RESUMO
INTRODUCTION: Neoadjuvant endocrine therapy (NET) is recommended for the treatment of invasive breast cancer (BC), particularly luminal subtypes, in locally advanced stages. Previous randomized studies have demonstrated the benefits of aromatase inhibitors in this context. However, NET is typically reserved for elderly or frail patients who may not tolerate neoadjuvant chemotherapy. Identifying non-responsive patients early and extending treatment for responsive ones would be ideal, yet optimal strategies are awaited. AIMS: This non-randomized phase 2 clinical trial aims to assess NET feasibility and efficacy in postmenopausal stage II and III luminal BC patients, identifying predictive therapeutic response biomarkers. Efficacy will be gauged by patients with Ki67 ≤ 10% after 4 weeks and Preoperative Endocrine Prognostic Index (PEPI) scores 0 post-surgery. Study feasibility will be determined by participation acceptance rate (recruitment rate ≥50%) and inclusion rate (>2 patients/month). METHODS: Postmenopausal women with luminal, HER2-tumors in stages II and III undergo neoadjuvant anastrozole treatment, evaluating continuing NET or receiving chemotherapy through early Ki67 analysis after 2 to 4 weeks. The study assesses NET extension for up to 10 months, using serial follow-ups with standardized breast ultrasound and clinical criteria-based NET suspension. Clinical and pathological responses will be measured overall and in the luminal tumor A subgroup. Toxicity, health-related quality of life, and circulating biomarkers predicting early NET response will also be evaluated.
Assuntos
Anastrozol , Neoplasias da Mama , Estudos de Viabilidade , Terapia Neoadjuvante , Humanos , Anastrozol/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Pós-Menopausa , Antineoplásicos Hormonais/uso terapêutico , Idoso , Inibidores da Aromatase/uso terapêutico , Inibidores da Aromatase/administração & dosagem , Antígeno Ki-67/análise , Antígeno Ki-67/metabolismo , Adulto , Ensaios Clínicos Fase II como AssuntoRESUMO
BACKGROUND: Breast cancer (BC) remains a significant health care challenge, and treatment approaches continue to evolve. Among these, neoadjuvant endocrine therapy (NET) has gained prominence, particularly for postmenopausal, hormone-receptor positive, HER2-negative (HR+/HER2-) BC patients. Despite this, a significant gap exists in identifying patients who stand to benefit from NET. The objective of this study was to assess whether Magee equations (MEs) could serve as predictors of response to NET. METHODS: This retrospective study included adult patients with invasive BC who underwent NET followed by curative surgery. Assessment of sociodemographic, clinical, and tumor-related variables was conducted. The ME1, ME2, ME3, and ME mean were analyzed to explore their predictive role for NET response. Receiver operating characteristic (ROC) curves were employed, along with the determination of optimal cutoff points. Logistic regression models were utilized to identify the most significant predictors of pathological response. RESULTS: Among the 75 female participants, the mean age was 69.4 years, with the majority being postmenopausal (n = 72, 96%) and having an ECOG-PS of 0/1 (n = 63, 84%). Most patients were classified as luminal A (n = 41, 54.7%). ME3 emerged as a promising predictor, boasting an AUC of 0.734, with sensitivity of 90.62% and specificity of 57.50% when the threshold was ≤ 19.97. In univariate analysis, clinical staging (p = 0.002), molecular subtype (p = 0.001), and ME3 (continuous = 0.001, original 3-tier: p = 0.013, new 2-tier: <0.001) categories exhibited significant associations with pathological response. In the multivariate model, clinical staging and new 2-tier ME3 (<20 vs. ≥20) were included as significant variables. CONCLUSIONS: Patients with ME3 < 20 have a higher likelihood of presenting a pathological response, offering a cost-effective alternative tool to Oncotype DX. Larger future studies with a prospective design are awaited to confirm our findings.
RESUMO
OBJECTIVE: This study aims to investigate the presence of Cytomegalovirus (CMV), herpes virus simplex (HSV), and parvovirus B19 (PVB19) in the placental tissue of patients who underwent abortions without an otherwise-defined aetiology. STUDY DESIGN: This cross-sectional study was conducted in a high-risk obstetric maternity facility at a University Hospital in Belo Horizonte, Brazil, from January 2013 to December 2015. We included placenta samples obtained from spontaneous abortions of unknown aetiology. Seventy placenta samples were identified and were classified according to histopathological characteristics. All samples were analysed using immunohistochemistry and polymerase chain reaction for CMV, PVB19, and HSV. The clinical variables were collected from the medical records of patients to verify the association of infection with villitis. The patients were divided into the following groups: I) with villitis (n = 28) and II) without villitis (n = 42). METHODS: Immunohistochemistry used monoclonal anti-CMV antibody (NCL-CMVpp65, Leica Biosystems, Wetzlar, Germany), anti-PVB19 antibody (NCL-PARVO, Leica Biosystems, Wetzlar, Germany), and anti-HSV1/HSV2 antibodies (NCL-HSV-1 and HSV2, Leica Biosystems, Wetzlar, Germany). The data were analysed using the Statistical Package for Social Sciences (SPSS Inc, Chicago, IL) 19.0. RESULTS: Viral agents were detected in five patients (7.14%) in the villitis group. Three patients were positive for CMV, one for PVB19, and one for HSV type 2. Foetal and maternal complications were significantly higher in the group with villitis compared with those in the group without villitis (p = .002). CONCLUSIONS: The prevalence of transplacental viral infections as a cause of spontaneous abortion should be considered high in the placenta with villitis. Thus, this study highlights the need for developing diagnostic tests to clarify the aetiology of abortion and foetal loss.