Eduardo Camargo Millen

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.

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.

Immune profiling in residual disease: refining risk stratification after neoadjuvant therapy in HER2-positive breast cancer

Introduction: Health-related quality of life (HRQoL) has become a key outcome in evaluating breast cancer patients, influencing treatment decisions and long-term prognosis. Different surgical approaches and adjuvant therapies may significantly impact various HRQoL domains, including physical, emotional, and social well-being. This study aimed to assess HRQoL in public sector employees undergoing surgical treatment for breast cancer, comparing different surgical approaches (conservative, radical, and oncoplastic) and analyzing the impact of chemotherapy and radiotherapy on HRQoL outcomes. Methods: This was a cross-sectional, observational study conducted at Hospital do Servidor Público Estadual de São Paulo (HSPE) between 2021 and 2024. A total of 600 female patients diagnosed with non-metastatic breast cancer who underwent surgical treatment were included. HRQoL was assessed using the validated EORTC QLQ-C30 and QLQ-BR23 questionnaires. Statistical analyses included ANOVA and multivariate regression models, adjusting for confounding variables. Results: Patients who underwent conservative surgery had significantly better HRQoL scores compared to those undergoing oncoplastic or radical surgery. Surprisingly, oncoplastic surgery was associated with lower global HRQoL (β=-16.27; p=0.003), cognitive function (β=-22.34; p<0.001), and social function (β=-19.15; p<0.001). Chemotherapy was linked to persistent cognitive impairment and increased systemic side effects. The mean body image score was highest in the conservative surgery group (80.9) compared to mastectomy (45.8; p=0.003). Common symptoms included fatigue, pain, and insomnia. Conclusions: Surgical approach plays a crucial role in HRQoL outcomes for breast cancer patients. Contrary to expectations, oncoplastic techniques were associated with worse quality of life scores, highlighting the need for personalized treatment decisions. Chemotherapy had a significant negative impact on cognitive function and symptom burden. These findings emphasize the importance of incorporating HRQoL assessments in clinical practice to optimize patient-centered treatment strategies and postoperative rehabilitation.