Metastatic Axillary Lymph Nodes Research Articles

Abstract PO5-07-05: Deep learning can diagnose axillary lymph node metastases on optical virtual histologic images in breast cancer patients during surgery

Abstract Background: Reliable identification of axillary lymph node (ALN) involvement in patients with breast cancer allows for definitive axillary dissection at the time of the initial surgery, thus avoiding the need for a separate axillary surgery. However, conventional intraoperative ALN diagnostic methods are time-consuming and labor-intensive and can result in tissue destruction. Dynamic full field optical coherence tomography, also called dynamic cell imaging (DCI), has been developed and validated to offer rapid and label-free histologic approximations of metastatic and non-metastatic ALNs. In this study, we aim to optimize the diagnostic pipeline with an automated approach and present the results of using a deep learning (DL) algorithm with DCI to predict ALN status intraoperatively in patients with breast cancer. Methods: Breast cancer patients who required ALN staging were enrolled prospectively in this study. DCI was applied to bisected fresh lymph nodes in a non-destructive manner, and the specimens were subsequently sent for histopathological examination, regarded as the gold standard for comparison. A DL model was trained and fine-tuned on over 80,000 DCI images, and the results were mapped to slide level to predict ALN diagnosis. Results: Total 607 DCI slides of ALNs with 112,852 cropped patches were included in the study. The DL model was trained and validated on a dataset containing 481 slides and tested on an independent testing dataset with 126 slides. In the test set, the DL algorithm yielded accuracy for prediction of ALN status, with sensitivity and specificity of 91.9% and 95.5% and an area under the receiver operating characteristic curve (AUC) of 0.937 (95% confidence interval [CI]: 0.912-0.957) at slide level. Conclusion: These results demonstrate that the integration of DCI with DL is rapid, reduces labor requirements and minimizes tissue destruction. Meanwhile, this algorithm had high classification accuracy to predict the metastatic burden of ALNs for patients with breast cancer. Citation Format: Shuwei Zhang, Houpu Yang, Jin Zhao, Shu Wang. Deep learning can diagnose axillary lymph node metastases on optical virtual histologic images in breast cancer patients during surgery [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-07-05.

Abstract PO3-02-09: Breast cancer in women under the age of 40 years.A south Wales UK reflection on incidence, tumour biology and outcomes over 10 years

Abstract Introduction: The incidence of breast cancer in the under 40-year-old age group is approximately 7% (Anders et al., 2009). Studies suggests that the management of Breast cancer in adolescent and young women is more challenging, with this age group under-represented in clinical trials. We investigated the management and outcomes of a cohort of 98 patients seen between 2013 and 2023 in the Hywel Dda NHS University Health Board, Wales, UK. Methods: A retrospective review was performed. Demographic, surgical and outcome data for patients under the age of 40 years was collated and analysed. Results: The cohort size was 98, representing 2.45% of the breast cancer population treated in the Health Board during this timeframe. The age of the cohort ranged from 23 years to 40 years, 12 out of 98 (12.24%) were under 30 years. Mean age was 35.28 years. Unfortunately, 8.16% (8/98) of the cohort died between 12 months to 96 months. Two patients were lost to follow up. Tumour biology results confirmed that most of the cohort had invasive ductal carcinoma (IDC), with 13.27% Grade 1, 37.76 % Grade 2 and 40.82% Grade 3. There were 4 (4.08%) invasive lobular carcinomas (ILC) in the cohort, 2 Grade 2 and 2 Grade 3. The remaining tumour groups were, 1 case of DCIS (Grade-2 intermediate grade), Grade-1 mucinous carcinoma, 1 Grade-1 ductal-lobular breast cancer and 1 medullary carcinoma. 10.20% of the cohort had triple negative cancers (ER, PR, Her-2 negative) and 10.20% were ER, PR, HER2 positive [Triple positive]. 40.82% metastatic axillary lymph nodes involvement on histology either on presentation or following sentinel node biopsy. Operative details confirmed that the 51.02% (50/98) of the cohort underwent mastectomy. 10 out of those 50 patients underwent contralateral risk reducing mastectomy .46 patients had breast conservation surgery. One patient is awaiting surgery, the other has been diagnosed with metastatic breast cancer at diagnosis. Patients received both neoadjuvant and adjuvant chemotherapy depending on initial assessment and MDT discussion [ACP, FEC, Taxane and platinum-based chemotherapy, Anti Her-2]. NAC was provided for all HER-2+ patients. Endocrine treatment and ovarian function suppression, and adjuvant Radiotherapy was also given. Some patients had a complete pathological response to NAC; however, some did not respond well. In addition, 10.20% of the cohort underwent bilateral salpingo-oophorectomy during their treatment and follow up. Genetic assessment confirmed that 3/98 (3.06%) of the cohort were BRCA2 positive, one BRCA1 carrier, 2 patients were BRCA negative, two have been referred for genetics assessment and two still awaiting consultation with genetics. In one patient somatic mutation was found in PTEN, BIRC3, HRAS, TP53, PMS, (5 gene panel). In one patient, panel was reassuring. PALB-2, TP53 was also reassuring in one patient. One patient who passed away at the age of 34 did not have any alteration in 5 gene panel. Three patients developed other malignancies during the 10-year period: 1 uterine, 1 cervix, 1 papillary thyroid cancer. 6/98 (6.12%) developed metastatic disease and one developed a local recurrence. One patient developed metastasis while pregnant, and by contrast one patient gave birth to a baby after stopping her endocrine treatment. One patient who passed away had no response to neoadjuvant chemotherapy (NAC). Discussion: The results from the cohort confirm that the incidence of TNBC and triple positive cancers is like that found in the general breast cancer population (10-15%). Our engagement with the genetics team has increased since the initial 2013 cohort. There is now an established system for referrals for young women with breast cancer. It is probably not surprising that other primary invasive cancers were found, whilst on follow up. Citation Format: Sohail Khan, Saira Khawaja, Yousef Sharaiha, Asma Munir, Anita Huws. Breast cancer in women under the age of 40 years.A south Wales UK reflection on incidence, tumour biology and outcomes over 10 years [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-09.

Abstract PO4-22-08: Ten-Year Oncologic Outcomes in T1-3N1 Breast Cancer After Targeted Axillary Sampling: A Retrospective Study

Abstract Background Targeted axillary sampling (TAS) is a new surgical concept for the assessment of axillary lymph node status in breast cancer that is hypothesized to be more effective at minimizing postoperative morbidities than axillary lymph node dissection (ALND), provided the metastatic axillary lymph node can be accurately detected without missing data; however, the oncologic outcomes over long-term follow-up have not been sufficiently investigated. This was a retrospective analysis to evaluate the 10-year oncologic outcomes in T1-3N1 breast cancer after TAS. Methods Clinically, we defined TAS as removal of a bunch of ALNs located around SLNs and targeted LNs, but without full exposure of the axillary vein, long thoracic nerve and thoracodorsal nerve. Between 2008 and 2013, 230 female patients with cT1-3N1 breast cancer underwent breast and axillary surgery (ALND, n = 171; TAS, n = 59) at our institute. After TAS was applied, additional axillary radiotherapy was performed. Various postoperative complications, including postoperative seroma, lymphedema, and 10-year oncological outcomes, were evaluated and compared between the ALND and TAS groups. Results Although overall survival during the 10-year follow-up period was better in the TAS group, there was no statistically significant difference in oncologic outcomes, including locoregional recurrence, distant metastasis, and overall survival (p = 0.395, 0.818, and 0.555, respectively). Furthermore, the incidence of lymphedema on the ipsilateral arm was significantly higher in the ALND group (p < 0.001). Conclusions The 10-year oncological outcomes of TAS were not inferior to those of conventional ALND in T1-3N1 breast cancers; however, the incidence of lymphedema was significantly higher in the ALND group. Citation Format: Byeongju Kang, Jeeyeon Lee, Yee Soo Chae, Ho Yong PARK, Jin Hyang Jung. Ten-Year Oncologic Outcomes in T1-3N1 Breast Cancer After Targeted Axillary Sampling: A Retrospective Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-22-08.

Abstract PO2-23-04: Magnetic Seeds, used to Locate the Metastatic Axillary Lymph Node placed before Neoadjuvant Chemotherapy for Breast Cancer Treatment, do not interfere the pre-surgical MRI Breast response assessment

Abstract Background: Axillary management in clinically node-positive patients who converted to ycN0 after neoadjuvant chemotherapy (NAC) for breast cancer (BC) remains under research with the aim of de-escalation of axillary lymph node dissection (ALND). A magnetic seed is one of the several positive lymph nodes marking techniques used in targeted axillary dissection (TAD) for patients with cN1 breast cancer undergoing neoadjuvant systemic therapy. It has been criticized for its potential masking effect due to the artefact it produces in the MRI sequences used to assess a proper breast response. This study evaluates if the magnetic seeds placed before NAC for guided TAD have influenced in the breast MRI response assessments. Methods: From October 2021 to June 2023, patients with cT0-4 cN1 breast cancer who were candidates for primary systemic treatment were prospectively recruited. Once a breast lesion and axillary node positivity were confirmed, a based hydrogel marker and a magnetic seed, respectively, were placed prior NAC. Once systemic treatment was completed, imaging techniques were used to assess the response, with MRI being the imaging technique of choice to assess breast response and axillary ultrasound the imaging technique of choice to assess axillary response. Surgical pathological confirmation of response in the axilla was by TAD, including sentinel lymph node and magnetic clipped node resection. Results: A total of 43 patients were included and their characteristics are shown in Table 1. In 16 patients (37%) the tumour was located in the upper outer quadrant (UOQ). In this group, the susceptibility artefact produced by the magnetic seed in the MRI created a black hole obscuring the axilla with a mean diameter of 69 mm (range: 57-76 mm). In no case did the halo interfere with the correct MRI visualisation of the breast marker. By MRI, the mean distance of the artifact halo from the breast marker or residual breast lesion was 40 mm (range: 13-79 mm). Overall, complete radiological response (ycCR) was reported in 20 patients (46%), breast only in 21 (49%) and axilla only in 38 (88%) patients. In 5 patients, preoperative axillary ultrasound revealed residual axillary disease, confirmed by FNA, lead to direct ALND. In the remaining 38 patients the axillary TAD assessment was completed. In all cases, the magnetic clipped node was successfully surgically removed. Pathological complete response (pCR) was confirmed in 9 (21%), breast only in 11 (26%) and axilla only in 13 (30%) patients. MRI diagnostic performance in detecting residual breast disease after NAC was not altered by the magnetic clipped node artifact when comparing the tumour location in the UOQ to the other quadrants (AUC 0.764 vs. 0.702; p=0.698). Conclusions: Surgical axillary staging remains the most reliable method for assessing the axillary response after NAC. Target axillary dissection guided by magnetic seed placed before NAC is an effective and accurate technique. The artifact generated in the MRI does not interfere with the pre-surgical breast response assessment after neoadjuvant systemic treatment. Table 1: Patients and tumor characteristics Citation Format: Martin Espinosa-Bravo, Joaquin Rivero Deniz, Clara Morales Comas, Javier de la Torre Fernandez de Vega, Irene Vives Rosello, Enrica Esposito, Vicente Peg Camara, María De Les Neus Rus Calafell, Ignacio Miranda Gomez, Christian Siso Raber. Magnetic Seeds, used to Locate the Metastatic Axillary Lymph Node placed before Neoadjuvant Chemotherapy for Breast Cancer Treatment, do not interfere the pre-surgical MRI Breast response assessment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-04.

Deep Learning Prediction of Axillary Lymph Node Metastasis in Breast Cancer Patients Using Clinical Implication-Applied Preprocessed CT Images.

Background: Accurate detection of axillary lymph node (ALN) metastases in breast cancer is crucial for clinical staging and treatment planning. This study aims to develop a deep learning model using clinical implication-applied preprocessed computed tomography (CT) images to enhance the prediction of ALN metastasis in breast cancer patients. Methods: A total of 1128 axial CT images of ALN (538 malignant and 590 benign lymph nodes) were collected from 523 breast cancer patients who underwent preoperative CT scans between January 2012 and July 2022 at Hallym University Medical Center. To develop an optimal deep learning model for distinguishing metastatic ALN from benign ALN, a CT image preprocessing protocol with clinical implications and two different cropping methods (fixed size crop [FSC] method and adjustable square crop [ASC] method) were employed. The images were analyzed using three different convolutional neural network (CNN) architectures (ResNet, DenseNet, and EfficientNet). Ensemble methods involving and combining the selection of the two best-performing CNN architectures from each cropping method were applied to generate the final result. Results: For the two different cropping methods, DenseNet consistently outperformed ResNet and EfficientNet. The area under the receiver operating characteristic curve (AUROC) for DenseNet, using the FSC and ASC methods, was 0.934 and 0.939, respectively. The ensemble model, which combines the performance of the DenseNet121 architecture for both cropping methods, delivered outstanding results with an AUROC of 0.968, an accuracy of 0.938, a sensitivity of 0.980, and a specificity of 0.903. Furthermore, distinct trends observed in gradient-weighted class activation mapping images with the two cropping methods suggest that our deep learning model not only evaluates the lymph node itself, but also distinguishes subtler changes in lymph node margin and adjacent soft tissue, which often elude human interpretation. Conclusions: This research demonstrates the promising performance of a deep learning model in accurately detecting malignant ALNs in breast cancer patients using CT images. The integration of clinical considerations into image processing and the utilization of ensemble methods further improved diagnostic precision.

Predictors of Unilateral Arm Lymphedema in Non-obese Locoregionally Advanced Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy, Modified Radical Mastectomy, and Postoperative Irradiation.

The most dreaded long-term complication of axillary lymph node dissection remains upper arm lymphedema. Our study has strategized the three most common identified causes of post treatment arm lymphedema, i.e., obesity, radiation, and neoadjuvant chemotherapy and tried to identify the histopathological and clinical or surgical factors which can predict arm lymphedema. This is a prospective observational study was conducted at a tertiary care referral centre in India, with strict inclusion criteria of BMI <30 kg/m2, age <75 years, presence of metastatic axillary node proven by FNAC, received anthracycline based neoadjuvant chemotherapy and postoperative nodal irradiation, and completed 24 months of regular follow-up. Total of 70 patients were included in the study. The mean age of the patients was 50.3 years (±12.9). lymphovascular invasion, total number of lymph nodes removed from level III, total number of days drain was left in situ and maximum drain output were found to be significantly (p<0.05) associated with arm lymphedema. In patients undergoing modified radical mastectomy with level III dissection, and postoperative irradiation, the incidence of unilateral arm lymphedema is significantly influenced by several clinicopathological factors like the total number of lymph nodes removed in level III, higher maximal drain output, prolonged duration of drain placement and the presence of lymphovascular invasion.

Predicting three or more metastatic nodes using contrast-enhanced lymphatic US findings in early breast cancer

ObjectivesTo develop and validate a nomogram for predicting ≥ 3 metastatic axillary lymph nodes (ALNs) in early breast cancer with no palpable axillary adenopathy by clinicopathologic data, contrast-enhanced (CE) lymphatic ultrasound (US), and grayscale findings of sentinel lymph nodes (SLNs).Materials and methodsWomen with T1-2N0 invasive breast cancer were consecutively recruited for the CE lymphatic US. Patients from Center 1 were grouped into development and internal validation cohorts at a ratio of 2:1. The external validation cohort was constructed from Center 2. The clinicopathologic data and US findings of SLNs were analyzed. A nomogram was developed to predict women with ≥ 3 metastatic ALNs. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration curve analysis.ResultsOne hundred seventy-nine from Center 1 were considered the development cohorts. The remaining 90 participants from Center 1 were internal cohorts and 197 participants from Center 2 were external validation cohorts. The US findings of no enhancement (odds ratio (OR), 15.3; p = 0.01), diffuse (OR, 19.1; p = 0.01) or focal eccentric (OR, 27.7; p = 0.003) cortical thickening, and absent hilum (OR, 169.7; p < 0.001) were independently associated with ≥ 3 metastatic ALNs. Compared to grayscale US or CE lymphatic US alone, the nomogram showed the highest AUC of 0.88 (0.85, 0.91). The nomogram showed a calibration slope of 1.0 (p = 0.80–0.81; Brier = 0.066–0.067) in validation cohorts in predicting ≥ 3 metastatic ALNs.ConclusionPatients likely to have ≥ 3 metastatic ALNs were identified by combining the lymphatic and grayscale US findings of SLNs. Our nomogram could aid in multidisciplinary treatment decision-making.Trial registrationThis trial is registered on www.chictr.org.cn: ChiCTR2000031231. Registered March 25, 2020.Critical relevance statementA nomogram combining lymphatic CEUS and grayscale US findings of SLNs could identify early breast cancer patients with low or high axillary tumor burden preoperatively, which is more applicable to the Z0011 era. Our nomogram could be useful in aiding multidisciplinary treatment decision-making for patients with early breast cancer.Key points• CEUS can help identify and diagnose SLN in early breast cancer preoperatively.• Combining lymphatic and grayscale US findings can predict axillary tumor burden.• The nomogram showed a high diagnostic value in validation cohorts.Graphical

Evaluation of Approaches for the Assessment of HER2 Expression in Breast Cancer by Radionuclide Imaging Using the Scaffold Protein [99mTc]Tc-ADAPT6.

Due to its small size and high affinity binding, the engineered scaffold protein ADAPT6 is a promising targeting probe for radionuclide imaging of human epidermal growth factor receptor type 2 (HER2). In a Phase I clinical trial, [99mTc]Tc-ADAPT6 demonstrated safety, tolerability and capacity to visualize HER2 expression in primary breast cancer. In this study, we aimed to select the optimal parameters for distinguishing between breast cancers with high and low expression of HER2 using [99mTc]Tc-ADAPT6 in a planned Phase II study. HER2 expression was evaluated in primary tumours and metastatic axillary lymph nodes (mALNs). SPECT/CT imaging of twenty treatment-naive breast cancer patients was performed 2 h after injection of [99mTc]Tc-ADAPT6. The imaging data were compared with the data concerning HER2 expression obtained by immunohistochemical evaluation of samples obtained by core biopsy. Maximum Standard Uptake Values (SUVmax) afforded the best performance for both primary tumours and mALNs (areas under the receiver operating characteristic curve (ROC AUC) of 1.0 and 0.97, respectively). Lesion-to-spleen ratios provided somewhat lower performance. However, the ROC AUCs were still over 0.90 for both primary tumours and mALNs. Thus, lesion-to-spleen ratios should be further evaluated to find if these could be applied to imaging using stand-alone SPECT cameras that do not permit SUV calculations.

The Prognostic Value of Tumor Budding in Breast Biopsies and its Relationship with Survival: A Cross Sectional Study

Abstract: Background: In 1954 Imai described Tumor Budding (TB), as a tumor sprouting at the invasive tumor front of colorectal carcinomas. TB is associated with poor prognosis. TB has prognostic importance in invasive ductal carcinoma of the breast. Objective: The present study aims to examine TB in breast needle core biopsy specimens with invasive ductal type carcinoma, and its relationship with other clinicopathological parameters and overall survival. Materials and Methods: From February 2015 to December 2022, patients who had undergone breast carcinoma surgery at the Bolu Abant Izzet Baysal Training and Research Hospital and had preoperative needle core biopsies at the same center were retrospectively analyzed. Needle core biopsy slides were re-evaluated for TB. Tumor size, and nodal status, were retrieved from pathology reports. Overall survival was considered. Analysis of the data was done with statistical software (SPSS 18.0 for Windows, IBM Inc., Chicago, IL, USA). Results: 122 patients were enrolled in the study. The mean age of the study and control groups were 55±12 years and 54±11 years, respectively. TB was identified in 68 (55%) patients; the rest 54 (45%) patients didn’t have any TB. The median value of the metastatic axillary lymph node in the TB absent group was 0 (0-51); in the TB group was 1 (0-21), and this was statistically significant (p=0.03). Lymphovascular invasion was detected in 33 patients (48.5%) in the TB present group and in 14 patients (25.9%) in the TB absent group. That was statistically significant (p=0.01). In the overall survival analysis, mean survival times were lower in the TB group compared to the TB absent group, but it was not statistically significant (p=0.33). Conclusion: In conclusion, tumor budding is a robust prognostic indicator; therefore, assessing tumor budding especially in core needle biopsy specimens will be very helpful for individual treatment options.

Correlation Between Quantitative Parameters Obtained by Dual Energy Spectral CT and Prognostic Histopathological Factors and Biomarkers in Breast Cancer

Rationale and ObjectivesTo investigate the correlation between quantitative parameters obtained by dual energy spectral computed tomography (DESCT) and various histopathological factors and biomarkers associated with the prognosis of breast cancer. Materials and MethodsQuantitative parameters such as iodine content (IC), normalized IC (nIC), iodine enhancement (IE) and normalized IE (nIE) were measured on virtual monochromatic images and iodine mapping images obtained from DESCT in 116 female breast cancer patients. The relationship between these parameters and prognostic biomarkers such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and Ki67 levels, as well as the correlation with histological grade (HG), lymphovascular invasion (LVI), and metastatic axillary lymphadenopathy (LAP) were evaluated. ResultsER-negative tumors had significantly higher values of IC, nIC, IE, and nIE compared to ER-positive tumors. PR-negative tumors had significantly higher values of IE and nIEc compared to PR-positive tumors. HER2 overexpressed and Ki-67 high proliferation tumors showed significantly higher values of all quantitative parameters compared to HER2 negative and Ki-67 low proliferation tumors. All quantitative parameters were significantly higher in HG 3 tumors, tumors with detected LVI, and tumors with metastatic axillary LAP compared to low-grade tumors, LVI-negative tumors and tumors without metastatic axillary lymph nodes, respectively. ConclusionQuantitative parameters of IC and IE obtained from DESCT have shown potential for predicting prognosis in breast cancer patients. Higher values of these parameters have been found to correlate with poor prognostic biomarkers and histopathological features. These results suggest that quantitative DESCT imaging may offer an additional benefit in the noninvasive prediction of breast cancer prognosis.

Nomogram Utilizing ABVS Radiomics and Clinical Factors for Predicting ≤ 3 Positive Axillary Lymph Nodes in HR+ /HER2- Breast Cancer with 1–2 Positive Sentinel Nodes

BackgroundIn HR+/HER2- breast cancer patients with ≤3 positive axillary lymph nodes (ALNs), genomic tests can streamline chemotherapy decisions. Current studies, centered on tumor metrics, miss broader patient insights. Automated Breast Volume Scanning (ABVS) provides advanced 3D imaging, and its potential synergy with radiomics for ALN evaluation is untapped. ObjectiveThis study sought to combine ABVS radiomics and clinical characteristics in a nomogram to predict ≤3 positive ALNs in HR+/HER2- breast cancer patients with 1-2 positive sentinel lymph nodes (SLNs), guiding clinicians in genetic test candidate selection. MethodsWe enrolled 511 early-stage breast cancer patients: 362 from A Hospital for training and 149 from B Hospital for validation. Using LASSO logistic regression, primary features were identified. A clinical-radiomics nomogram was developed to predict the likelihood of ≤3 positive ALNs in HR+/HER2- patients with 1-2 positive SLNs. We assessed the discriminative capability of the nomogram using the ROC curve. The model's calibration was confirmed through a calibration curve, while its fit was evaluated using the Hosmer-Lemeshow (HL) test. To determine the clinical net benefits, we employed the Decision Curve Analysis (DCA). ResultsIn the training group, 81.2% patients had ≤3 metastatic ALNs, and 83.2% in the validation group. We developed a clinical-radiomics nomogram by analyzing clinical characteristics and rad-scores. Factors like positive SLNs (OR=0.077), absence of negative SLNs (OR=11.138), lymphovascular invasion (OR=0.248), and rad-score (OR=0.003) significantly correlated with ≤3 positive ALNs. The clinical-radiomics nomogram, with an AUC of 0.910 in training and 0.882 in validation, outperformed the rad-score-free clinical nomogram (AUCs of 0.796 and 0.782). Calibration curves and the HL test (P-values 0.688 and 0.691) confirmed its robustness. DCA showed the clinical-radiomics nomogram provided superior net benefits in predicting ALN burden across specific threshold probabilities. ConclusionsWe developed a clinical-radiomics nomogram that integrated radiomics from ABVS images and clinical data to predict the presence of ≤3 positive ALNs in HR+/HER2- patients with 1-2 positive SLNs, aiding oncologists in identifying candidates for genomic tests, bypassing ALND. In the era of precision medicine, combining genomic tests with SLNB refines both surgical and systemic patient treatments.

Discordance of Biomarker Expression Profile between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis in Preoperative Core Needle Biopsy

Background: Breast cancer (BC) is a heterogeneous disease made up of clones with different metastatic potential. Intratumoral heterogeneity may cause metastases to show divergent biomarker expression, potentially affecting chemotherapy response. Methods: We investigated the immunohistochemical (IHC) and FISH profile of estrogen receptors (ER), progesterone (PR) receptors, Ki67, and HER2 in a series of BC-matched primary tumors (PTs) and axillary lymph node (ALN) metastases in pre-operative core needle biopsies (CNBs). Phenotypical findings were correlated to morphological features and their clinical implications. Results: Divergent expression between PTs and ALNs was found in 10% of the tumors, often involving multiple biomarkers (12/31, 39%). Most (52%) displayed significant differences in ER and PR staining. HER2 divergences were observed in almost three-quarters of the cases (23/31, 74%), with five (16%) switching from negativity to overexpression/amplification in ALNs. Roughly 90% of disparities reflected significant morphological differences between PTs and ALN metastases. Less than half of the discrepancies (12/31, 39%) modified pre/post-operative treatment options. Conclusions: We observed relevant discrepancies in biomarker expression between PTs and metastatic ALNs in a noteworthy proportion (10%) of preoperative BC CNBs, which were often able to influence therapies. Hence, our data suggest routine preoperative assessment of biomarkers in both PTs and ALNs in cases showing significant morphological differences.

Whole-tumor histogram models based on quantitative maps from synthetic MRI for predicting axillary lymph node status in invasive ductal breast cancer

PurposeTo investigate the potential of using histogram analysis of synthetic MRI (SyMRI) images before and after contrast enhancement to predict axillary lymph node (ALN) status in patients with invasive ductal carcinoma (IDC). MethodsFrom January 2022 to October 2022, a total of 212 patients with IDC underwent breast MRI examination including SyMRI. Standard T2 weight images, DCE-MRI and quantitative maps of SyMRI were obtained. 13 features of the entire tumor were extracted from these quantitative maps, standard T2 weight images and DCE-MRI. Statistical analyses, including Student’s t-test, Mann-Whiney U test, logistic regression, and receiver operating characteristic (ROC) curves, were used to evaluate the data. The mean values of SyMRI quantitative parameters derived from the conventional 2D region of interest (ROI) were also evaluated. ResultsThe combined model based on T1-Gd quantitative map (energy, minimum, and variance) and clinical features (age and multifocality) achieved the best diagnostic performance in the prediction of ALN between N0 (with non-metastatic ALN) and N+ group (metastatic ALN ≥ 1) with the AUC of 0.879. Among individual quantitative maps and standard sequence-derived models, the synthetic T1-Gd model showed the best performance for the prediction of ALN between N0 and N+ groups (AUC = 0.823). Synthetic T2_entropy and PD-Gd_energy were useful for distinguishing N1 group (metastatic ALN ≥ 1 and ≤ 3) from the N2-3 group (metastatic ALN > 3) with an AUC of 0.722. ConclusionsWhole-tumor histogram features derived from quantitative parameters of SyMRI can serve as a complementary noninvasive method for preoperatively predicting ALN metastases.

Peut-on surseoir au curage axillaire en cas de carcinome mammaire invasif avec envahissement ganglionnaire ?

ObjectivesThe indications and modalities of breast and axillary surgery are undergoing profound change, with the aim of personalizing surgical management while avoiding over-treatment. To update best practices for axillary surgery, four questions were selected by the Senology Commission of the Collège National des Gynécologues et Obstétriciens Français (CNGOF), focusing on, firstly, the definition and evaluation of targeted axillary dissection (TAD) techniques; secondly, the possibility of surgical de-escalation in case of initial lymph node involvement while performing initial surgery; thirdly, in case of surgery following neo-adjuvant systemic therapy (NAST), and fourthly, contra-indications to de-escalation of axillary surgery to allow access to particular adjuvant systemic therapies. MethodsThe Senology Commission based its responses primarily on an analysis of the international literature, clinical practice recommendations and national and international guidelines. ResultsFirstly, TAD is a technique that combines excision of clipped metastatic axillary node(s) and the axillary sentinel lymph nodes (ASLNs). The detection rate and sensitivity are increased but it still needs to be standardized and practices better evaluated. Secondly, TAD represents an alternative to axillary clearance in cases of metastatic involvement of a single node that can be resected. Thirdly, neither TAD nor ASLN alone is recommended in France after NAST outside of clinical trials, although it is used in several countries in cases of complete pathological response in the lymph nodes, and when at least three lymph nodes have been removed. Fourthly, as some adjuvant targeted therapies are indicated in cases of lymph node invasion of more than three lymph nodes, the place of TAD in this context remains to be defined. ConclusionAxillary surgical de-escalation can limit the morbidity of axillary clearance. Having proved that TAD does not reduce patient survival, it will most probably replace axillary clearance in well-defined indications. This will require prior standardization of the method and its indications and contra-indications, particularly to enable the use of new targeted therapies.

The value of microvascular Doppler ultrasound technique, qualitative or quantitative shear-wave elastography of breast lesions for predicting axillary nodal burden in patients with breast cancer.

The status of the axillary lymph node (ALN) in patients with breast cancer can critically inform clinical decision-making and prognosis. Preoperative evaluation of limited nodal burden (0-2 metastatic ALNs) and high nodal burden (≥3 metastatic ALNs) is vital for individual treatment in patients with breast cancer. Thus, this study aimed to evaluate the value of Angio-PLUS (AP; Aixplorer, SuperSonic Imagine) and the qualitative and quantitative shear-wave elastography (SWE) of breast lesions to predict limited or high axillary nodal burden and to develop a model for predicting limited or high axillary nodal burden. From March 2020 to November 2022, a total of 232 consecutive patients with breast cancer comprising 232 breast lesions were enrolled retrospectively from Yueyang Central Hospital. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), accuracy, and area under the receiver operating characteristic curve (AUC) of AP, qualitative SWE, quantitative SWE, and the predictive model for evaluating limited or high axillary nodal burden were compared. There was no significant difference in AP patterns between the limited nodal burden group and high nodal burden group. The best cutoff values of Emin (the minimal value of the first Q-box), Emean (the mean value of the first Q-box), Emax (the maximum value of the first Q-box), Eratio (ratio of the first Q-Box and the second Q-Box) and standard deviation for predicting limited or high nodal burden were 80.85 KPa, 133.45 KPa, 153.40 KPa, 9.95, and 19.25 KPa, respectively. The Emax had the highest AUC, and its sensitivity, specificity, PPV, NPV, accuracy, and AUC were 71.64%, 56.36%, 40.00%, 83.04%, 60.78%, and 0.640 [95% confidence interval (CI): 0.575-0.702], respectively. The sensitivity, specificity, PPV, NPV, accuracy, and AUC of seven color patterns for qualitative SWE were 71.64%, 74.55%, 53.33%, 86.62%, 73.71%, and 0.731 (95% CI: 0.669-0.787), respectively, which was significantly higher than all the other quantitative SWE parameters. ALN evaluation in ultrasound and qualitative SWE were independent risk factors for predicting limited or high nodal burden according to a binary logistics regression analysis. The AUC of the predictive model based on independent risk factors was 0.820 (95% CI: 0.765-0.867), which was significantly higher than that of the other independent risk factors. The seven color patterns in the qualitative SWE of breast lesions were valuable for predicting limited or high nodal burden for patients with breast cancer. Compared with quantitative SWE, qualitative SWE exhibited a better diagnostic performance. Breast lesions present no findings, vertical stripes, and spot patterns were important indicators for limited nodal burden. The predictive model developed in this study could be a simple, noninvasive, and convenient method for predicting limited or high nodal burden, which would be beneficial for clinical decision-making and individual treatment to improve prognosis.

11C] Methionine-PET Imaging as a Cancer Biomarker for Methionine Addiction and Sensitivity to Methionine-restriction-based Combination Chemotherapy.

Methionine addiction is a fundamental and universal hallmark of cancer, termed the Hoffman effect. Methionine addiction of cancer is greater than glucose addiction, termed the Warburg effect, as shown by the comparison of PET imaging with [11C]methionine and [18F]fluorodeoxyglucose. The aim of the present study was to determine whether [11C]methionine PET (MET-PET) images could be a biomarker of methionine addiction of cancer and potential response to methionine-restriction-based combination chemotherapy. In the present study a patient with invasive lobular carcinoma of the breast metastatic to axillary lymph nodes was imaged by both MET-PET and [18F]fluorodeoxyglucose PET (FDG-PET) before and after combination treatment with methionine restriction, comprising a low-methionine diet and methioninase, along with first-line chemotherapy. MET-PET gave a much stronger and precise image of the patient's metastatic axillary lymph nodes than FDG-PET. The patient had a complete response to methionine restriction-based chemotherapy as shown by MET-PET. MET-PET imaging is a biomarker of methionine-addicted cancer and potential response to methionine-restriction-based chemotherapy.

Non-invasive prediction model of axillary lymph node status in patients with early-stage breast cancer: a feasibility study based on dynamic contrast-enhanced-MRI radiomics.

Accurate axillary evaluation plays an important role in prognosis and treatment planning for breast cancer. This study aimed to develop and validate a dynamic contrast-enhanced (DCE)-MRI-based radiomics model for preoperative evaluation of axillary lymph node (ALN) status in early-stage breast cancer. A total of 410 patients with pathologically confirmed early-stage invasive breast cancer (training cohort, N = 286; validation cohort, N = 124) from June 2018 to August 2022 were retrospectively recruited. Radiomics features were derived from the second phase of DCE-MRI images for each patient. ALN status-related features were obtained, and a radiomics signature was constructed using SelectKBest and least absolute shrinkage and selection operator regression. Logistic regression was applied to build a combined model and corresponding nomogram incorporating the radiomics score (Rad-score) with clinical predictors. The predictive performance of the nomogram was evaluated using receiver operator characteristic (ROC) curve analysis and calibration curves. Fourteen radiomic features were selected to construct the radiomics signature. The Rad-score, MRI-reported ALN status, BI-RADS category, and tumour size were independent predictors of ALN status and were incorporated into the combined model. The nomogram showed good calibration and favourable performance for discriminating metastatic ALNs (N + (≥1)) from non-metastatic ALNs (N0) and metastatic ALNs with heavy burden (N + (≥3)) from low burden (N + (1-2)), with the area under the ROC curve values of 0.877 and 0.879 in the training cohort and 0.859 and 0.881 in the validation cohort, respectively. The DCE-MRI-based radiomics nomogram could serve as a potential non-invasive technique for accurate preoperative evaluation of ALN burden, thereby assisting physicians in the personalized axillary treatment for early-stage breast cancer patients. This study developed a potential surrogate of preoperative accurate evaluation of ALN status, which is non-invasive and easy-to-use.

Optimization of supraclavicular lymph node clinical target volume delineation in high-risk breast cancer: a single center experience and recommendation

BackgroundProphylactic irradiation of supraclavicular lymph node drainage areas can improve the regional control rate of lymph node-positive or lymph node-negative disease but a locally-advanced stage breast cancer, and it can reduce breast cancer-related mortality. However, many controversies exist in the clinical target volume delineation of supraclavicular lymph node drainage in patients with breast cancer.MethodsWe retrospectively analyzed 42 patients with breast cancer and supraclavicular lymph node metastasis at our hospital between January 2017 and December 2021. Among these cases, 32 were locally advanced and 10 were stage IV at initial treatment. A patient with breast cancer who did not undergo dissection of the supraclavicular and infraclavicular lymph nodes at our hospital was selected as a standard patient. A contrast-enhanced computed tomography (CT) scan for positioning was used as a template image, and blood vessels, muscles, and bony landmarks were used as references for positioning. The metastatic supraclavicular lymph nodes were identified in all enrolled patients and projected into the template CT images.ResultsThe metastastic pattern of supraclavicular lymph node in breast cancer was proposed: distribution along the posterolateral border of the internal jugular vein (medial supraclavicular group) and along the transverse jugular vein (lateral supraclavicular group). We theorized that the lateral and posterior borders of the clinical target volume in the supraclavicular region should include the lymph nodes in the posterior triangle of the neck (level V) in high-risk individuals. If the metastatic axillary lymph node is extensive, then the superior border of the supraclavicular region should be moved upward appropriately.ConclusionsThis study analyzed patients with breast cancer and supraclavicular lymph node metastasis at initial treatment, explored the metastastic pattern of supraclavicular lymph node, and applied anatomical knowledge to further optimize the target volume delineation of supraclavicular lymph node drainage area in high-risk breast cancer.

Nomogram based on multiparametric analysis of early-stage breast cancer: Prediction of high burden metastatic axillary lymph nodes.

The Z0011 and AMAROS trials found that axillary lymph node dissection (ALND) was no longer mandatory for early-stage breast cancer patients who had one or two metastatic axillary lymph nodes (mALNs). The aim of our study was to establish a nomogram which could be used to quantitatively predict the individual likelihood of high burden mALN (≥3 mALN). We retrospectively analyzed 564 women with early breast cancer who had all undergone both ultrasound (US) and magnetic resonance imaging (MRI) to examine axillary lymph nodes before radical surgery. All the patients were divided into training (n = 452) and validation (n = 112) cohorts by computer-generated random numbers. Their clinicopathological features and preoperative imaging associated with high burden mALNs were evaluated by logistic regression analysis to develop a nomogram for predicting the probability of high burden mALNs. Multivariate analysis showed that high burden mALNs were significantly associated with replaced hilum and the shortest diameter >10 mm on MRI, with cortex thickness >3 mm on US (p < 0.05 each). These imaging criteria plus higher grade (grades II and III) and quadrant of breast tumor were used to develop a nomogram calculating the probability of high burden mALNs. The AUC of the nomogram was 0.853 (95% CI: 0.790-0.908) for the training set and 0.783 (95% CI: 0.638-0.929) for the validation set. Both internal and external validation evaluated the accuracy of nomogram to be good. A well-discriminated nomogram was developed to predict the high burden mALN in early-stage breast patients, which may assist the breast surgeon in choosing the appropriate surgical approach.

Axilla View of Mammography in Preoperative Axillary Lymph Node Evaluation of Breast Cancer Patients: A Pilot Study

PurposeThis study aimed to explore a novel position of mammography named axilla view in axillary lymph node (ALN) evaluation in breast cancer. Patients and MethodsPatients were prospectively enrolled and scheduled for mammography before surgery. Investigated imaging patterns included mediolateral oblique (2D-MLO) and axilla view (2D-axilla) of mammography, and axilla view of digital breast tomosynthesis (3D-axilla). The correlation of ALN numbers between imaging and pathology was analyzed. Diagnostic performance was analyzed via AUC. Results75 patients were included. A larger and clearer axillary region was displayed in axilla view. The total number of ALNs detected under 2D/3D-axilla view was significantly higher than that under 2D-MLO view (4.6 vs. 2.5, P < .001; 5.6 vs. 4.6, P = .034). Correlations between number of positive ALNs detected under 2D/3D-axilla view and pathologically confirmed metastatic ALNs were stronger than 2D-MLO view (Pearson correlation coefficients: 0.7084,0.7044 and 0.4744). The proportion of cases with ≥5 positive ALNs detected under 3D-axilla view was significantly higher than that under 2D-MLO (38.2% vs. 14.7%, P = .028). The overweight and obese group showed a higher AUC value than the underweight and lean group in ALN evaluation, although not significantly (2D-MLO: 0.7643 vs. 0.6458, P = .2656; 2D-axilla: 0.8083 vs. 0.6586, P = .1522; 3D-axilla: 0.8045 vs. 0.6615, P = .1874). This difference was more pronounced in axilla view. ConclusionAxilla view exhibited advantages over conventional MLO view in the extent of axilla displayed by mammography in breast cancer. Further studies with larger sample sizes are needed.