De-escalation Of Axillary Surgery Research Articles

Prognostic Importance of Axillary Lymph Node Response to Neoadjuvant Systemic Therapy on Axillary Surgery in Breast Cancer-A Single Center Experience.

Neoadjuvant systemic treatment (NST) is the standard treatment for HER2+, triple-negative (TN), and highly proliferative luminal HER2- early breast cancer. Pathologic complete response (pCR) after NST is associated with improved outcomes. We evaluated the predictive factors for axillary-pCR (AXpCR) and its impact on the extent of axillary node surgery. This retrospective study included 92 patients (median age of 50.4 years) with an initially node-positive disease. Patients were treated with molecular subtype-specific NST (4.3% were luminal A-like, 28.3% luminal HER2-, 26.1% luminal HER2+, 18.5% HER2+ non-luminal, and 22.8% TN). Axillary-, breast- and total-pCR were achieved in 52.2%, 48.9%, and 38% of patients, respectively. In a binary logistic regression model for the whole population, the only independent factor significantly associated with AXpCR was breast-pCR (OR 7.4; 95% CI 2.6-20.9; p < 0.001). In patients who achieved breast-pCR, aggressive subtypes (HER2+ and TN; OR 11.24) and clinical tumor stage (OR 0.10) had a significant impact on achieving AXpCR. Axillary lymph node dissection was avoided in 53.3% of patients. In conclusion, in node-positive patients with HER2+ and TN subtypes, who achieved breast-pCR after NST, de-escalation of axillary surgery could be considered in most cases.

Comparison of clinical characteristics between ACOSOG Z0011-eligible cohort and sentinel lymph node-positive breast cancer patients in Hong Kong.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial resulted in de-escalation of axillary surgery among early-stage breast cancer patients with low-volume sentinel lymph node (SLN) disease undergoing breast-conserving surgery and radiation therapy. Nevertheless, the mastectomy rate in the Chinese population remains high. This study compared the clinical characteristics of the ACOSOG Z0011-eligible cohort with SLN-positive breast cancer patients in Hong Kong. This retrospective analysis of a prospectively maintained database at a university-affiliated breast cancer centre in Hong Kong was performed from June 2014 to May 2019. The database included all patients with clinical tumour (T) stage T1 or T2 invasive breast carcinoma, no palpable adenopathy, one or two positive SLNs on histological examination, and no prior neoadjuvant systemic treatment. Comparisons were made between the mastectomy and breast-conserving treatment groups in our cohort, along with the sentinel-alone arm in the ACOSOG Z0011 trial. One hundred and seventy-one patients met the inclusion criteria: 112 underwent mastectomy and 59 underwent breast-conserving treatment. Our mastectomy group had higher prevalences of T2 tumours (P<0.001), lymphovascular invasion (P<0.001), and SLN macrometastases (P=0.004) compared with the ACOSOG Z0011 cohort. However, in our patient population, mean pathological size slightly differed between the mastectomy and breast-conserving treatment groups (2.2 cm vs 1.8 cm; P=0.005). Other histopathological features were similar. This study demonstrated that clinicopathological features were comparable between SLN-positive breast cancer patients undergoing mastectomy and those undergoing breast-conserving treatment. Low-risk SLN-positive mastectomy patients may safely avoid completion axillary lymph node dissection.

Deep learning to predict breast cancer sentinel lymph node status on INSEMA histological images

BackgroundSentinel 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. MethodsUsing 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. ResultsNone 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. ConclusionsEmploying 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.

Prediction of negative axillary node clearance by sentinel node-positive to total node ratio: a retrospective cohort study.

Increasing evidence suggests that de-escalation of axillary surgery is safe, without significantly impacting patient outcome. Obtaining positive lymph nodes at a sentinel lymph node biopsy (SNB) can guide decisions toward the requirement of axillary nodal clearance (ANC). However, methods to predict how many further nodes will be positive are not available. This study investigates the feasibility of predicting the likelihood of a negative ANC based on the ratio between positive nodes and the total number of lymph nodes excised at SNB. Retrospective data from January 2017 to March 2022 was collected from electronic medical records. Patients with oestrogen receptor (ER) positive and HER2 negative receptor disease were included in the study. ER-negative and HER2-positive disease was excluded, alongside patients who had chemotherapy before ANC. Of 102 patients, 58.8% (n=60) had no macrometastasis at ANC. On average, 2.76 lymph nodes were removed at SNB. A higher SNB ratio of positive to total nodes [OR 11.09 (CI 95% 2.33-52.72), P=0.002] had a significant association with positive nodes during ANC. SNB ratio less than or equal to 0.33 (1/3) had a specificity of 79.2% in identifying cases that later had a negative completion ANC, with a 95.8% specificity of no further upgrade of nodal staging. A low SNB ratio of less than 0.33 (1/3) has a high specificity in excluding the upgradation of nodal staging on completion of ANC, with a false-negative rate of less than 5%. This may be used to identify patients with a low risk of axillary metastasis, who can avoid ANC.

The Role of Sentinel Lymph Node Biopsy in Breast Cancer Patients Who Become Clinically Node-Negative Following Neo-Adjuvant Chemotherapy: A Literature Review.

In clinically node-positive (cN+) breast cancer (BC) patients who become clinically node-negative (cN0) following neoadjuvant chemotherapy (NACT), sentinel lymph node biopsy (SLNB) after lymphatic mapping with lymphoscintigraphy is not widely accepted; therefore, it has become a topic of international debate. Our literature review aims to evaluate the current use of this surgical practice in a clinical setting and focuses on several studies published in the last six years which have contributed to the assessment of the feasibility and accuracy of this practice, highlighting its importance and oncological safety. We have considered the advantages and disadvantages of this technique compared to other suggested methods and strategies. We also evaluated the role of local irradiation therapy after SLNB and state-of-the-art SLN mapping in patients subjected to NACT. A comprehensive search of PubMed and Cochrane was conducted. All studies published in English from 2018 to August 2023 were evaluated. Breast units are moving towards a de-escalation of axillary surgery, even in the NACT setting. The effects of these procedures on local irradiation are not very clear. Several studies have evaluated the oncological outcome of SLNB procedures. However, none of the alternative techniques proposed to lower the false negative rate (FNR) of SLNB are significant in terms of prognosis. Based on these results, we can state that lymphatic mapping with SLNB in cN+ BC patients who become clinically node-negative (ycN0) following NACT is a safe procedure, with a good prognosis and low axillary failure rates.

Invited Commentary: De-escalation of axillary surgery in node-positive breast cancer patients after neoadjuvant therapy

The surgical management of patients presenting with node-positive breast cancer who receive neoadjuvant chemotherapy has been an area of focus and debate as neoadjuvant chemotherapy regimens increasingly eradicate the nodal disease. Axillary lymph node dissection has been the standard surgical approach, which carries morbidity risks of lymphedema, pain, and limited range of motion. Although there has been interest in de-escalating axillary surgery, hurdles must be addressed. The first is finding an accurate way to assess nodal response. Many trials have looked at this using the false negative rate as the defining endpoint, all finding that surgical techniques such as using a dual tracer technique, adding immunohistochemistry, and ensuring removal of the node that had biopsy-confirmed disease at diagnosis can impact the accuracy of minimally invasive approaches to evaluate the axilla. However, the second hurdle of defining the impact of minimizing axillary surgery on locoregional and overall outcomes has yet to be answered. Ongoing trials may give us insights over the next few years.

167P Deep learning-based whole slide image analysis to predict sentinel node status in the INSEMA cohort

As further de-escalation of axillary surgery is ongoing, new biomarkers that convey the same prognostic information as sentinel node status are called for. To predict sentinel node status, we trained a deep learning (DL) image analysis model on H&E-stained whole slide images (WSIs) of primary tumors. For training, we used cases from the INSEMA standard arm (n=762, ca. 94 % HR+/HER2-, 3.5 % G3, less than 1% pT3/4, 13 % SLN-positive) and a cohort from the Women’s Clinic in Mannheim, Germany (n=150, all HR+/HER2-, G2, pT1/2, ca. 16 % SLN positive). We also fitted a logistic regression with clinical data (pT stage, Ki-67) for this task. Models were tested on a holdout INSEMA set (n=381), and the image model also on the higher risk TCGA BRCA cohort (n=650, ca. 72% HR+, ca. 55% SLN+). Vice versa, we trained a model on TCGA WSIs and tested it on the other cohorts. During training, the image and the clinical model yielded Areas under the Receiver Operating Characteristic Curve (AUROCs) of 0.62 and of 0.77 on the Mannheim WSIs, respectively. However, performance of the image model was random on the INSEMA (determined by blinded assessment) and TCGA BRCA test sets. The clinical classifier retained an AUROC of 0.62 on the INSEMA set. Inclusion of the image classifier output in the logistic regression did not improve performance on INSEMA. The image model trained on TCGA also yielded random performance on the INSEMA and Mannheim cohorts. Image analysis algorithms trained on H&E stains of the primary tumors from INSEMA or TCGA using established techniques were unable to predict sentinel status, which may suggest a lack of systematic histological differences by lymph node status in these cohorts. Thus, DL-based WSI analysis may not be a good strategy to replace sentinel node assessment, especially in low- to intermediate-risk, hormone receptor-positive breast cancer.

Axillary staging in node-positive breast cancer converting to node negativity through neoadjuvant chemotherapy: Current evidence and perspectives.

Over the recent years, axillary staging of initially node-positive breast cancer patients converting to clinical node negativity after neoadjuvant chemotherapy has seen rapid changes. This narrative review aims to give a contemporary overview over published evidence and clinical practice, and thus provide some guidance to the surgical community in the process of re-evaluating and re-shaping surgical practice. The search strategy aimed at finding relevant studies. Only articles in English were considered. The introduction of modern techniques offer more precise staging surgery and thus hopefully reduced arm morbidity. Clinical practice has however diverged both within countries and internationally. While some countries have adapted de-escalated axillary staging techniques such as targeted axillary dissection, targeted lymph node biopsy or sentinel lymph node biopsy, others continue to recommend a full axillary lymph node dissection. With the implementation of new techniques, many questions arise, regarding aspects of oncological safety, technical performance, budget and practicality, patient selection and indications for different levels of axillary staging procedures. There is a growing body of evidence on de-escalation of axillary surgery in the setting of cN+ → ycN0 breast cancer treated with neoadjuvant chemotherapy. However, standards differ between countries and future studies are necessary to fully assess the optimal strategy for these patients.

Trends of axillary surgery in breast cancer patients with axillary lymph node metastasis: a comprehensive single-center retrospective study.

Based on the results of previous trials, de-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) has increased in patients with axillary lymph node (ALN) metastasis at presentation. This study aimed to review the trends of axillary surgery by time period and molecular subtype in patients with ALN metastasis. We analyzed the rates of sentinel lymph node biopsy (SLNB) and ALN dissection (ALND) based on time period and subtype. The time period was divided into 3 subperiods to determine the rate of axillary surgery type over time (period 1, from 2009 to 2012; period 2, from 2013 to 2016; and period 3, from 2017 to July 2019). From 2009 to July 2019, 2,525 breast cancer patients underwent surgery. Based on subtype, the ALND rate of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) disease decreased by 13.0% from period 1 to period 3 (period 1, 99.4%; period 2, 97.5%; and period 3, 86.4%; P < 0.001). Conversely, the ALND rate in HR+/HER2+, HR-/HER2+, and triple-negative breast cancer (TNBC) significantly decreased by 43.7%, 48.8%, and 35.2% in period 1, period 2, and period 3, respectively (P < 0.001). In the patient group receiving NAC, HR+/HER2- had a significantly higher ALND rate (84.1%) than HR+/HER2+, HR-/HER2+, and TNBC (60.8%, 62.3%, and 70.7%, respectively; P < 0.001). The SLNB rate in patients with ALN metastasis has increased over time. However, the ALND rate in HR+/HER2- was significantly higher than in other subtypes.

Machine Learning-Based Epigenetic Classifiers for Axillary Staging of Patients with ER-Positive Early-Stage Breast Cancer.

In the era of molecular stratification and effective multimodality therapies, surgical staging of the axilla is becoming less relevant for patients with estrogen receptor (ER)-positive early-stage breast cancer (EBC). Therefore, a nonsurgical method for accurately predicting lymph node disease is the next step in the de-escalation of axillary surgery. This study sought to identify epigenetic signatures in the primary tumor that accurately predict lymph node status. We selected a cohort of patients in The Cancer Genome Atlas (TCGA) with ER-positive, HER2-negative invasive ductal carcinomas, and clinically-negative axillae (n = 127). Clinicopathological nomograms from the Memorial Sloan Kettering Cancer Center (MSKCC) and the MD Anderson Cancer Center (MDACC) were calculated. DNA methylation (DNAm) patterns from primary tumor specimens were compared between patients with pN0 and those with > pN0. The cohort was divided into training (n = 85) and validation (n = 42) sets. Random forest was employed to obtain the combinations of DNAm features with the highest accuracy for stratifying patients with > pN0. The most efficient combinations were selected according to the area under the curve (AUC). Clinicopathological models displayed a modest predictive potential for identifying > pN0 disease (MSKCC AUC 0.76, MDACC AUC 0.69, p = 0.15). Differentially methylated sites (DMS) between patients with pN0 and those with > pN0were identified (n = 1656). DMS showed a similar performance to the MSKCC model (AUC = 0.76, p = 0.83). Machine learning approaches generated five epigenetic classifiers, which showed higher discriminative potential than the clinicopathological variables tested (AUC > 0.88, p < 0.05). Epigenetic classifiers based on primary tumor characteristics can efficiently stratify patients with no lymph node involvement from those with axillary lymph node disease, thereby providing an accurate method of staging the axilla.

Incidence of treatment effect in patients with an axillary pathologic complete response after neoadjuvant chemotherapy for breast cancer

Background: De-escalation of axillary surgery following neoadjuvant chemotherapy (NACT) for patients with node positive disease at diagnosis have focused on ensuring a low false negative rate for those who undergo sentinel lymph node biopsy (SLNB) only. Histopathological evidence of treatment effect is one surrogate that supports an axillary pathological complete response (pCR). This study aimed to assess rates of histological treatment effect in patients who have an axillary pCR following axillary surgery post NACT.

De-escalation of axillary surgery: Targeted axillary dissection with Magseed localisation or sentinel node biopsy after neoadjuvant treatment in node positive patients - The west of Scotland experience

Introduction: For patients with node positive disease who are exceptional responders targeted axillary dissection (TAD) or sentinel node biopsy (SNB) may be offered for staging. We describe clinicopathological outcomes after TAD with magseed localisation (TADm), wire localisation or no preoperative localisation (TAD) or SNB in three units in the West of Scotland.

Tailored axillary surgery facilitated by axillary Magseed placement

Introduction: De-escalation of axillary surgery in the treatment of node positive breast cancer is facilitated by marking biopsy-proven involved nodes. During the POSNOC study, women with 1 or 2 imaging-abnormal lymph nodes had Magseeds inserted to ensure retrieval of the node(s) at surgery. Such imaging-abnormal lymph nodes may not mandate axillary lymph node dissection (ALND) and several trials (e.g. TAXIS) are currently in progress. We report our experience using the paramagnetic Magseed marker in this context.

Abstract ES8-2: Can radiation replace ALND after positive SLNB?

Abstract Growing recognition of the adverse impact of lymphedema on quality of life of survivors of breast cancer has motivated efforts to identify alternatives to axillary lymph node dissection. In some patients who have positive sentinel lymph nodes, radiation therapy may provide a more tolerable alternative to ALND without compromising disease control. This session will focus on the results of the key randomized trials directly evaluating this question: AMAROS and OTOASOR, as well as the implications of other trials that can help to identify patients in whom de-escalation of axillary surgery appears safe. Citation Format: R Jagsi. Can radiation replace ALND after positive SLNB? [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES8-2.

Axillary Ultrasound Evaluation in Breast Cancer Patients: A Multidisciplinary Viewpoint and Middle Ground.

Over the past decade, there has been a trend toward de-escalation of axillary surgery. Certain patients may now forego axillary lymph node dissection even in the setting of a positive sentinel lymph node biopsy (SLNB), and some patients may not even undergo a SLNB. However, there is wide variability in the imaging approach to assessing axillary lymph nodes in patients with breast cancer. Approaches range from performing axillary US in all patients with newly diagnosed breast cancer to omitting axillary imaging evaluation in all patients. This article provides a multidisciplinary middle ground approach for axillary nodal evaluation. The clinical impact and rationale for appropriate axillary nodal imaging are discussed and an imaging algorithm is proposed.

Axillary surgery in node-positive breast cancer

Long-term follow-up data from multicenter phase III non-inferiority trials confirmed the safety of omission of axillary dissection in selected patients with clinically node-negative, sentinel node-positive breast cancer. Several ongoing trials investigate extended eligibility of the Z0011 protocol in the adjuvant setting. De-escalation of axillary surgery in patients with clinically node-positive breast cancer is currently limited to the neoadjuvant setting, where the sentinel procedure is used to determine nodal pathological complete response. Targeted axillary dissection lowers the false-negative rate of the sentinel procedure, which, however, is consistently associated with a very low risk of axillary recurrence in several recent single-center series. Axillary dissection remains standard care in patients with residual disease after neoadjuvant chemotherapy while the results of Alliance A011202 are pending. The TAXIS trial investigates the role of tailored axillary surgery in patients with clinically node-positive breast cancer, a novel concept designed to selectively remove positive nodes in the adjuvant and neoadjuvant setting.

Factors Associated with Nodal Pathologic Complete Response Among Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: Results of CALGB 40601 (HER2+) and 40603 (Triple-Negative) (Alliance).

De-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) requires careful patient selection. We seek to determine predictors of nodal pathologic complete response (ypN0) among patients treated on CALGB 40601 or 40603, which tested NAC regimens in HER2+ and triple-negative breast cancer (TNBC), respectively. A total of 760 patients with stage II-III HER2+ or TNBC were analyzed. Those who had axillary surgery before NAC (N = 122), or who had missing pretreatment clinical nodal status (cN) (N = 58) or ypN status (N = 41) were excluded. The proportion of patients with ypN0 disease was estimated for those with and without breast pathologic complete response (pCR) according to pretreatment nodal status. In 539 patients, the overall ypN0 rate was 76.3% (411/539) to 93.2% (245/263) in patients with breast pCR and 60.1% (166/276) with residual breast disease (RD) (P < 0.0001). For patients who were cN0 pretreatment, the ypN0 rate was 88.8% (214/241), 96.3% (104/108) with breast pCR, and 82.7% (110/133) with RD. For patients who were cN1, 66.2% (157/237) converted to ypN0, 91.7% (111/121) with breast pCR and 39.7% (46/116) with RD. For patients who were cN2/3, 65.6% (40/61) converted to ypN0, 88.2% (30/34) with breast pCR and 37.0% (10/27) with RD. On multivariable analysis, only pretreatment clinical nodal status and breast pCR/RD were associated with ypN0 status (both P < 0.0001). Breast pCR and pretreatment nodal status are predictive of ypN0 axillary nodal involvement, with < 5% residual nodal disease among cN0 patients who experience breast pCR. These findings support the incorporation of axillary surgery de-escalation strategies into NAC trials.

ASO Author Reflections: Moving the Ball Forward Toward De-Escalation of Axillary Surgery for Patients with Clinically Node-Positive Disease.

ASO Author Reflections: Moving the Ball Forward Toward De-Escalation of Axillary Surgery for Patients with Clinically Node-Positive Disease.

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.