Purpose: Neoadjuvant endocrine treatment (NET) has become a useful tool for the downstaging of luminal-like breast cancers in postmenopausal patients. It enables us to increase breast- conserving surgery (BCS) rates, provides an opportunity for us to assess in vivo NET effectiveness, and allows us to study any biological changes that may act as valid biomarkers. The purpose of this study was to evaluate the safety and effectiveness of NET, and to assess the role of Ki67 proliferation rate changes as an indicator of endocrine responsiveness. Methods: From 2016 to 2020, a single-institution cohort of patients, treated with NET and further surgery, was evaluated. In patients with Ki67 ≥ 10%, a second core biopsy was performed after four weeks. Information regarding histopathological and clinical changes was gathered. Results: A total of 115 estrogen receptor-positive (ER+)/HER2-negative patients were included. The median treatment duration was 5.0 months (IQR: 2.0–6.0). The median maximum size in the surgical sample was 40% smaller than the pretreatment size measured by ultrasound (p < 0.0001). The median pretreatment Ki67 expression was 20.0% (IQR: 12.0–30.0), and was reduced to 5.0% (IQR: 1.8–10.0) after four weeks, and to 2.0% (IQR: 1.0–8.0) in the surgical sample (p < 0.0001). BCS was performed on 98 patients (85.2%). No pathological complete responses were recorded. A larger Ki67 fold change after four weeks was significantly related to a PEPI score of zero (p < 0.002). No differences were observed between luminal A- and B-like tumors, with regard to fold change and PEPI score. Conclusions: In our cohort, NET was proven to be effective for tumor size and Ki67 downstaging. This resulted in a higher rate of conservative surgery, aided in therapeutic decision making, provided prognostic information, and constituted a safe and well-tolerated approach.

Background: Breast cancer remains the most commonly diagnosed cancer in women. Breast-conserving surgery (BCS) is the standard approach for small low-risk tumors. If the efficacy of cryoablation is demonstrated, it could provide a minimally invasive alternative to surgery. Purpose: To determine the success of ultrasound-guided cryoablation in achieving the absence of Residual Invasive Cancer (RIC) for patients with ER + /HER2- tumors ≤ 2cm and sonographically negative axillary nodes. Materials and Methods: This prospective study was carried out from April 2021 to June 2023, and involved 60 preoperative cryoablation procedures on ultrasound-visible, node-negative (cN0) infiltrating ductal carcinomas (IDC). Standard diagnostic imaging included mammography and tomosynthesis, supplemented by ultrasound-guided biopsy. MRI was performed in patients with associated intraductal carcinoma (DCIS) and an invasive component on core needle biopsy (18 out of 22 cases). All tumors were tagged with ferromagnetic seeds. A triple-phase protocol (freezing–thawing-freezing) with Argon was used, with an average procedure duration of 40 min. A logistic regression model was applied to determine significant correlation between RIC and the study variables. Results: Fifty-nine women (mean age 63 ± 8 years) with sixty low-risk unifocal IDC underwent cryoablation prior to surgery. Pathological examination of lumpectomy specimens post-cryoablation revealed RIC in only one of 38 patients with pure IDC and in 4 of 22 mixed IDC/DCIS cases. All treated tumors had clear surgical margins, with no significant procedural complications. Conclusions: Cryoablation was effective in eradicating 97% of pure infiltrating ER + /HER2-tumors ≤ 2cm, demonstrating its potential as a surgical alternative in selected patients. Graphical

Purpose: Recently, authors have shown increasing interest in the emerging HER2-low subtype in breast cancer. These tumors are currently classified and treated as HER2-negative tumors. Neoadjuvant endocrine therapy (NET) has been used to achieve tumor downstaging and assess treatment response in postmenopausal women with low-grade luminal HER2-negative tumors. This study aimed to determine whether the response to NET was affected by low levels of HER2 expression in luminal tumors. Methods: The study was a single-centered retrospective investigation. Data were gathered from the medical records of patients from 2017 to 2023. All patients had luminal HER2-negative tumors and were treated with NET and subsequent surgery. Results: In total, 175 tumors were analyzed; 24.0% of the tumors were HER2-zero, 48.0% were HER2-low 1+, and 28.0% were HER2-low 2+. No significant differences were found when assessing NET response between the three groups, nor when evaluating tumor features. Response to NET was influenced by estrogen receptor levels, histological subtype and histological grade at diagnosis, Ki67 levels at interim biopsy, and NET duration. No differences were found for progression-free survival (PFS) or overall survival (OS) between HER2 groups. The group with Ki67 ≤ 10% at interim biopsy had longer PFS than the Ki67 > 10% group (p < 0.05). No differences for OS were found between these groups. Conclusions: Response to NET was not influenced by low levels of HER2 expression in luminal tumors when compared to HER2-zero tumors. PFS was longer for patients who had lower Ki67 levels at interim biopsy after NET.

Purpose: Marker placement in a pathological node improves extirpation rates in breast cancer cases with limited axillary involvement. Our goal was to assess the current indications for seed-marked axillary lymph node dissection (SMALND). Methods: We conducted a descriptive observational study, including 93 patients with cN1 breast cancer treated between January 2019 and December 2023. Seed placement was performed under ultrasound guidance, days before the procedure. Intraoperative detection was achieved using a probe, and resection was confirmed radiologically. Results: The primary indication was post-neoadjuvant therapy (72 patients: 60 for chemotherapy and 12 for hormone therapy), followed by initial surgery (14) and a single axillary recurrence (8). The extirpation rate of the marked axillary lymph node was 100%. In targeted axillary dissection (TAD), the concordance rate between the sentinel node and the marked axillary node was 85%. In the 12 cases of initial surgery, axillary lymphadenectomy was avoided because the marked node matched the sentinel node and was the only one involved. Conclusions: The use of seeds was proven to be highly useful in axillary surgery, both in cases of negativization following neoadjuvant therapy and in those with low axillary involvement or a single axillary recurrence.

Human epidermal growth factor receptor 2 (HER2)-enriched breast cancers (BC) present the highest rates of pathological response to primary systemic therapy (PST), but they are also the ones that tend to be larger at diagnosis, with microcalcifications and, often, with axillary involvement. If we do not have a reliable method to predict the degree of response, we may not be able to transfer the benefits of PST to surgery. The post-PST surgery planning is guided by the findings in the magnetic resonance imaging (MRI), whose predictive capacity, although high, is far from optimal. Thus, it seems interesting to find other variables to improve it. A retrospective observational study including women with HER2 BC treated with PST and further surgery was conducted. Information regarding clinical, radiological, and histopathological variables was gathered from a total of 132 patients included. Radiological complete response (rCR) was achieved in 65.9% of the sample, and pathological complete response (pCR), according to Miller and Payne criteria, in 58.3% of cases. A higher Ki67 value, the absence of Hormonal Receptors expression, and an rCR was significantly related to a pCR finding. This information impacts directly in surgery planning, as it permits adjustment of the breast resection volume.

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.