Wire-Free Targeted Axillary Dissection: A Pooled Analysis of 1300+ Cases Post-Neoadjuvant Systemic Therapy in Node-Positive Early Breast Cancer.

Recent advances in neoadjuvant systemic therapy (NST) have significantly improved pathologic complete response rates in early breast cancer, challenging the role of axillary lymph node dissection in nose-positive patients. Targeted axillary dissection (TAD) integrates marked lymph node biopsy (MLNB) and tracer-guided sentinel lymph node biopsy (SLNB). The introduction of new wire-free localisation markers (LMs) has streamlined TAD and increased its adoption. The primary endpoints include the successful localisation and retrieval rates of LMs. The secondary endpoints include the pathological complete response (pCR), SLNB, and MLNB concordance, as well as false-negative rates. Seventeen studies encompassing 1358 TAD procedures in 1355 met the inclusion criteria. The localisation and retrieval rate of LMs were 97% and 99%. A concordance rate of 67% (95% CI: 64-70) between SLNB and MLNB was demonstrated. Notably, 49 days (range: 0-272) was the average LM deployment time to surgery. pCR was observed in 46% (95% CI: 43-49) of cases, with no significant procedure-related complications. Omitting MLNB or SLNB would have under-staged the axilla in 15.2% or 5.4% (p = 0.0001) of cases, respectively. MLNB inclusion in axillary staging post-NST for initially node-positive patients is crucial. The radiation-free Savi Scout, with its minimal MRI artefacts, is the preferred technology for TAD.

Assessing the Efficacy of Radioactive Iodine Seed Localisation in Targeted Axillary Dissection for Node-Positive Early Breast Cancer Patients Undergoing Neoadjuvant Systemic Therapy: A Systematic Review and Pooled Analysis.

Targeted axillary dissection (TAD), employing marked lymph node biopsy (MLNB) alongside sentinel lymph node biopsy (SLNB), is increasingly recognised for its efficacy in reducing false negative rates (FNRs) in node-positive early breast cancer patients receiving neoadjuvant systemic therapy (NST). One such method, 125I radioactive seed localisation (RSL), involves implanting a seed into a biopsy-proven lymph node either pre- or post-NST. This systematic review and pooled analysis aimed to assess the performance of RSL in TAD among node-positive patients undergoing NST. Six studies, encompassing 574 TAD procedures, met the inclusion criteria. Results showed a 100% successful deployment rate, with a 97.6% successful localisation rate and a 99.8% retrieval rate. Additionally, there was a 60.0% concordance rate between SLNB and MLNB. The FNR of SLNB alone was significantly higher than it was for MLNB (18.8% versus 5.3%, respectively; p = 0.001). Pathological complete response (pCR) was observed in 44% of cases (248/564). On average, the interval from 125I seed deployment to surgery was 75.8 days (range: 0-272). These findings underscore the efficacy of RSL in TAD for node-positive patients undergoing NST, enabling precise axillary pCR identification and facilitating the safe omission of axillary lymph node dissection.

Evaluating Magnetic Seed Localization in Targeted Axillary Dissection for Node-Positive Early Breast Cancer Patients Receiving Neoadjuvant Systemic Therapy: A Comprehensive Review and Pooled Analysis.

Background/Objectives: De-escalation of axillary surgery is made possible by advancements in both neoadjuvant systemic therapy (NST) and in localisation technology for breast lesions. Magseed®, developed in 2013 by Dr. Michael Douk of Cambridge, United Kingdom, is a wire-free localisation technology that facilitates the localisation and retrieval of lymph nodes for staging. Targeted axillary dissection (TAD), which entails marked lymph node biopsy (MLNB) and sentinel lymph node biopsy (SLNB), has emerged as the preferred method to assess residual disease in post-NST node-positive patients. This systematic review and pooled analysis evaluate the performance of Magseed® in TAD. Methods: The search was carried out in PubMed and Google Scholar. An assessment of localisation, retrieval rates, concordance between MLNB and SLNB, and pathological complete response (pCR) in clinically node-positive patients post NST was undertaken. Results: Nine studies spanning 494 patients and 497 procedures were identified, with a 100% successful deployment rate, a 94.2% (468/497) [95% confidence interval (CI), 93.7-94.7] localisation rate, a 98.8% (491/497) retrieval rate, and a 68.8% (247/359) [95% CI 65.6-72.0] concordance rate. pCR was observed in 47.9% (220/459) ) [95% CI 43.3-52.6] of cases. Subgroup analysis of studies reporting the pathological status of MLNB and SLNB separately revealed an FNR of 4.2% for MLNB and 17.6% for SLNB (p = 0.0013). Mean duration of implantation was 37 days (range: 0-188). Conclusions: These findings highlight magnetic seed localisation's efficacy in TAD for NST-treated node-positive patients, aiding in accurate axillary pCR identification and safe de-escalation of axillary surgery in excellent responders.

Evaluating Radar Reflector Localisation in Targeted Axillary Dissection in Patients Undergoing Neoadjuvant Systemic Therapy for Node-Positive Early Breast Cancer: A Systematic Review and Pooled Analysis.

SAVI SCOUT® or radar reflector localisation (RRL) has proven accurate in localising non-palpable breast and axillary lesions, with minimal interference with MRI. Targeted axillary dissection (TAD), combining marked lymph node biopsy (MLNB) and sentinel lymph node biopsy (SLNB), is becoming a standard post-neoadjuvant systemic therapy (NST) for node-positive early breast cancer. Compared to SLNB alone, TAD reduces the false negative rate (FNR) to below 6%, enabling safer axillary surgery de-escalation. This systematic review evaluates RRL's performance during TAD, assessing localisation and retrieval rates, the concordance between MLNB and SLNB, and the pathological complete response (pCR) in clinically node-positive patients post-NST. Four studies (252 TAD procedures) met the inclusion criteria, with a 99.6% (95% confidence [CI]: 98.9-100) successful localisation rate, 100% retrieval rate, and 81% (95% CI: 76-86) concordance rate between SLNB and MLNB. The average duration from RRL deployment to surgery was 52 days (range:1-202). pCR was observed in 42% (95% CI: 36-48) of cases, with no significant migration or complications reported. Omitting MLNB or SLNB would have under-staged the axilla in 9.7% or 3.4% (p = 0.03) of cases, respectively, underscoring the importance of incorporating MLNB in axillary staging post-NST in initially node-positive patients in line with the updated National Comprehensive Cancer Network (NCCN) guidelines. These findings underscore the excellent efficacy of RRL in TAD for NST-treated patients with positive nodes, aiding in accurate axillary pCR identification and the safe omission of axillary dissection in strong responders.

Reevaluating Axillary Lymph Node Dissection in Total Mastectomy for Low Axillary Burden Breast Cancer: Insights from a Meta-Analysis including the SINODAR-ONE Trial.

Complete axillary lymph node dissection (cALND) was previously the standard of care for breast cancer (BC) patients with axillary node disease or macro-metastases found via sentinel lymph node biopsy (SLNB). However, due to significant morbidity, contemporary management now considers a more selective approach, influenced by studies like ACOSOG Z0011. This trial showed that cALND could be omitted without compromising local control or survival in patients with low axillary nodal disease burden undergoing breast-conserving therapy, radiotherapy, and systemic therapy. The relevance of this approach for women with low axillary nodal burden undergoing total mastectomy (TM) remained unclear. A PubMed search up to September 2023 identified 147 relevant studies, with 6 meeting the inclusion criteria, involving 4184 patients with BC and low-volume axillary disease (1-3 positive lymph nodes) undergoing TM. Postmastectomy radiotherapy receipt was similar in both groups. After a mean 7.2-year follow-up, both the pooled results and the meta-analysis revealed no significant differences in overall survival. The combined analysis of the published studies, including the subgroup analysis of the SINODAR-One trial, indicates no survival advantage for cALND over SLNB in T1-T2 breast cancer patients with 1-3 positive sentinel lymph nodes (pN1) undergoing mastectomy. This suggests that, following a multidisciplinary evaluation, cALND can be safely omitted. However, the impact of other patient, tumor, and treatment factors on survival requires consideration and therefore further prospective trials are needed for conclusive validation.

Omitting Sentinel Lymph Node Biopsy after Neoadjuvant Systemic Therapy for Clinically Node Negative HER2 Positive and Triple Negative Breast Cancer: A Pooled Analysis.

Recent advances in systemic treatment for breast cancer have been underpinned by recognising and exploiting subtype-specific vulnerabilities to achieve higher rates of pathologic complete response (pCR) after neo-adjuvant systemic therapy (NAST). This down-staging of disease has permitted safe surgical de-escalation in patients who respond well. Triple-negative (TNBC) or HER2-positive breast cancer is most likely to achieve complete radiological response (rCR) and pCR after NAST. Hence, for selected patients, particularly those who are clinically node-negative (cN0) at diagnosis, the probability of disease in the sentinel node after NAST could be low enough to justify omitting axillary surgery. The aim of this pooled analysis was to determine the rate of sentinel node positivity (ypN+) in patients with TNBC or HER2-positive breast cancer who were initially cN0, achieving rCR and/or pCR in the breast after NAST. MedLine was searched using appropriate search terms. Five studies (N = 3834) were included in the pooled analysis, yielding a pooled ypN+ rate of 2.16% (95% CI: 1.70-2.63). This is significantly lower than the acceptable false negative rate of sentinel lymph node biopsy (SLNB) and supports consideration of omission of SLNB in this subset of patients.

Simultaneous Salvage Auto-augmentation: Contemporary Strategy for Management of the Breast Explantation Patient.

The treatment of patients requiring explantation of breast prostheses is a complicated clinical issue, for which a consensus regarding the best way forward is still evolving. We believe that simultaneous salvage auto-augmentation (SSAA) is a viable option for the treatment of patients with explantation. Methods: Sixteen cases (32 breasts) were reviewed over a 19-year period. The management of the capsule is based on intraoperative findings and not on preoperative evaluation because of the poor interobserver correlation of Baker grades. Results: The mean age and clinical follow-up duration were 48 years (range: 41-65) and 9 months, respectively. We observed no complications, and only one patient underwent unilateral surgical revision of the periareolar scar, under local anaesthesia. Conclusions: This study suggests that SSAA with or without autologous fat injection is a safe option for women undergoing explantation, with potential aesthetic and cost-saving benefits. In the current climate of public anxiety regarding breast implant illness, breast implant-associated atypical large cell lymphoma, and asymptomatic textured implants, it is anticipated that the number of patients desiring explantation and SSAA will continue to increase.

Breast Tumour Kinase (Brk/PTK6) Contributes to Breast Tumour Xenograft Growth and Modulates Chemotherapeutic Responses In Vitro.

Breast tumour kinase (Brk/PTK6) is overexpressed in up to 86% of breast cancers and is associated with poorer patient outcomes. It is considered a potential therapeutic target in breast cancer, even though the full spectrum of its kinase activity is not known. This study investigated the role of the kinase domain in promoting tumour growth and its potential in sensitising triple negative breast cancer cells to standard of care chemotherapy. Triple negative human xenograft models revealed that both kinase-inactive and wild-type Brk promoted xenograft growth. Suppression of Brk activity in cells subsequently co-treated with the chemotherapy agents doxorubicin or paclitaxel resulted in an increased cell sensitivity to these agents. In triple negative breast cancer cell lines, the inhibition of Brk kinase activity augmented the effects of doxorubicin or paclitaxel. High expression of the alternatively spliced isoform, ALT-PTK6, resulted in improved patient outcomes. Our study is the first to show a role for kinase-inactive Brk in human breast tumour xenograft growth; therefore, it is unlikely that kinase inhibition of Brk, in isolation, would halt tumour growth in vivo. Breast cancer cell responses to chemotherapy in vitro were kinase-dependent, indicating that treatment with kinase inhibitors could be a fruitful avenue for combinatorial treatment. Of particular prognostic value is the ratio of ALT-PTK6:Brk expression in predicating patient outcomes.

De-Escalation of Breast Cancer Surgery Following Neoadjuvant Systemic Therapy.

Breast cancer treatment has seen many advances in recent decades, lessening the morbidity to patients, while improving outcomes. Central to these gains has been the introduction of breast conserving surgery and neoadjuvant systemic therapy (NST). There is a considerable interest in further de-escalation of the treatment of breast cancer, which is being studied in several ongoing randomised trials. We aimed to appraise the current literature regarding the various aspects of de-escalation of surgical treatment of breast cancer after NST, and attempt to prognosticate the future course of breast oncotherapy.

Pre-pectoral Immediate Breast Reconstruction Following Conservative Mastectomy Using Acellular Dermal Matrix and Semi-smooth Implants.

BACKGROUND/AIM: Improvements in acellular dermal matrix (ADM) and surgical techniques have facilitated pre-pectoral immediate breast reconstruction (IBR). Outer shell texturing is a key risk factor for anaplastic large cell lymphoma, prompting this evaluation of reconstruction with nano-textured rounded implants. PATIENTS AND METHODS: Fifty-one consecutive patients underwent 72 pre-pectoral ADM-assisted (fenestrated SurgiMend™) IBRs using nano-textured implants (Sebbin™). Patients were invited to complete a satisfaction questionnaire, including aesthetic outcome (linear scale 0-10) during follow-up. RESULTS: Average mastectomy weight was 300 g (range=83-1,018 g). After a mean follow-up of 18.3 month, 2 patients (2.8%) had minor wound complications. One patient suffered nipple necrosis. Capsular contracture occurred in 5 cases (6.9%) and significant rippling in one case. No implants were lost. Patient-reported aesthetic outcomes had a mean score of 9.3 (range=3-10; N=71). CONCLUSION: Pre-pectoral ADM-assisted IBR using semi-smooth implants following NSM is reliable and safe, with a low incidence of complications and high patient satisfaction.

Is Autologous Fat Grafting an Oncologically Safe Procedure following Breast Conserving Surgery for Breast Cancer? A Comprehensive Review.

BACKGROUND: Autologous fat grafting (AFG) is a recognized surgical procedure to correct deformities following breast conservation surgery (BCS) for breast cancer. However, there are concerns about the oncological safety of this technique. In this study we have reviewed the current literature to assess whether AFG adversely influences the oncological outcome after BCS for breast cancer. METHODS: We have searched the medical literature using the Embase and PubMed search engines from conception until May 2019 to identify all relevant studies of patients who underwent AFG after BCS. Meta-analysis and meta-regression methodologies were used to calculate the overall relative risk (RR) of loco-regional recurrence (LRR) rates for case-control and case series studies (with historical controls) respectively. RESULTS: We have identified 26 eligible studies with a total of 1640 patients who had undergone fat transfer after lumpectomy for breast cancer. The meta-analysis of 11 studies revealed an overall RR for LRR of 0.82 [95% confidence interval (CI):0.14-1.66]. The meta-regression of case series revealed an overall incidence of LRR of 1.85% compared with 2.53% for historical controls. CONCLUSIONS: Our study lends further support to the notion that fat transfer after lumpectomy for breast cancer does not seem to increase the risk of LRR. However further prospective research is required in order to confirm this.

Pathologic Response of Associated Ductal Carcinoma In Situ to Neoadjuvant Systemic Therapy: A Systematic Review.

Contrary to traditional assumptions, recent evidence suggests that neoadjuvant systemic therapy (NST) given for invasive breast cancer may eradicate co-existent ductal carcinoma in-situ (DCIS), which may facilitate de-escalation of breast resections. The aim of this systematic review was to assess the eradication rate of DCIS by NST given for invasive breast cancer. Searches were performed in MEDLINE using appropriate search terms. Six studies (N = 659) in which pathological data were available regarding the presence of DCIS prior to neoadjuvant chemotherapy (NACT) were identified. Only one study investigating the impact of neoadjuvant endocrine therapy (NET) met the search criteria. After pooled analysis, post-NACT pathology showed no residual DCIS in 40.5% of patients (267/659; 95% CI: 36.8-44.3). There was no significant difference in DCIS eradication rate between triple negative breast cancer (TNBC) and HER2-positive disease (45% vs. 46% respectively). NET achieved eradication of DCIS in 15% of patients (9/59). Importantly, residual widespread micro-calcifications after NST did not necessarily indicate residual disease. In view of the results of the pooled analysis, the presence of extensive DCIS prior to NST should not mandate mastectomy and de-escalation to breast conserving surgery (BCS) should be considered in patients identified by contrast enhanced magnetic resonance imaging (CE-MRI).

The Evolving Role of Radiofrequency Guided Localisation in Breast Surgery: A Systematic Review.

Wire-guided localisation (WGL) has been the gold-standard for localising non-palpable breast lesions before excision. Due to its drawbacks, various wireless alternatives have been developed, including LOCalizer™, which is based on radio-frequency identification (RFID) technology. In this systematic review, we consulted EMBASE, Medline and PubMed databases using appropriate search terms regarding the use of RFID technology in the localisation of occult breast lesions. Retrospective and prospective studies were included if they quoted the number of patients, rate of successful placement, retrieval rate, margin positivity rate and the re-excision rate. In addition, studies comparing RFID to WGL were also included and analysed separately. Seven studies were included in this systematic review spanning 1151 patients and 1344 tags. The pooled deployment rate was 99.1% and retrieval rate was 100%. Re-excision rate was 13.9%. One complication was identified. Two studies compared RFID with WGL (128 vs. 282 patients respectively). For both techniques the re-excision rate was 15.6% (20/128 vs. 44/282 respectively, p value is 0.995). Based on our review, LOCalizer™ is safe and non-inferior to WGL in terms of successful localisation and re-excision rates. However, further research is required to assess the cost effectiveness of this approach and its impact on the aesthetic outcome compared with WGL and other wire free technologies to better inform decision making in service planning and provision.

Reflector-Guided Localisation of Non-Palpable Breast Lesions: A Prospective Evaluation of the SAVI SCOUT® System.

Wire-guided localisation (WGL) has been the mainstay for localising non-palpable breast lesions before excision. Due to its limitations, various wireless alternatives have been developed. In this prospective study, we evaluate the role of radiation-free wireless localisation using the SAVI SCOUT® system at the London Breast Institute. A total of 72 reflectors were deployed in 67 consecutive patients undergoing breast conserving surgery for non-palpable breast lesions. The mean interval between deployment and surgery for the therapeutic cases was 18.8 days (range: 0-210). The median deployment duration was 5 min (range: 1-15 min). The mean distance from the lesion was 1.1 mm (median distance: 0; range: 0-20 mm). The rate of surgical localisation and retrieval of the reflector was 98.6% and 100%, respectively. The median operating time was 28 min (range: 15-55 min) for the therapeutic excision of malignancy and 17 min (range: 15-24) for diagnostic excision. The incidence of reflector migration was 0%. Radial margin positivity in malignant cases was 7%. The median weight for malignant lesions was 19.6 g (range: 3.5-70 g). Radiologists and surgeons rated the system higher than WGL (93.7% and 98.6%, respectively; 60/64 and 70/71). The patient mean satisfaction score was 9.7/10 (n = 47, median = 10; range: 7-10). One instance of signal failure was reported. In patients who had breast MRI after the deployment of the reflector, the MRI void signal was <5 mm (n = 6). There was no specific technique-related surgical complication. Our study demonstrates that wire-free localisation using SAVI SCOUT® is an effective and time-efficient alternative to WGL with excellent physician and patient acceptance.

Sensitivity, Specificity and the Diagnostic Accuracy of PET/CT for Axillary Staging in Patients With Stage I-III Cancer: A Systematic Review of The Literature.

BACKGROUND/AIM: Axillary lymph node (ALN) status plays a key role in the staging of breast cancer. Positron Emission Tomography/Computed Tomography (PET/CT) using 18-Fluorodeoxyglucose (18FDG) can visualise ALN metastasis. However, its utility compared to current methods is unclear. We systematically reviewed the role of 18FDG PET/CT in breast cancer staging. MATERIALS AND METHODS: PubMed, Ovid and Cochrane were searched systematically up until August 2020. Included papers had true positive (TP), false positive (FP), true negative (TN) and false negative (FN) rates, sensitivity, specificity, accuracy, positive (PPV) and negative predictive value (NPV). RESULTS: Nine studies (n=1486) were included, showing: i) sensitivity=52.2%, ii) specificity=91.6%, iii) PPV=77.8%, iv) NPV=77.2, and v) accuracy=77.3%. CONCLUSION: 18FDG-PET/CT has a low sensitivity but high specificity for ALN disease. Therefore, ultrasound-guided biopsy could be considered in a positive CT/PET. Modest accuracy prohibits the use of 18FDG-PET/CT alone in axillary staging. Prospective research using standardised protocols and quantitative cut-off points is warranted.

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

BACKGROUND/AIM: 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. MATERIALS AND METHODS: We appraised studies and guidelines published regarding this topic and discussed them in this mini-review. RESULTS AND CONCLUSION: 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.

Stratification Using hTERT and Stem Cell Markers Confers a Good Prognosis in Invasive Breast Cancer.

BACKGROUND/AIM: In this study, we aimed to investigate the prognostic role of a previously identified panel of 10 stem cell markers stratified against the catalytic subunit of telomerase (hTERT) in human breast cancer. MATERIALS AND METHODS: The mRNA copy numbers of these genes were determined using real time quantitative PCR in 124 breast cancer tissues and adjacent non-cancerous tissues. Relations between mRNA levels and survival were analysed using Kaplan-Meier plots and Cox regression analysis. RESULTS: Five genes (BMI1, NES, POU5F1, ALDH1A2 and CDKN1A) correlated with survival when stratified with hTERT and predicted overall (Wilcoxon: p=0.004; Cox: p=0.006) and disease-free (Wilcoxon: p<0.000; Cox: p=0.000) survival. CONCLUSION: This panel of genes stratified by hTERT could open new avenues for the development of new prognostic tools, as well as for the identification of new research directions regarding breast oncogenesis.

Locoregional therapy of the primary tumour in de novo stage IV breast cancer in 216 066 patients: A meta-analysis.

Patients presenting with de novo stage IV metastatic breast cancer have a complex disease which is normally treated with palliative intent and systemic therapy. However, there is mounting evidence that resection of the primary tumour and/or localised radiotherapy (locoregional therapy; LRT) could be associated with overall survival improvements. We aimed to conduct a meta-analysis to inform decision making. Using the PubMed, Cochrane and Ovid SP databases, a literature review and meta-analysis were conducted to assess the effect of LRT on overall survival. Studies were analysed for the impact of LRT on survival. All forms of LRT resulted in a significant 31.8% reduction in mortality (N = 42; HR = 0.6823 (95% CI 0.6365; 0.7314)). Surgical resection resulted in a significant 36.2% reduction in mortality (N = 37; HR = 0.6379 (95% CI 0.5974; 0.6811)). The prospective trials reported a 19.23% reduction in mortality which was not statistically significant (N = 3, HR = 0.8077 (95% CI 0.5704; 1.1438). 216 066 patients were included. This is the largest meta-analysis regarding this question to date. Our meta-analysis shows that LRT of the primary tumour seems to improve overall survival in de novo stage IV disease. Therefore, this therapeutic option should be considered in selected patients after a careful multidisciplinary discussion.