Breast cancer (Tokyo, Japan)最新文献

{"title":"Time toxicity in breast cancer care: a nationwide cross-sectional survey of multidimensional time burden in Japan.","authors":"Hitomi Suzuki, Misato Tsukuda, Nobuko Ueda, Tomoko Yodogawa, Yukinori Arata, Tsukushi Kaji, Shotaro Oshikawa","doi":"10.1007/s12282-026-01926-4","DOIUrl":"https://doi.org/10.1007/s12282-026-01926-4","url":null,"abstract":"<p><strong>Background: </strong>Time toxicity has increasingly been recognized as an important dimension of cancer care alongside traditional clinical outcomes such as survival and toxicity. Although breast cancer therapy has become increasingly individualized, limited evidence exists regarding time toxicity beyond hospital-based care. This study aimed to quantify and characterize time toxicity in patients with breast cancer in Japan.</p><p><strong>Methods: </strong>A nationwide cross-sectional web-based survey of female patients was conducted in Japan. Among 866 respondents, the analysis focused on 598 patients with breast cancer. The survey assessed care-related time, non-care time, family caregiving time, information-seeking time, subjective distress associated with time burden, and activity restrictions.</p><p><strong>Results: </strong>The median waiting time for outpatient consultations was 60 min. The median hospital stay per visit was 240 min for chemotherapy and 40 min for radiotherapy. Overall, 69.1% of patients perceived hospital stay as \"long\" and 67.8% as \"distressing.\" Patients required a median of 10 days of rest during peak treatment-related symptom burden and an additional 15 min per outing for appearance-related care. Participants reported that family members spent a median of 25.5 h per month providing caregiving support. Patients also reported substantial time spent seeking information after diagnosis and forgoing work, travel, and exercise.</p><p><strong>Conclusions: </strong>Time toxicity in breast cancer care extends beyond hospital visits to include substantial non-care time and family caregiving time. Recognizing time toxicity as a potentially modifiable dimension of treatment burden may help inform treatment planning, supportive care, and shared decision-making in breast cancer care.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limited clinical value of routine PET/CT in early-stage breast cancer: a multicenter retrospective study.","authors":"Kassem Salam, Hasan Numan, Ali Elhadi Zreik, Mohamad Baqer Skaini, Ali Ghais, Chadi Abou Khater, Dany Nassar, Hady Ghanem, Fadi El Karak, Malek Safa, Nagi Saghir, Hiba Moukadem, Arafat Tfayli","doi":"10.1007/s12282-026-01927-3","DOIUrl":"https://doi.org/10.1007/s12282-026-01927-3","url":null,"abstract":"<p><strong>Background: </strong>Staging of breast cancer at diagnosis is essential for prognosis and guiding treatment decisions. The role of ^18F-FDG positron emission tomography/computed tomography (PET/CT) in patients with asymptomatic early-stage breast cancer remains controversial because of the low prevalence of distant metastasis and risk of false-positive findings.</p><p><strong>Materials and methods: </strong>This is a retrospective multicenter cohort study across three tertiary centers in Lebanon. Adult patients with newly diagnosed stage I or IIA breast cancer who underwent PET/CT for initial staging between January 2019 and December 2024 were included. Patients receiving neoadjuvant therapy prior to imaging or with more advanced disease were excluded. Descriptive statistics were used to summarize outcomes, including rates of disease upstaging and false-positive findings.</p><p><strong>Results: </strong>A total of 435 patients were included. Most tumors were invasive ductal carcinoma (88.0%) and hormone receptor-positive (ER 88.5%, PR 81.4%), with HER2 positivity in 17.7%. PET/CT resulted in stage upstaging in 23 patients (5.3%), 12 patients upstaged to stage IIA, 5 to stage IIB, and 6 to stage IV. However, histopathology confirmed distant metastases in only 3 patients (0.7%, 3/435). Overall, upstaging was pathologically confirmed in 11 patients, whereas it was not confirmed in 12 patients, with the discordant cases being predominantly attributable to false-positive nodal findings. PET/CT findings led to treatment modification in only 0.9% (4/435) of the cohort.</p><p><strong>Conclusion: </strong>In this cohort of asymptomatic patients with clinical stage I-IIA breast cancer, PET/CT rarely identifies additional metastatic disease and frequently results in false-positive findings. These results suggest a selective, risk-adapted use of PET/CT rather than routine staging in early-stage breast cancer, particularly in resource-constrained healthcare settings, and should be interpreted in the context of the study's retrospective design.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of four breast lymphoedema patient reported outcome measures in women following breast conserving surgery and radiotherapy: examination of frequencies of symptoms and measurement properties.","authors":"Nicola Fearn, Sharon Kilbreath, Elizabeth Dylke, Wei Wang, Catalina Llanos, Verity Ahern, Elisabeth Elder, Farid Meybodi, Nicholas Olsen, Kirsty Stuart","doi":"10.1007/s12282-026-01919-3","DOIUrl":"https://doi.org/10.1007/s12282-026-01919-3","url":null,"abstract":"<p><strong>Background: </strong>Lymphoedema of the breast is a potential consequence of breast cancer treatment. Questionnaires exist to quantify breast symptoms but evidence for measurement properties is limited. This study aimed to evaluate measurement properties of breast lymphoedema questionnaires and report on frequency and severity of breast symptoms in women with breast cancer.</p><p><strong>Methods: </strong>Women following breast conserving surgery and radiotherapy were recruited. Four questionnaires, Breast Lymphoedema Severity Symptom questionnaire (BLYSS), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Breast Symptom Subscale (EORTC-QLQ-BSS), Lymphoedema Symptom Intensity and Distress scale-Trunk (LSIDS-T) and Breast Oedema Bother scale (BOB), were completed three and nine-months after radiotherapy. Measurement properties and breast symptoms were evaluated.</p><p><strong>Results: </strong>Questionnaires were completed by 164 women at three-months, and 152 at nine-months post radiotherapy. Internal consistency was strong for all questionnaires (McDonald's Omega and Cronbach's ⍺ ≥0.7). Correlation between BLYSS and EORTC-QLQ-BSS and BOB visual analogue scale (BOB-VAS) met the hypothesised level (r_s ≥ 0.7) demonstrating construct validity. Exploratory factor analysis demonstrated single factors for individual tools and four factors when all four questionnaires were combined: pain, swelling, breast sensations and hardness. Responsiveness was high for BLYSS and moderate for EORTC-QLQ-BSS and BOB-VAS. Over half the women experienced symptoms ≥twice/week at mild-extreme severity. Breast pain, hardness, oversensitivity and swelling were most reported symptoms.</p><p><strong>Conclusion: </strong>The BLYSS demonstrated the strongest measurement properties among the PROMs evaluated with strong internal consistency, construct validity and responsiveness. Breast symptoms were commonly experienced by women after breast cancer treatment.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Target trial emulation of first-line ribociclib versus palbociclib in hormone receptor-positive, HER2-negative metastatic breast cancer: a comparative effectiveness study.","authors":"Xiaoyi Zhang, Po-Huang Chen, Wei-Cheng Chang, Hong-Jie Jhou, Hsin-Yu Chen, Li-Ting Kao, Tina Yi-Jin Hsieh, Ming-Shen Dai, Na Xiao, Cho-Hao Lee","doi":"10.1007/s12282-026-01921-9","DOIUrl":"https://doi.org/10.1007/s12282-026-01921-9","url":null,"abstract":"<p><strong>Background: </strong>Head-to-head randomized trials of CDK4/6 inhibitors are lacking. We emulated a target trial of first-line ribociclib versus palbociclib in hormone receptor-positive, HER2-negative metastatic breast cancer.</p><p><strong>Methods: </strong>Using TriNetX (January 2014-March 2025), adults initiating first-line endocrine therapy plus ribociclib or palbociclib underwent 1:1 propensity score matching. The primary outcome was all-cause mortality. The co-primary calendar-restricted survival analysis applied a year-level restriction beginning January 1, 2017, the calendar year of ribociclib market entry.</p><p><strong>Results: </strong>The prescription-confirmed cohort comprised 11,685 patients; 4394 were matched (2197 per group; mean age 60.2 years; 97.9% female). In the whole-period co-primary analysis, ribociclib was associated with longer overall survival (hazard ratio [HR] 0.82, 95% CI 0.73-0.92) and a 48-month restricted mean survival difference of 1.7 months (95% CI 0.5-2.8). The all-initiator analysis removing the second-prescription requirement yielded HR 0.86 (95% CI 0.75-0.99) but did not restrict calendar time. The separately matched calendar-restricted co-primary analysis (from 2017; 1924 per arm) yielded HR 0.90 (95% CI 0.82-0.99); residual temporal confounding could favor ribociclib. Exploratory analyses showed lower cause-specific hazards of recorded hematologic events (neutropenia HR 0.69, thrombocytopenia HR 0.52, anemia HR 0.80) and higher hazards of recorded QT prolongation and dermatologic events (HR 1.61 and 1.41); no detectable differences were observed for healthcare utilization or severe infections.</p><p><strong>Conclusions: </strong>Both co-primary analyses showed an association with longer overall survival for ribociclib, with attenuation in the calendar-restricted analysis (HR 0.90, 95% CI 0.82-0.99). These findings are hypothesis-generating, not evidence of superiority, and require randomized confirmation.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preoperative CA15-3 as a predictor of axillary lymph node metastasis and prognosis in women with breast cancer: a GRADE-assessed systematic review and meta-analysis.","authors":"Mansour Bahardoust, Anita Rezaei, Anahita Hosseinali, Golnaz Ranjbarpazuki, Sajad Salehi, Meisam Haghmoradi, Shoboo Rahmati, Nahid Nafissi","doi":"10.1007/s12282-026-01924-6","DOIUrl":"https://doi.org/10.1007/s12282-026-01924-6","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) is the leading cause of cancer-related death among women. Axillary lymph node metastasis (ALNM) is a key prognostic factor, yet its assessment relies on invasive procedures. The prognostic value of preoperative CA15-3 remains controversial. We aimed to evaluate the association between preoperative CA15-3 levels and overall survival (OS), disease-free survival (DFS), and ALNM in breast cancer patients.</p><p><strong>Methods: </strong>We systematically searched PubMed, Scopus, Web of Science, Embase, and Cochrane Library up to January 2026. Cohort studies assessing preoperative CA15-3 and OS, DFS, or ALNM were included. Pooled hazard ratios (HRs) for OS and DFS, as well as pooled odds ratios (ORs) with 95% confidence intervals (CIs) for metastasis outcomes (Any metastasis or ALNM), were calculated using random-effects models.</p><p><strong>Results: </strong>Thirty-one cohort studies comprising 178,047 patients were included. Elevated CA15-3 was significantly associated with worse OS (HR: 1.91; 95% CI: 1.67-2.15), poorer DFS (HR: 2.04; 95% CI: 1.78-2.31), and increased metastasis risk (OR: 2.73; 95% CI: 2.04-3.42). The strongest association was observed for ALNM (OR: 3.08; 95% CI: 2.09-4.08). Subgroup and meta-regression analyses confirmed consistent findings across regions and identified age, tumor stage, and CA15-3 cutoff as heterogeneity sources.</p><p><strong>Conclusions: </strong>Elevated preoperative CA15-3 is significantly associated with reduced survival and increased ALNM risk. This association remained significant after adjustment for tumor characteristics in most primary studies, suggesting CA15-3 may reflect more aggressive tumor biology. These findings support CA15-3's potential as an adjunctive biomarker; however, prospective validation is warranted.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term outcomes of invasive lobular carcinoma compared with invasive ductal carcinoma in HR-positive/HER2-negative breast cancer: a focus on luminal subtypes.","authors":"Sayoko Kakimoto, Hiroyuki Yamamoto, Junki Koike, Koichiro Tsugawa","doi":"10.1007/s12282-026-01922-8","DOIUrl":"https://doi.org/10.1007/s12282-026-01922-8","url":null,"abstract":"<p><strong>Background: </strong>Invasive lobular carcinoma (ILC) differs from invasive ductal carcinoma (IDC) in clinicopathological characteristics, treatment responsiveness, and recurrence patterns. However, its long-term prognostic significance, particularly in hormone receptor (HR)-positive/HER2-negative disease, remains incompletely understood.</p><p><strong>Methods: </strong>We retrospectively analyzed 2,423 women with clinical stage I-III breast cancer who underwent partial mastectomy or total mastectomy between January 2013 and December 2017, including 2,262 patients with IDC and 161 with ILC. The primary endpoint was invasive breast cancer-free survival (iBCFS), and overall survival (OS) was evaluated as a secondary endpoint. Multivariable Cox proportional hazards models were used to compare outcomes between ILC and IDC. Subtype-specific analyses were restricted to HR-positive/HER2-negative luminal A-like and luminal B-like tumors defined according to the St. Gallen 2013 criteria. Exploratory analyses assessed the associations of neoadjuvant and adjuvant chemotherapy with outcomes.</p><p><strong>Results: </strong>Compared with IDC, ILC was more frequently ER-positive/HER2-negative, had lower Ki-67, and presented with more advanced pathological tumor burden. Five-year iBCFS was 84.9% in ILC and 91.5% in IDC (log-rank p = 0.053). In the adjusted overall model, ILC tended to be associated with poorer iBCFS (hazard ratio [HR] 1.43, 95% confidence interval [CI] 0.94-2.19; p = 0.096). In subtype-specific analyses, ILC was not significantly associated with iBCFS in luminal A-like disease (HR 1.15, 95% CI 0.67-1.98; p = 0.619), whereas the adverse prognostic association of ILC was more apparent in luminal B-like disease (HR 1.47, 95% CI 1.03-2.09; p = 0.033). The histology-by-subtype interaction was not statistically significant. In luminal disease, neoadjuvant chemotherapy was not independently associated with improved outcomes after adjustment for pretreatment clinical stage, whereas adjuvant chemotherapy was associated with better iBCFS in the combined luminal ILC group.</p><p><strong>Conclusions: </strong>ILC tended to be associated with poorer long-term invasive outcomes than IDC, particularly in HR-positive/HER2-negative disease. The adverse prognostic association of ILC was more apparent in luminal B-like tumors than in luminal A-like tumors. These findings support a risk-adapted approach to ILC that integrates histology, tumor burden, and proliferative activity. Further validation in larger prospective studies is warranted.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of exercise and educational programs on long-term quality of life, anxiety, and depression in breast cancer survivors: an exploratory secondary analysis of the Setouchi breast project-10 randomized controlled trial.","authors":"Azusa Jo, Takayuki Iwamoto, Kengo Kawada, Youko Suzuki, Kyoko Hara, Seiji Yoshitomi, Daisuke Takabatake, Shinichiro Kubo, Yutaka Ogasawara, Shozo Ohsumi, Masahiko Ikeda, Hiroyoshi Doihara, Yuri Mizota, Seiichiro Yamamoto, Naruto Taira","doi":"10.1007/s12282-026-01920-w","DOIUrl":"https://doi.org/10.1007/s12282-026-01920-w","url":null,"abstract":"<p><strong>Background: </strong>Advances in early detection and multimodal therapy have increased the population of long-term breast cancer survivors, underscoring the importance of survivorship care focused on health-related quality of life (HRQoL). Although exercise and educational interventions show short-term benefits, their long-term sustainability remains unclear. This study evaluated the longitudinal effects of these interventions on HRQoL and psychological outcomes after initial treatment.</p><p><strong>Methods: </strong>This secondary analysis of the Setouchi Breast Project-10 randomized controlled trial included 342 patients with stage 0-III breast cancer within one year of treatment completion, assigned to usual care (n = 114), education (n = 120), or exercise (n = 108). HRQoL was assessed using FACT-B and its subscales, and psychological outcomes using HADS at baseline and 2, 4, 6, and 12 months. Responder analyses based on minimally important differences and mixed-effects models for repeated measures were conducted.</p><p><strong>Results: </strong>The education group showed greater early improvement in the FACT-B Trial Outcome Index at 2 months versus control (51% vs. 32%, p = 0.003). Although MID analyses suggested deterioration in some global domains at 12 months in the exercise group, longitudinal analyses demonstrated sustained improvement in the breast cancer subscale in both intervention groups. No consistent between-group differences were observed in global HRQoL or HADS scores.</p><p><strong>Conclusions: </strong>This exploratory secondary analysis suggests that physician-led educational interventions and structured exercise may contribute to maintaining breast cancer-specific HRQoL, particularly in disease-specific domains. However, global HRQoL and psychological outcomes did not show consistent improvements, and a tendency toward deterioration was observed in some indicators for the exercise group at 12 months. These findings should be interpreted with caution, but they suggest that low-cost educational approaches could be a resource-efficient option in survivorship care.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mindful eating as a supportive intervention for breast cancer survivors: a pilot randomized controlled trial.","authors":"Dilşat Baş, Gizem Ağır, Özlem Sönmez, Ece Öneş","doi":"10.1007/s12282-026-01917-5","DOIUrl":"https://doi.org/10.1007/s12282-026-01917-5","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) survivors often face weight management and disordered eating challenges that may impair quality of life. This pilot randomized controlled trial evaluated the effects of a six-session mindful eating intervention on eating behaviors and body composition in BC survivors.</p><p><strong>Methods: </strong>Breast cancer survivors were enrolled in a pilot randomized clinical trial and randomly assigned to mindful eating intervention plus treatment-as-usual (TAU + MEI, n = 13) or treatment-as-usual alone (TAU, n = 15). Intuitive and mindful eating were assessed using the Intuitive Eating Scale-2 (IES-2) and the Mindful Eating Questionnaire-30 (MEQ-30). Anthropometric measures were assessed monthly over six months. Longitudinal changes were analyzed using repeated-measures ANOVA and generalized estimating equations (GEE).</p><p><strong>Results: </strong>Reliance on hunger and satiety cues increased significantly over time in both groups (TAU: p = 0.004; TAU + MEI: p = 0.007). Significant improvements were observed in selected mindful eating dimensions, including disinhibition, emo-tional eating, eating control, and eating with attention and intention (all p < 0.05). MEQ-30 total scores increased significantly in both groups (TAU: p < 0.001; TAU + MEI: p = 0.010). Waist circum-ference decreased significantly in the TAU group (p = 0.002), while hip circumference decreased in the TAU + MEI group (p = 0.009). GEE analysis showed that participation in the TAU + MEI group was independently associated with lower BMI over time (p = 0.013), whereas HR(+)/HER2(-) sub-type and chronic disease were associated with higher BMI (all p < 0.05).</p><p><strong>Conclusions: </strong>Both TAU and TAU + MEI were associated with improvements in selected eating-behavior and anthropometric outcomes over time, including indicators of central adiposity, with no clear overall superiority of TAU + MEI across the outcomes assessed. These exploratory findings support further investigation of incorporating mindful eating into standard nutritional care for breast cancer survivors.</p><p><strong>Trial registration: </strong>The study was retrospectively registered at ClinicalTrials.gov (Identifier: NCT07007104; registration date: 28 May 2025.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical impact of ENIGMA-based variant reclassification on genotype-phenotype analyses in BRCA1- and BRCA2-associated hereditary breast and ovarian cancer.","authors":"Said Furkan Yildirim, Pervin Demir, Hakan Kosku, Bulent Yalcin, Ahmet Cevdet Ceylan","doi":"10.1007/s12282-026-01913-9","DOIUrl":"https://doi.org/10.1007/s12282-026-01913-9","url":null,"abstract":"<p><strong>Background: </strong>Accurate interpretation of BRCA1 and BRCA2 variants is essential for meaningful genotype-phenotype correlations and informed clinical decision-making. However, general frameworks such as the ACMG 2015 criteria frequently result in high rates of variants of uncertain significance (VUS), which may generate misleading clinicopathological associations and complicate genetic counseling.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 3,706 individuals tested for BRCA1/2 variants due to BRCA-related malignancies in a large Turkish cohort. Variants were initially classified according to ACMG 2015 criteria and subsequently re-evaluated using ENIGMA consensus recommendations. Clinicopathological data were compared between variant categories before and after reclassification.</p><p><strong>Results: </strong>Pathogenic or likely pathogenic variants were detected in 6.7% of patients, while 3.8% were initially classified as VUS. Following ENIGMA-guided reclassification, a substantial proportion of VUS, particularly missense variants lacking functional impact, were reclassified as benign or likely benign. Clinicopathological differences observed between ACMG-defined pathogenic and VUS groups-including age at onset, tumor distribution, receptor status, and progression-free survival-were eliminated after ENIGMA-based reassessment, revealing biological heterogeneity within the VUS category. Post-reclassification analyses allowed more precise distinction of benign variant profiles, refining genotype-phenotype interpretations.</p><p><strong>Conclusions: </strong>ENIGMA-guided variant interpretation enhances analytical precision, reduces false-positive associations, and improves clinical utility in hereditary breast and ovarian cancer genetics, offering a more reliable framework for genetic counseling and risk assessment in populations with diverse variant spectra.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triggering receptors expressed on myeloid cells (TREM-1) and TREM-2 as predictors of pathological complete response to neoadjuvant therapy in triple-negative breast cancer.","authors":"Nazan Demir, İvo Gökmen, Duygu Bayır Garbioğlu, Ebru Taştekin, Emre Işık, Erkan Özcan, Bülent Erdoğan, Sernaz Topaloğlu, Bahadır Köylü, Cevat İlteriş Kıkılı, Fatih Kemik, İrfan Çiçin, Fatih Selçukbiricik, Muhammet Bekir Hacıoğlu","doi":"10.1007/s12282-026-01918-4","DOIUrl":"https://doi.org/10.1007/s12282-026-01918-4","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, characterized by early metastasis, high recurrence rates, and limited targeted therapy options. Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a well-established prognostic surrogate for long-term outcome, yet reliable predictive biomarkers remain elusive. TREM-1 and TREM-2 are key immune modulators that shape the balance between proinflammatory and immunosuppressive signaling within the tumor microenvironment (TME). This study aimed to evaluate the predictive utility of TREM-1 and TREM-2 expression for pCR in TNBC after NACT.</p><p><strong>Methods: </strong>Pre-treatment biopsies from 71 patients with early or locally advanced TNBC treated with chemotherapy-based NACT were analyzed by immunohistochemistry (IHC) for TREM-1 and TREM-2. Stromal/TIL H-scores were used for the final analysis. Clinical records were reviewed for treatment regimen. Cutoff values were determined using receiver operating characteristic (ROC) analysis based on the Youden index, and multivariable logistic regression was used to identify independent predictors of pCR.</p><p><strong>Results: </strong>High stromal TREM-1 expression (> 90) independently predicted higher pCR rates (OR 12.25; p = 0.003), whereas high stromal TREM-2 expression (> 10) correlated with lower pCR likelihood (OR 0.105; p = 0.030). The predefined high Ki-67 group and lower T-stage also predicted pCR. In secondary analyses, tumor-cell TREM-1 and TREM-2 expression were not significantly associated with pCR.</p><p><strong>Conclusion: </strong>The opposing associations of stromal TREM-1 and TREM-2 with pCR suggest that the TIL-mediated tumor microenvironment may play an important role in shaping treatment sensitivity in TNBC. High TREM-1 expression is linked to an inflammatory, treatment-responsive phenotype, whereas high TREM-2 expression reflects an immunosuppressive, resistant state. Their combined evaluation may provide clinically meaningful insights for predicting therapeutic response and for developing novel immunomodulatory strategies in TNBC.</p>","PeriodicalId":520574,"journal":{"name":"Breast cancer (Tokyo, Japan)","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}