Background:Triple-negative breast cancer (TNBC) is a heterogeneous disease lacking approved targeted therapies and standardized treatment regimens. Among its molecular subtypes, luminal androgen receptor-positive (LAR+) TNBC is characterized by reduced proliferative activity and a lower sensitivity to chemotherapy. The tumor immune microenvironment (TIME) plays a critical role in shaping treatment responses; however, its spatial organization and cellular composition in LAR+ TNBC remain poorly understood. Methods:In this exploratory study, we performed multiplex immunofluorescence analysis to characterize 18 immune and tumor cell subtypes in paired pre- and post-neoadjuvant therapy (NAT) samples from small, exploratory cohort of patients with LAR+ TNBC, stratified by pathological complete response (pCR). We assessed immune cell composition, expression of exhaustion markers, and spatial relationships among cellular populations to explore TIME features associated with different pathological responses. Results:Patients who achieved pCR displayed higher pre-treatment densities of specific immune subsets, including CD20+PD-1+, CD4+FOXP3+, and CD8+PD-1+TIM3+ cells, consistent with an immune-enriched microenvironment. Spatial analyses revealed distinct patterns between Responders (Resp) and Non-Responders (NoResp). In Resp, tumor cells (PANCK+) were initially located closer to PD-L1-expressing tumor cells (PANCK+PD-L1+), with this proximity decreasing after NAT. In contrast, in non-Resp, immunosuppressive tumor cells moved closer to tumor cells following treatment. Moreover, NAT in Resp was associated with a spatial repositioning of CD4+ and CD8+ T cells toward tumor cells. B cells and regulatory B cells (Bregs) also exhibited differential spatial dynamics between the two groups. Conclusions:This exploratory analysis describes distinct immune compositions and spatial arrangements of the TIME in LAR+ TNBC. Our findings suggest that specific immune enrichments and spatial remodeling patterns may differ between patients with different pathological outcomes, whereas the persistence of immunosuppressive niches characterizes non-Resp. Given the small sample size and the inclusion of immune checkpoint inhibitors in a subset of patients, all of whom achieved pCR, these observations should be considered strictly hypothesis-generating. Larger and more homogeneous cohorts will be required to validate these findings and to determine their potential clinical relevance.

BACKGROUND:The role of sentinel lymph node biopsy in patients with ductal carcinoma in situ undergoing mastectomy remains controversial. Current guidelines recommend sentinel lymph node biopsy at the time of mastectomy because of concerns regarding occult invasive disease and the loss of lymphatic mapping after breast removal. However, axillary metastases are uncommon in ductal carcinoma in situ, and routine sentinel lymph node biopsy may represent overtreatment in selected patients. This study aimed to identify clinicopathologic factors associated with nodal positivity in order to support a selective approach to sentinel lymph node biopsy. METHODS:We retrospectively reviewed 188 consecutive patients with a preoperative diagnosis of ductal carcinoma in situ who underwent mastectomy with immediate implant-based reconstruction between 2014 and 2024 at a single institution. Clinicopathologic characteristics, rates of upstaging to invasive carcinoma, and sentinel lymph node status were analyzed. Associations between nodal involvement and clinical or pathologic variables were evaluated, and findings were compared with predictors identified in the literature. RESULTS:Sentinel lymph node biopsy was performed in all patients. Overall, 49 patients (26.1%) were upstaged to invasive carcinoma. Sentinel lymph node metastases (pN1mi/pN1) were identified in 13 patients (6.9%). Multifocal disease (P = .023), the presence of an invasive component (P < .001), histologic subtype (P < .001), and pathologic tumor size (P < .0001) were significantly associated with nodal positivity. No significant associations were observed with menopausal status, tumor grade, or hormone receptor and human epidermal growth factor receptor 2 status. CONCLUSION:Routine sentinel lymph node biopsy may not be necessary for all patients with ductal carcinoma in situ undergoing mastectomy with immediate reconstruction. Careful patient selection based on preoperative risk factors can allow safe omission of sentinel lymph node biopsy, reducing surgical morbidity without compromising oncologic safety. Our findings suggest that routine sentinel lymph node biopsy in this specific setting may represent systematic overtreatment.

BACKGROUND:The Oncoplastic Breast Surgery represents a philosophy that prioritizes both oncologic and aesthetic outcomes, introduced to overcome the limitations of conventional breast-conserving surgery. Over the years, it has demonstrated oncological safety along with numerous advantages, particularly related to patients' satisfaction and quality of life, which make acceptable complication rate as high as 16%. OBJECTIVES:The J-mammaplasty is rarely cited in the oncoplastic approach, while it represents the standard of choice at our Institution. The aim of this study is to report our large experience of J-mammaplasty in level II oncoplastic breast surgery. METHODS:This study enrolled 157 patients who underwent quadrantectomies and J-scar oncoplasties over a period of 3 years. Patients' demographics and morphological breast features were collected preoperatively using photos, while procedure specific variables were recorded intraoperatively. Complications were identified during follow-up visits. After a minimum of 12 months, surgeon and patients' reported outcomes were recorded. RESULTS:J-type oncoplastic reduction mammaplasty was optimally applied to a wide range of patients' characteristics, including large breasts and 3rd degree ptosis, as well as different tumour features like location, with lateral quadrants being the most common. The overall complication rate was 7%. CONCLUSIONS:The J mammoplasty has been applied to oncoplastic breast surgery and refined for the reconstructive purpose for over 20 years at our Institution. It represents a highly versatile, safe technique with high patients' satisfaction.

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. FUNDING:US National Institutes of Health, National Cancer Institute.

Residual microcalcifications after neoadjuvant chemotherapy (NAC) in breast cancer remain a complex diagnostic and therapeutic challenge. Although NAC has significantly improved pathologic complete response (pCR) rates and transformed surgical approaches, the persistence or evolution of microcalcifications may not accurately reflect residual disease. This discrepancy complicates radiologic interpretation, impacts surgical decision-making, and may lead to overtreatment or unnecessary mastectomies. This review synthesizes current evidence on the radiologic-pathologic correlation of post-NAC microcalcifications, their prognostic value, and their relevance to guiding surgical management in contemporary precision oncology. A narrative review of the literature was performed, focusing on imaging evolution after NAC, pathologic correlations, predictive and prognostic implications, and the role of microcalcifications in defining optimal surgical strategies, ranging from breast-conserving surgery to mastectomy. Emerging contributions from digital breast tomosynthesis, contrast-enhanced mammography (CEM), Magnetic Resonance (MR) and radiomics are also examined. Studies consistently demonstrate that residual microcalcifications are often poor predictors of viable tumor tissue after NAC. Up to half of cases with persistent calcifications may reflect minimal or absent residual invasive cancer, whereas calcifications may also persist in areas of treatment-induced necrosis or fibrosis. Reliance on calcifications alone may therefore lead to unnecessary extensive resections. Conversely, specific morphologic patterns, especially fine pleomorphic or branching calcifications, are more strongly associated with residual malignancy. Advanced imaging and radiomics show promise in improving predictive accuracy. Residual microcalcifications after NAC should not be interpreted as a direct surrogate of residual disease. A multimodal assessment integrating imaging evolution, tumor biology, and treatment response is essential to optimize surgical planning and avoid overtreatment. Precision surgery in the NAC era increasingly requires individualized decision-making supported by advanced imaging and robust radiologic-pathologic correlation.

Introduction:Pre-pectoral implant-based breast reconstruction (IBR) has emerged as a promising alternative to conventional subpectoral approaches following nipple- or skin-sparing mastectomy. However, long-term oncological safety, complication profiles, and outcomes in specific subgroups, such as patients receiving radiation therapy (RT), remain under investigation. Contemporary evidence is mainly derived from retrospective studies with limited follow-up, reporting heterogeneous results. The I-PREPARE trial (EUBREAST-11R) was initiated by the EUBREAST (European Breast Cancer Research Association of Surgical Trialists, https://www.eubreast.org/) in order to provide high-quality data on the outcomes of pre-pectoral IBR in terms of oncological safety, complications, aesthetic results, and patient-reported outcomes, with particular attention to the impact of RT. Methods:The I-PREPARE trial is a prospective, international, observational cohort study assessing outcomes of IBR after therapeutic mastectomy. Adult women undergoing nipple- or skin-sparing mastectomy followed by pre-pectoral IBR (with or without synthetic/biologic mesh) are eligible. Primary endpoint is implant loss at 3 months; secondary endpoints include early and late onset complications, reoperations (≤24 months), quality of life (6, 12, and 24 months), and time to start of adjuvant treatments. Tertiary endpoints will address oncological outcomes (loco-regional recurrence, disease-free survival, breast cancer specific survival, distant-disease-free survival, overall survival, implant-associated anaplastic T-cell non-Hodgkin lymphoma). The evaluation of these endpoints will be undertaken only subject to the availability of additional dedicated funding. Data are collected via a secure eCRF and the EUBreast patient App for smartphones (https://apps.apple.com/it/app/eubreast/id6469623234; https://play.google.com/store/apps/details?id=com.brightfish.appstore.eubreast.patient&hl=it&pli=1). The study plans to enrol 1,236 patients across multiple centres and countries. The study was registered on ClinicalTrials.gov under the Trial Registration Number NCT05817175. Conclusion:The I-PREPARE trial (EUBREAST-11R) aims to generate high-quality real-world evidence on the safety, efficacy, and patient-reported outcomes of pre-pectoral IBR. This initiative will address current knowledge gaps on the outcomes of pre-pectoral IBR and could help clinical decision-making for patient selection, surgical planning, and multidisciplinary care in breast reconstruction.

Background: Exercise oncology research supports multicomponent interventions as complementary therapies to improve quality of life in breast cancer (BC) survivors. Nonetheless, evidence on sport-specific, engaging approaches, such as boxing-based concurrent training, remains scarce. Method: This case study aimed to evaluate the feasibility and safety, and to explore the effects of a 16-week adapted boxing protocol. Two BC survivors with a history of triple-negative BC in treatment were enrolled. The protocol integrated aerobic, strength/power, coordination, balance and boxing-specific exercises through individually adapted, progressive sessions performed twice a week. Outcomes were assessed pre- and post-intervention and included: (I) compliance and adverse event related to the protocol, (II) functional tests (handgrip, single leg stance, 30 s sit-to-stand, trunk/shoulder mobility tests, VO2max); (III) body composition parameters (fat mass, fat-free mass,); and (IV) validated questionnaires (EORTC QLQ-C30, FA12, PSQI, BIS, HADS, IPAQ). Results: Compliance was high and no serious adverse events were detected. Sit-to-stand performance, as well as VO2max and mobility/balance, improved in both patients after the intervention. Participant A showed a favorable body modulation. Participant B, on the other hand, reported a stable weight. Participant A reported large improvements across QLQ-C30 domains, while participant B exhibited mixed results, with improved emotional functioning and pain but declines in cognitive/social functioning. Conclusions: The boxing-based concurrent training protocol was feasible, safe, and well-tolerated. Despite the limitation of the case study, the observed functional and psychosocial positive changes highlight the need for adequately larger controlled trials to clarify the training protocol efficacy in order to optimize this exercise approach in BC survivors.

Background/Objectives: Insomnia is one of the most prevalent and persistent symptoms among patients with breast cancer, yet it remains under-recognized and undertreated in routine clinical practice. Beyond its impact on sleep quality, insomnia is increasingly understood as a multidimensional condition involving neurobiological, psychological, and behavioral mechanisms, closely intertwined with cancer-related stress and psychiatric comorbidities. This narrative review aims to provide a comprehensive and integrative overview of insomnia in breast cancer, focusing on its epidemiology, pathophysiological underpinnings, neuropsychiatric correlates, and clinical implications, while highlighting gaps in current research and management. Methods: A narrative review of the literature was conducted, including studies published in major medical databases (PubMed, Scopus, and Web of Science) up to 2025. Relevant articles addressing insomnia, sleep disturbances, psychiatric symptoms, and neurobiological mechanisms in breast cancer populations were selected and synthesized. Results: Insomnia affects a substantial proportion of breast cancer patients across the disease trajectory, from diagnosis to survivorship. Its etiology is multifactorial, involving dysregulation of the hypothalamic-pituitary-adrenal axis, inflammatory processes, and circadian rhythm, as well as treatment-related factors such as chemotherapy, endocrine therapy, and menopausal symptoms. Insomnia frequently co-occurs with depression, anxiety, fatigue, and pain, forming symptom clusters that significantly impair quality of life and may influence clinical outcomes. Emerging evidence supports a bidirectional relationship between insomnia and psychiatric vulnerability, suggesting a shared neurobiological substrate within the brain-body stress axis. Conclusions: Insomnia in breast cancer should be conceptualized as a neuropsychiatric condition embedded within a broader stress-related symptom network rather than as an isolated sleep disturbance. Improved screening, interdisciplinary management, and the integration of evidence-based interventions such as cognitive behavioral therapy for insomnia are essential. Research should focus on personalized and mechanistically informed approaches to better address this highly prevalent yet insufficiently managed condition.

INTRODUCTION:Pleomorphic (PLCIS) and florid (FLCIS) lobular carcinoma in situ are uncommon entities, characterized by significant architectural distortion and cellular atypia. Their rarity poses three key clinical challenges: diagnostic variability, histologic upgrade and risk of local recurrence (LR). Currently, no standardized management guidelines exist. This systematic review provides the most comprehensive synthesis to date of the available evidence on clinical, radiologic, pathologic, and molecular characteristics of P/FLCIS, and evaluates outcomes associated with different treatment strategies. METHODS:A systematic literature search was conducted across major biomedical databases up to June 2025. Eligible studies were original case series reporting primary data on P/FLCIS. RESULTS:From 5402 screened records, 38 studies were included, comprising 629 total cases: 411 PLCIS, 98 FLCIS, and 120 categorized as LCIS with pleomorphic or non-classic features. The pooled upgrade rate was 35.3% (PLCIS 35.1%, FLCIS 33.3%; p = 0.843), predominantly to invasive carcinoma (28.8%). Among 258 pure P/FLCIS cases with available follow-up (median, 50 months) the overall LR rate was 12.4% (PLCIS 13.1%, FLCIS 9.1%; p = 0.618), with invasive recurrences representing the majority (62.5%; p = 0.04). Margin status was significantly associated with risk of LR (positive margins 38.2%, close margins (<2 mm) 20.0%, negative margins 3.0%; p < 0.001). Data on adjuvant treatments were inconsistent and heterogeneous. CONCLUSIONS:Given the high upgrade rate and significant risk of LR for P/FLCIS, complete surgical excision with negative margins is strongly advised to ensure definitive diagnosis and reduce future breast events. The role of adjuvant therapies remains unclear, highlighting the urgent need for standardized, multicenter studies to guide optimal clinical management.

e12673 Background: The role of neoadjuvant chemotherapy (NACT) in stage II-III hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer remains controversial due to low pathological complete response (pCR) rates. Recent evidence from the NATALEE trial subgroup analysis presented at San Gallen 2025 identified prior NACT as an independent negative prognostic factor for invasive disease-free survival (iDFS) in HR+/HER2- early breast cancer, raising concerns about the optimal sequencing of systemic therapy in this population. Whether NACT or adjuvant chemotherapy (ACT) provides better survival outcomes in HR+/HER2- breast cancer is an ongoing debate with significant clinical implications. Methods: Six hundred fifty-five patients (pts) with HR+/HER2- locally advanced breast cancer at stage II-III undergoing NACT (429 pts) or ACT (226 pts) between 2005 and 2021 were identified from Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome. Propensity score matching (PSM) was employed to create cohorts with balanced baseline characteristics across different categories (age, menopausal status, grading, stage, Ki67, ER, PgR, HER2). The efficacy of NACT and ACT in terms of overall survival (OS) and real-world invasive disease-free survival (rwiDFS) was evaluated using Kaplan-Meier analysis and the Cox proportional hazards model. Results: Using PSM, a total of 432 pts was ultimately included in the study (216 vs 216). OS was significantly longer for ACT versus NACT (NR vs 229 months mOS, 96.8% vs 90.6% survival rate at 5 years, HR 0.58, 95% CI 0.36-0.95, p = 0.03). The rwiDFS was longer for ACT versus NACT (NR vs 135 months, 91.6% vs 74.8% survival rate at 5 years, HR 0.63, 95% CI 0.43-0.92, p = 0.017). Patients who underwent ACT had significantly better OS compared to those who did not achieve pCR after NACT (HR 0.56, 95% CI 0.38-0.82, p = 0.016), while no significant difference was observed compared to patients who achieved pCR after NACT (HR 1.81, 95% CI 0.9-3.6, p = NS). Conclusions: In stage II-III HR+/HER2- breast cancer, NACT was associated with inferior OS and rwiDFS compared to ACT, consistent with NATALEE trial findings identifying NACT as an adverse prognostic factor. NACT should be reserved for selected cases requiring downstaging. While neoadjuvant CDK4/6 inhibitors have shown limited efficacy in replacing chemotherapy, emerging oral SERDs and PROTACs may improve pCR rates and bridge the efficacy gap in this subtype.

IntroductionPrepectoral direct-to-implant (DTI) breast reconstruction has gained popularity due to reduced morbidity and improved aesthetic and functional outcomes. However, thin mastectomy flaps (<1 cm, R1 following the Rancati classification) are traditionally considered at higher risk of complications, often leading surgeons to prefer subpectoral or staged approaches. This study evaluates whether prepectoral DTI reconstruction can be safely performed in patients with thin mastectomy flaps, challenging the traditional view that these patients are unsuitable candidates.Materials and methodsA retrospective single-center analysis was conducted on 1239 patients undergoing immediate prepectoral DTI breast reconstruction after nipple-sparing (NSM), skin-sparing (SSM), or skin-reducing mastectomy (SRM) between August 2018 and June 2025 (1663 mastectomies). Patients with prior radiotherapy were excluded. Intraoperative flap thickness was categorized as Group 1 (5–6 mm), Group 2 (7–9 mm), and Group 3 (≥ 10 mm). The primary endpoint were early postoperative complications (<30 days), classified as major or minor.ResultsOverall, 152 mastectomies (9.14%) developed early complications. Complication rates were comparable across flap-thickness groups (Group 1: 10.48%, Group 2: 9.57%, Group 3: 8.66%; p = 0.704). Rates of wound dehiscence, infection, implant extrusion, and minor complications did not significantly differ among the groups. Ischemic complications requiring revision were more frequent in thinner flaps (2.1% in Group 1 vs. 0.51% and 0.43% in Groups 2 and 3), although absolute numbers remained low. Periprosthetic seromas showed a statistically significant but clinically modest difference.ConclusionsFlap thickness alone is not an independent predictor of early morbidity in prepectoral DTI reconstruction. When intraoperative perfusion is adequate and a standardized protocol is used, even flaps <1 cm can be safely subjected to DTI prepectoral reconstruction. These findings support expanding prepectoral indications to selected patients with thin mastectomy flaps.

Breast cancer remains a global health concern, with post-traumatic psychological changes, both positive and negative, during treatment and survivorship. This systematic review aimed to examine the prospective predictors of Posttraumatic Growth (PTG) and Posttraumatic Depreciation (PTD), as well as their temporal dynamics in women diagnosed with breast cancer. PubMed, Scopus, CINAHL, and PsycINFO were systematically searched on 31st January 2025, using a combination of terms and Boolean operators, following PRISMA guidelines. A narrative synthesis was conducted, classifying included studies into investigations of prospective predictors of PTG/PTD and of longitudinal changes in PTG/PTD levels; findings were summarised in tabular form, and the Quality in Prognosis Studies tool was used for the assessment of study risk of bias. Eighteen studies met the inclusion criteria and were included in this review. No longitudinal studies were found investigating PTD. For PTG, several biopsychosocial predictors emerged, highlighting substantial heterogeneity across studies. Many variables showed only limited evidence, preventing conclusive inferences. Only illness-specific stress demonstrated strong evidence as a positive predictor of PTG, while clinical factors were inconclusive. Regarding PTG trajectories, studies reported significant increases over time, with mixed evidence concerning the timing and pattern of these changes. The findings suggest that PTG and its prospective factors, both positive and negative, should be monitored over time in BC patients across all disease stages, from treatment to survivorship, to inform personalized psychological support programs. Future research should also investigate PTD alongside PTG and adopt standardized timeframes to objectively assess changes in posttraumatic outcomes.

Breast cancer represents a paradigmatic model of precision oncology, with treatment strategies increasingly guided by molecular profiling and biomarker-driven targeted therapies. Despite these advances in biological personalization, clinical outcomes remain strongly influenced by psychological and psychiatric factors that are still insufficiently integrated into oncological decision-making. This gap underscores the need for a broader, person-centered model of personalization that extends beyond tumor biology. This narrative review synthesizes current evidence on contemporary personalized strategies in breast cancer management, with a specific focus on the integration of precision oncology and psycho-oncology. A structured literature search was conducted across major biomedical databases to identify studies addressing molecular stratification, targeted treatments, psychiatric comorbidity, psychological profiles, and psycho-oncological interventions relevant to treatment personalization. While molecular classification and biomarker-guided therapies have substantially improved breast cancer outcomes, high rates of depression, anxiety, psychological distress, and maladaptive coping styles are consistently reported across disease stages. These psychological and psychiatric dimensions significantly influence treatment adherence, tolerability, quality of life, and ultimately clinical outcomes. Growing evidence supports the systematic use of psychological screening tools and tailored psycho-oncological interventions, both psychological and pharmacological, as integral components of personalized cancer care. Integrated care models combining oncological and psycho-oncological expertise are associated with improved patient-reported outcomes and may enhance overall therapeutic effectiveness. True personalization in breast cancer treatment extends beyond biological precision and requires the structured integration of psycho-oncological assessment and intervention into routine clinical pathways. Bridging precision oncology and psycho-oncology enables a more comprehensive, patient-centered approach, optimizing adherence, quality of life, and long-term outcomes. Future strategies should prioritize multidisciplinary models of care and the development of integrated clinical frameworks to achieve genuinely personalized breast cancer management.

The paradigm shift toward precision oncology in advanced breast cancer has increased therapeutic complexity, prolonging survival for many patients while simultaneously expanding the temporal burden associated with cancer care. Time toxicity, defined as the cumulative time spent receiving, accessing, coordinating, and recovering from medical interventions, is increasingly recognized as a clinically meaningful but still under-assessed dimension of patient-centered value. Beyond its organizational and economic implications, time toxicity may exert profound psychological and psychiatric effects, particularly in patients with advanced disease, for whom time represents not only a practical resource but also an existential, relational, and emotional domain. This narrative review examines how objective and subjective dimensions of time toxicity may inform patient-centered decision-making in advanced breast cancer. We summarize current evidence on the temporal demands of cancer care in advanced breast cancer and their psychological and relational consequences, focusing on how these factors can be discussed in patient-centered treatment decisions. From a value-based oncology perspective, the review examines how treatment optimization, subcutaneous formulations, oral therapies, telemedicine-based surveillance, decentralized care models, and early psycho-oncological assessment may reduce non-value-added time in clinical settings while preserving quality of care. Methodological challenges in measuring time toxicity and correlating it with overall survival, health-related quality of life, anxiety, depression, demoralization, and illness-related distress are also discussed. Incorporating time toxicity into shared decision-making may help clinicians move beyond traditional efficacy endpoints. It may support a more comprehensive approach in which survival benefit, psychological well-being, personal priorities, and the subjective value of time are considered together.

The coexistence of cancer and bipolar disorder (BD) represents a clinically relevant yet underexplored challenge at the intersection of psychiatry and oncology. Patients with BD may face increased vulnerability during cancer care due to biological, pharmacological, and psychosocial factors. At the same time, cancer and its treatments may destabilize mood and complicate psychiatric management. This narrative review synthesizes current evidence on the bidirectional relationship between BD and cancer. A literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science for articles published between 2000 and 2026 using combinations of the terms “bipolar disorder”, “cancer”, “neoplasms”, “inflammation”, “HPA axis”, “drug interactions”, and “psycho-oncology”. Population-based studies, clinical cohorts, systematic reviews, and mechanistic studies were prioritized to examine epidemiological associations, shared biological pathways, treatment-related psychiatric complications, and pharmacological interactions. Available evidence suggests that the relationship between BD and cancer is multifactorial and bidirectional. Patients with BD may experience higher cancer burden and poorer oncological trajectories due to lifestyle factors, healthcare disparities, and systemic biological vulnerabilities including chronic inflammation, neuroendocrine dysregulation, and oxidative stress. Conversely, cancer-related inflammation, corticosteroid exposure, chemotherapy, and immunotherapy may precipitate mood destabilization. Psychotropic-oncologic drug interactions further complicate treatment management. Emerging evidence also highlights the potential role of intracellular stress signaling and immune-related pathways linking psychiatric and oncologic processes. The intersection of BD and cancer represents a “double burden” shaped by biological, clinical, and psychosocial mechanisms. Improved collaboration between psychiatry and oncology, early psychiatric screening in cancer care, and careful pharmacological monitoring are essential to optimize outcomes in this vulnerable population.

Background Recent trials suggest omission of sentinel lymph node biopsy (SLNB) for selected early-stage breast cancer patients. However, invasive lobular carcinoma (ILC) is underrepresented, and retrospective data indicate higher rates of nodal metastases, raising concerns about axillary understaging. This study aimed to evaluate the prevalence and predictors of nodal metastases in early-stage, clinically node-negative ILC.Methods This study retrospectively analyzed 491 patients with estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, clinical T1, clinically node-negative ILC who underwent breast-conserving surgery at our institution between 2004 and 2024. The exclusion criteria ruled out neoadjuvant therapy, tumor larger than 2 cm, and metastatic disease at diagnosis or prior breast cancer.Results Among 491 patients, 392 (79.8 %) were pN0, whereas 99 (20.2 %) had nodal metastases (pN1mi-pN3). Pathologic tumor size was significantly associated with axillary nodal involvement (p = 0.004). In contrast, histologic subtype was not significantly associated with nodal status (p = 0.15), although pleomorphic tumors demonstrated numerically higher rates of nodal involvement than classic invasive lobular carcinoma. Menopausal status was not predictive of nodal positivity (p = 0.96).Conclusions Approximately one (20.2 %) in five patients with early-stage, clinically node-negative ILC harbors occult axillary nodal metastases. Pathologic tumor size emerged as the primary determinant of nodal involvement. Pleomorphic variants showed a tendency toward higher nodal burden. These findings indicate that omission of SLNB in ILC may carry a risk of axillary understaging with potential therapeutic implications. Pending evidence from prospective studies specifically designed for lobular histology, SLNB should continue to be considered an essential component of axillary evaluation in this subgroup.