as the impact of volume of LN disease on the choice of axillary management. The roles of surgical excision, radiotherapy and systemic therapy as treatment modalities for LN metastases will also be explored with particular emphasis on the use of neo-adjuvant chemotherapy (NACT). Lastly, new innovations in contrast-enhanced ultrasound (CEUS) will be discussed as a potential test for precise and personalised axillary staging. The results of the ACOSOG Z011 trial are widely accepted and axillary conservation is now part of mainstream practice in many parts of the World for patients with sentinel lymph node (SLN) metastases and clinical T1/ T2 N0 M0 tumours who had breast-conserving surgery alongside adjuvant whole breast radiotherapy and systemic therapy. Determining the volume of metastatic disease in the axilla is important for treatment decisions and de-escalation of axillary surgery after NACT in patients with biopsy proven pretreatment LN metastases may become part of routine practice for selected patients once long-term outcomes are known. Novel methods to identify LN metastases have been developed over the last 10 years including the use of injected microbubbles and CEUS to locate and biopsy sentinel lymph nodes (SLN). Technological advances including ultrafast and super-resolution ultrasound have the potential to increase the diagnostic accuracy of axillary CEUS. The main drawback to current axillary management is the lack of a reliable objective test to quantify LN metastases. The de-escalation of axillary surgery is timely but without an objective non-invasive imaging test to replace the axillary lymph node dissection (ALND), clinicians are reliant on predictive medicine rather than precision diagnostics to plan individual treatment. New innovations in CEUS have the potential to provide a reproducible non-invasive test, which can be used in the future to investigate LN metastases in patients with breast cancer.

Axillary lymph node surgical treatment

Nowadays, the overall attention is focused on de-escalating treatments for breast cancer (BC) including surgery, radiotherapy and chemotherapy. The introduction of sentinel lymph node biopsy (SLNB) has led to less invasive surgical approaches for accurately staging the axilla, with axillary lymph node dissection (ALND) progressively confined to a limited group of patients. One of the goal of surgery in de-escalating approaches is to reduce surgical morbidity by restricting or avoiding axillary surgery with no effect on survival. In this context the importance of imaging study for preoperative identification of axillary metastasis, in order to reduce axillary surgery, is gradually improving while the role of intraoperative assessment of sentinel nodes is progressively becoming limited to restricted groups of patients. According to the results of the ACOSOG Z0011 and following the most important guidelines, ALND can be safely omitted in selected patients treated with breast conserving surgery (BCS) with one or two positive SLNB while the adoption of SLNB positive alone in patients undergoing mastectomy is not yet defined. The increased employment of neoadjuvant chemotherapy (NAC) and the use of SLNB in patients after NAC plays an important role in de-escalation of axillary surgery in this group of patients. However current studies on this topic are still controversial, mainly about clinically positive lymph nodes (cN+) pre NAC patients or how to manage positive SLNB in post NAC patients. Some authors have collected predictive factors of positive non sentinel lymph nodes (NSLNs) in nomograms, considered an useful tool to avoid unnecessary further surgery. Elderly women represent specific group of patients where the axillary approach needs to be properly resized. The management of axilla in BC is in continuous evolution and ongoing studies could make even SLNB useless in the next future.