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Clinical characteristics and prognostic impact of HER2 low expression in breast cancer subtypes from a Brazilian realworld cohort
(2026) Mattar, André; Antonini, Marcelo; Cavalcante, Francisco Pimentel; Zerwes, Felipe Pereira; Millen, Eduardo Camargo; Brenelli, Fabricio Palermo; Frasson, Antônio Luiz; Madeira, Marcelo; Teixeira, Marina Diógenes; Amorim, Andressa Gonçalves; Oliveira, Larissa Chrispim de; Soares, Leonardo Ribeiro
Breast cancer (BC) is the most prevalent cancer among Brazilian women, yet related data remain limited. The HER2-low classification has gained significance with the advent of targeted therapies. This study aimed to assess survival outcomes of HER2-low BC compared to other subtypes in a real-world Brazilian cohort. We analyzed data from 8,485 breast cancer patients treated at Pérola Byington Hospital between 2010 and 2019. Overall survival (OS) was the primary endpoint, stratified by cancer subtype. The t-test and chi-square test evaluated variable associations, while multivariate analysis calculated odds ratios and 95% confidence intervals. Cox regression assessed survival, and Kaplan–Meier curves illustrated OS differences. The patients with HER2-low breast cancers showed significantly better overall survival than those with the triple-negative subtype (p < 0.01). However, they had significantly poorer overall survival than those with the Luminal A-like subtype (p < 0.01). The patients with triple-negative HER2-low disease had a higher risk of mortality than those with HER2-0 (p < 0.01). Finally, patients who achieved pathological complete response experienced significantly better overall survival than those who did not (p < 0.01). Our findings highlight triple negative HER2-low BC as a distinct subtype identifiable via standard immunohistochemistry, beyond just biomarker status. The study underscores the prognostic diversity among BC subtypes and emphasizes the importance of personalized treatment strategies.
Trastuzumab deruxtecan in human epidermal growth factor receptor 2-positive breast cancer brain metastases: a systematic review and updated meta-analysis
(2025) Michelon, Isabella Ferreira; Castro, Caio Ernesto do Rêgo; Madeira, Thiago Magalhães; Dacoregio, Maria Inez; Stecca, Carlos Eduardo; Soares, Leonardo Ribeiro; Saeed, Anwaar; Vilber, Maysa; Cavalcante, Ludimila
Background: Trastuzumab deruxtecan (T-DXd) has shown promising activity in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and central nervous system (CNS) involvement. In this updated meta-analysis, we explore the effectiveness of T-DXd in a large subset of patients with HER2-positive BC and CNS disease. Methods: A systematic search was made on September 16th, 2024, for studies investigating T-DXd in the scenario of HER2-positive BC and brain metastases (BMs) and/or leptomeningeal disease (LMD). We used random effects models for all statistical analyses. Results: We included 18 studies with 786 HER2-positive BC patients with CNS involvement (16 studies with 750 BMs patients and three studies with 36 LMD patients). We observed high overall antitumor responses (objective response rate [ORR], 60.4 %; disease control rate [DCR], 94.4 %; and clinical benefit rate [CBR], 79.3 %) and a 12-month PFS of 64.7 % and OS of 82.7 %. Intracranial ORR, DCR, and CBR were seen in 62.2 %, 88.6 %, and 68.6 % of patients, respectively, and 67.4 % achieved intracranial PFS at 12 months. Both stable and active BMs subgroups derived similar benefit from T-DXd. Better intracranial responses were seen for 33 patients with untreated BMs compared to 56 patients with previously treated or progressing lesions (odds ratio 3.82, 95 % confidence interval 1.3–10.8, p = 0.01). For the LMD group, T-DXd elicited intracranial ORR and CBR in 59.4 % and 94.1 % of patients, respectively. Conclusions: This updated meta-analysis continues to support the overall and intracranial activity of T-DXd in patients with HER2-positive BC and CNS involvement, including those with LMD.
Prognostic impact of real-world immunohistochemical changes in breast cancer treated with neoadjuvant chemotherapy
(2026) Antonini, Marcelo; Mattar, André; Madeira, Marcelo; Félix, Letícia Xavier; Araújo, Júlio Antônio Pereira de; Cavalcante, Francisco Pimentel; Zerwes, Felipe Pereira; Brenelli, Fabricio Palermo; Frasson, Antonio Luiz; Millen, Eduardo Camargo; Soares, Leonardo Ribeiro
Purpose To evaluate the rate and types of immunohistochemical (IHC) changes after neoadjuvant chemotherapy (NAC) and their influence on disease-free survival (DFS) and overall survival (OS) in breast cancer patients, with a focus on conversions such as HR+/HER-2+ to HR-/HER-2- and their implications for treatment adjustments. Methods This retrospective cohort study included 369 female patients aged 18 years or older with nonmetastatic breast cancer treated with NAC between January 2011 and January 2023. Patients who did not achieve complete pathological response were evaluated for changes in IHC profiles, including hormone receptor (HR) status, HER-2 expression, and Ki-67 index. Prognostic outcomes were assessed using Kaplan-Meier survival analysis and multivariate Cox regression models. Results IHC changes were observed in 41.7% of patients. Among those initially classified as HR-/HER-2-, 50.9% gained HR expression, and 14.1% acquired HER-2 expression. In HR+/HER-2+ cases, 70.8% experienced a loss of HER-2 expression. Patients with HER-2+ tumors exhibited more frequent IHC changes compared to HER-2- cases (P < .0001). After a median follow-up of 47.7 months, local recurrences occurred in 10.3% of patients, distant metastases in 29.5%, and 25.5% had died. Patients with IHC changes demonstrated significantly worse DFS and OS (P = .002), with the poorest outcomes associated with conversion to HR-/HER-2- (P < .001). Conclusion Post-NAC IHC changes are common and associated with poor prognosis, especially in patients losing HR and HER-2 expression. Monitoring IHC shifts is critical for guiding personalized treatment and improving prognostic evaluation.
Breast cancer stage, molecular subtype and survival in patients with obesity: a real-world study
(2025) Mattar, André; Antonini, Marcelo; Cavalcante, Francisco Pimentel; Zerwes, Felipe Pereira; Millen, Eduardo Camargo; Brenell, Fabricio Palermo; Frasson, Antônio Luiz; Soares, Leonardo Ribeiro; Madeira, Marcelo; Teixeira, Marina Diógenes
Background: Breast cancer (BC) is a leading cause of cancer-related deaths worldwide. Obesity, an established risk factor for BC in postmenopausal women, may also affect prognosis. This study evaluated the impact of obesity on the survival of BC patients treated at a public reference center in Brazil. Methods: A retrospective cohort study was conducted with 7,424 BC patients treated at Hospital da Mulher (São Paulo, Brazil) from January 2011 to June 2021. Patients were categorized into four groups based on body mass index (BMI): underweight, healthy weight, overweight, and obese. Clinical, pathological, staging, and immunohistochemistry data were analyzed. Survival outcomes (overall and progression-free) were assessed using Kaplan-Meier estimates, with comparisons via logistic and Cox regression. Results: Among the patients, 67.81% were overweight or obese, and 64.82% were postmenopausal (assumed ≥50 years old). A total of 6,992 patients were included in the survival analysis, with 3.79% succumbing to BC. No statistically significant differences in overall or progression-free survival were observed across BMI categories. Conclusions: While obesity is highly prevalent among Brazilian women with BC, it did not significantly impact survival outcomes in this study. These findings underscore the need for prospective studies to explore potential confounding factors and long-term effects, as well as to inform tailored interventions in similar healthcare settings.
Technical, social, and economic characteristics of mammography screening in Goiás: ecological study after the implementation of a mammography quality control program
(2025) Corrêa, Rosangela da Silveira; Peixoto, João Emílio; Freitas-Junior, Ruffo; Bastos, Suzana Alves; Rodrigues, Danielle Cristina Netto; Tanaka, Rodrigo Massakatsu Nishiharu; Marins, Lucy Aparecida Parreira; Soares, Leonardo Ribeiro
Objective: The aim of this study was to evaluate technical, social, and economic aspects characterizing opportunistic breast cancer screening in a state in central Brazil. Methods: A survey was conducted to quantify the number of mammography machines and evaluate the imaging technology, the geographical distribution of the scanners, the number of mammograms performed at each center, the cost of the exams, and sources of payment. Data from this study were compared with data from a similar study conducted in 2008. Results: In Goiás, 164 mammography units were operational, with 66 (40%) serving the Sistema Único de Saúde (SUS). Approximately 400,896 scans were performed in 2019, averaging 204 scans/month (ranging from 5 to 1,000), at a cost of R$ 41,931,120.00. Screening coverage was 31.2%, with 6.4% of these scans being performed within the SUS. No correlation was found between the municipal Human Development Index (HDI) and mammography coverage in the health regions (HRs) (p=0.10). Compared with the 2008 results, the percentage of computed radiography systems increased from 24.3% to 86.7%, and digital radiography was introduced (7.3%). Conclusion: In 2019, breast cancer screening coverage in Goiás reached 31.1%, with 6.4% of scans being conducted within the SUS. The geographic distribution of mammography units is heterogeneous, and productivity is low. Compared to 2008, availability increased, and the standard of the equipment improved.
CADONOT: comparing axillary dissection or not in breast cancer surgery
(2025) Mattar, André; Antonini, Marcelo; Cavalcante, Francisco Pimentel; Zerwes, Felipe Pereira; Millen, Eduardo Camargo; Brenelli, Fabricio Palermo; Frasson, Antonio Luiz; Okumura, Patrícia Carvalho Baruel; Okumura, Lucas Miyake; Soares, Leonardo Ribeiro
Introduction Sentinel lymph node biopsy (SLNB) is the gold standard for the axillary evaluation of clinically node-negative early breast cancer. The ACOSOG Z0011 study demonstrated the safety of omitting axillary dissection for limited SLNB disease, with other trials confirming SLNB alone or with axillary radiotherapy (AR) as non-inferior. Methods We followed PRISMA guidelines and registered at PROSPERO. Using Medline, Embase, and Cochrane, we reviewed randomized controlled trials (2010–2024). Outcomes, including 5-, 8-, and 10-year OS, DFS, recurrence rates, and lymphedema, were analyzed with R software and assessed for bias (Cochrane RoB) and evidence quality (GRADE). The focus was ALND vs. SLNB, alone or with AR, in cT1-T3 BC with 1–2 metastatic SLNs. Results Thirteen articles from seven randomized controlled trials (RCTs) were included, covering 7338 women with a follow-up period of 2.8–10 years. SLNB was associated with a 65 % lower risk of lymphedema than ALND, with no significant differences in the 5-, 8-, or 10-year OS, DFS, or recurrence rates. A meta-analysis comparing micrometastasis and macrometastasis showed no impact on outcomes, indicating that ALND may be unnecessary in either case. Recurrence rates also did not differ between SLNB and ALND, reinforcing SLNB's significantly lower lymphedema risk of SLNB. Conclusions This systematic review and meta-analysis support SLNB as a safe and effective alternative to ALND in early-stage BC with 1–2 positive SLNs, providing comparable survival and recurrence outcomes, with fewer complications.
Is axillary surgery still justified in DCIS diagnosed via vacuum-assisted biopsy?
(2025) Ramos, Marcellus do Nascimento Moreira; Mattar, André; Antonini, Marcelo; Zerwes, Felipe Pereira; Cavagna, Felipe Andreotta; Cavalcante, Francisco Pimentel; Millen, Eduardo Camargo; Brenelli, Fabricio Palermo; Madeira, Antonio Luiz; Madeira, Marcelo; Soares, Leonardo Ribeiro
Background The role of axillary surgery in ductal carcinoma in situ (DCIS) remains controversial, particularly for cases diagnosed via vacuum-assisted biopsy (VAB), which may reduce “upstage” to invasive disease. This study evaluates the incidence of axillary metastasis and pathologic upstaging in DCIS to identify subgroups where axillary staging can be safely omitted. Methods A retrospective cohort of 494 patients with pure DCIS diagnosed by VAB (2011–2019) was analyzed. Patients were stratified by age, nuclear grade, comedonecrosis, and surgical approach (breast-conserving surgery [BCS] vs. mastectomy). Axillary management included sentinel node biopsy (SNB), axillary dissection (AD), or omission. Multivariate logistic regression identified predictors of axillary surgery and upstaging to invasive carcinoma. Results Most patients underwent BCS (72.7%), with axillary evaluation performed in 35.1% of BCS cases versus 91.9% of mastectomies (p<0.001). Only 3.8% (19/494) were upstaged to invasive carcinoma, and nodal involvement occurred in 1.2% (3/250) of axillary procedures—all in patients with invasive foci on final pathology. No pure DCIS cases had nodal metastasis. Younger age (<40 years, p=0.039), high nuclear grade (grade 3, p=0.006), and mastectomy (p<0.001) independently predicted axillary surgery. Comedonecrosis and palpable lesions were associated with higher SNB rates but not nodal positivity. Conclusions Routine axillary surgery is unnecessary in VAB-diagnosed DCIS. Omission of SNB appears safe for patients undergoing BCS without high-risk features (palpability, high grade). Axillary staging may be reserved for mastectomy candidates or those with suspicions imaging of invasive disease.
Disparities in breast cancer screening, stage at diagnosis, and treatment in Brazil: a warning of the need to change public policies
(2026) Freitas-Junior, Ruffo; Rocha, Aline Ferreira Bandeira de Melo; Soares, Leonardo Ribeiro; Ferreira, Glalber Luiz da Rocha
Background Breast cancer (BC) is the most prevalent form of cancer in Brazilian women, contributing significantly to cancer-related mortality, particularly when diagnosed at advanced stages. Methods This ecological, temporal series study evaluated breast cancer mammography screening rate, clinical staging, and the time from diagnosis to treatment initiation in women of 40–49, 50–69 and ≥ 70 years of age in Brazil, its geographical regions, and states between 2013 and 2022. The data were extracted from databases of the Unified Health System (DATASUS). Results There was a decreasing trend in mammography screening rate for the 40-49-year age group between 2013 and 2020 (Annual Percentual Change- APC= -10.79; p<0.001), and stability in 2020–2022. Rates for the 50-69-year group remained stable, while fell for women ≥ 70 years of age (APC= -6.27; p<0.001) between 2013 and 2022. Cases of advanced stages at diagnosis tended to increase in all age groups: 40–49 (APC=1.71; p<0.001), 50–69 (APC=1.43; p<0.001) and ≥ 70 years (APC=1.82; p=0.001). The mammography screening rate was low for all the age groups and all geographical regions, with lower rates found for the 40–49 and ≥ 70-year age groups. The poorest screening rates were seen in the regions North, Northeast and Midwest, revealing regional disparities. The proportion of cases diagnosed at advanced stages (III/IV) increased, particularly in 40–49 and ≥ 70-year age groups. Time from diagnosis to treatment initiation exceeded 60 days in >50% of cases in all age groups, with an increasing trend in women of 50–69 (APC=1.27; p<0.001) and ≥ 70 years of age (APC=1.83; p<0.001). Conclusions This study highlights the urgent need for public policies to increase BC mammography screening rate beyond the 50-69-year age group, and to guarantee equitable access to early diagnosis and timely treatment, particularly in less affluent areas. Dealing with these disparities is crucial to improving BC outcomes in Brazil, positively influencing clinical stage at diagnosis, treatment efficacy, and ultimately, survival and mortality.
Overall survival in breast cancer patients: analysis of a 27- year historical cohort
(2026) Rocha, Marina Elias; Rahal, Rosemar Macedo Sousa; Soares, Leonardo Ribeiro; Oliveira, José Carlos; Freitas-Junior, Ruffo
Background: This study aimed to analyzed overall survival and prognostic factors in a 27-year historical cohort of women with breast cancer in the Brazilian city of Goiânia. Methods: This retrospective cohort study used data from the population-based cancer registry in Goiânia, Goiás, Brazil, to evaluate overall survival between 1988 and 2015. Survival curves were constructed using the Kaplan-Meier method and compared with the log-rank test. Multivariate Cox regression analysis was performed to evaluate predictors of survival, with significance established at p<0.05. Results: The most common age group among the 7,395 women included in this study was 50-69 years (45.4%). The majority had localized breast cancer (62.4%) and the luminal A subtype (50.1%). The median survival was 122 months, with a 5-year overall survival rate of 83.1% and a 10-year overall survival rate of 65.5%. When evaluating ethnicity, survival was found to be greater for among white women compared to black women (mean of 120 months versus 110 months). In the Cox regression analysis, the following factors were found to be associated with decreased overall survival: age >70 years (HR: 1.33; p<0.001), histologic grade III (HR: 1.21; p=0.042), estrogen receptor-negative breast cancer (HR: 1.26; p=0.010), progesterone receptor-negative breast cancer (HR: 1.47; p=0.041), triple-negative subtype (HR: 2.36; p=0.008) and regional disease extension (HR: 1.73; p=0.023) or metastasis (HR: 2.67; p=0.012). Conclusion: During the study period, the overall survival rate in this cohort of women with breast cancer was 83.1% at five years and 65.5% at ten years. Different clinical, biological and tumor-related factors significantly affected prognosis in this population.
Comparison of functional performance, kinesiophobia, muscle strength, quality of life, and fatigue between mastectomy and quadrantectomy in breast cancer survivors
(2025) Marques, Vitor Alves; Santos, Wanderson Divino Nilo dos; Silva, Maria Sebastiana; Ferreira Júnior, João Batista; Soares, Leonardo Ribeiro; Silva, Naiany Pereira; Freitas-Junior, Ruffo; Vieira, Carlos Alexandre
Introduction: Mastectomy and quadrantectomy are the two primary surgical procedures performed on breast cancer survivors. This study aimed to compare functional performance, kinesiophobia, and muscle strength between women who were subjected to mastectomy and those who underwent quadrantectomy. Methods: A total of 27 participants were included, divided into a mastectomy group (mean age 51.0, standard deviation ±7.83 years) and a quadrantectomy group (mean age 53.5±9.33 years). Functional performance was assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire; kinesiophobia was measured with the Tampa Scale of Kinesiophobia (TSK); quality of life was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Breast Cancer module version 23 (EORTC BR-23); fatigue was analyzed with the Functional Assessment of Cancer Therapy – Breast cancer with arm subscale (FACT-B+4); and muscle strength was obtained through the bilateral isometric strength (BIS) and one-repetition maximum (1RM) tests. Data normality was verified using the Kolmogorov–Smirnov test. The unpaired t-test was applied to normally distributed variables, while the Mann–Whitney test was used for non-normally distributed variables. The significance level was set at p≤0.05. Results: No significant differences were found between groups regarding muscle strength (p=0.213), functional performance (p=0.635), or kinesiophobia (p=0.752). However, the mastectomy group reported lower scores in the breast symptoms domain of quality of life (p=0.050). Conclusion: Although no significant differences were observed in muscle strength, functional performance, or kinesiophobia, women in the mastectomy group reported worse quality of life in the breast symptoms domain.
Comparative discourse analysis of logical memory recall in normal elderly from rural and urban areas
(2025) Araújo, Lúcia Inês de; Silva, Sérgio Leme da; Caixeta, Leonardo Ferreira
This study examined the nature of errors in prose recall made in normal aging from different cultural backgrounds: rural and urban areas. Objective: The aim of this study was to examine the nature of errors in prose recall made in normal aging from different cultural backgrounds. Methods: We evaluated neurologically normal elderly divided into two groups: 12 subjects resident in a rural area in Central Brazil (group 1, called “Interior”) and 10 subjects from a metropolitan area in a big city in Central Brazil (group 2, called “Metropolis”). Responses by 22 nondemented older adults to the Logical Memory subtest of the Wechsler Memory Scale were examined in a propositional analysis. Results: Healthy older adults from rural areas (interior group) showed good immediate recalls, but had deficits in retention over a delay. Subjects from urban areas made errors of omission, not commission, at immediate recall. Conclusion: These errors probably reflect difficulty with attentional control rather than memory per se. There are differences in the performance of the elderly when considering different levels of education for neuropsychological tests associated with immediate recalls (but not with delayed recall), suggesting that working memory systems may be more impacted by years of schooling than the coding memory system.
Ampliando as indicações da bupropiona: uma breve atualização
(2025) Caixeta, Leonardo Ferreira; Vargas, Ciro Mendes; Nogueira, Yanley Lucio; Rabahi, Arthur; Assunção, Marcos Paulo do Carmo; Caixeta, Victor de Melo
Introduction: The use of bupropion has expanded, and emerging indications have sparked interest in the molecule for depressive endophenotypes as well as conditions beyond depression. Accordingly, the aim of this work was to provide an update on the clinical pharmacology of bupropion, including emerging therapeutic indications. Methodology:We conducted a brief review and update on various aspects of bupropion, from components of its pharmacological action, its usefulness in different pharmacological combinations, to new indications in modern psychiatry. Results:Bupropion has very specific niche indications, not limited to mood disorders, such as smoking, pseudobulbar affect, and apathy. Positive therapeutic results have also been observed in bipolar depression, geriatric depression, seasonal depression, social anxiety disorder, and dysthymia. The combination of bupropion with dextromethorphan may be useful in the treatment of pseudobulbar affect and (secondary) depression and agitation in Alzheimer's disease. It should rarely be used as monotherapy, presenting value in pharmacological combinations with a well-defined rationale. Conclusion:Bupropion's mode of action has opened a new front for treating depression beyond serotonergic mechanisms. Despite being on the market for a long time, bupropion maintains its usefulness in antidepressant prescriptions and has sparked new indications in different areas of psychiatry, particularly in combination with other drugs.
Immunohistochemical changes after neoadjuvant chemotherapy and their impact on breast cancer survival: a systematic review and meta-analysis
(2025) Antonini, Marcelo; Mattar, André; Facina, Gil; Cavalcante, Francisco Pimentel; Zerwes, Felipe Pereira; Brenelli, Fabricio Palermo; Frasson, Antônio Luis; Millen, Eduardo Camargo; Campos, Rodrigo Caires; Feélix, Letícia Xavier; Vieira, Juliana Calado; Soares, Leonardo Ribeiro
Changes in immunohistochemical (IHC) profiles following neoadjuvant chemotherapy (NAC) may impact therapeutic decisions and prognosis in breast cancer patients. However, the clinical significance of these biomarker conversions remains uncertain. To evaluate the frequency of IHC marker conversion (estrogen receptor [ER], progesterone receptor [PR], and HER2) after NAC and its association with pathological complete response (pCR), overall survival (OS), and disease-free survival (DFS). We conducted a systematic review and meta-analysis of cohort studies reporting pre- and post-NAC IHC profiles in breast cancer. A comprehensive search was performed in PubMed, Embase, Scopus, and Web of Science. The ROBINS-I tool was used to assess risk of bias. Random-effects models were applied to calculate pooled conversion rates and assess the prognostic impact of IHC changes. Twenty-four studies (n = 5891 patients) were included. The pooled conversion rates were 9.2% for ER, 15.1% for PR, 8.6% for HER2. Loss of hormone receptor positivity was associated with a lower pCR rate and worse DFS (HR 1.42; 95% CI, 1.11-1.81). HER2 gain correlated with improved pCR. High heterogeneity was observed, and sensitivity analyses confirmed the robustness of the results. IHC profile changes after NAC are frequent and clinically relevant. Loss of hormone receptor expression may indicate poorer prognosis, while HER2 gain suggests improved treatment sensitivity. Reassessment of IHC markers post-NAC should be considered to optimize adjuvant therapy decisions.
Oncological outcomes with and without axillary lymph node dissection in patients with residual micrometastases after neoadjuvant chemotherapy (OPBC-07/microNAC): an international, retrospective cohort study
(2026) Montagna, Giacomo; Alvarado, Michael; Myers, Sara; Mrdutt, Mary M.; Sun, Susie X.; Sevilimedu, Varadan; Barrio, Andrea V.; Bruele, Astrid Botty van den; Boughey, Judy Caroline; Boyle, Marissa K.; Soares, Leonardo Ribeiro
Background Despite the paucity of outcome data, axillary lymph node dissection (ALND) is increasingly being omitted in patients with positive sentinel lymph nodes after neoadjuvant chemotherapy, particularly in those with low-volume residual disease. We investigated oncological outcomes in patients with breast cancer and residual micrometastases in the sentinel lymph nodes treated with or without ALND. Methods OPBC-07/microNAC was a retrospective cohort study, using data obtained from the institutional databases of 84 cancer centres in 30 countries. Patients aged 18 years or older with clinical T1–4, N0–3 breast cancer at diagnosis treated with neoadjuvant chemotherapy followed by surgery between Jan 1, 2013, and May 31, 2023, who were found to have residual micrometastases (metastasis measuring >0·2 mm or >200 cells, not exceeding 2·0 mm in size) on frozen section or on final paraffin sections as determined by sentinel lymph node biopsy, targeted axillary dissection (sentinel lymph node biopsy with single or dual-tracer mapping plus image-guided localisation of the initially biopsy-proven and clipped node), or the marking axillary lymph nodes with radioactive iodine seeds (MARI) procedure were eligible for inclusion. The primary endpoint was the 5-year rate of any axillary recurrence (isolated or combined with local or distant recurrence) stratified by type of axillary surgery. Given the median follow-up, here we report 3-year rates and exploratory 5-year estimates. This study was registered with ClinicalTrials.gov, NCT06529302. Findings 1585 female patients with ypN1mi disease were analysed, of whom 804 (50·7%) underwent ALND and 781 (49·3%) did not. Of 1585 women, 238 (15·0%) self-identified as Asian, 65 (4·1%) as Black, 200 (12·6%) as Hispanic, 968 (61·1%) as White, and 114 (7·2%) as unknown race and ethnicity. 925 (58·4%) of 1585 women had cT2 tumours, 1054 (66·5%) were node positive, and 1267 (79·9%) received nodal radiotherapy. The median follow-up was 3·1 years (IQR 1·8–5·2). The 3-year rate of any axillary recurrence (isolated or combined with local or distant recurrence) for the entire cohort was 2·0% (95% CI 1·3–2·9), with no statistical difference identified by extent of axillary surgery. However, patients with triple-negative disease who did not receive ALND had significantly higher rates of any axillary recurrence than women treated with ALND (8·7% [95% CI 4·4–15·0] vs 2·4% [95% CI 0·7–6·5], p=0·018). On multivariable analysis, triple-negative breast cancer (hazard ratio 3·83 [95% CI 1·72–8·52]) and omission of nodal radiotherapy (2·62 [1·19–5·73]) but not omission of ALND (0·86 [0·37–2·00]) were independently associated with an increased risk of any axillary recurrence. Interpretation Overall, these results do not support ALND for all patients with ypN1mi on sentinel lymph node biopsy treated with nodal radiotherapy; however, tumour biology should be taken into account when considering ALND omission.
Da empatia ao algoritmo: a cognição social frente à inteligência artificial
(2025) Santos, Tiago Fernando Figueiredo; Caixeta, Leonardo Ferreira
Introduction: The advancement of artificial intelligence (AI) has profoundly reshaped human interactions, raising questions about its relationship with social cognition, the ability to perceive, interpret, and respond to others' mental states. Objective: To analyze the bidirectional relationship between social cognition and AI, addressing challenges in computational modeling of human social intelligence and potential impacts of interaction with intelligent machines on coping with or exacerbating loneliness. Method: Opinion article based on narrative literature review, analyzing empirical and theoretical studies on social neuroscience, human-robot interaction, and loneliness management through AI technologies. Results: The complexity of human social cognition remains the main challenge for AI naturalization. Neuroscientific evidence reveals distinct patterns of brain activation in interactions with embodied versus non-embodied agents, suggesting hierarchy in social cognitive functions. AI technologies demonstrate therapeutic potential in managing loneliness but also risks of amplifying this phenomenon. Conclusion: Analysis of human-AI interaction provides valuable insights into neural mechanisms of social cognition, showing that interpersonal imaginative processes remain distinctively human. Clinical use of AI requires careful consideration of its limitations and potential paradoxical effects.
Oral manifestations of Morgellons disease: current understanding of a psychiatric condition – a case series
(2025) Stiernhuvud, Fabiola; Caixeta, Leonardo Ferreira; Herrera Martínez, Manuela; Labruzzi, Camilo Manuel Abalos
Morgellons disease is a rare controversial illness in individuals which is characterized by having a fixed, false belief (delusion) in which they are infested by non-living organisms, despite medical evidence which proves the contrary. The symptoms can appear solely in the oral cavity, a condition that had not previously been described in the dental literature. The underlying mechanisms behind these findings remain unclear; moreover, established diagnostic criteria or effective treatments were unsuccessful. This case report highlights the sensations of feeling hair and threads between the teeth of patients with Morgellons disease, as well as an unusual perception of the tongue and saliva that was self-reported. Conventional medical treatments have not been effective in alleviating those oral symptoms. Taking into account the scarcity of cases in the dental literature, the article underscores the importance of interdisciplinary approaches, in order to enhance diagnosis and treatment by integrating oral and mental health care.
Autism spectrum disorders and personality disorders: differential diagnosis or comorbidity?
(2025) Santos, Tiago Fernando Figueiredo; Caixeta, Leonardo Ferreira
Objective: The clinical overlap between autism spectrum disorder (ASD) and Personality Disorders (PDs) poses significant diagnostic challenges. Shared features—such as social communication difficulties, rigidity, and emotional dysregulation—often lead to misdiagnosis or delayed diagnosis, especially in adults and underrepresented populations (e.g., women). Methods: This narrative review synthesizes current evidence on the differential diagnosis and comorbidity of ASD and PDs to guide clinical practice. Results: Findings highlight substantial symptom overlap, particularly in social cognition and emotional regulation. For instance, both ASD and Schizotypal PD may exhibit social withdrawal, while ASD and Borderline PD share impulsivity and identity disturbances—though with distinct etiologies (neurodevelopmental vs. trauma-related). Conclusions: Clinicians must adopt a developmental perspective to disentangle ASD from PDs, integrating longitudinal history, neuropsychological testing, and multidisciplinary evaluations. Future research should prioritize biomarker-based diagnostics and tailored interventions for comorbid presentations.
GlyT1 (SLC6A9) inhibition in neurological and psychiatric disorders
(2026) Cavalcante, Daniel Pereira; Carvalho, Gustavo Almeida; Nunes, Antonio Ítalo dos Santos; Quintanilha, Amanda Rodrigues; Nascimento, Lucas Rodrigues Couto; Caixeta, Leonardo Ferreira; Ulrich, Alexander Henning; Gomez, Renato Santiago; Pinto, Mauro Cunha Xavier
Glycine is a fundamental neuroactive amino acid that serves dual roles in the central nervous system: acting as a primary inhibitory neurotransmitter via strychnine-sensitive glycine receptors and as an essential co-agonist at the N-methyl-Daspartate (NMDA) receptor. This dual functionality is important for maintaining the excitation–inhibition balance, synaptic plasticity, and network stability. The spatial and temporal availability of glycine is strictly regulated by two high-affinity, Na+/Cl−-dependent transporters: GlyT1 (SLC6A9) and GlyT2 (SLC6A5). These transporters exhibit distinct cellular distributions and functional specializations. GlyT1 is predominantly expressed in astrocytes and specific neuronal populations, where it buffers ambient glycine levels to modulate NMDA receptor activity. In contrast, GlyT2 is primarily localized to presynaptic terminals of glycinergic neurons, where it facilitates vesicular refilling essential for inhibitory signaling. This review provides a comprehensive overview of glycine metabolism, the structural biology and transport cycles of SLC6 glycine transporters, and the neuroanatomical framework of GlyT1 function. We further synthesize pharmacological advances in GlyT1 inhibition, evaluating both sarcosine-derived and non-sarcosine inhibitors, such as NFPS (ALX-5407), bitopertin, and iclepertin. The clinical and preclinical evidence for GlyT1 as a therapeutic target in psychiatric, neurological, and neurodegenerative disorders is critically assessed. Finally, we address key translational challenges, including dosing constraints, compensatory mechanisms, and SLC6 family selectivity, while highlighting the potential of structure-guided design to refine GlyT1-targeted therapies.
Suicídio étnico: um fenômeno evitável entre crianças indígenas da Amazônia brasileira
(2025) Caixeta, Leonardo Ferreira; Azevêdo, Paulo Verlaine Borges e; Vargas, Ciro Mendes; Nogueira, Yanley Lucio; Dangoni Filho, Iron; Caixeta, Victor de Melo
The indigenous population is particularly vulnerable to psychiatric disorders and suicide, as recorded worldwide among various ethnic groups and ancestral peoples. We present a case report to illustrate the psychopathological phenomenon of psychotic depression with suicidal behavior in a Karajá indigenous child, documenting the possibility of successful medical intervention to prevent suicide, despite the obstacles posed by the Brazilian government that hinders the treatment of this vulnerable and at-risk population, clearly revealing the neglect of psychiatric care for Brazilian indigenous children. Indigenous children seem especially vulnerable to psychiatric disorders and suicide, even though they are culturally more isolated than adults and have had less exposure to non-indigenous culture. This serious situation and public health problem among indigenous people are still interpreted in a romanticized, inappropriate manner, with a strong sociological bias, to the detriment of modern approaches to mental health based on Neurosciences. Denying children access to treatment, regardless of or because of their ethnicity, especially when their lives are at risk, may constitute a crime according to the standards regulating humanitarian treatment that our civilization has achieved.
Transtorno de personalidade orgânica secundária a neurocisticercose
(2025) Morais, Amanda Inês da Silva; Peleja, Alexandre Augusto de Castro; Caixeta, Leonardo Ferreira
Neurocysticercosis is the most common type of neuroparasitic infection. In this condition, the central nervous system (CNS) is infested with larvae from the tapeworm Taenia solium. Reported neuropsychiatric manifestations associated with neurocysticercosis include depression, cognitive dysfunction, dementia, and visual hallucinations. Organic personality disorder is a behavioral and personality change that may be a residual or concomitant disorder resulting from brain injury, dysfunction, or disease. There is no literature linking neurocysticercosis and personality disorders. In this article, we report a novel case of a 58-year-old man presenting with personality disorder after a neurocysticercosis episode. Upon evaluation, the patient displayed impulsivity, poor inhibitory control, expressed thoughts of killing his wife, and showed no remorse. He has a history of alcoholism and neurocysticercosis with 19 cysts on imaging studies at the age of 10. The patient’s personality prior to the neurocysticercosis episode was characterized as hyperthymic. Diagnostic hypotheses of bipolar affective disorder type 2, corticobasal dementia, and organic personality disorder secondary to neurocysticercosis are raised. The literature presents poorly understood mechanisms behind the development of mental disorders due to neurocysticercosis. Cases of mental disorders associated with neurocysticercosis and its high prevalence in the psychiatric population are welldocumented. We conclude that this report is novel and highly significant in encouraging further studies on mental disorders associated with neurocysticercosis, promoting clinical investigation of this condition in psychiatric patients, and encouraging investigation in patients with personality disorders.

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