Axillary Metastases Research Articles

Effectiveness of PET/CT and VATS for detecting and treating internal mammary lymph node metastasis: a case series.

We occasionally observed internal mammary lymph node metastases of breast cancer in a clinical setting. However, unlike a standard treatment in axillary metastasis, surgical resection for internal mammary lymph node metastasis is not prevalent because of unclear safety and benefits. Thus, we aimed to evaluate the diagnostic ability and clinical outcomes of positron emission tomography/computed tomography and video-assisted thoracoscopic surgery. We retrospectively investigated 34 patients with breast cancer with abnormal 18F-fluorodeoxyglucose uptake in internal mammary lymph nodes, at a single centre, between January 2015 and June 2022 and identified 11 female patients (mean age±SD, 51.5±12.9years) who underwent video-assisted thoracoscopic surgery resection. Positron emission tomography/computed tomography was used to determine the clinical stage. We reviewed the surgical pathology of eleven and two patients who underwent direct-view internal mammary lymph node resection to calculate the positive predictive value of positron emission tomography/computed tomography. Ipsilateral fluorodeoxyglucose accumulation was observed, with an average maximum standardized uptake value of 8.9 (range, 3.1-24.0). No perioperative complications occurred, and all patients who underwent video-assisted thoracoscopic surgery alone were discharged from the hospital on post-operative day 2 or 3. The estimated positive predictive value was 80%. All patients were alive, and seven of nine patients with metastasis were relapse-free, at a mean follow-up period of 17.9months (range, 1-51). However, two patients had recurrence at 16 and 14months after surgery for internal mammary lymph node relapse. Radiotherapy is the standard treatment for suspected internal mammary lymph node metastasis detected using positron emission tomography/computed tomography; however, we could safely perform minimally invasive video-assisted thoracoscopic surgery resection, leading to a definite pathological diagnosis.

Abstract 3186: Anti-tumor effects and immunological responses by aGalCer loaded antigen presenting cell infusion in the patients with malignant tumor

Abstract Natural Killer T (NKT) cells are unique lymphocyte lineage that present both NK and T cell phenotype. NKT cells hold strong direct cytotoxic ability toward tumor cells through glycolipid/CD1d complex on tumor cells, NKT cells secrete large amounts of IFNγ and stimulate CD8 and NK cells as indirect cytotoxic effects. To elicit NKT cells responses in cancer patients, adoptive transfer of α-galactosyl ceramide (αGalCer) loaded APCs was exploited in a decade. I summarized anti-tumor effects and immune reaction treated with this therapy in recent 3 years. Methods: For αGalCer loaded APCs, CD14-monocyte (MO) or mature dendritic cells (DC) was used. Monocytes isolated by leukapheresis were purified ether plastic adherence or CD14-positive selection. Plastic adherent monocytes were cultured for 6 days for differentiation into DC, then for an additional day for maturation with αGalCer loading. CD14-Mo was cultured for 2 days with GM-CSF and αGalCer. After cultivation, all cells were frozen and stored in liquid nitrogen until use. For tumor treatment, patients were injected αGalCer-DC at least 4 times via SC with 2 weeks interval or injected at least twice with αGalCer-CD14-Mo intravenously with 3-4 weeks interval. We evaluated safety and efficacy of αGalCer-APCs immunotherapy by CTCAE, tumor maker, RECIST and immunological analysis. Fifty patients were enrolled in this immunotherapy between 2020-2022. Results: In all cases, we could not observe any therapy-related adverse effects above CTCAE Grade 2. Several anti-tumor effects such as tumor marker reduction and/or tumor regression including CR were observed in 60.6% of evaluated cases. In the cases with iv injection of αGalCer-CD14-Mo, CD3+CD56+ circulating NKT (cNKT) cells were significantly increased after the therapy. In the cases with subcutaneous injection of αGalCer-DC, NK number was significantly increased. Also, cNKT cells and CD8 cells were increased with tendency of significance after the therapy. We obtained CR case in chemotherapy naïve DLBCL patient by αGalCer-DC therapy. After 6 injections, multiple LN swelling was disappeared completely. In another cases, breast cancer with axillary LN metastasis, we obtained rapid tumor regression with αGalCer-DC SC injection. In the case combined αGalCer-APCs with some cytotoxic chemotherapy or conventional radiation immune responses were abolished. In the cases combined αGalCer-APCs with taxane, platinum, gemcitabine-based chemotherapy, immune responses were clearly observed. Conclusion: αGalCer-APCs infusion efficiently promote cNKT response. cNKT response was clearly related with immune responses such as CD8/NK upregulation and anti-tumor effects. Immune responses induced by the therapy seemed to be abolished by combined conventional radiotherapy or several cytotoxic chemotherapies. αGalCer-APCs infusion might be promising for cancer therapy. Citation Format: Yoshinori Ito. Anti-tumor effects and immunological responses by aGalCer loaded antigen presenting cell infusion in the patients with malignant tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3186.

Clinical and pathological features analysis of invasive breast cancer with microcalcification.

Microcalcification (MC) is a valuable diagnostic indicator to detect invasive breast cancer (IBC). This study aimed to determine the clinicopathological features of IBC with MC and detect biomarkers related to the potential mechanism of the MC formation in IBC. Data from 364 patients with IBC were collected for the clinical characteristic analysis. The analysis of clinical data helped us to establish a predictive model of axillary node metastasis (ANM) before surgery. In addition, 49 tissue samples of IBC patients were collected to test the protein levels of osteocalcin (OCN) and hypoxia-inducible factor-1α (HIF-1α) by immunohistochemistry. Significant differences were observed in tumor size, age, ANM, HER2+ , TNM stage, and mutant P53 between samples from IBC patients with MC and samples from IBC patients without MC. Younger age, a larger tumor size, a higher number of childbirths, and MC were independent predictors for ANM in IBC. HIF-1α protein level was higher in tumor tissue than in normal tissue. High protein levels of OCN and HIF-1α are related to the complication of MC in IBC. Of the patients that exhibited high HIF-1α protein levels, the percentage of high OCN protein levels was larger in patients with ANM. Based on this study, we concluded that patients with MC had a comparatively poor prognosis. MC was an independent predictive factor associated with the risk of ANM. High protein levels of OCN and HIF-1α were associated with MC and ANM, which were also related to poor prognosis. OCN and HIF-1α had a positive correlation in IBC.

Axillary Metastasis from Occult Breast Cancer and Synchronous Lung Cancer: A Case Report

This is an 84-year-old woman found to have on exam two Right axillary masses by her Primary Care Physician. The patient was then sent to our institution for further evaluation, which surprisingly revealed a lung mass, but no primary breast mass. After biopsies, both areas revealed different immunohistochemistry. She underwent further treatment, with resection of both the lung and axillary tumors. This is an interesting case that report highlights the importance of having high index of suspicion of breast cancer in the setting of axillary mass and, the importance of differentiating associated synchronous versus metastatic cancer.

Abstract OT1-08-01: AXSANA – EUBREAST3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy

Abstract Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy (SLNB) alone are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study was initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with clinically axillary lymph node involvement metastasis scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without confirmation using a minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ-BR23, Lymph-ICF and SOC 13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: 2347 patients from 247 study sites and 23 countries were enrolled in the study between June 2020 and June 2022. Among 1804 patients with a defined surgical concept 758 women were scheduled for ALND, 722 for TAD, 232 for SLNB, 16 for TLNB and 19 for other procedures. A target lymph node was marked in 1215 patients, most frequently using clips/coils (982, 82.0%), followed by magnetic seeds (100, 8.4%), carbon ink (99, 8.3%), radar marker (21, 1.8%), radioactive seeds (5, 0.4%), and other techniques (8, 0.7%). Citation Format: Thorsten Kühn. AXSANA – EUBREAST3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-08-01.

Triple-Negative Apocrine Carcinomas: Toward a Unified Group With Shared Molecular Features and Clinical Behavior

Triple-negative apocrine carcinomas (TNACs) are rare breast tumors with limited studies evaluating their molecular characteristics and clinical behavior. We performed a histologic, immunohistochemical, genetic, and clinicopathologic assessment of 42 invasive TNACs (1 with a focal spindle cell component) from 41 patients, 2 pure apocrine ductal carcinomas in situ (A-DCIS), and 1 A-DCIS associated with spindle cell metaplastic carcinoma (SCMBC). All TNACs had characteristic apocrine morphology and expressed androgen receptor (42/42), gross cystic disease fluid protein 15 (24/24), and CK5/6 (16/16). GATA3 was positive in most cases (16/18, 89%), and SOX10 was negative (0/22). TRPS1 was weakly expressed in a minority of tumors (3/14, 21%). Most TNACs had low Ki67 proliferation (≤10% in 67%, 26/39), with a median index of 10%. Levels of tumor infiltrating lymphocytes were low (≤10% in 93%, 39/42, and 15% in 7%, 3/42). Eighteen percent of TNACs presented with axillary nodal metastasis (7/38). No patients treated with neoadjuvant chemotherapy achieved pathologic complete response (0%, 0/10). Nearly all patients with TNAC (97%, n = 32) were without evidence of disease at the time of study (mean follow-up of 62 months). Seventeen invasive TNACs and 10 A-DCIS (7 with paired invasive TNAC) were profiled by targeted capture-based next-generation DNA sequencing. Pathogenic mutations in phosphatidylinositol 3-kinase pathway genes PIK3CA (53%) and/or PIK3R1 (53%) were identified in all TNACs (100%), including 4 (24%) with comutated PTEN. Ras-MAPK pathway genes, including NF1 (24%), and TP53 were mutated in 6 tumors each (35%). All A-DCIS shared mutations, such as phosphatidylinositol 3-kinase aberrations and copy number alterations with paired invasive TNACs or SCMBC, and a subset of invasive carcinomas showed additional mutations in tumor suppressors (NF1, TP53, ARID2, and CDKN2A). Divergent genetic profiles between A-DCIS and invasive carcinoma were identified in 1 case. In summary, our findings support TNAC as a morphologically, immunohistochemically, and genetically homogeneous subgroup of triple-negative breast carcinomas and suggest overall favorable clinical behavior.

Prediction of Residual Axillary Nodal Metastasis Following Neoadjuvant Chemotherapy for Breast Cancer: Radiomics Analysis Based on Chest Computed Tomography.

To evaluate the diagnostic performance of chest computed tomography (CT)-based qualitative and radiomics models for predicting residual axillary nodal metastasis after neoadjuvant chemotherapy (NAC) for patients with clinically node-positive breast cancer. This retrospective study included 226 women (mean age, 51.4 years) with clinically node-positive breast cancer treated with NAC followed by surgery between January 2015 and July 2021. Patients were randomly divided into the training and test sets (4:1 ratio). The following predictive models were built: a qualitative CT feature model using logistic regression based on qualitative imaging features of axillary nodes from the pooled data obtained using the visual interpretations of three radiologists; three radiomics models using radiomics features from three (intranodal, perinodal, and combined) different regions of interest (ROIs) delineated on pre-NAC CT and post-NAC CT using a gradient-boosting classifier; and fusion models integrating clinicopathologic factors with the qualitative CT feature model (referred to as clinical-qualitative CT feature models) or with the combined ROI radiomics model (referred to as clinical-radiomics models). The area under the curve (AUC) was used to assess and compare the model performance. Clinical N stage, biological subtype, and primary tumor response indicated by imaging were associated with residual nodal metastasis during the multivariable analysis (all P < 0.05). The AUCs of the qualitative CT feature model and radiomics models (intranodal, perinodal, and combined ROI models) according to post-NAC CT were 0.642, 0.812, 0.762, and 0.832, respectively. The AUCs of the clinical-qualitative CT feature model and clinical-radiomics model according to post-NAC CT were 0.740 and 0.866, respectively. CT-based predictive models showed good diagnostic performance for predicting residual nodal metastasis after NAC. Quantitative radiomics analysis may provide a higher level of performance than qualitative CT features models. Larger multicenter studies should be conducted to confirm their performance.

Comparing the Efficiency of Imaging Modalities in Detection of Recurrent Breast Cancer.

To investigate the effectiveness of the different imaging modalities in detecting recurrence in breast cancer follow-up. Sixty-four women with recurrent breast cancer were examined between January 2020 and July 2022. Recurrency was divided into four categories: local; regional; second primary; and distant metastasis. The detectability of recurrent lesions with mammography (MG), ultrasound (US) and magnetic resonance imaging (MRI), was evaluated. In addition, recurrences that firstly appeared by positron emission tomography (PET) scan were recorded. Twenty-seven (42.2%) recurrences were local, 10 (15.6%) were regional and 27 (42.2%) were second primary. Forty-six (71.9%) of them were determined to have invasive carcinoma, 8 (12.5%) were ductal carcinoma in situ, and 10 (15.6%) were axillary metastases. Eight (12.5%) of them were first diagnosed by PET-computed tomography/MRI. Among the available images performed, 78.7% could be detected pathologically by MG, 95.2% by US, and 100% by MRI. Distant metastasis associated with other types of recurrence was detected in 6 (9.4%) cases. MRI is the most powerful imaging modality in detecting recurrent breast cancer. With the addition of US to routine MG follow-up, a higher rate and early detection of recurrent cancers can be achieved.

Detection of pathological response of axillary lymph node metastasis after neoadjuvant chemotherapy in breast cancer using multiphoton microscopy.

Neoadjuvant treatment is often considered in breast cancer patients with axillary lymph node involvement, but most of patients do not have a pathologic complete response to therapy. The detection of residual nodal disease has a significant impact on adjuvant therapy recommendations which may improve survival. Here, we investigate whether multiphoton microscopy (MPM) could identify the pathological changes of axillary lymphatic metastasis after neoadjuvant chemotherapy in breast cancer. And furthermore, we find that there are obvious differences in seven collagen morphological features between normal node and residual axillary disease by combining with a semi-automatic image processing method, and also find that there are significant differences in four collagen features between the effective and no-response treatment groups. These research results indicate that MPM may help estimate axillary treatment response in the neoadjuvant setting and thereby tailor more appropriate and personalized adjuvant treatments for breast cancer patients.

Predicting axillary nodal metastasis based on the side of asymmetrical cortical thickening in breast cancer: Evaluation with grayscale and microvascular imaging findings

PurposeTo investigate the relationship between sonographic findings and the axillary status, especially the side of thickening in the presence of cortical asymmetry. MethodsPatients with biopsy-proven axillary lymph node (ALN) metastasis were included in this study. The lymph nodes were divided into three groups depending on the type of cortical thickening as diffuse, closer (eccentric cortical thickening on the side near the tumor and/or breast) and distant (thickening on the further side) asymmetry. Longitudinal to transverse axis (L/T) ratio, the largest cortical thickness, cortex to hilum ratio (C/H), hilar status (normal/displaced/absent), orientation (parallel/vertical), capsular integrity (sharp/indistinct), vascularisation pattern (hilar/peripheral/penetrant/anarchic/avascular) on superb microvascular imaging (SMI) and presence of conglomeration were recorded for each lymph node. Axillary nodal status on 18F-FDG PET-CT/MRI scans was recorded, if available. Features of the breast lesions like size, laterality, nuclear grade, hormone receptor status and the level of Ki-67 expression have been added. ResultsA total of 219 metastatic ALNs [diffuse (n = 122), closer asymmetry (n = 71), distant asymmetry (n = 26)] were evaluated. By the univariate analysis, ALN metastasis was significantly associated with the presence of closer asymmetrical cortical thickening (p < 0,0001), C/H ratio (p = 0.001), cortical thickness (p = 0.001), hilar status (p < 0.005) and vascular pattern (p < 0.005). L/T ratio was only a statistically significant parameter for lymph nodes with diffuse cortical enlargement in predicting metastasis, and conglomeration was also observed only in this group (p < 0.05). By multivariate analysis, nodal metastasis was significantly associated with asymmetrical cortical thickening (p = 0.001), C/H ratio (p = 0.005) and vascular pattern (p < 0.0001). ConclusionAsymmetrical cortical enlargement on the side closer to the breast, C/H ratio and abnormal microvascular pattern are the independent predictors of axillary nodal involvement. Closer asymmetry is an eligible, easy-to-detect grayscale US finding to decide sampling that highly predicts ALN metastasis.

Radiomics-based signature of breast cancer on preoperative contrast-enhanced MRI to predict axillary metastasis.

Aim: This study aimed to predict axillary metastasis using radiology features in dynamic contrast-enhanced MRI. Methods: This study included 243 breast lesions confirmed as malignant based on axillary status. Most outcome-predictive features were selected using four machine-learning algorithms. Receiver operating characteristic analysis was used to reflect diagnostic performance. Results: Least absolute shrinkage and selection operator was used to dimensionally reduce 1137 radiomics features to threefeatures. Three optimal radiomics features were used to model construction. The logistic regression model achieved an accuracy of 97% and 85% in the training and test groups. Clinical utility was evaluated using decision curve analysis. Conclusion: The novel combination of radiomics analysis and machine-learning algorithm could predict axillary metastasis and prevent invasive manipulation.

Is Pathologic Axillary Staging Valid If Lymph Nodes Are Less than 10 with Axillary Lymph Node Dissection after Neoadjuvant Chemotherapy?

Introduction: The aim of this study was to evaluate the prognostic value of the number of lymph nodes removed in breast cancer patients who undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC). Methods: We included patients who were diagnosed with invasive breast cancer and cytology with proven involved axillary node metastasis at diagnosis and treated with NAC followed by curative surgery at Samsung Medical Center between January 2007 and December 2015. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Results: Among 772 patients with NAC and ALND, there were 285 ypN0, 258 ypN1, 135 ypN2, and 94 ypN3 cases. The median follow-up duration was 69.0 months. The group with less than 10 lymph nodes number (<10 nodes group) included 123 patients and the group with 10 or more lymph nodes number (≥10 nodes group) included 649 patients. There were no significant differences in DFS (p = 0.501) or OS (p = 0.883) between the two groups. In the ypN0 subgroup, the <10 nodes group had worse DFS than ≥10 nodes group (p = 0.024). In the ypN1 subgroup, there were no significant differences in DFS (p = 0.846) or OS (p = 0.774) between the two groups. In the ypN2 subgroup, the <10 nodes group had worse DFS (p = 0.025) and OS (p = 0.031) than ≥10 nodes group Conclusion: In ypN0 and ypN2 subgroups, breast cancer patients with less than 10 lymph nodes number in ALND after NAC might be considered for additional staging or closer surveillance when compared to patients with 10 or more than lymph node.

86 (PB-086) Poster - Magnetic delayed sentinel lymph node dissection in primary systemic therapy. Implications for enhanced axillary mapping (Update)

Background: Superparamagnetic Iron Nanoparticles (SPIO) have been used for Sentinel Lymph Node Detection in breast cancer with equivalent efficacy to Radioisotope (RI) ± blue dye while facilitating logistics and leading to successful SLND even when injected up to eight weeks before surgery. However, neither the role of SPIO for SLND after primary systemic therapy (PST) nor the maximum timeframe from SPIO administration to successful SLND have been adequately defined. Methods: Patients originally cN0/1 planned for PST were included. All with cN0 axilla underwent SLND while patients with cN1 who converted to ycN0 received targeted axillary dissection (TAD) with a paramagnetic clip. All patients received SPIO either before PST or before surgery and RI was injected on the day of surgery. Results: In total, 114 patients were included in the analysis (median age 56 yrs; iqr 45, 68, median BMI 25.1 kg/m2; iqr 22.9, 28.8), of which 91 (79.8%) received chemotherapy ± targeted therapies and 23 (20.2%) endocrine therapy. SLND was performed in 81 (71.1%) and TAD in 33 (28.9%) of patients. SPIO was injected within a week to surgery in 74 (64.9%) patients and longer than a week before in 40 (35.1%), in a median of 2 days (range 0–248) for the entire cohort. At least one SLN was detected in 97.4% with SPIO and 92.1% with RI (p = 0.149) while the combination was successful in 100%. At least one SLN was concordant for SPIO and RI in 83.3% of patients. The median (iqr) lymph node yield was 3 (2,4) for SPIO, 2 (2,3) for RI and 3 (2,4) for the combination (p < 0.001). Time from SPIO injection to surgery affected detection (Spearman’s rho: 0.194, p = 0.039) but not number of SLNs (rho: −0.062, p = 0.511) or concordance per patient (rho: −0.057, p = 0.544). The addition of SPIO to RI significantly increased overall detection rate (difference 7.9%, p = 0.008), but the addition of RI to SPIO did not significantly improve overall detection (difference 2.6%, p = 0.248). In patients undergoing TAD (n = 33), detection was 100% for SPIO and 90.9% for RI (p = 0.248). The index node was magnetic in 89.3% and radioactive in 64.3% (p = 0.035), an outcome not affected by any factors. A median (iqr) of 1 (1,2) axillary metastases were found in 25 patients (21.9%). SPIO detection was 100% and RI detection was 70.8% (p = 0.023). SPIO detected more metastatic SLNs than RI (median[iqr] 1 (1,1) vs 1 (0,1); p = 0.005). In completion ALND, additional metastatic nodes were found in one patient (4%). Conclusions: In this well-defined single-arm cohort study, SPIO performed comparably to RI, but detected more SLNs and had higher detection of metastatic SLNs. Injection before PST is not only feasible, but does not seem to affect concordance with RI. These findings support the use of SPIO in PST patients and motivate more dedicated research in the concept of delayed SLND in this setting. No conflict of interest.

Oncological Outcomes of Nipple-Sparing Mastectomy in an Unselected Population Evaluated in a Single Center

Nipple-sparing mastectomy (NSM) has been traditionally used in selected cases with tumor-to-nipple distance > 2 cm and negative frozen section of the base of the nipple. Recommending NSM in unselected populations remains controversial. The present study evaluated the oncological outcomes of patients submitted to NSM in an unselected population seen at a single center. This retrospective cohort study included unselected patients with invasive carcinoma or ductal carcinoma in situ (DCIS) who underwent NSM in 2010 to 2020. The endpoints were locoregional recurrence, disease-free survival (DFS), and overall survival (OS), irrespective of tumor size or tumor-to-nipple distance. Seventy-six patients (mean age 46.1 years) (58 invasive carcinomas/18 DCIS) were included. The most invasive carcinomas were hormone-positive (60%) (HER2 overexpression: 24%; triple-negative: 16%), while 39% of DCIS were high-grade. Invasive carcinomas were T2 in 66% of cases, with axillary metastases in 38%. Surgical margins were all negative. All patients with invasive carcinoma received systemic treatment and 38% underwent radiotherapy. After a mean of 34.8 months, 3 patients with invasive carcinoma (5.1%) and 1 with DCIS (5.5%) had local recurrence. Two patients had distant metastasis and died during follow-up. The 5-year OS and DFS rates for invasive carcinoma were 98% and 83%, respectively. In unselected cases, the 5-year oncological outcomes following NSM were found to be acceptable and comparable to previous reports. Further studies are required.

Programmed cell death 1 and programmed cell death ligand 1 expression in invasive breast carcinoma using CAL10 and NAT105 immunostaining

ABSTRACT Increased incidence of breast cancer has stimulated development of new diagnostic and therapeutic methods. The programmed cell death 1 (PD1) pathway and its inhibitors are promising avenues for investigation. PD1 includes PD ligands 1 (PDL1) and 2 (PDL2). We investigated the expression of PD1 and PDL1 in invasive breast carcinomas using immunohistochemical staining. We used 171 invasive breast carcinoma specimens from which tissue microarray blocks were created. Immunohistochemical staining of PD1 using NAT105, and PDL1 using CAL10 was performed on tissue microarray sections. NAT105 and CAL10 are useful clones for detecting expression of PD1 and PDL1. PD1 and PDL1 immunostaining was significantly stronger in carcinomas with basal-like phenotype compared to other molecular breast cancer types. PD1 and PDL1 expression also was associated with a high histologic grade and a high Ki-67 index. PD1 expression also was associated with lymphovascular invasion and axillary metastasis. PD1 and PDL1 expression is associated with aggressive tumor behavior and a basal-like phenotype in breast cancer. We suggest that inhibition of the PD1/PDL1 pathway, particularly in triple negative breast carcinomas with basal-like phenotype, might be useful for targeted immunotherapy.

Exploring the Integrated Role of AKT2, CD44v6, And MT1-MMP as Predictors of Axillary Lymph Node Metastasis in Invasive Breast Carcinoma of No Special Type.

Invasive breast carcinoma of no special type (IBC-NST) is the most common type of breast cancer, which mainly causes axillary lymph-node metastasis (ALNM). Building on our previous research, we wanted to explore the optimal combination of AKT2, CD44v6, and MT1-MMP for the ALNM prediction. The presence or absence of ALNM was used to separate 46 paraffin blocks containing IBC-NST primary tumors into two groups. Age, tumor grade, tumor size, receptor status (ER, PR, HER2, Ki-67, TOP2A), and test biomarker expression were evaluated. Biomarker expressions were assessed by IHC staining and categorized according to their respective cut-offs from our previous study, while other data were collected from archives. Data was gathered and analyzed using univariate, multivariate, and AUROC models. The expression of CD44v6 (OR: 12.77, 95% CI: 2.18-87.12, P=0.005) was identified as the independent variable for ALNM. Meanwhile, AKT2 expression (OR: 3.22, 95% CI: 0.36-22.41, P=0.237) and MT1-MMP expression (OR: 5.35, 95% CI: 0.83-34.54, P=0.078) did not demonstrate a statistically significant independent association in respect to ALNM. Combining AKT2 and MT1-MMP on CD44v6 increased overall accuracy by 4% compared to CD44v6 alone (AUROC 0.89 vs. 0.85). The combined usage of AKT2, CD44v6, and MT1-MMP revealed no significant change compared to CD44v6 alone. Due to the cost and practicality, we propose using CD44v6 as a predictor biomarker of ALNM in IBC-NST.

Is the Platelet-Lymphocyte Ratıo a Useful Tool for Predicting Sentinel Lymph Node Metastasıs in Breast Cancer Patients Receiving Neoadjuvant Therapy?

Aim: Breast cancer is one of the cancers with the highest morbidity and mortality in women. Surgical excision of axillary lymph nodes facilitates staging and provides regional control in those with axillary metastases. Although SLNB is routinely performed in the management of patients with cN0 disease who underwent primary surgery, it is controversial when to perform SLNB in patients receiving neoadjuvant chemotherapy. In our study, we evaluated the success of the platelet/lymphocyte ratio before and after neoadjuvant therapy in predicting sentinel lymph node metastases in breast cancer patients receiving neoadjuvant therapy.&#x0D; &#x0D; Materials-Methods: Patients who received neoadjuvant chemotherapy for locally advanced breast cancer in our clinic were evaluated. Among these patients, patients with histopathologically proven axilla metastases but no pathological lymph nodes in clinical examination and imaging methods after neoadjuvant therapy were evaluated.&#x0D; &#x0D; Results: An average of 3.81 lymph node excisions were performed for sentinel lymph node sampling. We studied the PLR cut-off value with Roc-curve analysis. We found the cut-off value of 138.88 with a standard error of 0.061 (p=0.001). Patients with high PLR are more likely to have sentinel lymph node metastases than patients with low PLR (OR= 1.013, 95%Cl: 1.005-1.021, p=0.002). We also found a significant positive correlation between PLR and the number of metastatic sentinel lymph nodes (p=0.005). Each unit increase in PLR can cause an increase of 0.004 units in the number of metastatic sentinel lymph nodes.&#x0D; Conclusion: In patients receiving neoadjuvant chemotherapy, PLR plays an important role in predicting sentinel lymph node metastasis as a practical, simple, and inexpensive hematological indicator and may facilitate the selection of an appropriate treatment plan before surgery.&#x0D; Keywords: Sentinel lymph node, Breast cancer, inflammatory parameters

Contrast-enhanced lymphatic US can improve the preoperative diagnostic performance for sentinel lymph nodes in early breast cancer.

ObjectivesTo evaluate the preoperative diagnostic value of contrast-enhanced lymphatic ultrasound (CEUS) for the sentinel lymph node (SLN) status in early breast cancer.Materials and methodsWe prospectively recruited 102 consecutive patients with clinically node-negative early breast cancer from July 2021 to October 2021. All patients underwent conventional US and percutaneous CEUS examinations. The CEUS of SLNs were classified into four enhancement patterns: homogeneous (I), featured inhomogeneous (II), focal defect (III), and no enhancement (IV). The diagnostic performance of conventional US and CEUS for SLN metastasis was assessed by receiver operating characteristic (ROC) curves and decision curves.ResultsA total of 78 women were enrolled in this study, including 55, 18, and 5 patients with negative axilla, 1–2, and ≥ 3 metastastic SLNs pathologically, respectively. The identification rate of SLNs by CEUS was 100%. Patterns I and II can select 91.7% (44/48) of patients with disease-free axilla, while patterns III and IV had higher percentages of metastasis (65.2%, p < 0.001 and 57.1%, p < 0.002, respectively). For the SLN metastatic burden, 100% (48/48) of patients with pattern I/II had ≤ 2 metastatic SLNs. Compared with conventional US, the CEUS enhancement patterns showed significant improvement in diagnosing metastatic SLNs (0.813 vs 0.601, p < 0.001). CEUS had greater clinical benefits and correctly reclassified 48% of metastatic SLNs (p < 0.001) without sacrificing the classification accuracy of negative SLNs (p = 0.25), and could improve prediction accuracy by 0.42 (p < 0.001).ConclusionsCEUS demonstrated better diagnostic performance and greater clinical benefits than conventional US for the preoperative diagnosis of SLNs, showing its potential to select candidates for precluding axillary surgery in early breast cancer.Key Points• The homogeneous and featured inhomogeneous enhancement of SLNs are highly suggestive of negative LNs, while focal defect (p < 0.001) and no enhancement (p < 0.002) patterns had higher percentages of metastasis.• The proportion of SLNs with highly suspicious signs on conventional US increases as the type of enhancement pattern increases (no suspicious signs in pattern I/II, 34.8% in pattern III, and 85.7% in pattern IV).• Compared with conventional US, CEUS improved the area under the receiver operating characteristic curve (0.813 vs. 0.601, p < 0.001) and had greater clinical benefits (IDI = 0.42, p < 0.001) for the diagnosis of axillary metastasis.

Clinicopathologic Features of Metaplastic Breast Carcinoma: Experience From a Tertiary Cancer Center of North India.

IntroductionMetaplastic breast cancer (MBC) is a rare malignancy that accounts for < 1% of all breast cancers. The aim of this study is to evaluate the clinicopathologic characteristics of MBC patients treated at a tertiary cancer center.Materials and methodsIn this study, the authors retrospectively analyzed the prospectively maintained data of MBC patients treated at a tertiary cancer care center in North India between January 2019 and July 2022.ResultsA total of 28 MBCs were identified. The median age of presentation was 47 years (range 27-81 years). Seventeen patients (60.7%) presented with clinical T3/T4 disease, and axillary nodal involvement was detected in 11 patients (39.3%) at presentation. Two patients had metastatic disease at presentation. A preoperative diagnosis of MBC on core biopsy was attained in five patients (17.9%), and the most common histologic subtype was sarcomatoid carcinoma. Triple-negative receptor status was observed in 15 patients (53.6%). Six patients (21.4%) underwent upfront breast conservation surgery and another six (21.4%) upfront mastectomy. Thirteen patients (46.4%) underwent mastectomy following neoadjuvant therapy. Definitive axillary nodal metastasis was found in eight patients (32%). Following neoadjuvant chemotherapy, five patients (35.7%) had stable disease, disease progression was evident in five patients (35.7%), partial response in four patients (28.6%), and no patient evinced complete response. Adjuvant postoperative radiation therapy was administered in 16 patients (57.1%). At a median follow-up of 13.2 months (range 4-26 months), 16 patients (57.1%) were alive with no evidence of disease, one patient (3.6%) was alive with disease, nine patients (32.1%) died of disease, and two patients (7.2%) died of other causes. One patient suffered from locoregional recurrence and nine patients developed distant metastasis.ConclusionMBC is an infrequent entity among breast carcinomas in India, which is similar to the reports of MBC worldwide. The diagnosis of MBC is difficult and requires the use of immunohistochemistry. Most of the cases in our study presented with a larger tumor size; however, they displayed a relatively lower incidence of nodal involvement as well as hormone receptor negativity. Being a rare and heterogeneous disease, large-scale studies are essential for better understanding and management of these tumors.

Locoregional relapse after sparing mastectomies and immediate reconstruction in women with breast cancer

IntroductionIn recent years, cultural changes in today's society and improved risk assessment have increased the indication for mastectomies in women with breast cancer. Various studies have confirmed the oncological safety of sparing mastectomies and immediate reconstruction. The objective of this study is to analyze the incidence of locoregional relapses of this procedure and its impact on reconstruction and overall survival. Patients and methodsProspective study of patients with breast carcinoma who underwent a sparing mastectomy and immediate reconstruction. Locoregional relapses and their treatment and their impact on survival were analyzed. ResultsThe study group is made up of 271 women with breast carcinoma treated with a skin-sparing mastectomy and immediate reconstruction. The mean follow-up was 7.98 years and during the same 18 locoregional relapses (6.6%) were diagnosed: 72.2% in the mastectomy flap and 27.8% lymph node. There were no significant differences in the pathological characteristics of the primary tumor between patients with and without locoregional relapse, although the percentage of women with hormone-sensitive tumors was higher in the group without relapse. Patients with lymph node relapse had larger tumors (80% T2-T3) and 60% had axillary metastases at diagnosis, compared to 7.7% of women with skin relapse (p = 0.047). All patients operated on for locoregional relapse preserved their reconstruction. The incidence of metastases and deaths was significantly higher in patients with a relapse, causing a non-significant decrease in overall survival. ConclusionLocoregional relapses are a rare event in women with a sparing mastectomy and immediate reconstruction. Most patients with locoregional relapse can preserve their initial reconstruction through local resection of the tumor and adjuvant and / or neoadjuvant therapies.