Breast Cancer

Optimal sequencing of antibody–drug conjugates (ADCs) is an important clinical issue in metastatic breast cancer. However, data on datopotamab deruxtecan (Dato-DXd) following trastuzumab deruxtecan (T-DXd) have not been reported. This study evaluated real-world outcomes of Dato-DXd in patients with hormone receptor–positive, HER2-negative metastatic breast cancer, focusing on prior T-DXd exposure. This single-center retrospective study included patients who received at least one dose of Dato-DXd by December 2025. Outcomes were evaluated overall and by prior T-DXd exposure. Endpoints included disease control rate (DCR), objective response rate (ORR), time to treatment failure (TTF), and progression-free survival (PFS). Among patients who received prior T-DXd, TTF with T-DXd and subsequent Dato-DXd was compared. A total of 45 patients were analyzed: 19 had prior T-DXd exposure and 26 were T-DXd-naïve. The cohort was heavily pretreated with a median of six prior treatment lines and three prior chemotherapy regimens for metastatic disease. Overall, the DCR and ORR were 57.8

Pegfilgrastim, a long-acting granulocyte colony-stimulating factor (G-CSF), is used to prevent febrile neutropenia (FN) in breast cancer patients undergoing chemotherapy. However, a small subset of patients still develops FN. This study aimed to assess the real-world incidence of FN and identify potential risk factors in this specific population. This retrospective study included breast cancer patients who received pegfilgrastim prophylaxis at Tokyo Medical University Hospital between February 2019 and December 2024. Inclusion required pegfilgrastim use at least once during chemotherapy. FN was defined as an absolute neutrophil count below 500/µL (or a predicted ANC below 1,000/µL) and an axillary temperature 37.5 °C or higher. Cases of FN and associated risk factors were analyzed using logistic regression models. This study included 378 patients (median age 53). Tumor subtypes were luminal (50.0

Breast cancer is the most common cancer among women in Jordan, with many cases detected at advanced stages, leading to higher costs and poorer outcomes. Despite mammography’s proven benefits for early detection, its use remains low. This study evaluates the cost-effectiveness and budget impact of implementing mammography screening in Jordan’s healthcare system. A cost-effectiveness analysis was conducted from the perspective of the Jordanian healthcare system, comparing mammography-based screening with no screening (opportunistic detection) among women ≥ 40 years. A Markov model estimated disease progression, costs, and quality-adjusted life years (QALYs), using primarily local/regional data, supplemented by international sources when necessary. Results were expressed as incremental cost-effectiveness ratios (ICERs), i.e., cost per QALY gained. Sensitivity analyses tested model robustness. A budget impact analysis (BIA) assessed the financial implications of implementing nationwide screening. Comparing mammography-based screening with no screening among women ≥ 40 years, ICER was estimated at 5341 per QALY gained, which is well below Jordan’s willingness-to-pay threshold. Over a lifetime horizon, mammography screening among eligible women aged 40–50 years was projected to prevent 779 breast cancer deaths. Both one-way and probabilistic sensitivity analyses confirmed the robustness of the base-case results under uncertainty. Over five years, nationwide screening yielded net savings of17.6 million compared to current screening estimates. Mammography-based breast cancer screening appears to be a cost-effective strategy in Jordan, with potential to reduce breast cancer mortality. These findings suggest possible improvements in population health outcomes and more efficient use of healthcare resources.

Endocrine therapy (ET) is the backbone of HR+/HER2 − breast cancer management, yet acquired resistance commonly emerges despite aromatase inhibitors (AIs) and CDK4/6 inhibitors. A key actionable mechanism is treatment-selected ESR1 mutation, detectable in circulating tumor DNA (ctDNA) before radiographic progression. This narrative review summarizes (i) next-generation estrogen receptor (ER)–targeting agents (oral SERDs and novel ER degraders), (ii) the rationale for ESR1-guided endocrine switching, and (iii) practical considerations for implementing a ctDNA-enabled “monitor–trigger–switch” strategy in routine care. Oral SERDs are moving from late-line salvage toward earlier settings, supported by post–CDK4/6 efficacy signals in ESR1-mutant disease and by prospective molecular switching trials. PADA-1 and SERENA-6 provide prospective evidence that intervention at molecular progression can delay radiographic progression in selected patients. However, available SERENA-6 data remain interim, OS is immature, and implementation outside trial settings requires careful attention to assay validity, monitoring burden, cost, and risk of overtreatment from ambiguous low-level ctDNA findings. We also discuss early-stage implications, including emerging signals that adjuvant oral SERDs may improve invasive disease-free survival, raising questions regarding patient selection and integration with existing escalation strategies. ctDNA-enabled, ESR1-guided switching has the potential to shift endocrine management from reactive treatment changes at clinical progression toward earlier molecular interception of resistance in selected patients.

In hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2-) metastatic breast cancer (mBC), cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have transformed long-term disease control; however, survival trajectories remain markedly heterogeneous. While a subset of patients experiences early progression reflecting endocrine-resistant and biologically aggressive disease, others maintain durable endocrine-sensitive control for several years. As a result, baseline survival estimates calculated from treatment initiation become progressively less representative for patients who remain progression-free during ongoing therapy. We therefore evaluated landmark-based conditional survival outcomes in a real-world cohort of patients receiving first-line CDK4/6i-based therapy. We retrospectively evaluated 390 patients with HR+/HER2- mBC treated with first-line CDK4/6i plus endocrine therapy. Landmark analyses were performed at 6, 12, 24, and 36 months following treatment initiation. Conditional progression-free survival (cPFS), conditional overall survival (cOS), and post-landmark OS according to progression status were estimated using Kaplan–Meier analyses from each landmark time point. Baseline clinicopathological factors were additionally evaluated using landmark-specific logistic regression analyses. Median progression-free survival (PFS) and overall survival (OS) from treatment initiation were 29.2 months (95

Pentraxin 3 (PTX3) is an inflammatory mediator involved in tumorigenesis; however, its role in tumor immune evasion remains elusive. Herein, we demonstrate that PTX3 promotes immune evasion in breast cancer by upregulating PD-L1. RT-qPCR and Western blot were performed to assess PD-L1 expression in human and murine breast cancer cells. Cell surface PD-L1 was assayed by flow cytometry. Small interfering RNA and CRISPR-Cas9 were used to inhibit PTX3 expression. Co-culture experiments were conducted to evaluate the suppressive effects of tumor cells on CD8 + T cell activation. An immunocompetent BALB/c mouse allograft model was utilized, and tumor-infiltrating CD8 + T cells were analyzed by flow cytometry and immunohistochemistry. PTX3 enhanced PD-L1 protein levels through the inhibition of autophagy. PTX3 increased the expression of the E3 ligase RNF216 and caused Beclin-1 degradation, which suppressed autophagy, thereby preventing autophagy–mediated PD-L1 degradation. Co-culture experiments demonstrate that PTX3-overexpressing breast cancer cells suppressed CD8 + T cell function, as evidenced by reduced production of IFN-γ and Granzyme B, whereas PTX3-depleted cells had the opposite effects. In vivo allograft studies revealed that depletion of PTX3 reduced PD-L1 expression, enhanced CD8 + T cell infiltration, and inhibited tumor growth in immunocompetent mice. PTX3 promotes PD-L1 expression and immune evasion in breast cancer. Therefore, targeting PTX3 may represent a potential therapeutic strategy to counteract this immune escape.

Intraoperative indocyanine green (ICG) fluorescence angiography (ICG-FA) is commonly used to detect areas with poor perfusion. Fat necrosis caused by poor perfusion is often associated with the use of deep inferior epigastric perforator (DIEP) flaps. We report the development of an effective ICG-FA algorithm to prevent the occurrence of fat necrosis in the use of DIEP flaps. Fifty patients who underwent unilateral breast reconstruction using a DIEP flap and intraoperative ICG-FA were included. ICG-FA was performed after free-flap elevation to determine the extent of blood flow in the main perforating branch and the need for additional anastomosis (AA). Data on the presence of AA, vessels used, flap utilization rate, and postoperative course were collected and investigated. AA was performed in 24 of the 50 patients (48

The rising proportion of patients diagnosed with early-stage breast cancer (BC) has shifted the focus of oncological care toward patient-reported outcomes (PROs) as an important component of treatment evaluation. Nevertheless, data on the association between body composition and BC-specific PROs remain scarce and mainly retrospective. This study aimed to evaluate the association between preoperative bioelectrical impedance analysis (BIA) parameters and BC-specific PROs measured using the EORTC QLQ-BR23. This prospective study included 81 patients with histologically confirmed BC qualified for surgical treatment. Body composition was assessed preoperatively using multi-frequency BIA. BC-specific PROs was evaluated using the EORTC QLQ-BR23 questionnaires. Statistical analysis included the Mann-Whitney U test and Kruskal-Wallis ANOVA for group comparisons and Spearman’s rank correlation coefficient to assess associations between variables. Significant associations were observed between selected BIA parameters and PROs in BC patients. Higher phase angle and reactance values were positively correlated with body image, whereas higher lower-limb fat-free mass percentage and elevated TBW/FFM ratios were associated with poorer sexual functioning and enjoyment. In addition, body composition parameters differed across molecular subtypes with HER2-positive patients demonstrating lower values of total body water, fat-free mass, skeletal muscle mass and basal metabolic rate. These findings support the clinical utility of BIA as a complementary tool for personalized assessment linking physiological status with tumor characteristics and PROs.

Therapeutic mammoplasty (TM) is a well-established oncoplastic breast-conserving technique, particularly for patients with large ptotic breasts. However, evidence on the oncologic safety and cosmetic outcomes in East Asian patients who meet these anatomical criteria remains limited. This study evaluated the outcomes of TM combined with contralateral reduction mammoplasty in a cohort of East Asians. We conducted a single-center retrospective observational study of consecutive patients who underwent TM with simultaneous contralateral reduction mammoplasty for breast cancer between April 2014 and March 2024. The primary endpoint was oncologic safety, assessed using the positive margin rate and local recurrence. The secondary endpoints included 1-year cosmetic outcomes, assessed using BCCT.core and the Harvard scale by blinded physicians. A total of 104 patients were included (mean age: 59.6 ± 10.6 years, mean body mass index: 28.4 ± 5.1 kg/m2, mean tumor size: 22.0 ± 11.5 mm). Positive margins occurred in 5 patients; 4 underwent additional resection and 1 received boost irradiation alone. At a median follow-up of 58.6 months, no local recurrence occurred, whereas distant recurrence occurred in 1 patient. Perioperative complications occurred in 27 patients, with 6 requiring reoperation; no cases of nipple necrosis were reported. Among 100 evaluable patients, excellent or good cosmetic outcomes were achieved in 83.0

Targeted axillary dissection (TAD) is a less invasive alternative to axillary lymph node dissection (ALND) for patients with clinically node-positive breast cancer who convert to node-negative status after neoadjuvant chemotherapy (NAC). However, the effect of preoperative ultrasound visibility of different clip types on TAD outcomes remains unclear. We conducted a single-center retrospective cohort study of patients with biopsy-proven axillary node-positive breast cancer who underwent NAC followed by TAD between August 2017 and December 2024. Two ultrasound-visible clips, the UltraCor™ Twirl™ (Twirl) and HydroMARK™, were evaluated. Outcomes included ultrasound visibility, clipped node retrieval success, localization techniques, and false-negative rate (FNR). Twenty-nine patients were included (Twirl, n = 15; HydroMARK, n = 14). Ultrasound visibility was higher with Twirl than with HydroMARK (86.7

BARD1 germline pathogenic variants (gPV) have been primarily associated with moderate breast cancer risk but their rarity limits accurate risk assessment and tailored follow-up guidelines. Our study evaluates the association between BARD1 gPV and breast cancer while exploring the role of BARD1 in mammary oncogenesis. In this case-control study, 7,309 women with breast cancer and no gPV identified in the French hereditary breast and ovarian cancer (HBOC) gene panel at the Institut Curie were compared to 57,681 female controls from the gnomAD European non-cancer database. Tumors were analyzed for biallelic BARD1 inactivation and homologous recombination deficiency (HRD). A significant association was observed between BARD1 gPV and breast cancer (OR = 5.2, 95

Sentinel lymph node biopsy (SLNB) is the standard procedure for axillary staging. However, its necessity in older patients (≥ 70 years) with HR+/HER2– T1 breast cancer remains debated in the context of contemporary de-escalation strategies. Existing evidence often incompletely accounts for the competing risk of death in this population. We evaluated the association between SLNB and breast cancer–specific death (BCSD) using real-world data. Women aged ≥ 70 years with HR+/HER2– T1 (≤ 20 mm) breast cancer treated with breast-conserving surgery between 2010 and 2021 were identified from the SEER database and classified into SLNB and No-SLNB groups. Propensity score matching (PSM) and Fine–Gray competing risk models were used to estimate subdistribution hazard ratios (sHRs) for BCSD and other-cause death (OCD). A prognostic nomogram was constructed. Among 47,838 eligible patients, 37,732 underwent SLNB and 10,106 did not. After PSM, SLNB was associated with a lower 5-year cumulative incidence of BCSD (2.50

Although the incidence of breast cancer is increasing rapidly in Japan, the number of specialized physicians remains insufficient, threatening the sustainability and geographic equity of care delivery. This growing mismatch between clinical demand and workforce capacity reflects not only numerical shortages, but also structural weaknesses in training, retention, and career development pathways. To address these workforce challenges, the Japanese Breast Cancer Society launched the Multi Institutional bReast cAncer Young team No.1 (MIRAY1) as a youth-driven, society-endorsed initiative focused on recruitment, education, and career development of future breast cancer specialists. MIRAY1 employs an innovative matrix structure where members belong to both one of six task groups and one of seven regional divisions. Each task group is designed to address specific challenges identified in the current breast cancer workforce pipeline; for example, limited early exposure, attrition during early and mid-career stages, and declining international mobility. Early activities have demonstrated high engagement among medical students and young physicians through hands-on education, digital communication, and peer-led networking. MIRAY1 represents a potentially sustainable workforce development model not only for Japan but also for other Asian countries facing similar challenges in oncology care.

Understanding how lifestyle habits influence breast cancer survival is crucial for improving long-term outcomes and guiding individualized care. The purpose of this study is to comprehensively understand how dietary habits, exercise frequency, sleep quality and the frequency of tobacco and alcohol use affect the survival of breast cancer patients by analyzing the synergistic effects of multiple lifestyle habits. We analyzed data from 21,219 female breast cancer patients in the UK Biobank, a large-scale population-based cohort. Three feature selection methods were applied to identify key prognostic variables. Five survival risk models were compared to investigate the relationship between breast cancer survival and lifestyle habits. Kaplan-Meier survival analysis and SHapley Additive exPlanations (SHAP) interpretability analysis were performed on risk scores calculated from the best-performing model. Through feature selection, we identified that age, Body Mass Index (BMI), smoking status, and treatment pill intake were pinpointed as critical characteristics influencing the survival of breast cancer patients. Among all models, the eXtreme Gradient Boosting (XGBoost) model demonstrated the highest predictive performance (3 years: AUC = 0.748, 6 years: AUC = 0.749, 9 years: AUC = 0.765). Kaplan-Meier analysis showed that patients classified as high-risk based on the median risk score had significantly worse survival outcomes (P < 0.0001). SHAP analysis further confirmed the dominant influence of key characteristics on mortality risk. This study highlights the prognostic value of lifestyle habits in breast cancer survival. By integrating routine health indicators into interpretable machine learning models, our findings provide a practical foundation for individualized risk assessment and lifestyle-based intervention strategies.

Breast cancer is a biologically diverse disease with distinct molecular subtypes, each linked to specific risks and outcomes. However, subtype-specific risk factors remain insufficiently explored, particularly in diverse populations such as Indian women. This study examined the associations of reproductive, lifestyle, and psychosocial factors with the risk of developing breast cancer subtypes defined by hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status. We conducted a multicentric matched case–control study among Indian women at three tertiary cancer centres. Pathologically confirmed breast cancer cases and age-matched controls were recruited, and detailed information on socio-demographic, reproductive, lifestyle, and psychosocial characteristics was collected through structured interviews. Breast cancer cases were classified into four molecular subtypes (HR+HER2−, HR+HER2+, HR−HER2+, and HR−HER2−). Multivariable conditional logistic regression models were used to estimate subtype-specific odds ratios and 95

Background Variants of uncertain significance (VUS) in BRCA2 remain a major challenge in the clinical management of breast cancer, particularly in Asian populations where population-specific reference data are limited. Functional assays may provide complementary biological evidence to support interpretation of these variants. Patients and methods: Three BRCA2 missense VUS—c.5969A > C (p.Asp1990Ala), c.3671G > A (p.Gly1224Asp), and c.5459G > A (p.Cys1820Tyr)—were selected based on their frequency in Korean cohorts and/or strong family history of breast cancer. Full-length BRCA2 constructs harboring each variant were introduced into BRCA2 -knockout DLD-1 cells. Functional consequences were evaluated using cellular sensitivity assays following cisplatin treatment and ionizing radiation, response to the PARP inhibitor olaparib, and homologous recombination (HR) efficiency assessed by a GFP-based reporter system. Results Cells expressing BRCA2 p.Asp1990Ala consistently demonstrated increased sensitivity to cisplatin, ionizing radiation, and olaparib, comparable to pathogenic controls. In addition, GFP-based HR assays revealed a marked reduction in HR repair efficiency in p.Asp1990Ala-expressing cells. In contrast, cells expressing BRCA2 p.Gly1224Asp or p.Cys1820Tyr exhibited DNA damage responses, drug sensitivity profiles, and HR activity similar to wild-type BRCA2 across all assays. Conclusions Among the three BRCA2 VUS analyzed, p.Asp1990Ala exhibited a pathogenic-like functional phenotype characterized by impaired homologous recombination repair, whereas p.Gly1224Asp and p.Cys1820Tyr appeared functionally neutral. These findings highlight the functional heterogeneity of BRCA2 VUS and support the role of functional assays as complementary tools for variant interpretation in breast cancer.