Objective This study aimed to compare one-step nucleic acid amplification (OSNA) with conventional histopathological ultrastaging for sentinel lymph node (SLN) assessment in patients diagnosed with uterine-confined endometrial cancer. The primary endpoint was to evaluate their differences in diagnostic performance in routine clinical practice. The secondary endpoint was to evaluate differences on oncological outcomes. Methods We conducted a multicentre retrospective study including patients with preoperatively uterine-confined endometrial cancer who underwent SLN biopsy. Two independent cohorts were analysed: one in which conventional ultrastaging (serial haematoxylin and eosin staining and immunohistochemistry [IHC]) was performed, and another assessed using OSNA. Only patients with a minimum follow-up of two years were included in the analysis. Results A total of 945 patients were included (IHC: 653; OSNA: 292). Overall, 11.6% (n=109) of cases were positive, predominantly with low-volume disease –isolated tumor cells 3.0% (n=28), micrometastases 4.0% (n=38), macrometastases 4.6% (n=43). Both methods demonstrated high diagnostic accuracy with low false-negative rates (overall 1.9%; IHC 1.6%, OSNA 2.8%). Median follow-up was 3.6 years. Three-year overall survival was 92.2% (95% confidence interval [CI] 90.0–93.9%), with comparable survival rates between IHC (92.8%, 95% CI 90.2–94.7%) and OSNA (90.9%, 95% CI 86.2–94.0%; p-value = 0.929). The ultrastaging method was not associated with overall survival in the cox multivariate analysis. Conclusion SLN assessment using OSNA and conventional IHC ultrastaging did not show significant differences regarding accuracy in detecting nodal metastases and yielded comparable oncological outcomes, both in overall and disease free survival. These findings reflect real world clinical practice, supporting the reliability of both techniques for endometrial cancer staging and suggest that the choice of SLN evaluation method does not affect long term patient outcomes.

OBJECTIVE:This study aimed to compare one-step nucleic acid amplification with conventional histopathological ultrastaging for sentinel lymph node assessment in patients with uterine-confined endometrial cancer. The primary endpoint was to evaluate differences in diagnostic performance in routine clinical practice. The secondary endpoint was to evaluate differences in oncological outcomes. METHODS:We conducted a multi-center retrospective study including patients with pre-operatively uterine-confined endometrial cancer who underwent sentinel lymph node biopsy. Two independent cohorts were analyzed: one in which conventional ultrastaging (serial hematoxylin and eosin staining and immunohistochemistry) was performed, and another assessed using one-step nucleic acid amplification. Only patients with a minimum follow-up of 2 years were included in the analysis. RESULTS:A total of 945 patients were included (immunohistochemistry = 653; one-step nucleic acid amplification = 292). Overall, 11.6% (n = 109) of cases were positive, predominantly with low-volume disease-isolated tumor cells 3.0% (n = 28), micrometastases 4.0% (n = 38), macrometastases 4.6% (n = 43). Both methods demonstrated high diagnostic accuracy with low false-negative rates (overall 1.9%; immunohistochemistry = 1.6%, one-step nucleic acid amplification = 2.8%). Median follow-up was 3.6 years. Three-year overall survival was 92.2% (95% confidence interval 90.0% to 93.9%), with comparable survival rates between immunohistochemistry (92.8%, 95% confidence interval 90.2% to 94.7%) and one-step nucleic acid amplification (90.9%, 95% confidence interval 86.2% to 94.0%, p =.929). The ultrastaging method was not associated with overall survival in the Cox multi-variate analysis. CONCLUSIONS:Sentinel lymph node assessment using one-step nucleic acid amplification and conventional immunohistochemistry ultrastaging did not show significant differences in accuracy for detecting nodal metastases and yielded comparable oncological outcomes, both in overall and disease -free survival. These findings reflect real-world clinical practice, supporting the reliability of both techniques for endometrial cancer staging and suggesting that the choice of sentinel lymph node evaluation method does not affect long-term patient outcomes.

Objective This study aimed to assess the frequency of MDM4 amplification in endometrial carcinomas and its association with clinicopathological features, particularly relapse risk in early-stage low-grade endometrioid endometrial carcinoma. Methods We conducted a case-control study including 110 stage I to II low-grade endometrioid endometrial carcinomas (39 relapsing and 71 non-relapsing tumors) and an additional cohort of 82 high-grade endometrial carcinomas. An independent retrospective cohort of 194 early-stage low-grade endometrioid endometrial carcinomas was used to validate the results. MDM4 amplification was analyzed by fluorescent in situ hybridization. Gene expression of MDM4 and GADD45A was measured by quantitative real-time polymerase chain reaction. Immunohistochemistry assessed hormone receptor status, p53, and mismatch repair proteins. POLE and CTNNB1 mutations were evaluated by Sanger sequencing. Results MDM4 amplification was detected in 31 of 186 tumors (16.7%): 14 of 104 low-grade endometrioid endometrial carcinomas (13.5%) and 17 of 82 high-grade endometrial carcinomas (20.7%). Among low-grade endometrioid endometrial carcinomas, amplification was significantly more frequent in relapsing tumors (11/38, 28.9%) than in non-relapsing ones (3/66, 4.5%) (p <.01). Concordant MDM4 amplification status was observed between biopsies and hysterectomy samples. In some relapsing cases, amplification emerged during disease progression. Multi-variable Cox regression identified MDM4 amplification as an independent predictor of relapse, alongside lymphovascular space invasion, tumor necrosis, and myometrial invasion. In the independent cohort, MDM4 amplification was associated with progression-free survival. Conclusions Our study suggested that MDM4 amplification is a potential predictor of the risk of recurrence in early-stage low-grade endometrioid endometrial carcinoma that can be easily evaluated in endometrial samples.

OBJECTIVE:This European multicenter study aimed to assess the diagnostic accuracy of one-step nucleic acid amplification (OSNA) as the primary endpoint by comparing this method with ultrastaging for the detection of sentinel node metastases in endometrial cancer patients. METHODS:European multicenter prospective performance study including data from 10 centers across 5 European countries. Each node, upon removal of surrounding adipose tissue, was sliced in 2 mm thick sections and equally distributed between ultrastaging and OSNA. OSNA is based on cytokeratin-19 detection, serving as a metastatic marker. Sensitivity, specificity, and concordance of OSNA versus ultrastaging were calculated at nodal and patient levels. RESULTS:Seven hundred forty-three sentinel nodes from 366 patients were evaluated. Compared to ultrastaging, OSNA showed concordance, specificity, and sensitivity of 95%, 97.6%, and 41.2% at the nodal level and 93.2%, 96.2%, and 47.8% at the patient level, respectively. In reverse analysis, when compared to OSNA, the ultrastaging showed a sensitivity of 45.2% and 45.8% at the nodal and patient levels, respectively. Irrespective of the size of metastasis, both methods agreed in 14 positive and 692 negative nodes (95%). This resulted in 24 (6.56%) patients with a positive OSNA and 23 (6.28%) patients with a positive ultrastaging finding. The number of discordant nodes was 47 (6.33%), 40 (85.1%) of them were micrometastases. Benign epithelial inclusions occurred in 4 nodes (0.54%) and 4 patients (1.09%). CONCLUSION:Compared with ultrastaging, OSNA showed high concordance and specificity, but sensitivity was low-similar to ultrastaging compared with OSNA as an index test in reverse analysis. The main limitation in comparing the two approaches by splitting the sentinel nodes was the tissue allocation bias. As reflected in the number of discordant cases, especially at the micrometastases level. The distribution of patients with node metastases was comparable between the two methods at both the nodal and patient levels. TRIAL REGISTRATION:German Clinical Trial Register: Nr. DRKS00021520.

Between 20% and 30% of endometrial cancer (EC) cases show mismatch repair deficiency (dMMR), and its characterisation is recommended in these tumours for molecular classification, screening of Lynch syndrome, and as a predictive biomarker for immunotherapy. The aim of this study was to explore two tests developed by Promega (OncoMate MSI Dx Analysis System and long mononucleotide repeat (LMR) microsatellite instability (MSI) analysis system). DNA from 126 EC tumours had been screened for MMR status by immunohistochemistry (IHC). Overall, 67 (53.2%) dMMRs and 59 (46.8%) proficient (pMMR) were included. The same cases were additionally explored for MMR genomic status, with 55 (43.7%) cases presenting an altered genomic pattern, and 69 (54.8%) with no genomic alterations. There were 71 (56.3%) microsatellite stability (MSS) cases for OncoMate and 69 (54.8%) for LMR, and 37 (29.4%) microsatellite instability (MSI) cases for OncoMate and 44 (34.9%) for LMR. Differences between the test assignments were significant (p < 0.001), with an increased proportion of correctly classified cases for the LMR assay, taking the IHC result as the reference. The respective sensitivity and specificity of the LMR assay was 95.5% and 68.1%, versus 86.5% and 53.5% for the OncoMate assay. In conclusion, the new LMR MSI Analysis System had a higher correlation with IHC, including cases that could be misdiagnosed due to minimal shifts, as well as higher sensitivity and specificity than the OncoMate panel. The best method regarding the use of dMMR/MSI as a response biomarker for immune checkpoint inhibitors requires further investigation.

Background/Objectives: The EndoPredict® assay has been widely used in recent years to estimate the risk of distant recurrence and the absolute chemotherapy benefit for patients with estrogen (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, there are no well-defined criteria for selecting patients who may benefit from the test. The aim of this study was to develop a novel nomogram to estimate the probability of obtaining a high-risk EndoPredict® result in clinical practice. Methods: The study cohort comprised 348 cases of T1-3/N0-1a/M0 ER-positive/HER2-negative breast carcinoma. A multivariate analysis was conducted using a training cohort (n = 270) based on clinicopathological features that demonstrated a statistically significant correlation with the EndoPredict® result in a univariate analysis. The predictive model was subsequently represented as a nomogram to estimate the probability of obtaining a high-risk result in the EndoPredict® assay. The predictive model was then validated using a separate validation cohort (n = 78). Results: The clinicopathological features incorporated into the nomogram included tumor size, tumor grade, sentinel lymph node status, pN stage, and Ki67. The internal validation of the model yielded an area under the curve (AUC) of 0.803 (95% CI = 0.751, 0.855) in the receiver operating characteristic (ROC) curve for the training cohort, with an optimal sensitivity and specificity at a threshold of 0.536. The external validation yielded an AUC of 0.789 (95% CI = 0.689, 0.890) in its ROC curve, with optimal sensitivity and specificity achieved at a threshold of 0.393. Conclusions: This study presents, for the first time, the development of a clinically accessible nomogram designed to estimate the probability of obtaining a high-risk result in the EndoPredict® assay. The use of easily available clinicopathological features allows for the optimization of patient selection for the EndoPredict® assay, ensuring that those who would most benefit from undergoing the test are identified.

Introduction: Following up on treated high-grade cervical intraepithelial neoplasia (HSIL/CIN) lesions poses a challenge. Cervical cytology often has a high false-negative rate, while high-risk human papillomavirus (HR-HPV) DNA testing, though sensitive, lacks specificity. The detection of messenger RNA of the HR-HPV E6 and E7 oncoproteins (E6/E7 mRNA) is proposed as an indicator of viral integration, which is crucial for identifying severe lesions. Additionally, HPV vaccination could reduce recurrence rates in patients treated for high-grade cervical intraepithelial neoplasia. Objective: Our study aimed to assess the clinical utility of E6/E7 mRNA determination in the follow-up of HPV-immunized patients who were treated for HSIL/CIN. Methods: We conducted a retrospective observational study including 407 patients treated for HSIL/CIN. The recurrence rate and the validity parameters of E6/E7 mRNA testing were analyzed. Results: The recurrence rate for high-grade lesions was 1.7%. This low percentage might be related to the vaccination of patients who were not immunized before treatment. The sensitivity of the E6/E7 mRNA test was 88% at the first clinical visit, reaching 100% in the second and third reviews. Specificity was 91% at the first visit, 92% at the second, and 85% at the third. Regarding predictive values, the positive predictive value was 18% at the first visit, 10% at the second, and 14% at the third, while the negative predictive value was 100% across all follow-up visits. Conclusions: The E6/E7 mRNA test appears to be an effective tool for ruling out recurrence after treatment for HSIL/CIN lesions in HPV-immunized patients.

Endometrial carcinoma is the most frequent gynecologic malignancy in western countries. In recent years, mutations in CTNNB1 have been associated with worse prognosis in low-risk carcinomas. However, there is a lack of understanding of the proteomic implications of CTNNB1 mutations in this type of tumor. In this study, we performed shotgun proteomics using Formalin-Fixed Paraffin-Embedded (FFPE) tissue samples of CTNNB1 mutated and wild-type low-risk endometrial carcinomas. A publicly available proteomic and transcriptomic database was used to validate results. Differential protein expression and Gene Set Enrichment Analysis revealed dysregulation of pathways associated with cell keratinization, immune response modulation, and intracellular calcium regulation. CTNNB1 mutated tumors showed immune dysregulation at multiple levels including cytokine secretion, cell adhesion, and lymphocyte activation. These results were supported by tissue multiplex immunofluorescence analysis, demonstrating reduced CD8 tumor-infiltrating lymphocytes and different immune spatial interaction patterns. Intracellular calcium dysfunction was associated with key transcript dysregulation. We found an increased expression of CAMK2A and ROR2, suggesting a potential role for non-canonical Wnt pathway activation in CTNNB1 mutated tumors.

The purpose of this study was to evaluate the suitability of formalin-fixed and paraffin-embedded (FFPE) samples and fixed fresh (FF) samples for single-cell RNA sequencing (scRNAseq). To this end, we compared single-cell profiles from FFPE and matched FF tissue samples of one invasive carcinoma of no special type carcinoma (invasive ductal carcinoma-IDC) and one invasive lobular carcinoma (ILC) to assess consistency in cell type distribution and molecular profiles. The results were validated using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and electron microscopy. Additionally, immune cell proportions identified by IHC were quantified using QuPath and compared to the scRNAseq results. FFPE- and FF-derived libraries demonstrated high-quality sequencing metrics, and cellular heterogeneity was similar. No exclusive cell populations were identified by either approach. The four samples analysis identified six types of epithelial cells, as well as tumoral microenvironment populations. The scRNAseq results from epithelial neoplastic cells were concordant with common IHC markers. The proportion of immune cells identified by IHC in FFPE sections were similar to those obtained by scRNAseq. We identified and validated a previously poorly recognized subpopulation of neoplastic multi-ciliated cells (MCCs) (FOXJ1, ROPN1L). Analysis of FOXJ1 in 214 ER-positive invasive carcinomas demonstrated protein expression in one third of tumors, suggesting frequent focal MCC differentiation. Our results support the suitability of scRNAseq analysis using FFPE tissue, and identified a subpopulation of neoplastic MCC in breast cancer.

The image-based determination of proteins with spatial context has revolutionized our understanding of biology in different fields, including developmental biology, immunology, and oncology. The popularization of multiplex and high-plex tissue imaging methods has allowed researchers to simultaneously interrogate multiple tissue proteins with high spatial resolution in a single tissue section. Although these technologies offer many opportunities, analytical challenges have also emerged. Currently, no single analytical pipeline covers the entire spectrum of analyses required to harness the potential of these spatial platforms. Here, we present Comprehensive Spatial Methods (CSM), an R-based analysis toolbox designed to analyze multiplex and high-plex omics with high spatial resolution. CSM covers all the analytical steps, from cell and tissue segmentation and protein expression normalization to cell phenotyping, spatial heterogeneity analysis, cell-to-cell spatial interaction determination and cellular neighborhood analysis. CSM relies on top-performing R libraries to deliver a user-friendly experience. We test the performance of CSM on a set of multiplex and high-plex images of endometrial, breast and colorectal carcinomas and non-tumoral lymph node, skin and lung tissue. We demonstrate that the ability of CSM to phenotype and quantify cells is better than that of other state-of-the-art resources. In addition, we show that the different approaches implemented in CSM for assessing cell phenotypes, spatial heterogeneity, cell-to-cell interactions and tissue neighborhoods cover a broad range of analytical scenarios. The freely available CSM toolbox covers many of the analytical needs of researchers working with spatially resolved histopathology data.

Incorporation of pathological and (not mandatory) molecular features into the new FIGO 2023 staging system has generated some controversy. Several validations have been published recently that demonstrated the higher prognostic precision of FIGO 2023 compared to the previous FIGO 2009 scheme. In the present article, the authors want to respond to some concerns that were raised by some pathologists and clinicians.

Purpose This study aimed to validate the classification of breast cancer (BC) patients in progression risk groups based on total tumor load (TTL) value to predict lymph node (LN) affectation after neo-adjuvant systemic therapy (NAST) obtained in the NEOVATTL study. Methods/patients This was an observational, retrospective, international, multicenter study including patients with infiltrating BC who received NAST followed by sentinel lymph node biopsy (SLNB) analyzed with one-step nucleic acid amplification (OSNA) from nine Spanish and two Italian hospitals. Patients were classified into three groups according to the progression risk, measured as disease-free survival (DFS), based on TTL values (> 250, 250–25,000, and > 25,000 copies/μL). The previous (NEOVATTL study) Cox regression model for prognosis was validated using prognostic index (PI) and Log ratio test (LRT) analyses; the value of TTL for axillary non-SLN affectation was assessed using receiver operating characteristic (ROC) curves. Results We included 263 patients with a mean age of 51.4 (± SD 10.5) years. Patients with TTL > 25,000 copies/μL had a shorter DFS (HR 3.561 [95% CI 1.693−7.489], p = 0.0008 vs. TTL ≤ 25,000). PI and LRT analyses showed no differences between the two cohorts ( p = 0.2553 and p = 0.226, respectively). ROC analysis showed concordance between TTL and non-SLN involvement (area under the curve 0.828), with 95.7% sensitivity and 92.9% specificity at a TTL cut-off of > 15,000 copies/μL. Conclusions In BC patients who had received NAST and underwent SLNB analysis using OSNA, a TTL value of > 25,000 copies/μL was associated with a higher progression risk and > 15,000 copies/μL was predictive of non-SLN involvement.

Abstract Objective: 1st: Assess the presence of residual infiltrating component in the surgical specimen of patients with Luminal Her2- tumors ≤ 2cm and ultrasound-negative axilla, following ultrasound-guided cryoablation. 2nd: Demonstrate that preoperative seed placement prior to cryoablation does not interfere with tumor cell elimination by freezing. Methods: Between April 2021 and April 2023, we performed preoperative cryoablation on 52 patients aged 53 to 79 years (mean 64) with 52 unifocal invasive ductal carcinomas (IDC) measuring 4 to 20 mm (mean 10), low grade (24 G1, 28 G2), 31 Luminal A and 21 B, Ki67 between 3 and 30% (mean 13). On ultrasound, all IDCs were visible and axilla-negative. 26 of them (50%) were referred from the screening program of the Community of Madrid. The tumor-to-skin surface distance ranged from 2 to 18 mm (mean 9 mm). All patients underwent mammography-tomosynthesis, staging, and biopsy under ultrasound guidance. The minimum time elapsed until surgery was 6 days, and the maximum was 78 days (mean 22). All patients underwent mammography-tomosynthesis, staging, and biopsy under ultrasound guidance. MRI was performed to rule out extensive intraductal component in 17 out of 20 patients with associated intraductal carcinoma (IDC) in the diagnostic biopsy. Preoperative marking with ferromagnetic seed placement was performed in all cases prior to cryoablation, using a single dose of anesthesia and through the same skin access. We used the ICEfx Galil Boston Scientific cryoablation system with 17G or 14G needles, applying the standard triple-phase protocol: freezing-passive thawing-freezing for approximately 40 minutes. The correct placement of the seed was subsequently confirmed by mammography. Results: There were no significant complications in any case. Out of 52 low-risk unifocal IDCs: -32 were pure IDCs (without associated intraductal component in diagnostic biopsy): no residual IDC was identified in the tumor specimen. -20 were mixed IDCs (with associated IDC in the diagnostic biopsy): *In 4 cases, residual IDC was found in the surgical specimen, with some foci of IDC remaining at the periphery of the post-cryoablation necrosis. *In 8 patients, foci of IDC were detected distant from the cryoablation zone. The pathologist determined that all samples had tumor-free margins. Conclusions: Cryoablation is effective in 100% of cases for pure infiltrating tumors ≤ 2cm. The presence of scattered IDC nests away from the cryoablation zone or at the margin of fat necrosis does not indicate technique failure, as all surgical specimens were determined to have tumor-free margins by the pathologist. For mixed infiltrating tumors, the ice ball should broadly cover the tumor size estimated by ultrasound and MRI. Standard adjuvant treatment will equalize the risk of recurrence with conventional lumpectomy. Table 1: 52 cases IDC unifocal ≤2cm Table 2: IDC Pure ≤2cm. Table 3: IDC mixed: IDC+DCIs ≤2cm Analysis of surgical specimen Citation Format: Maria José Roca Navarro, Pilar Zamora, Ylenia Navarro Monforte, Diego Garrido Alonso, Vicenta Córdoba Chicote, Teresa Diaz de Bustamante Durban, José María Oliver Goldaracena, Laura Yebenes Gregorio, Covadonga Marti, Jose Ignacio Sanchez-Mendez, Elisa Moreno, Laura Frías Aldeguer, Adolfo Loayza Galindo, Alberto Berjón García, Marcos Melendez Gisper, Carmen Martín Hervás, Lara Miralles, Cristina Escabias del Pozo, Younes Abadi, Elisa York Pineda, Gonzalo Garzón Moll, David Hardisson Hernáez, Alicia Hernández Gutiérrez, César Casado Sánchez, Virginia Martínez Marín, Shirin Zarbakhsh, Joaquin Gomez Ramirez. Preoperative cryoablation in 52 Her2- Luminal invasive ductal carcinomas ≤ 2cm. Analysis of the tumor specimen [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 PO2-01-12.

Triple-negative breast cancer (TNBC) is challenging to treat because of its lack of specific molecular targets. The IMMUNOPEG study aimed to evaluate a novel structured method for interpreting TNBC immunohistochemistry specimens processed with VENTANA PD-L1 (SP142) assay. The study involved 10 pathologists who evaluated 50 different immunohistochemistry specimens of TNBC with programmed death ligand 1 (PD-L1) expression considered challenging and that were previously evaluated by the scientific committee, using the NAVIFY Digital Pathology platform. Initially, the overall percent agreement (OPA) was 74%, with a negative percent agreement (NPA) of 68.2% for samples classified as negative, and a positive percent agreement (PPA) of 94.5% for positive samples. After training on the method, the OPA improved significantly to 81.6%, with the NPA increasing to 80.5% and the PPA decreasing to 85.5%. The mean percentage of the tumor area occupied by PD-L1-stained immune cells decreased from 2.5% to 1.6% post-training, approaching to the scientific committee's consensus of 1.029%. The study found that the pathologists' confidence in their assessments increased significantly when using the structured method, which was found to be easy to use by 9 out of 10 pathologists. All pathologists agreed that the structured method was useful for assessing PD-L1 expression. The study suggests that this method has potential value in interpreting challenging cases of PD-L1 immunohistochemistry (IHC) in TNBC. Further refinement and a training protocol may be necessary to enhance the method's efficiency. The potential for generalizing this structured method to other IHC procedures and pathologies warrants additional research.

Abstract OBJECTIVE To evaluate the efficacy of combined treatment with ultrasound-guided cryoablation and endocrine therapy (ET) in hormone receptor-positive (ER+), HER2-negative (HER-) invasive breast cancer (BC) patients with clinical stage I/II who are not candidates for axillary surgery. PATIENTS AND METHODS Patients with ER+, HER- invasive BC in clinical stage I/II who did not undergo sentinel lymph node biopsy (SLNB) or target axillary dissection (TAD) were included. They received treatment consisting of ultrasound-guided cryoablation combined with daily letrozole 2.5 mg orally. Cryoablation was performed as the initial treatment for BC < 15mm, followed by adjuvant ET, while neoadjuvant ET was administered for 6-12 months before cryoablation for BC ≥ 15mm. Cryoablation was performed using the ICEfx Galil argon gas system (Boston Scientific, USA) and the ProSense liquid nitrogen system (IceCure Medical Ltd, Caesarea, Israel). Follow-up breast ultrasound examinations were conducted every six months. Patients with a minimum follow-up of 12 months after cryoablation were included in the study. Core needle biopsies were performed if recurrence was suspected, and rescue cryoablation was considered for confirmed relapse. The tolerance and safety of the procedures were recorded. RESULTS From March 2019 to July 2023, a total of 96 patients with 105 ER+, HER2- invasive BC in clinical stage I/II who did not undergo SLNB or TAD were treated with ultrasound-guided cryoablation and ET. Among them, 58 patients (aged 58-96 years, mean 83, SD ±7.64) with 64 BC lesions (ranging from 5 to 60mm, mean 17, SD ±13.75) were followed up for a minimum of 12 months, with a mean follow-up period of 24 months (ranging from 12 to 50 months). The invasive carcinomas included 40 ductal, 16 lobular, 5 colloid, and 3 papillary cases. The ipsilateral breast tumor recurrence rate was 1,72% (1/58 patients). One patient with lobular carcinoma experienced a relapse at 17 months. Rescue cryoablation was performed, and after 25 months, she remains free of recurrence. Therefore, local control was achieved in all patients. Six patients died from causes unrelated to BC during the follow-up period. All procedures were well-tolerated with local anesthesia, and no serious complications were reported. CONCLUSION Ultrasound-guided cryoablation with ET constitutes an effective combined treatment for the local control of ER+, HER2- BC in patients with clinical stage I/II and omission for surgical axillary staging. Cryoablation is a very well tolerated procedure without morbidity. Citation Format: José María Oliver Goldaracena, Pilar Zamora, Covadonga Marti, Vicenta Córdoba Chicote, Maria José Roca Navarro, Diego Garrido Alonso, Ylenia Navarro Monforte, Teresa Diaz de Bustamante Durban, Fernando García Martínez, Jose Ignacio Sanchez-Mendez, Elisa York Pineda, Laura Yebenes Gregorio, Adolfo Loayza, Laura Frías Aldeguer, Elisa Moreno Palacios, Marcos Melendez Gisper, Joaquin Gomez Ramirez, Luis Asensio Gómez, Virginia Martínez Marín, David Hardisson Hernáez, Alberto Berjón García. Cryoablation and endocrine therapy for clinical stage I/II, ER+ breast cancer in patients with omission of surgical axillary staging. 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 PO1-01-07.