Francisco Pimentel Cavalcante

Early breast cancer may induce a systemic immune response before abundant tumor-derived material reaches the circulation, creating a potential source of amplified liquid-biopsy biomarkers. However, the extent to which host-response signatures can support early detection or population screening before diagnosis remains uncertain. This structured narrative review examines the biological basis, analytical platforms, evidence, clinical roles, and translational requirements of circulating autoantibodies, leukocyte transcriptomic and epigenetic profiles, immune-cell phenotypes, adaptive immune-receptor repertoires, soluble mediators, extracellular vesicles, and integrated multi-omics. PubMed/MEDLINE and citation networks were searched through August 31, 2026 using a predefined diagnostic review framework. Evidence was organized by intended use, sample timing, comparator spectrum, and validation maturity, with appraisal informed by established diagnostic-accuracy and prediction-model standards. Proof-of-concept estimates include a mean area under the curve of 0.96 for a machine-learning T-cell receptor model in 98 women, 80.8% sensitivity and 61.6% specificity for a 28-autoantibody panel, and an external-validation area under the curve of 0.951 for a 20-analyte proteome-metabolome model involving 662 participants. These estimates are not directly comparable: most derive from retrospective case-control or diagnostic cohorts with established cancer, healthy or benign comparators, post-diagnosis sampling, data-driven thresholds, and limited independent validation. Consequently, discrimination between known cases and controls must not be equated with detection of occult disease or population screening utility. Breast-specific prediagnostic evidence and screening validation remain sparse. Host-response signatures are therefore best considered investigational, complementary biological sensors rather than replacements for mammography. Their most plausible future roles include triage after equivocal imaging, enrichment for supplemental imaging, and longitudinal surveillance in high-risk populations. Translation requires prospective prediagnostic cohorts, representative benign and inflammatory controls, locked algorithms, high-specificity performance, calibration at screening prevalence, external validation, subgroup fairness, reproducibility, and evidence that testing improves cancer yield or stage distribution without unacceptable false-positive procedures, overdiagnosis, cost, or inequity.

Risk-reducing mastectomy is a well-established strategy for patients at high risk of developing breast cancer, particularly those with known genetic mutations. However, in women presenting with large breasts and significant ptosis, skin-reducing mastectomy with immediate reconstruction is associated with higher rates of surgical complications, including skin flap necrosis, wound dehiscence, and implant-related issues. In this context, a staged surgical approach has been proposed as a safe alternative. The case of a 48-year-old asymptomatic woman carrying a germline pathogenic mutation in the TP53 gene, consistent with Li-Fraumeni syndrome, who presented with large breasts and grade III ptosis is reported. In this patient, a two-stage risk-reducing surgical approach was adopted. Initially, the patient underwent reduction mammoplasty to improve breast shape and optimize skin envelope conditions. This was followed by bilateral nipple-sparing mastectomy with immediate prepectoral implant-based reconstruction assisted by a bioabsorbable synthetic matrix (GORE® BIO-A®). The study was approved by the Institutional Ethics Committee (CAAE: 73596023.4.1001.5040), and written informed consent was obtained. Postoperatively, the patient developed a localized hematoma and partial superficial nipple necrosis, both of which were managed conservatively without the need for surgical reintervention. At 60 days of follow-up, the patient presented satisfactory aesthetic outcomes, with good breast contour, no requirement for opioid analgesia, and absence of animation deformity. A staged surgical approach may reduce complications and enhance aesthetic outcomes in patients with large and ptotic breasts undergoing risk-reducing mastectomy. Prepectoral reconstruction using a bioabsorbable synthetic matrix appears to be a safe and effective option in carefully selected cases. Further prospective studies are necessary to validate these findings and establish long-term outcomes.

Purpose: The MammaPrint™ (MP) 70-gene signature, identifies hormone receptor-positive (HR+), HER2-negative breast cancer patients with low genomic risk who are candidates for de-escalation of the systemic therapies employed. Knowing that MP was validated in an exclusively European cohort and understanding the heterogeneity of breast tumors in different populations, we proposed a study to analyze MP performance in the Brazilian population. Methods: Retrospective, prognostic evaluation, real-world cohort study of HR+, HER2- breast cancer patients who underwent MP in Brazil from January 2016 to December 2020 (AGEMA-BRA). Results: Of the 953 patients with high clinical risk, 407 (42.7%) had high genomic risk, and 546 (57.3%) had low genomic risk to MP. In the analysis of epidemiological, clinical, and anato-mopathological data correlating high and low risk to MP, and among the subgroups with low-risk, ultra-low risk, high-risk 1 and high-risk 2, only the histological grade showed statistical significance. Distant metastasis-free survival (DMFS) was 97.8% and overall survival (OS) was 99.8% with a mean follow-up of 40.8 months, with no difference between high and low genomic risk. Conclusions: Applying the MP signature in the AGEMA-BRA cohort enabled greater chemotherapy de-escalation with better DMFS than observed in the MINDACT pivotal study. Equivalent DMFS and OS results between high and low genomic risk carriers demonstrate the appropriate selection of patients by MP to receive or not receive adjuvant chemotherapy. These data make it possible to validate the performance of the signature in the Brazilian population and confirm the importance of testing it in different populations.

Introduction: Breast cancer (BC) is the most common disease among women worldwide. Improvements in screening and treatment have increased survival rates, making survivorship issues such as return to work (RTW) increasingly relevant. RTW is associated with better quality of life (QoL), psychological well-being, and social reintegration. However, factors influencing RTW among breast cancer survivors vary according to clinical, sociodemographic, and occupational conditions. This study aimed to evaluate the RTW rate among public employees in São Paulo, Brazil, diagnosed with non-metastatic BC and treated surgically. Methods: A longitudinal study was conducted among female public employees diagnosed with non-metastatic BC who underwent surgical treatment between October 2021 and December 2022. Sociodemographic, clinical, and work-related variables were collected at baseline and during follow-up. QoL was assessed using validated questionnaires, and logistic regression analyses were performed to evaluate associations between clinical, sociodemographic, and temporal factors influencing RTW. Results: The RTW rate was high, with most participants returning to work within six months. Age, tumor stage, chemotherapy, and education level were not significantly associated with RTW over time. However, improved QoL was correlated with successful RTW across several domains, including body image and functionality. Conclusions: RTW among public employees was primarily influenced by QoL rather than clinical or sociodemographic factors. The longitudinal design highlights the dynamic relationship between QoL improvements and RTW outcomes. Policymakers and healthcare providers should integrate QoL assessments into survivorship care plans and promote flexible work policies to improve occupational reintegration.

Breast-conserving surgery (BCS) followed by adjuvant radiotherapy is the standard of care for early-stage breast cancer. However, reoperations after BCS may compromise aesthetic outcomes, increase surgical complications, and cause psychological distress. This study aimed to determine the reoperation rate after BCS in a multi-institutional cohort from Brazil and to identify predictive factors associated with reoperation. This retrospective multicenter cohort study included female breast cancer patients (AJCC clinical stage 0-III) who underwent BCS followed by adjuvant radiotherapy at six treatment centers in Brazil between January 2016 and December 2022. Logistic regression was used to assess the association between potential risk factors and reoperation. The overall reoperation rate was 5.2%, with a higher rate in the public hospital (9.9%) than in private hospitals (4.8%). Patients had a mean age of 58.2 years, with 70.5% aged over 50; 58.3% were White, and 89.8% were treated in private settings. The most common histological type was invasive ductal carcinoma (67.0%), with AJCC stage I (49.3%) and hormone receptor-positive tumors (54.6%) predominating. Logistic regression showed that ductal carcinoma in situ (DCIS) was significantly associated with an increased risk of reoperation (OR 2.59, 95% CI 1.08-5.76, p = 0.024), whereas the absence of multifocal tumors was associated with a reduced risk (OR 0.37, 95% CI 0.16-0.98, p = 0.031). Reoperation after BCS was infrequent in this cohort. DCIS was associated with an increased risk of reoperation, whereas the absence of multifocal disease was associated with a reduced risk. Higher reoperation rates observed in the public hospital should be interpreted with caution given the limited representation of this setting.

Introduction: The 2025 International Symposium on Breast Diseases of Inland São Paulo addressed clinically relevant controversies in the management of breast cancer in special situations, including inflammatory carcinoma, axillary micrometastases after neoadjuvant chemotherapy, early luminal tumors in elderly women, and the use of vaginal estrogen therapy after breast cancer treatment. Methods: Four priority topics were presented in evidence-based lectures, followed by expert panel discussions and anonymous electronic voting. Consensus was predefined as agreement of at least 75% among panelists. Results: No consensus was reached regarding the use of sentinel lymph node biopsy in inflammatory carcinoma, although 73% of panelists voted against its performance. Likewise, no consensus was achieved on omitting axillary lymph node dissection in patients with axillary micrometastases after neoadjuvant chemotherapy, despite 61% considering this approach feasible. In elderly women with early luminal tumors, the most frequently selected option was to maintain standard treatment (29%), with no consensus supporting treatment de-escalation. In contrast, consensus was reached regarding the safety of vaginal estrogen therapy after breast cancer treatment, with 88% of panelists supporting its use in appropriately selected patients. Conclusions: These guidelines summarize expert-based recommendations for the management of breast cancer in challenging clinical scenarios and reinforce the importance of individualized, multidisciplinary decision-making. Sentinel lymph node biopsy was generally not supported in inflammatory carcinoma, and vaginal estrogen therapy was considered safe in selected breast cancer survivors. Greater caution remains warranted regarding treatment de-escalation in elderly women with early luminal tumors and omission of axillary lymph node dissection in the setting of residual micrometastatic nodal disease after neoadjuvant chemotherapy.

PURPOSELimited access to contemporary anti-HER2 therapies in Brazil’s public healthcare system (Sistema Único de Saúde -SUS) may contribute to avoidable mortality among women with HER2-positive early breast cancer. We estimated the number of potentially preventable deaths associated with incorporating adjuvant trastuzumab emtansine (T-DM1) and perioperative pertuzumab into SUS.METHODSWe developed a static decision-tree microsimulation model with an 8-year time horizon. The study population was derived from nationwide real-world data from DATASUS, which captures all patients treated within SUS. Three treatment strategies were evaluated: (1) current SUS standard (perioperative trastuzumab only), (2) incorporation of adjuvant T-DM1 for patients with residual invasive disease after neoadjuvant therapy, and (3) a gold-standard regimen including perioperative pertuzumab and response-guided adjuvant T-DM1. Clinical inputs were obtained from the NeoSphere, APHINITY, and KATHERINE trials. Probabilistic sensitivity analysis with 100,000 simulations was performed to estimate mortality outcomes and 95% confidence intervals (CIs).RESULTSA total of 22,432 women with stage II–III HER2-positive breast cancer were identified. The projected mean number of deaths at 8 years was 3,606 (95% CI, 3,082–4,180) under the SUS standard, 2,672 (95% CI, 2,244–3,147) with adjuvant T-DM1, and 2,390 (95% CI, 2,034–2,790) with the gold-standard regimen. Incorporation of T-DM1 was associated with 934 fewer deaths (25.9% relative reduction), whereas full adoption of the gold-standard strategy was associated with 1,216 fewer deaths (33.7% relative reduction).CONCLUSIONExpanding access to adjuvant T-DM1 and perioperative pertuzumab within SUS could meaningfully reduce mortality and narrow disparities in outcomes for Brazilian women with HER2-positive early breast cancer.