Pre-surgical cryoablation in ≤ 2 cm ER + /HER2-tumors. Prognostic factors for the presence of residual invasive carcinoma.

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.

Survival in pregnancy-associated breast cancer patients compared to non-pregnant controls.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is a rare entity whose prognosis has previously been studied and is subject to controversy. METHODS: Survival of patients with PABC diagnosed between 2009 and 2021 with breast cancer during pregnancy or until 1 year after childbirth was compared with non-pregnant patients with breast cancer from the same period at La Paz University Hospital. Cox proportional hazards regression was used to compare disease-free (DFS) and overall (OS) survival between the groups, adjusting for grade and pathologic stage. RESULTS: Among the 89 included patients with breast cancer, 34 were diagnosed during pregnancy, and 55 were not pregnant. The pregnant patients were more likely to have grade 3 tumors (61.3% vs 37%, p = 0.023) and an advanced stage (pathologic stage III-IV: 44.1% vs 17.6%, p = 0.008). Median follow-up was 47 months for the pregnant group and 46 months for the control group. After adjustments for tumor grade and pathologic stage, OS was comparable between the groups (HR 2.03; 95% CI 0.61 to 6.79; P = 0.25). CONCLUSIONS: The outcome of women diagnosed with PABC is comparable to young non-pregnant controls. However, it should be taken into account that PABC has a more aggressive phenotype.

Breast-Conserving Surgery Guided with Magnetic Seeds vs. Wires: A Single-Institution Experience.

PURPOSE: The aim of this study is to describe our initial experience using magnetic seeds (Magseed®) to guide breast-conserving surgery in non-palpable breast lesions and compare the use of magnetic seed with wires to guide breast-conserving surgery in terms of clinical and pathological characteristics. METHODS: We performed a retrospective study including all breast-conserving surgeries for non-palpable breast lesions under 16 mm from June 2018 to May 2021. We compared breast-conserving surgeries guided with magnetic seeds (Magseed®) to those guided with wires, analyzing tumor and patient characteristics, surgical time, and pathological results of the surgical specimens. RESULTS: Data from 225 cases were collected, including 149 cases guided by magnetic seeds and 76 cases guided by wires. The breast lesion was localized in every case. Both cohorts were similar regarding clinical and pathological characteristics. We found significant statistical differences (p < 0.02) in terms of the median volume (cm3) of the excised specimen, which was lower (29.3%) in the magnetic seed group compared with the wire group (32.5 [20.5-60.0]/46.0 [20.3-118.7]). We did not find significant differences regarding surgical time (min) or the affected or close margins. CONCLUSION: In our experience, the use of magnetic seed (Magseed®) is a feasible option to guide breast-conserving surgery of non-palpable lesions and enabled us to resect less breast tissue.

Surgical Interest of an Accurate Real-World Prediction of Primary Systemic Therapy Response in HER2 Breast Cancers.

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.

EMD-based data augmentation method applied to handwriting data for the diagnosis of Essential Tremor using LSTM networks.

The increasing capacity of today's technology represents great advances in diagnosing diseases using standard procedures supported by computer science. Deep learning techniques are able to extract the characteristics of temporal signals to study their patterns and diagnose diseases such as essential tremor. However, these techniques require a large amount of data to train the neural network and achieve good results, and the more data the network has, the more accurate the final model implemented. In this work we propose the use of a data augmentation technique to improve the accuracy of a Long short-term memory system in the diagnosis of essential tremor. For this purpose, the multivariate Empirical Mode Decomposition method will be used to decompose the original temporal signals collected from control subjects and patients with essential tremor. The time series obtained from the decomposition, covering different frequency ranges, will be randomly shuffled and combined to generate new artificial samples for each group. Then, both the generated artificial samples and part of the real samples will be used to train the LSTM network, and the remaining original samples will be used to test the model. The experimental results demonstrate the capability of the proposed method, which is compared to a set of 10 different data augmentation methods, and in all cases outperforms all other methods. In the best case, the proposed method increases the accuracy of the classifier from 83.20% to almost 93% when artificial samples are generated, which is a promising result when only small databases are available.

The Clinical Impact of Neoadjuvant Endocrine Treatment on Luminal-like Breast Cancers and Its Prognostic Significance: Results from a Single-Institution Prospective Cohort Study.

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.

[The impact of the first wave of the COVID-19 pandemic on oncological patients in a tertiary hospital]. / Impacto de la primera ola de la pandemia de COVID-19 en la atención a pacientes oncológicos en un hospital terciario.

BLACKGROUND: The COVID-19 pandemic has over-burdened the Spanish health service and, as a result, affected the treatment and management of oncological patients. The aim of this study is to make a descriptive analysis of the management of oncological patients and the functioning of the tumour committees in the University Hospital La Paz (Madrid) during the first wave of the pandemic. MATERIALS AND METHODS: A descriptive analysis was made, based on the results of a questionnaire given to all 18 adult tumour committees and 3 paediatric tumour committees in the University Hospital La Paz. Further information was obtained from all the hospital services involved in the diagnosis and treatment of oncological patients. RESULTS: During the first wave of the pandemic, there was a significant decrease in diagnostic tests. For many weeks, the majority of oncological surgical procedures were delayed or referred to other hospitals. Highly beneficial systemic and radiotherapeutic treatments were maintained and preoperative treatment was increased. The diagnosis and treatment of paediatric tumours was unaltered. Tumour committees were affected but each one adjusted in a different way. All the departments involved in the diagnosis and treatment of oncological patients made contingency plans to minimalize the effect on patients. CONCLUSION: This study shows how the management of oncological patients and the functioning of tumour committees was affected during the COVID-19 pandemic.

Analysis of Fine Motor Skills in Essential Tremor: Combining Neuroimaging and Handwriting Biomarkers for Early Management.

Essential tremor (ET) is a highly prevalent neurological disorder characterized by action-induced tremors involving the hand, voice, head, and/or face. Importantly, hand tremor is present in nearly all forms of ET, resulting in impaired fine motor skills and diminished quality of life. To advance early diagnostic approaches for ET, automated handwriting tasks and magnetic resonance imaging (MRI) offer an opportunity to develop early essential clinical biomarkers. In this study, we present a novel approach for the early clinical diagnosis and monitoring of ET based on integrating handwriting and neuroimaging analysis. We demonstrate how the analysis of fine motor skills, as measured by an automated Archimedes' spiral task, is correlated with neuroimaging biomarkers for ET. Together, we present a novel modeling approach that can serve as a complementary and promising support tool for the clinical diagnosis of ET and a large range of tremors.

The Present and Future of Neoadjuvant Endocrine Therapy for Breast Cancer Treatment.

Endocrine therapy (ET) has established itself as an efficacious treatment for estrogen receptor-positive (ER+) breast cancers, with a reduction in recurrence rates and increased survival rates. The pre-surgical approach with chemotherapy (NCT) has become a common form of management for large, locally advanced, or high-risk tumors. However, a good response to NCT is not usually expected in ER+ tumors. Good results with primary ET, mainly in elderly women, have encouraged studies in other stages of life, and nowadays neoadjuvant endocrine treatment (NET) has become a useful approach to many ER+ breast cancers. The aim of this review is to provide an update on the current state of art regarding the present and the future role of NET.

External validation of a prognostic model based on total tumor load of sentinel lymph node for early breast cancer patients.

BACKGROUND: A prognostic model based on the results of molecular analysis of sentinel lymph nodes (SLN) is needed to replace the information that staging the entire axilla provided. The aim of the study is to conduct an external validation of a previously developed model for the prediction of 5-year DFS in a group of breast cancer patients that had undergone SLN biopsy assessed by the One Step Nucleic Acid Amplification (OSNA) method. METHODS: We collected retrospective data of 889 patients with breast cancer, who had not received systemic treatment before surgery, and who underwent SLN biopsy and evaluation of all SLN by OSNA. The discrimination ability of the model was assessed by the area under the ROC curve (AUC ROC), and its calibration by comparing 5-years DFS Kaplan-Meier estimates in quartile groups of model predicted probabilities (MPP). RESULTS: The AUC ROC ranged from 0.78 (at 2 years) to 0.73 (at 5 years) in the training set, and from 0.78 to 0.71, respectively, in the validation set. The MPP allowed to distinguish four groups of patients with heterogeneous DFS (log-rank test p < 0.0001). In the highest risk group, the HR were 6.04 [95% CI 2.70, 13.48] in the training set and 4.79 [2.310, 9.93] in the validation set. CONCLUSIONS: The model for the prediction of 5-year DFS was successfully validated using the most stringent form of validation, in centers different from those involved in the development of the model. The external validation of the model confirms its utility for the prediction of 5-year DFS and the usefulness of the TTL value as a prognostic variable.

Fibromatosis mamaria. Reporte de dos casos clínicos y revisión bibliogáfica / Mammary fibromatosis. Two case report and review of literatura

RESUMEN Introducción y objetivos: La fibromatosis produce tumores benignos pero localmente agresivos, que afectan a los tejidos blandos. A nivel mamario, representa tan sólo el 0.2% de las neoplasias de la mama. Nuestro objetivo con el presente artículo es profundizar en el conocimiento de la fibromatosis mamaria, a través del estudio de dos casos clínicos, mostrando sus características clínico-radiológicas e histológicas, e intentar establecer un protocolo de actuación adecuado. Métodos: Estudio retrospectivo de dos casos clínicos de fibromatosis mamaria diagnosticados en el Hospital Universitario La Paz entre los años 2018 y 2019. Resultados: Presentaremos dos pacientes con diagnóstico de fibromatosis mamaria, ambas debutaron con la autopalpación de un nódulo mamario. Al realizarles una ecografía, se visualizó un nódulo sólido, mal definido y axila ecográficamente negativa, que precisó de biopsia-aspiración con aguja gruesa. En los dos casos, se decidió resección quirúrgica de la lesión. Seguimiento mediante exploración mamaria y pruebas de imagen periódicas. Conclusiones: Aunque se trata de una entidad benigna, la fibromatosis mamaria puede simular un proceso maligno, tanto clínica como radiológicamente, por lo que precisa de un estudio histológico. A pesar de que la diseminación metastásica es muy poco frecuente, no se debe olvidar el carácter agresivo a nivel local de esta patología, y sus altas tasas de recurrencia. Como tratamiento, se debe realizar una resección quirúrgica, aunque recientemente se ha contemplado la opción de vigilancia estrecha sin tratamiento. No existe evidencia científica que justifique la utilización de otros tratamientos como la radioterapia o el tratamiento hormonal.

ABSTRACT Introduction and objectives: Fibromatosis produces benign but locally aggressive tumours that affect soft tissues. At breast level, it represents only 0.2% of breast neoplasms. Our goal with this article is to increase knowledge on breast fibromatosis, through the study of two clinical cases; explaining their clinical-radiologic and histological characteristics. Additionally, try to establish an adequate protocol, for the management of the disease and for its subsequent monitoring. Methods: A retrospective study about two clinical cases of breast fibromatosis diagnosed in La Paz Hospital between 2018-2019. Results: both patients presented with clinical manifestations, autopalpation of a breast nodule. A breast ultrasound was performed and a solid nodule was visualized, with poorly defined edges and ecographically negative armpit. A core needle biopsy was performed to confirm the histological diagnosis. In both clinical cases, the treatment was surgical resection of the lesion. Periodic revisions are being performed in order to exclude recurrence. Conclusions: Although it is a benign disease, breast fibromatosis can simulate a malignancy, both in a clinical and radiological way, so histological study is mandatory in order to achieve an accurate diagnosis. Even metastatic dissemination is extremely rare, the local aggressive nature and high rates of recurrence for fibromatosis makes surgical excision, with wide free margins, the most important tool in treatment, although the possibility of close surveillance without treatment is recently being contemplated. There is no scientific evidence to justify the use of other treatments such as radiotherapy or hormonal treatment.

Discrete Cosine Transform for the Analysis of Essential Tremor.

Essential tremor (ET) is the most common movement disorder. In fact, its prevalence is about 20 times higher than that of Parkinson's disease. In addition, studies have shown that a high percentage of cases, between 50 and 70%, are estimated to be of genetic origin. The gold standard test for diagnosis, monitoring and to differentiate between both pathologies is based on the drawing of the Archimedes' spiral. Our major challenge is to develop the simplest system able to correctly classify Archimedes' spirals, therefore we will exclusively use the information of the x and y coordinates. This is the minimum information provided by any digitizing device. We explore the use of features from drawings related to the Discrete Cosine Transform as part of a wider cross-study for the diagnosis of essential tremor held at Biodonostia. We compare the performance of these features against other classic and already analyzed ones. We outperform previous results using a very simple system and a reduced set of features. Because the system is simple, it will be possible to implement it in a portable device (microcontroller), which will receive the x and y coordinates and will issue the classification result. This can be done in real time, and therefore without needing any extra job from the medical team. In future works these new drawing-biomarkers will be integrated with the ones obtained in the previous Biodonostia study. Undoubtedly, the use of this technology and user-friendly tools based on indirect measures could provide remarkable social and economic benefits.

Comparison of risk classification between EndoPredict and MammaPrint in ER-positive/HER2-negative primary invasive breast cancer.

PURPOSE: To compare the concordance in risk classification between the EndoPredict and the MammaPrint scores obtained for the same cancer samples on 40 estrogen-receptor positive/HER2-negative breast carcinomas. METHODS: Formalin-fixed, paraffin-embedded invasive breast carcinoma tissues that were previously analyzed with MammaPrint as part of routine care of the patients, and were classified as high-risk (20 patients) and low-risk (20 patients), were selected to be analyzed by the EndoPredict assay, a second generation gene expression test that combines expression of 8 genes (EP score) with two clinicopathological variables (tumor size and nodal status, EPclin score). RESULTS: The EP score classified 15 patients as low-risk and 25 patients as high-risk. EPclin re-classified 5 of the 25 EP high-risk patients into low-risk, resulting in a total of 20 high-risk and 20 low-risk tumors. EP score and MammaPrint score were significantly correlated (p = 0.008). Twelve of 20 samples classified as low-risk by MammaPrint were also low-risk by EP score (60%). 17 of 20 MammaPrint high-risk tumors were also high-risk by EP score. The overall concordance between EP score and MammaPrint was 72.5% (κ = 0.45, (95% CI, 0.182 to 0.718)). EPclin score also correlated with MammaPrint results (p = 0.004). Discrepancies between both tests occurred in 10 cases: 5 MammaPrint low-risk patients were classified as EPclin high-risk and 5 high-risk MammaPrint were classified as low-risk by EPclin and overall concordance of 75% (κ = 0.5, (95% CI, 0.232 to 0.768)). CONCLUSIONS: This pilot study demonstrates a limited concordance between MammaPrint and EndoPredict. Differences in results could be explained by the inclusion of different gene sets in each platform, the use of different methodology, and the inclusion of clinicopathological parameters, such as tumor size and nodal status, in the EndoPredict test.

[Co-expression of estrogen receptors and Her2/neu in breast cancer. Neoadjuvant chemotherapy sentinel lymph node and hormonotherapy]. / Cancer de mama con Her-2-neu y receptores hormonales positivos. Quimioterapia neoadyuvante, biopsia de ganglio centinela y tratamiento hormonal.

Neoadjuvant chemotherapy is an interesting option in the therapy of some breast cancer cases. Cases in which the timing for sentinel lymph node biopsy is controversial. Co-expression of estrogen receptors and Her2/neu (c-erbB-2) in breast cancer may imply hormone resistance, especially to tamoxifen. We present a clinic case with co-expression of estrogen receptors and Her2/neu that was treated with neoadjuvant chemotherapy and previous sentinel lymph node biopsy followed by breasttumorectomy with axillar lymphadenectomy, radiotherapy and hormonotherapy with letrozol, geserelina and trastuzumab. A good treatment response was found.