Axillary Node Research Articles

Electrical lymph node scanning (ELS) system for real-time intra-operative detection of involved axillary lymph nodes in adjuvant breast cancer patients

Lymph node (LN) status is an essential prognostic factor in breast cancer (BC) patients, with an important role in the surgical and therapeutic plan. Recently, we have been developed a novel system for real-time intra-operative electrical LN scanning in BC patients. The ELS scores were calibrated by pathological evaluation of the LNs. Herein, we evaluated the efficacy of ELS in a prospective study for non-chemo-treated breast cancer patients. This is a prospective study in which ELS scores are blind for pathologists who declare the clearance or involvement of LNs based on permanent pathology as the gold standard. ELS and frozen-section (FS) pathology results were achieved intra-operatively, and samples were sent for the permanent pathology. The score of ELS did not affect the surgeons’ decision, and the treatment approach was carried out based on FS pathology and pre-surgical data, such as imaging and probable biopsies. Patients were recruited from October 2021 through November 2022, and 381 lymph nodes of 97 patients were included in the study. In this study we recruited 38 patients (39.2%) with sentinel lymph node biopsy (SLNB) and 59 patients (60.8%) with ALND. Of the 381 LNs scored by ELS, 329 sentinel LNs underwent routine pathology, while others (n = 52) underwent both FS and permanent pathology. ELS showed a sensitivity of 91.4% for node-positive patients, decreasing to 84.8% when considering all LNs. Using ROC analysis, ELS diagnosis showed a significant AUC of 0.878 in relation to the permanent pathology gold standard. Comparison of ELS diagnosis for different tumor types and LN sizes demonstrated no significant differences, while increasing LN size correlated with enhanced ELS sensitivity. This study confirmed ELS’s efficacy in real-time lymph node detection among non-chemo-treated breast cancer patients. The use of ELS’s pathological scoring for intra-operative LN diagnosis, especially in the absence of FS pathology or for non-sentinel LN involvement, could improve prognosis and reduce complications by minimizing unnecessary dissection.

Oncologic outcomes of de-escalating axillary treatment in clinically node-positive breast cancer patients treated with neoadjuvant systemic therapy – A two center cohort study

BackgroundThe aim of the present study was to report the 5-year axillary recurrence-free interval (aRFI) in clinically node-positive breast cancer patients treated according to a de-escalating axillary treatment protocol after neoadjuvant systemic therapy (NST). MethodsAll patients diagnosed in two hospitals between October 2014 and March 2021 were identified retrospectively. Data on diagnostic workup, treatment and follow-up was collected. Adjuvant axillary treatment was considered based on the initial staging using 18F-FDG PET/CT and the results of axillary lymph node marking with a radioactive-iodine seed protocol or a targeted axillary dissection procedure. Follow-up was updated until 27th April 2024. Kaplan-Meier curves were calculated to report the 5-year aRFI with corresponding 95 % confident intervals (95%-CI). ResultsA total of 199 patients were included. Axillary pathological complete response was reported in 66 (33.2 %). Based on the treatment protocol and initial clinical staging, no adjuvant axillary treatment was indicated in 30 patients (15 %), while 139 (70 %) received axillary radiotherapy without performance of an axillary lymph node dissection (ALND). The remaining 30 patients (15 %) underwent an ALND with additional locoregional radiotherapy. A median follow-up of 62 months (30–106) showed that 4 (2 %) patients experienced an axillary recurrence after 7, 8, 36 and 36 months, respectively. In all 4 patients, synchronous distant metastases were diagnosed. The estimated 5-year aRFI was 97.8 % (95%-CI 95.6–99.9 %) ConclusionAlthough longer follow-up should be awaited before final conclusions can be drawn regarding the oncological safety of this approach, the implementation of a de-escalating axillary treatment protocol appears to be safe since the estimated 5-year aRFI is 97.8 %.

Diagnostic performance analysis of Xpert MTB/RIF in lymph node tuberculosis: A retrospective study

AimsTo retrospectively analyze the diagnostic efficacy of Xpert MTB/RIF (Xpert) in lymph node tuberculosis (LNTB). MethodsSensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of Xpert, pathological examination and culture for LNTB were calculated. Results421 suspected LNTB cases were categorized into the LNTB group (377 cases) and non-LNTB group (44 cases). The sensitivities of Xpert, pathological examination, and culture were 72.15%, 20.69%, 30.24%, respectively, with NPVs of 29.53%, 12.83%, 14.33%. The AUC values were 0.861, 0.603, 0.651, respectively. The sensitivity of Xpert varied across sample types: tissue (64.73%), puncture fluid (74.42%), and pus (96.05%). For specific lymph node locations, the sensitivity was head-and-neck (72.51%), mediastinal (84.21%), and axillary (45.83%). ConclusionsXpert demonstrates high diagnostic value for LNTB, particularly in pus samples. It also performs better in mediastinal and head-and-neck lymph node samples compared to axillary lymph node samples.

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

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

Ultrasound versus MRI for evaluation of silicone leakage from silicone breast implants

BackgroundImplant ruptures and gel bleed are not uncommon among women with silicone breast implants. While magnetic resonance imaging (MRI) is traditionally considered the gold standard diagnostic modality, recent studies suggest ultrasound might be an acceptable alternative. This study compares the efficacy of ultrasound and MRI in assessing implant integrity. MethodsWomen with silicone breast implants underwent a breast and axillary ultrasound and MRI on the same day. All tests were assessed by experienced radiologists. The accuracy, sensitivity, and specificity of ultrasound and MRI for implant rupture detection and silicone depositions in axillary lymph nodes were evaluated. FindingsA total of 104 women participated in the study. The accuracy, sensitivity, and specificity of ultrasound for detecting implant ruptures compared to MRI were 96 %, 95 %, and 96 %, respectively. MRI demonstrated significantly lower sensitivity (44 %) for detecting silicone depositions in axillary lymph nodes compared to ultrasound. A significant association was observed between the presence of enlarged axillary lymph nodes and/or axillary pain and the detection of silicone depositions in axillary lymph nodes on ultrasound (χ2 (1, N = 104) = 5·1, p = 0·024). Six women exhibited silicone depositions in axillary lymph nodes despite having intact first-pair implants, indicative of gel bleed. InterpretationUltrasound is nearly as effective as MRI for detecting breast implant ruptures and is superior for detecting silicone depositions in axillary lymph nodes. We therefore recommend initiating radiological examination in women with breast implants with a breast and axillary ultrasound, proceeding to MRI only if the ultrasound is inconclusive. The prevalence of gel bleed is understudied and its potential adverse health effects might be underestimated. Further research is needed to explore its potential association with development of systemic symptoms.

Development of a Preoperative Prediction Model Based on Spectral CT to Evaluate Axillary Lymph Node With Macrometastases in Clinical T1/2N0 Invasive Breast Cancer

ObjectivesTo develop a prediction model based on spectral computed tomography (CT) to evaluate axillary lymph node (ALN) with macrometastases in clinical T1/2N0 invasive breast cancer. MethodsA total of 217 clinical T1/2N0 invasive breast cancer patients who underwent spectral CT scans were retrospectively enrolled and categorized into a training cohort (n = 151) and validation cohort (n = 66). These patients were classified into ALN nonmacrometastases (stage pN0 or pN0 [i+] or pN1mi) and ALN macrometastases (stage pN1-3) subgroups. The morphologic criteria and quantitative spectral CT parameters of the most suspicious ALN were measured and compared. Least absolute shrinkage and selection operator (Lasso) was used to screen predictive indicators to build a logistic model. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate the models. ResultsThe combined arterial-venous phase spectral CT model yielded the best diagnostic performance in discrimination of ALN nonmacrometastases and ALN macrometastases with the highest AUC (0.963 in the training cohort and 0.945 in validation cohorts). Among single phase spectral CT models, the venous phase spectral CT model showed the best performance (AUC = 0.960 in the training cohort and 0.940 in validation cohorts). There was no significant difference in AUCs among the 3 models (DeLong test, P > .05 for each comparison). ConclusionA Lasso-logistic model that combined morphologic features and quantitative spectral CT parameters based on contrast-enhanced spectral imaging potentially be used as a noninvasive tool for individual preoperative prediction of ALN status in clinical T1/2N0 invasive breast cancers.

Meta-analysis on axillary lymph node metastasis rate in ductal carcinoma insitu with microinvasion.

To address the question of axillary lymph node staging in ductal carcinoma insitu with microinvasion (DCIS-MI), we retrospectively evaluated axillary lymph nodes metastasis (ALNM) rate in a cohort of postsurgical DCIS-MI patients. By analyzing these data, we aimed to generate clinically relevant insights to inform treatment decision-making for this patient population. A systematic search was conducted on PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang Database, Wipe, and China Biomedical Literature Database to identify relevant publications in any language. All the analyses were performed using Stata 16.0 software. Among the 28 studies involving 8279 patients, the pooled analysis revealed an ALNM rate of 8% (95% CI, 7% to 10%) in patients with DCIS-MI. Furthermore, the rates of axillary lymph node macrometastasis, micrometastasis, and ITC in patients with DCIS-MI were 2% (95% CI, 2% to 3%), 3% (95% CI, 2% to 4%), and 2% (95% CI, 1% to 3%), respectively. Moreover, 13 studies investigated the non-sentinel lymph node (Non-SLN) metastasis rate, encompassing a total of 1236 DCIS-MI cases. The pooled analysis identified a Non-SLN metastasis rate of 33% (95% CI, 14% to 55%) in patients with DCIS-MI. The SLNB for patients with DCIS-MI is justifiable and could provide a novel therapeutic basis for systemic treatment decisions.

Prognosis of locoregional recurrence after early breast cancer with immediate breast reconstruction.

e12595 Background: Several studies have shown no difference in the prognosis of breast cancer patients who underwent total mastectomy (MT) with or without immediate breast reconstruction (IBR), which is now a standard surgical technique in the treatment of breast cancer. While some studies have reported a poor prognosis for locoregional recurrence (LRR) following breast cancer surgery, the prognosis of LRR without simultaneous distant metastasis after IBR is not known. We conducted a multi-facility retrospective observational study to investigate the prognosis of breast cancer patients with LRR after IBR. Methods: Of the 4,726 primary breast cancer patients for whom IBR was performed at 12 Japanese medical facilities between January 1, 2008, and December 31, 2016, MT or skin-sparing mastectomy (SSM) was performed in 3,295 patients. LRR was observed in 87 of these patients, 17 of whom had distant metastasis (n=13) or metastasis to the supraclavicular or internal mammary lymph nodes (n=4) before LRR was excluded. The measured outcomes were IBR-LRR-related prognostic factors, five-year distant metastasis-free survival (DMFS), and five-year overall survival (OS). The statistical analyses employed Kaplan–Meier curves and a Cox proportional hazards model. Results: The median observation period was 39.3 months and the median age at which IBR was performed was 44 years. There were 61 cases (87.1%) of invasive cancer. Sixty-one cases (87.1%) were ER-positive, 54 (77.1%) were PR-positive, and 13 (19.7%) were HER2-positive. Fifteen cases (21.4%) had pathological lymph node metastasis (pN), 60 cases (85.7%) underwent implant reconstruction, 33 cases (47.1%) had a disease-free interval ≤ 36 months, 9 cases (12.9%) had regional lymph node recurrence (RR), and 65 cases (92.9%) underwent surgical resection to treat LRR. The five-year DMFS after LRR was 92.4%, and the five-year OS was 91.2%. The relationship between DMFS and clinical pathology factors was analyzed using a Cox proportional hazards model. Univariate analysis revealed significant differences for pN (HR 10.634, 95% CI 1.102–102.616, P=0.041) and RR (HR 9.960, 95% CI 1.400–70.862, P=0.022), and multivariate analysis indicated that RR was the only independent prognostic factor for DMFS (HR 7.834, 95% CI 1.085–56.587, P=0.041) (Table 1). Univariate analysis revealed significant differences for post-mastectomy radiation therapy (PMRT) (HR 130.676, 95% CI 1.552–412.278, P=0.023) and RR (HR 8.181, 95% CI 1.106–60.503, P=0.043), and multivariate analysis indicated that both PMRT (HR 61.281, 95% CI 2.540–1478.426, P=0.010) and RR (HR 15.687, 95% CI 1.354–181.772, P=0.028) were independent prognostic factors for OS. Conclusions: This is the first study to report the prognosis of breast cancer patients with LRR after IBR. Although these patients have a favorable prognosis overall, our results indicate that RR may be a significant factor for poor prognosis.

Trastuzumab, pertuzumab and nab-paclitaxel plus pyrotinib or not in neoadjuvant treatment of HER2-positive breast cancer: A multi-center, randomized, open-label, phase II study.

e12634 Background: Trastuzumab plus pertuzumab (TP) combined with chemotherapy is the standard neoadjuvant treatment regimen for HER2+ breast cancer. Anti-HER2 tyrosine kinase inhibitor, pyrotinib, shows great efficacy in HER2+ metastatic breast cancer, but lacking efficacy data on the basis of TP and chemotherapy in the neoadjuvant setting. This study aims to evaluate the efficacy and safety of TP plus nab-paclitaxel with or without pyrotinib as neoadjuvant treatment in HER2+ breast cancer. Methods: Stage II-III HER2+ breast cancer patients, stratified by disease stage (II vs. III) and hormone receptor (HR) status (positive vs. negative), were randomized 1:1 into the pyrotinib group or the control group. Both groups received a combination of 3-weekly TP and weekly nab-paclitaxel for 12 weeks. The pyrotinib group was concurrent given 320mg pyrotinib once daily. Primary endpoint was the total pathological complete remission (tpCR), defined as no invasive cancer in the breast and axillary lymph node. Results: From Nov 2020 to Apr 2023, a total of 109 patients were enrolled, with 108 receiving treatment: 55 in the pyrotinib group and 53 in the control group.The tpCR rate was 65.5% (95% CI: 51.4%, 77.8%) in the pyrotinib group, which shows no significant difference with the control group [60.4% (95% CI: 46.0%,73.5), P = 0.585). The breast pathological complete response (bpCR) rates were 70.9% (95% CI: 57.1%,82.4%) and 64.2%(95% CI: 49.8%,76.9%) in the pyrotinib and control group, respectively (P = 0.453). In the pyrotinib group, 52 (94.5%), 31 (56.4%), and 23 (41.8%) patients experienced dose-interruption, dose-reduction, and discontinuation of pyrotinib, respectively. The most common grade ≥3 adverse events in the pyrotinib and control groups were diarrhea (58.1% vs. 0%), decreased neutrophil count (23.6% vs. 15.1%), and decreased white blood cell count (16.4% vs. 7.5%). Conclusions: Our study showed pyrotinib didn’t significantly improve tpCR rate with pyrotinib on the basis of TP and nab-paclitaxel neoadjuvant therapy of HER2+ breast cancer. Concurrent pyrotinib treatment with TP was associated with a high rate of severe diarrhea. Further biomarker analyses are needed to identify which population would receive great benefit with neoadjuvant pyrotinib therapy in HER2+ breast cancer. Clinical trial information: NCT04398914 .

Exosomal HMGB1 educate PD-L1+-tumor associated macrophages via glycometabolic reprogramming to induce lung-tropic metastasis of triple negative breast cancer.

1090 Background: Lung metastasis occurs in one third of triple negative breast cancer (TNBC), the underlying molecular mechanism remains largely unclear. Mounting evidence suggests that PD-L1+-tumor associated macrophages (PD-L1+-TAMs) are closely associated with immune suppression, invasion, and metastasis. Tumor-derived exosomes have been reported to remodel tumor microenvironment and accelerate metastasis through packing and delivering a variety of biologically active molecules. The aim of this study was to investigate whether TNBC-derived exosomes were able to polarize lung macrophages towards PD-L1+-TAMs and promote a pre-metastatic immunosuppressive niche, therefore discovering the underlying mechanism of lung-tropic metastasis. Methods: Exosomes obtained from EO771 TNBC cell line (EO771/exo) and HC11 normal breast epithelial cell line (HC11/exo) were characterized. Absorption of exosomes by macrophages was observed by confocal microscopy. Mass spectrometry was used to identify the significantly highly expressed HMGB1 protein in EO771/exo, and ligands of HMGB1 on lung macrophages were detected by co-immunoprecipitation. Significance of EO771/exo and HMGB1 in inducing PD-L1+-TAMs and generating a pre-metastatic immunosuppressive niche were confirmed by both in vitro and in vivo studies. Functions of EO771/exo and HMGB1 on glycolysis and lactate production were evaluated by metabolism assays. Results: EO771/exo could polarize macrophages toward PD-L1+-TAMs and generate a pre-metastatic immunosuppressive niche. Mass spectrometry, clinical samples, and bioinformatics analysis showed that HMGB1 was significantly expressed in EO771/exo and was involved in cellular communication and metabolism processes. Co-immunoprecipitation and 3-dimensional modeling suggested a strong binding of HMGB1 with Tim-3 ligand on lung macrophages. Macrophages incubated with EO771/exo exhibited an enhanced glycolysis and lactate production. Flow cytometry demonstrated that green fluorescent protein (GFP)-EO771 tumor-bearing mice had more lung micro-metastases than brain and liver. Immunofluorescence and laser confocal microscopy demonstrated that EO771/exo were able to increase lung micro-metastases and escalate PD-L1 expression on lung macrophages. Moreover, elevated PD-L1+-TAMs and reduced CD3+CD8+ T lymphocytes were detected in TNBC positive axillary lymph nodes and lung metastasis specimens than TNBC negative axillary lymph nodes. Conclusions: Exosomal HMGB1 from TNBC could target Tim-3 ligand on lung macrophages and accelerate glycolysis and lactate production to induce PD-L1+-TAMs, thereby suppressing CD3+CD8+ T lymphocytes immunity and generating a pre-metastasis immune-suppressive niche. Our research would uncover a novel mechanism of lung-tropic metastasis.

Efficacy and safety of recombinant humanized anti-HER2 antibody-MMAE conjugate (RC48) in neoadjuvant for HER2-positive breast cancer: A single-arm phase II study.

e12636 Background: Breast cancer patients who achieve pCR after neoadjuvant therapy have a relatively good prognosis. Whether antibody‐drug conjugates (ADCs) can replace traditional chemotherapy combined with dual-target therapy in neoadjuvant therapy still needs to be explored. RC48 is a novel recombinant human anti-HER2 monoclonal antibody conjugated with a microtubule inhibitor (MMAE) via a cleavable linker, which can effectively kill HER2-positive tumors as well as tumors with low or heterogeneous HER2 expression through the bystander effect. The purpose of this study was to evaluate the efficacy and safety of RC48 in neoadjuvant treatment of HER2-positive breast cancer. Methods: Patients with HER2-positive breast cancer (size>20mm) or confirmed axillary lymph node metastasis were eligible and received RC48 at a dose of 2.5mg/kg alone every 2 weeks for 6 cycles followed by surgery. EC was administered postoperatively every 21 days for 4 cycles. Trastuzumab combined with pertuzumab was administered for 1 year in the adjuvant setting. The primary endpoints were ORR and pCR rates. Results: 23 patients had been enrolled, and all of them had completed surgical treatment. The median age was 45(38-70) years. The current results showed that 13.0% (3/23) achieved pCR, 78.3% (18/23) achieved PR, and 8.7% (2/23) experienced PD. The ORR was 91.3%. 42% (5/12) of patients with initially positive axillary lymph nodes turned negative after surgery. 11.8% (2/17) HR-/HER2+ patients achieved pCR. According to the proportion of target lesion reduction, patients were divided into mild response (0-50%) and moderate-to-severe response (51%-100%). In the HR-/HER2+ subtype group, 23.5% (4/17) had a mild response, and 76.5% (13/17) had a moderate-to-severe response. 6 patients with HR+ have been enrolled, and 16.7% (1/6) of them achieved pCR. All of HR+ subtypes had a moderate-to-severe response. No relevant serious (grade 3/4) toxicity has been reported. Conclusions: The present data showed an acceptable pCR rate with RC48 in HER2-positive breast cancer. Although the pCR rate was lower than the traditional chemotherapy combined with targeted therapy, the effect of rapid reduction of tumor volume was better (the moderate-severe remission rate was 82.6%). For HR+/HER2+ breast cancer, the ORR in this study reached 100%, indicating that the novel ADC had a significant inhibitory effect on the crosstalk between ER and HER2. And it was expected that the Destiny Breast 11 study would show similar results. This scheme had a good negative conversion rate for patients with positive axillary lymph nodes. Finally, RC48 provided a neoadjuvant treatment option with low toxicity and high patient compliance for HER2-positive breast cancer. Clinical trial information: NCT05134519 .

Intraoperative diagnosis of breast cancer metastasis in axillary lymph nodes: Cytological Smear vs. Frozen Section

BackgroundIntraoperative evaluation of axillary lymph nodes is sometimes required to determine the extent of surgery. In this study, we wished to assess the reliability of cytologic smear (CS) in determining lymph node involvement with tumor. Theoretically, CS provides more substance for examination than touch-imprint cytology and is faster to perform than frozen section (FS). We hypothesized that CS sensitivity for tumor cell detection in the lymph nodes would be similar to FS, at least 0.90. MethodsThis was a retrospective observational study at the Rambam Health Care Campus (January, 2013-June, 2020). Lymph nodes underwent intraoperative evaluation using either CS or FS, based on the availability of a cytologist at the time of the examination. Both intraoperative evaluations were compared to the final pathology following fixation with formalin. ResultsEighty-eight patients undergoing intraoperative analysis were analyzed (51 CS, 37 FS). False-negative tests were recorded in only 1 patient evaluated by each of the 2 methods. This resulted in sensitivity 0.91 (95%CI 0.59, 1.00) for CS and 0.88 (95%CI 0.47, 1.00) for FS, specificity 1.00 (95%CI 0.91, 1.00) for CS and 1.00 (95%CI 0.88, 1.00) for FS, positive predictive value 1.00 (95%CI 0.69, 1.00) for CS and 1.00 (95%CI 0.59, 1.00) for FS, and negative predictive value 0.98 (95%CI 0.87, 1.00) for CS and 0.97 (95%CI 0.83, 1.00) for FS. ConclusionsThe sensitivity of the CS in this study is comparable to that of FS and due to shorter analysis time required is the preferred method at our institution.

Oncologic outcome of response-guided axillary treatment in patients with cN1 breast cancer after primary systemic therapy.

514 Background: In breast cancer, the majority of clinically node positive (cN1) patients are treated with primary systemic treatment (PST), with increasing rates of axillary pathologic complete response (pCR). Evidence supporting tailoring axillary treatment according to the response is growing. However, it is still debatable whether ALND is beneficial in cN1 patients with residual nodal disease and if any further axillary treatment is necessary in patients achieving pCR. In this study, we present the four-year oncologic outcome of cN1 patients undergoing either axillary radiation treatment or no axillary treatment according to the ‘Marking Axillary lymph nodes with Radioactive Iodine seeds’ (MARI)-protocol. Methods: Between 2014 and 2021, we prospectively enrolled patients with node positive breast cancer and 1 - 3 involved axillary lymph nodes on FDG-PET/CT pre-PST, who were treated according to the MARI-protocol. Patients with residual disease of the MARI node (ypN1) received axillary radiotherapy (RT), while patients with a pCR of the MARI node (ypN0) received no further axillary treatment. The primary endpoint was the axillary recurrence rate. Secondary endpoints include invasive disease free survival (iDFS) and overall survival (OS), calculated using the Kaplan-Meier method. Results: Of the 367 included patients, more than half (54%, n= 198) had hormonal receptor positive (HR+)/Human Epidermal growth factor 2 negative (HER2-) breast cancer; 59 patients (16%) had HR+/HER2+; 39 patients (11%) had HR-/HER2+ and 71 patients (19%) had triple negative (TN) subtype. Median age was 49 (IQR 41 – 56) years. 231 (63%) patients who had ypN1 received RT and 136 patients (37%) who achieved ypN0 received no further axillary treatment. Median follow up was 49 (IQR 32 – 70) months. Axillary recurrence rate was 3.5% ( n= 8) in patients with ypN1 and 0.7% ( n= 1) in patients with ypN0. Most axillary recurrences ( n= 6) occurred simultaneously with distant metastases in the ypN1 group. In patients with ypN1, the iDFS was 86% and the OS 93%; in ypN0 patients, the iDFS was 93% and the OS 98%. Conclusions: Response-guided axillary treatment in patients with limited nodal disease according to the MARI protocol is associated with favorable oncologic outcome without performing ALND’s. De-escalation can therefore be considered safe. [Table: see text]

Major pathologic response and long-term clinical benefit in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer after neoadjuvant chemotherapy.

e12608 Background: Rates of pathological complete response (pCR) are much lower in patients with hormone receptor–positive (HR+) /HER2-negative (HER2-) breast cancer than in those with HER2-positive and triple-negative breast cancer (TNBC). The majority of HR+/HER2- breast cancer patients can also achieve long-term survival despite not attaining pCR, indicating limited prognostic value of pCR in this population. This study aimed to identify novel pathologic end points for predicting long-term outcomes in HR+/HER2- breast cancer after neoadjuvant chemotherapy. Methods: We analyzed HR+/HER2- breast cancer patients with stage II-III tumors who underwent curative surgery after neoadjuvant chemotherapy from three hospitals. Major pathologic response (MPR), defined as the presence of Miller-Payne grades 3-5 and positive lymph node ratio of ≤10%, was used as a pathological evaluation indicator. MPR evaluates the extent of residual invasive carcinoma in both the breast and axillary lymph nodes following neoadjuvant therapy. We assessed the association between MPR and event-free survival (EFS) and performed Multivariable Cox regression to identify independent factors associated with EFS. Results: From January 2010 to December 2020, 386 patients were included in the final analysis. The median age was 46 years. 244 patients (63.2%) were premenopausal, with 271 (70.2%) patients diagnosed with stage III disease. The predominant neoadjuvant chemotherapy regimen was anthracycline combined taxane (79.3%). 28 patients (7.3%) achieved pCR and 118 patients (30.6%) achieved MPR. The median duration of follow-up was 54.4 months. Multivariate analysis showed that PR expression, Clinical stage, Miller–Payne grades and Positive lymph node ratio were independent prognostic factors for EFS (all P values <0.05). The prognostic effect of MPR remained in multivariable models (hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.26–0.76; P = 0.008), with 5-year EFS of 87% vs. 68% in the non-MPR group. In non-pCR patients, those who achieved MPR exhibited a similar EFS compared with pCR patients (HR, 2.25; 95% CI, 0.51–9.84; P = 0.28). Conclusions: MPR was a novel pathologic end point for prognostic evaluation in HR+/HER2- breast cancer after neoadjuvant chemotherapy. Compared to pCR, MPR may hold greater applicability in the prognosis evaluation.

Personalizing Locoregional Therapy in Patients With Breast Cancer in 2024: Tailoring Axillary Surgery, Escalating Lymphatic Surgery, and Implementing Evidence-Based Hypofractionated Radiotherapy.

The management of axillary lymph nodes in breast cancer is continually evolving. Recent data now support omitting axillary lymph node dissection (ALND) in most patients with metastases in up to two sentinel lymph nodes (SLNs) during upfront surgery and those with residual isolated tumor cells after neoadjuvant chemotherapy (NACT). In the upfront surgery setting, ALND is still indicated, however, in patients with clinically node-positive breast cancer or more than two positive SLNs and, after NACT, in case of residual micrometastases and macrometastases. Omission of the sentinel lymph node biopsy (SLNB) can be considered in many postmenopausal patients with small luminal breast cancer, particularly when axillary ultrasound is negative. Several randomized controlled trials (RCTs) are currently aiming at eliminating the remaining indications for ALND and also establishing omission of SLNB in a broader patient population. The movement to deescalate axillary staging is in part because of the association between ALND and lymphedema, which is swelling of an extremity because of lymphatic damage and obstructed lymphatic drainage. To reduce the risk of developing this condition, patients undergoing ALND can undergo reverse mapping of the axilla and immediate reconstruction or bypass of the lymphatics from the involved extremity. Decongestion and compression are the foundation of conservative treatment for established lymphedema, while lymphovenous bypass and lymph node transfer are surgical procedures to address the physiologic dysfunction. Radiotherapy is an essential component of breast locoregional therapy: more than three decades of radiation research has optimized treatment according to patient's risk of local recurrence while substantially reducing the number of treatment visits. High-quality RCTs have shown the efficacy and safety of hypofractionation-more than 2Gy radiation dose per treatment (fraction)-significantly reducing the burden of radiotherapy treatment for many patients with breast cancer. In 2024, guidelines recommend no more than 15-16 fractions for whole-breast and nodal radiotherapy, with some recommending five fractions for whole-breast radiotherapy. In addition, simultaneous integrated boost (SIB) has been shown to be noninferior to sequential boost with regards to ipsilateral breast tumor recurrence with similar or reduced long-term side effects, also reducing overall treatment length. Further RCTs are underway investigating other indications for five fractions, including SIB and regional node irradiation, such that, in future, it may be possible for the majority of breast radiotherapy patients to be treated with a 1-week course. This manuscript serves to outline the latest updates on axillary surgical staging, lymphatic surgery, and evidence-based radiotherapy in the treatment of breast cancer.

Integration of Radiomics and Immune-Related Genes Signatures for Predicting Axillary Lymph Node Metastasis in Breast Cancer

BackgroundTo develop a radiogenomics nomogram for predicting axillary lymph node (ALN) metastasis in breast cancer and reveal underlying associations between radiomics features and biological pathways. Materials and methodsThis study included 1062 breast cancer patients, 90 patients with both DCE-MRI and gene expression data. The optimal immune-related genes and radiomics features associated with ALN metastasis were firstly calculated, and corresponding feature signatures were constructed to further validate their performances in predicting ALN metastasis. The radiogenomics nomogram for predicting the risk of ALN metastasis was established by integrating radiomics signature, immune-related genes (IRG) signature, and critical clinicopathological factors. Gene modules associated with key radiomics features were identified by weighted gene co-expression network analysis (WGCNA) and submitted to functional enrichment analysis. Gene set variation analysis (GSVA) and correlation analysis were performed to investigate the associations between radiomics features and biological pathways. ResultsThe radiogenomics nomogram showed promising predictive power for predicting ALN metastasis, with AUCs of 0.973 and 0.928 in the training and testing groups, respectively. WGCNA and functional enrichment analysis revealed that gene modules associated with key radiomics features were mainly enriched in breast cancer metastasis-related pathways, such as focal adhesion, ECM-receptor interaction, and cell adhesion molecules. GSVA also identified pathway activities associated with radiomics features such as glycogen synthesis, integration of energy metabolism. ConclusionThe radiogenomics nomogram can serve as an effective tool to predict the risk of ALN metastasis. This study provides further evidence that radiomics phenotypes may be driven by biological pathways related to breast cancer metastasis.

Axillary Node Metastases of Medullary Thyroid Cancer: A Hallmark of Terminal Disease.

Little is known about axillary node metastasis of medullary thyroid cancer (MTC). To address this, a comparative study of patients with and without axillary node metastases of MTC was conducted. Among 1215 consecutive patients with MTC, 482 patients had node-negative MTC and 733 patients node-positive MTC. Among the 733 patients with node-positive MTC, 4 patients (0.5%) had axillary node metastases, all of which were ipsilateral. Patients with axillary node metastases had 5.7-6.9-fold more node metastases removed, both at the authors' institution (medians of 34.5 vs. 5 metastases; p=0.011) and in total (medians of 57 vs. 10 metastases; p=0.013), developed more frequently distant metastases (3 of 4 vs. 178 of 729 patients, or 75 vs. 24%; p=0.049), specifically to bone (2 of 4 vs. 67 of 729 patients, or 50 vs. 9%; p=0.046) and brain (1 of 4 vs. 4 of 729 patients, or 25 vs. 0.5%; p=0.027), and more often succumbed to cancer-specific death (3 of 4 vs. 52 of 729 patients, or 75 vs. 14%; p=0.005). Altogether, patients with axillary node metastases revealed 4-8-fold more node metastases in the ipsilateral lateral neck (medians of 11 vs. 3 metastases; p=0.021) and in the ipsilateral central neck (medians of 8 vs. 1 metastases; p=0.079) patients without axillary node metastases. Cancer-specific survival of patients with vs. patients without axillary node metastases of MTC was significantly shorter (means of 41 vs. 224 months; plog-rank<0.001). These findings show that patients with axillary node metastases of MTC have massive metastatic dissemination with poor survival.

ETHAN: A phase II study comparing different endocrine therapies for male breast cancer.

TPS632 Background: Male breast cancer is a rare disease, and most cases are hormone receptor-positive (HR+). Due to a lack of clinical trials, male breast cancer has historically been treated based on data extrapolated from women. However, there are substantial knowledge gaps in the comparative efficacy, safety, and patient-reported outcomes of endocrine therapies for male breast cancer. While tamoxifen is the current standard of care, additional data are warranted for aromatase inhibitors (AI), gonadal suppression, and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Methods: This is an open-label, multicenter, randomized, phase II trial designed to evaluate different endocrine therapies in men with HR+ and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. A total of 60 men will be enrolled across nine (9) sites within the Translational Breast Cancer Research Consortium (TBCRC). Key eligibility criteria include male sex and stage I, II, or III HR+/HER2- breast cancer before surgical resection of the primary tumor and axillary nodes. Key exclusion criteria include prior anti-cancer therapy for the current breast cancer or any other malignancy within the past 12 months, and inflammatory breast cancer. The trial has two phases. The first phase is a window of opportunity component in which newly diagnosed men are randomized 1:1:1 to either tamoxifen (Arm A), anastrozole (Arm B), or anastrozole plus degarelix (Arm C) given for three weeks. The primary endpoint for the window phase is Ki-67 reduction from the baseline diagnostic biopsy to the research biopsy at the end of the window phase. The second phase consists of neoadjuvant treatment, in which the tamoxifen group is randomized 1:1 to tamoxifen (Arm D) versus tamoxifen plus abemaciclib (Arm E), and the anastrozole alone (Arm B) and anastrozole plus degarelix (Arm C) groups are merged and then randomized 1:1 to anastrozole plus degarelix (Arm F) versus anastrozole plus degarelix plus abemaciclib (Arm G). The duration of the neoadjuvant phase is four (4) months, and the primary endpoint of this phase is residual cancer burden (RCB) index at time of surgery. The trial is powered for the RCB endpoint in a 2 x 2 factorial design to detect a 0.6 unit decrease in RCB index with 80% power and alpha=10%. For the Ki-67 endpoint, we assume an approximately 50% reduction in Arms A and B; Arm C will be of interest if it leads to ≥80% reduction in Ki-67. Secondary endpoints include: estradiol and testosterone levels at baseline, end of window, and during neoadjuvant phase; preoperative endocrine prognostic index (PEPI) score at surgery; adverse events; and patient-reported outcomes (including quality of life). Tumor tissue will be collected for correlative analyses. The study opened to enrollment at Dana-Farber in October 2023, and additional sites will open in 2024. Clinical trial information: NCT05501704 .

Revealing undetected axillary sentinel node in neoadjuvant chemotherapy treated breast cancer

Revealing undetected axillary sentinel node in neoadjuvant chemotherapy treated breast cancer

Breast cancer recurrence rate after mastectomy in young females.

e12591 Background: Breast cancer is the most commonly diagnosed female cancer worldwide and the most common cause of cancer mortality in women. Surgical treatment of early breast cancer includes lumpectomy or mastectomy with or without reconstruction. Despite the surgeon’s best effort to perform a radical resection of the breast tissue during mastectomy to achieve locoregional control, residual fibroglandular tissue was found in 20% of breasts on postoperative breast MRI, which carries a risk of recurrence. Younger women with breast cancer have inferior survival rates despite receiving more aggressive therapy. Tumors in young women are more likely to be poorly differentiated, hormone receptor-negative, have a high proliferation index, and more lymphovascular invasion, which is partially explained by patients’ genetic profile. Another factor that could contribute to poor outcomes is the advanced stage at the time of diagnosis, including larger tumor size and higher rates of axillary lymph node positivity. This knowledge has motivated us to conduct this study that is dedicated to looking at the recurrence rate in young females following mastectomy. Methods: This is a retrospective study that collected data from young female patients who were diagnosed with breast cancer between January 2010 and August 2018, had an age at diagnosis of 18-45 years old, and underwent unilateral or bilateral mastectomy with or without reconstruction. The study also looked at the patient’s risk factors and genetic profile. Results: A total of 115 patients were diagnosed with early-stage breast cancer between January 2010 and August 2018 and underwent mastectomy. 81.74% were Caucasian females, and 8.7% were African American females. The mean age of diagnosis was 36.9 years. The mean BMI was 30.5 kg/m2. 59.13% of patients had a family history of breast cancer. The most common genetic mutations were BRCA1 at 7.83% and BRCA2 at 8.7%. 71% of patients underwent a bilateral mastectomy. 76% of patients had reconstruction. 77% of tumors were ER-positive, 68% PR-positive, and 26% HER2-positive. 49.4% of tumors were Nottingham grade 3. 52% of patients had no nodal involvement, while 35% had N1 disease. 34.6% had lymphovascular invasion. We found that 18/115 patients had recurrence of breast cancer following mastectomy. 5/17 patients had locoregional recurrence, while 12/17 patients had a distant recurrence; 1 patient’s recurrence data was unavailable. The median time to recurrence was 1147.5 days (335 to 3107). The 5-year recurrence free survival rate is 86% ± 3%. Conclusions: Our study found that 15.65% of young females had recurrence after mastectomy. To our knowledge, this is the first dedicated study to look at the recurrence rate after mastectomy in this young, high-risk patient population. Our study aims to encourage larger studies in young females with breast cancer to help tailor the treatment plan in this population.