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Medicine Dec 2022Axillary staging is 1 of the major issues of current breast cancer management after neoadjuvant systemic therapy (NST). Sentinel lymph node biopsy (SLNB) is an option...
Axillary staging is 1 of the major issues of current breast cancer management after neoadjuvant systemic therapy (NST). Sentinel lymph node biopsy (SLNB) is an option for clinically node negative patients. Axillary reverse mapping (ARM) was introduced to identify and preserve the lymphatic drainage from the arm. The aim of the presented study is to employ triple mapping (radiocolloid, blue dye and indocyanine green [ICG]) to assess the crossover rate and metastatic involvement of ARM nodes after NST. Clinically node positive patients before NST who were converted to N0 and scheduled for targeted axillary dissection were included. sentinel lymph node (SLN) mapping was performed via dual agent mapping. ICG was used for ARM procedure. Blue, hot and fluorescent nodes and lymphatics were visualized in the axilla using infrared camera system and dual opto-nuclear probe (Euoroprobe3). Fifty-two patients underwent targeted axillary dissection and ARM procedures 12 out of whom had axillary node dissection. 45 of the 52 patients had at least 1 hot or blue SLN identified intraoperatively. Of these, 61.5% cases had hot SLNs, 42.3% had hot and blue, 15.4% had hot/blue/fluorescent, 7.7% had blue/fluorescent, 6 11.5% had hot/fluorescent and 7 13.5% had only clipped nodes. The overall identification rate of ARM-nodes by means of ICG technique was 86.5%. Overall crossover of ARM nodes with SLNs was determined in 36.5%. The ICG intensity was found to be higher in both hot and blue SLNS (8 out of 18 ICG positive cases, 44.4%). In 3 of 52 patients (5.7%) metastatic SLNs were hot or blue but fluorescent which predicts metastatic involvement of the ARM-nodes. More than 1-third of the patients revealed a crossover between arm and breast draining nodes. The higher observed rate of overlap might partially explain why more patients develop clinically significant lymphedema after NST even after sentinel lymph node biopsy alone. The triple mapping provides valuable data regarding the competency of lymphatic drainage and would have the potential to serve selecting patients for lymphovenous by-pass procedures at the index procedure. NST reduces the metastatic involvement of the ARM nodes. However, conservative axillary staging with sparing ARM nodes after NST necessitates further studies with larger sample size and longer follow-up.
Topics: Humans; Female; Sentinel Lymph Node Biopsy; Indocyanine Green; Neoadjuvant Therapy; Axilla; Lymph Nodes; Lymph Node Excision; Breast Neoplasms; Coloring Agents
PubMed: 36596061
DOI: 10.1097/MD.0000000000032545 -
Breast Cancer Research and Treatment Aug 2021High-performing imaging and predictive markers are warranted to minimize surgical overtreatment of the axilla in breast cancer (BC) patients receiving neoadjuvant...
PURPOSE
High-performing imaging and predictive markers are warranted to minimize surgical overtreatment of the axilla in breast cancer (BC) patients receiving neoadjuvant chemotherapy (NACT). Here we have investigated whether axillary ultrasound (AUS) could identify axillary lymph node (ALN) metastasis (ALNM) pre-NACT and post-NACT for BC. The association of tumor, AUS features and mammographic density (MD) with axillary-pathological complete response (axillary-pCR) post-NACT was also assessed.
METHODS
The NeoDense-study cohort (N = 202, NACT during 2014-2019), constituted a pre-NACT cohort, whereas patients whom had a cytology verified ALNM pre-NACT and an axillary dissection performed (N = 114) defined a post-NACT cohort. AUS characteristics were prospectively collected pre- and post-NACT. The diagnostic accuracy of AUS was evaluated and stratified by histological subtype and body mass index (BMI). Predictors of axillary-pCR were analyzed, including MD, using simple and multivariable logistic regression models.
RESULTS
AUS demonstrated superior performance for prediction of ALNM pre-NACT in comparison to post-NACT, as reflected by the positive predictive value (PPV) 0.94 (95% CI 0.89-0.97) and PPV 0.76 (95% CI 0.62-0.87), respectively. We found no difference in AUS performance according to neither BMI nor histological subtype. Independent predictors of axillary-pCR were: premenopausal status, ER-negativity, HER2-overexpression, and high MD.
CONCLUSION
Baseline AUS could, to a large extent, identify ALNM; however, post-NACT, AUS was insufficient to determine remaining ALNM. Thus, our results support the surgical staging of the axilla post-NACT. Baseline tumor biomarkers and patient characteristics were predictive of axillary-pCR. Larger, multicenter studies are needed to evaluate the performance of AUS post-NACT.
Topics: Axilla; Breast Neoplasms; Female; Humans; Lymph Nodes; Neoadjuvant Therapy; Neoplasm Staging; Retrospective Studies; Sentinel Lymph Node Biopsy
PubMed: 34120224
DOI: 10.1007/s10549-021-06283-8 -
Current Oncology (Toronto, Ont.) Mar 2023Landmark trials (Z0011 and AMAROS) have demonstrated that axillary lymph node dissection (ALND) can be safely omitted in patients with breast cancer and 1-2 positive... (Review)
Review
Landmark trials (Z0011 and AMAROS) have demonstrated that axillary lymph node dissection (ALND) can be safely omitted in patients with breast cancer and 1-2 positive sentinel nodes. Extrapolating from these and other cardinal studies such as NSABP B-04, guidelines state that patients with 1-2 needle biopsy-proven positive lymph nodes undergoing upfront surgery can have sentinel lymph node biopsy (SLNB) alone. The purpose of this study is to systematically review the literature to identify studies examining the direct application of SLNB in such patients. EMBASE and Ovid MEDLINE were searched from inception to 3 May 2022. Studies including patients with nodal involvement confirmed on pre-operative biopsy and undergoing SLNB were identified. Studies with neoadjuvant chemotherapy were excluded. Search resulted in 2518 records, of which 68 full-text studies were reviewed, ultimately yielding only 2 studies meeting inclusion criteria. Both studies used targeted axillary surgery (TAS) with pre-operative localization of the biopsy-proven positive node in addition to standard SLNB techniques. In a non-randomized single-center prospective study, Lee et al. report no regional recurrences in patients undergoing TAS or ALND, and no difference in distant recurrence or mortality at 5 years. In the prospective multicenter TAXIS trial by Webber et al., the median number of positive nodes retrieved with TAS in patients undergoing upfront surgery was 2 (1, 4 IQR). Within the subset of patients who underwent subsequent ALND, 61 (70.9%) had additional positive nodes, with 26 (30.2%) patients having ≥4 additional positive nodes. Our review demonstrates that there is limited direct evidence for SLNB alone in clinically node-positive patients undergoing upfront surgery. Available data suggest a high proportion of patients with residual disease in this setting. While the totality of the data, mostly indirect evidence, suggests SLNB alone may be safe, we call on clinicians and researchers to prospectively collect data on this patient population to better inform decision-making.
Topics: Humans; Female; Sentinel Lymph Node Biopsy; Breast Neoplasms; Prospective Studies; Lymph Node Excision; Axilla; Multicenter Studies as Topic
PubMed: 36975448
DOI: 10.3390/curroncol30030235 -
Breast Cancer (Tokyo, Japan) Nov 2023The value and utility of axillary lymph node (ALN) evaluation with MRI in breast cancer were not clear for various intrinsic subtypes. The aim of the current study is to...
Diagnostic accuracy of pre-operative breast magnetic resonance imaging (MRI) in predicting axillary lymph node metastasis: variations in intrinsic subtypes, and strategy to improve negative predictive value-an analysis of 2473 invasive breast cancer patients.
BACKGROUND
The value and utility of axillary lymph node (ALN) evaluation with MRI in breast cancer were not clear for various intrinsic subtypes. The aim of the current study is to test the potential of combining breast MRI and clinicopathologic factors to identify low-risk groups of ALN metastasis and improve diagnostic performance.
MATERIAL AND METHODS
Patients with primary operable invasive breast cancer with pre-operative breast MRI and post-operative pathologic reports were retrospectively collected from January 2009 to December 2021 in a single institute. The concordance of MRI and pathology of ALN status were determined, and also analyzed in different intrinsic subtypes. A stepwise strategy was designed to improve MRI-negative predictive value (NPV) on ALN metastasis.
RESULTS
2473 patients were enrolled. The diagnostic performance of MRI in detecting metastatic ALN was significantly different between intrinsic subtypes (p = 0.007). Multivariate analysis identified tumor size and histologic type as independent predictive factors of ALN metastases. Patients with HER-2 (MRI tumor size ≤ 2 cm), or TNBC (MRI tumor size ≤ 2 cm) were found to have MRI-ALN-NPV higher than 90%, and these false cases were limited to low axillary tumor burden.
CONCLUSION
The diagnostic performance of MRI to predict ALN metastasis varied according to the intrinsic subtype. Combined pre-operative clinicopathologic factors and intrinsic subtypes may increase ALN MRI NPV, and further identify some groups of patients with low risks of ALN metastasis, high NPV, and low burdens of axillary disease even in false-negative cases.
Topics: Humans; Female; Lymphatic Metastasis; Breast Neoplasms; Predictive Value of Tests; Retrospective Studies; Lymph Nodes; Magnetic Resonance Imaging; Axilla; Sentinel Lymph Node Biopsy
PubMed: 37500823
DOI: 10.1007/s12282-023-01488-9 -
Oncotarget Dec 2023To examine the risk factors for arm morbidity following breast cancer treatments, taking a broad view of all types of physical morbidity, including prolonged pain,...
PURPOSE
To examine the risk factors for arm morbidity following breast cancer treatments, taking a broad view of all types of physical morbidity, including prolonged pain, lymphedema, decreased range of motion, and functional limitations.
METHODS
A systematic literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. Studies exploring the risk factors for prolonged arm morbidity following breast cancer surgery and treatments were included. The studies were assessed independently according to pre-eligibility criteria, following data extraction and methodological quality assessment.
RESULTS
1,242 articles were identified. After removing duplicates, the full texts of 1,153 articles were examined. Sixty-nine of these articles met the criteria and were included in the review. These 69 articles identified 29 risk factors for arm morbidity following treatments for breast cancer. The risk of bias was evaluated using NIH study quality assessment tools. The studies reviewed were published between 2001 and 2021 and included a total of 22,886 patients who were followed up for between three months and 10 years.
CONCLUSIONS
The main risk factors for long-term morbidity are removal of lymph nodes from the axilla, body mass index >30, having undergone a mastectomy, the stage of the disease, radiation therapy, chemotherapy, infection and trauma to the affected arm after surgery. An understanding of the risk factors for prolonged arm morbidity after surgery can help doctors and therapists in making personalized decisions about the need and timing of rehabilitation treatments.
Topics: Female; Humans; Arm; Breast Neoplasms; Lymph Node Excision; Mastectomy; Morbidity; Risk Factors
PubMed: 38039404
DOI: 10.18632/oncotarget.28539 -
European Journal of Cancer (Oxford,... Dec 2023Sentinel lymph node (SLN) status is a clinically important prognostic biomarker in breast cancer and is used to guide therapy, especially for hormone receptor-positive,...
BACKGROUND
Sentinel lymph node (SLN) status is a clinically important prognostic biomarker in breast cancer and is used to guide therapy, especially for hormone receptor-positive, HER2-negative cases. However, invasive lymph node staging is increasingly omitted before therapy, and studies such as the randomised Intergroup Sentinel Mamma (INSEMA) trial address the potential for further de-escalation of axillary surgery. Therefore, it would be helpful to accurately predict the pretherapeutic sentinel status using medical images.
METHODS
Using a ResNet 50 architecture pretrained on ImageNet and a previously successful strategy, we trained deep learning (DL)-based image analysis algorithms to predict sentinel status on hematoxylin/eosin-stained images of predominantly luminal, primary breast tumours from the INSEMA trial and three additional, independent cohorts (The Cancer Genome Atlas (TCGA) and cohorts from the University hospitals of Mannheim and Regensburg), and compared their performance with that of a logistic regression using clinical data only. Performance on an INSEMA hold-out set was investigated in a blinded manner.
RESULTS
None of the generated image analysis algorithms yielded significantly better than random areas under the receiver operating characteristic curves on the test sets, including the hold-out test set from INSEMA. In contrast, the logistic regression fitted on the Mannheim cohort retained a better than random performance on INSEMA and Regensburg. Including the image analysis model output in the logistic regression did not improve performance further on INSEMA.
CONCLUSIONS
Employing DL-based image analysis on histological slides, we could not predict SLN status for unseen cases in the INSEMA trial and other predominantly luminal cohorts.
Topics: Female; Humans; Axilla; Breast Neoplasms; Deep Learning; Lymph Node Excision; Lymph Nodes; Lymphadenopathy; Lymphatic Metastasis; Sentinel Lymph Node; Sentinel Lymph Node Biopsy
PubMed: 37890350
DOI: 10.1016/j.ejca.2023.113390 -
Annals of Surgical Oncology Oct 2021Surgical axillary staging demonstrating positive nodal disease before neoadjuvant chemotherapy (NAC) necessitates axillary lymph node dissection (ALND) post-NAC. Despite...
BACKGROUND
Surgical axillary staging demonstrating positive nodal disease before neoadjuvant chemotherapy (NAC) necessitates axillary lymph node dissection (ALND) post-NAC. Despite evidence supporting post-NAC surgical staging, we hypothesized that there is persistent use of pre-NAC staging and that it is associated with aggressive clinicopathologic features and a higher rate of subsequent ALND.
PATIENTS AND METHODS
Stage I-III breast cancer patients who underwent lymph node staging surgery and received NAC between 2013 and 2017 in the National Cancer Database were included. Sequence of staging surgery and chemotherapy administration was determined. Multivariable regression was used to assess characteristics associated with pre-NAC staging. Rate of ALND was compared between those who had pre- and post-NAC surgical axillary staging.
RESULTS
In total, 120,538 met inclusion; 68% received NAC first and 32% had pre-NAC staging. Pre-NAC staging surgery was associated with younger age (age < 30 versus 40-49 years, HR 1.1) and decreased with older age (ages 70-79/80+ versus 40-49 years, HR 0.86 and 0.73). Advancing clinical T stage, lobular subtype, higher grade, and HR+/HER2- subtype were also associated with pre-NAC surgical staging. Women who underwent pre-NAC surgical staging were more likely to undergo ALND.
CONCLUSIONS
Over 30% of women underwent surgical axillary staging prior to NAC, resulting in higher rates of ALND in this cohort. While certain features suggestive of aggressive behavior (grade and T stage) were associated with pre-NAC surgical axillary staging, women with more aggressive tumor subtypes (triple negative/HER2+) were less likely to undergo pre-NAC surgical axillary staging. Pre-NAC surgical axillary staging should be performed only in rare circumstances to avoid unnecessary ALND.
Topics: Adult; Aged; Axilla; Breast Neoplasms; Female; Humans; Lymph Node Excision; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Sentinel Lymph Node Biopsy
PubMed: 34379251
DOI: 10.1245/s10434-021-10628-4 -
Chinese Clinical Oncology Feb 2023Sentinel lymph node biopsy (SLNB) at upfront surgery is the gold-standard surgical method for axillary lymph node staging in early stage breast cancer: the technique... (Review)
Review
Sentinel lymph node biopsy (SLNB) at upfront surgery is the gold-standard surgical method for axillary lymph node staging in early stage breast cancer: the technique provides adequate information regarding axillary status, with similar oncological safety and lower morbidity compared to axillary dissection, despite the false negative rates. Neoadjuvant chemotherapy (NACT), traditionally used for locally advanced breast cancer, plays an important role in the treatment of early stage breast cancer, making downstaging possible in axillary lymph node and breast cancer, thus minimizing the impact of surgery and reducing morbidity, as well as enabling patients with residual disease to be selected for adjuvant treatment. In this respect, the role of SLNB has proved controversial, particularly in view of the lack of data from randomized clinical trials on this subject. Currently, the de-escalation of axillary surgery after NACT is mainly based on retrospectives studies and false negative rates. This paper reviews current evidence on the management of axillary surgery following NACT under different circumstances, with suggested recommendations in each scenario: clinically negative nodes at diagnosis and SLNB after NACT, clinically positive nodes at diagnosis and SLNB after NACT, positive SLNB following NACT and finally the possibility of omitting axillary surgery in good responders.
Topics: Humans; Female; Sentinel Lymph Node Biopsy; Neoadjuvant Therapy; Lymphatic Metastasis; Neoplasm Staging; Lymph Node Excision; Lymph Nodes; Breast Neoplasms
PubMed: 36922355
DOI: 10.21037/cco-22-110 -
Breast (Edinburgh, Scotland) Oct 2023The increasing use and effectiveness of primary systemic treatment (PST) enables tailored locoregional treatment. About one third of clinically node positive (cN+)...
The increasing use and effectiveness of primary systemic treatment (PST) enables tailored locoregional treatment. About one third of clinically node positive (cN+) breast cancer patients achieve pathologic complete response (pCR) of the axilla, with higher rates observed in Human Epidermal growth factor Receptor (HER)2-positive or triple negative (TN) breast cancer subtypes. Tailoring axillary treatment for patients with axillary pCR is necessary, as they are unlikely to benefit from axillary lymph node dissection (ALND), but may suffer complications and long-term morbidity such as lymphedema and impaired shoulder motion. By combining pre-PST and post-PST axillary staging techniques, ALND can be omitted in most cN + patients with pCR. Different post-PST staging techniques (MARI/TAD/SN) show low or ultra-low false negative rates for detection of residual disease. More importantly, trials using the MARI (Marking Axillary lymph nodes with Radioactive Iodine seeds) procedure or sentinel lymph node biopsy (SLNB) as axillary staging technique post-PST have already shown the safety of tailoring axillary treatment in patients with an excellent response. Tailored axillary treatment using the MARI procedure in stage I-III breast cancer resulted in 80% reduction of ALND and excellent five-year axillary recurrence free interval (aRFI) of 97%. Similar oncologic outcomes were seen for post-SLNB in stage I-II patients. The MARI technique requires only one invasive procedure pre-NST and a median of one node is removed post-PST, whereas for the SLNB and TAD techniques two to four nodes are removed. A disadvantage of the MARI technique is its use of radioactive iodine, which is subject to extensive regulations.
Topics: Humans; Female; Sentinel Lymph Node Biopsy; Breast Neoplasms; Iodine Radioisotopes; Neoadjuvant Therapy; Thyroid Neoplasms; Lymph Node Excision; Lymph Nodes; Triple Negative Breast Neoplasms; Axilla; Neoplasm Staging; Sentinel Lymph Node
PubMed: 37562108
DOI: 10.1016/j.breast.2023.06.011 -
World Journal of Surgical Oncology Apr 2021Due to the high variability of incidence and prevalence of intra-mammary lymph nodes (IMLNs), they might be overlooked during clinical and radiological examinations....
BACKGROUND
Due to the high variability of incidence and prevalence of intra-mammary lymph nodes (IMLNs), they might be overlooked during clinical and radiological examinations. Properly characterizing pathological IMLNs and detecting the factors that might influence their prevalence in different stages of breast cancer might aid in proper therapeutic decision-making and could be of possible prognostic value.
METHODS
Medical records were reviewed for all breast cancer patients treated at the National Cancer Institute of Cairo University between 2013 and 2019. Radiological, pathological, and surgical data were studied.
RESULTS
Intra-mammary lymph nodes were described in the final pathology reports of 100 patients. Five cases had benign breast lesion. Three cases had phyllodes tumors and two cases had ductal carcinoma in situ (DCIS). All ten cases were excluded. The remaining 90 cases all had invasive breast cancer and were divided into two groups: one group for patients with malignant IMLNs (48) and another for patients with benign IMLNs (42). Pathological features of the malignant IMLN group included larger mean tumor size in pathology (4.7 cm), larger mean size of the IMLN in pathology (1.7 cm), higher incidence of lympho-vascular invasion (65.9%), and higher rate of extracapsular extension in axillary lymph nodes (57.4%). In addition, the pathological N stage was significantly higher in the malignant IMLN group.
CONCLUSION
Clinicians frequently overlook intra-mammary lymph nodes. More effort should be performed to detect them during preoperative imaging and during pathological processing of specimens. A suspicious IMLN should undergo a percutaneous biopsy. Malignant IMLNs are associated with advanced pathological features and should be removed during surgery.
Topics: Axilla; Breast; Breast Neoplasms; Humans; Lymph Nodes; Lymphatic Metastasis; Prognosis; Sentinel Lymph Node Biopsy
PubMed: 33849561
DOI: 10.1186/s12957-021-02219-0