Pub Date : 2026-04-01Epub Date: 2026-01-19DOI: 10.1016/j.breast.2026.104706
Hannah Bacon , Xiang Y. Ye , Zhihui Amy Liu , Grace Lee , Ezra Hahn , Eitan Amir , Tony Tadic , Andrew Hope , C. Anne Koch
Purpose
The treatment of HER2-positive (HER2+) and triple negative (TN) breast cancer (BC) increasingly includes systemic therapies that can be associated with a risk of drug-induced pneumonitis and may overlap with the delivery of radiotherapy, which carries an independent risk of pneumonitis. The aim of this study is to characterize the interaction between trastuzumab-emtansine (T-DM1), pembrolizumab and radiotherapy in modulating the risk of pneumonitis in a real-world setting.
Methods
A retrospective, single institution, chart review identified patients with non-metastatic HER2+ or TN BC, who were treated with adjuvant radiotherapy between 2019 and 2024. Among this cohort the proportion with pneumonitis diagnosed within 1-year following completion of radiotherapy was evaluated. The association of grade ≥2 pneumonitis (G2P+) with clinical factors of interest was examined using univariate and multivariable logistic regression.
Results
Of 863 eligible patients, 528 were HER2+ and 335 were TN. Overall the rate of G2P+ was 2.8 %; 3.6 % for HER2+ and 1.5 % for TN patients. On univariate analysis, radiation treatment volume, clinical stage, and receipt of T-DM1 were associated with G2P+, however, only T-DM1 (OR = 4.16, 95 % CI = 1.59–10.92, p < 0.01) and clinical stage III vs. II (OR 2.69, 95 % CI 1.03–7.02, p = 0.04) remained significant on multivariable analysis.
Conclusion
Overall, the probability of G2P+ in patients receiving radiotherapy for HER2+ or TN BC is low. However, concurrent T-DM1 and radiotherapy was associated with significantly higher rates of pneumonitis than previously reported, suggesting a cautionary approach when combining the two therapies.
HER2阳性(HER2+)和三阴性(TN)乳腺癌(BC)的治疗越来越多地包括可能与药物性肺炎风险相关的全身治疗,并可能与放射治疗重叠,放射治疗具有独立的肺炎风险。本研究的目的是表征曲妥珠单抗-emtansine (T-DM1),派姆单抗和放疗在现实世界中调节肺炎风险的相互作用。方法对2019年至2024年间接受辅助放疗的非转移性HER2+或TN BC患者进行回顾性、单机构、图表回顾。在该队列中,评估放疗完成后1年内诊断为肺炎的比例。采用单因素和多因素logistic回归检验≥2级肺炎(G2P+)与临床相关因素的相关性。结果863例符合条件的患者中,HER2+ 528例,TN 335例,总体G2P+率为2.8%;HER2+为3.6%,TN为1.5%。在单因素分析中,放疗量、临床分期和接受T-DM1治疗与G2P+相关,但在多变量分析中,只有T-DM1 (OR = 4.16, 95% CI = 1.59-10.92, p < 0.01)和临床III期与II期(OR 2.69, 95% CI 1.03-7.02, p = 0.04)仍然具有显著性。结论总体而言,HER2+或TN BC放疗患者发生G2P+的概率较低。然而,同时使用T-DM1和放疗与肺炎的发病率显著高于之前的报道,这表明在联合使用这两种疗法时需要谨慎。
{"title":"Predictors of pneumonitis in patients treated with systemic therapy and radiotherapy for localized triple negative or HER2 positive breast cancer","authors":"Hannah Bacon , Xiang Y. Ye , Zhihui Amy Liu , Grace Lee , Ezra Hahn , Eitan Amir , Tony Tadic , Andrew Hope , C. Anne Koch","doi":"10.1016/j.breast.2026.104706","DOIUrl":"10.1016/j.breast.2026.104706","url":null,"abstract":"<div><h3>Purpose</h3><div>The treatment of HER2-positive (HER2+) and triple negative (TN) breast cancer (BC) increasingly includes systemic therapies that can be associated with a risk of drug-induced pneumonitis and may overlap with the delivery of radiotherapy, which carries an independent risk of pneumonitis. The aim of this study is to characterize the interaction between trastuzumab-emtansine (T-DM1), pembrolizumab and radiotherapy in modulating the risk of pneumonitis in a real-world setting.</div></div><div><h3>Methods</h3><div>A retrospective, single institution, chart review identified patients with non-metastatic HER2+ or TN BC, who were treated with adjuvant radiotherapy between 2019 and 2024. Among this cohort the proportion with pneumonitis diagnosed within 1-year following completion of radiotherapy was evaluated. The association of grade ≥2 pneumonitis (G2P+) with clinical factors of interest was examined using univariate and multivariable logistic regression.</div></div><div><h3>Results</h3><div>Of 863 eligible patients, 528 were HER2+ and 335 were TN. Overall the rate of G2P+ was 2.8 %; 3.6 % for HER2+ and 1.5 % for TN patients. On univariate analysis, radiation treatment volume, clinical stage, and receipt of T-DM1 were associated with G2P+, however, only T-DM1 (OR = 4.16, 95 % CI = 1.59–10.92, p < 0.01) and clinical stage III vs. II (OR 2.69, 95 % CI 1.03–7.02, p = 0.04) remained significant on multivariable analysis.</div></div><div><h3>Conclusion</h3><div>Overall, the probability of G2P+ in patients receiving radiotherapy for HER2+ or TN BC is low. However, concurrent T-DM1 and radiotherapy was associated with significantly higher rates of pneumonitis than previously reported, suggesting a cautionary approach when combining the two therapies.</div></div>","PeriodicalId":9093,"journal":{"name":"Breast","volume":"86 ","pages":"Article 104706"},"PeriodicalIF":7.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-31DOI: 10.1016/j.breast.2026.104711
Massimo Ferrucci , Daniele Passeri , Francesco Milardi , Giacomo Montagna , Anna C. Beck , Riccardo Audisio , Fredrick Wärnberg , Gianluca Franceschini , Lucio Fortunato , Matteo Ghilli , Valentina Guarneri , Alberto Marchet , Rocco Cappellesso , Angelo Paolo Dei Tos , Tari Ann King
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.
{"title":"Pleomorphic and florid lobular carcinoma in situ of the Breast: A systematic review of current evidence and knowledge gaps","authors":"Massimo Ferrucci , Daniele Passeri , Francesco Milardi , Giacomo Montagna , Anna C. Beck , Riccardo Audisio , Fredrick Wärnberg , Gianluca Franceschini , Lucio Fortunato , Matteo Ghilli , Valentina Guarneri , Alberto Marchet , Rocco Cappellesso , Angelo Paolo Dei Tos , Tari Ann King","doi":"10.1016/j.breast.2026.104711","DOIUrl":"10.1016/j.breast.2026.104711","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":9093,"journal":{"name":"Breast","volume":"86 ","pages":"Article 104711"},"PeriodicalIF":7.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-19DOI: 10.1016/j.breast.2026.104704
K.G. Svalheim , N.K. Andresen , C. Bjerre , B. Gilje , E.H. Jakobsen , R.S. Falk , B. Naume , S. Kaasa , J.A. Kyte
Background
The ALICE trial demonstrated that adding atezolizumab to anthracycline-based immunomodulatory chemotherapy improved progression-free survival (PFS) in patients with metastatic triple-negative breast cancer (mTNBC), including those with PD-L1–negative tumors. Here, we report the patient-reported outcome measures (PROMs).
Methods
Patients were randomized to receive chemotherapy plus atezolizumab (atezo-chemo) or chemotherapy plus placebo (placebo-chemo). PROMs were collected at baseline and weeks 9, 17, 25, and 49 using the EORTC QLQ-C15-PAL, Chalder Fatigue Questionnaire (CFQ), and Numeric Rating Scale (NRS) for pain.
Results
PROMs were available from 64 of 68 patients. At week 9, mean changes from baseline favored the atezo-chemo arm across all QLQ-C15-PAL domains, CFQ scores, and NRS pain intensity. Time-to-deterioration analyses also favored atezo-chemo, with statistically significant hazard ratios for global quality of life (QoL; HR 0.24), emotional functioning (HR 0.30), and pain (HR 0.20). Pain—a pre-specified cardinal symptom—improved in the atezo-chemo group at all time points. At 12 months, PROMs indicated sustained tolerability. Better baseline PROM scores were associated with improved PFS and overall survival, especially among patients treated with atezolizumab. Patients with >median QoL score at baseline recorded improved PFS when treated with atezolizumab (HR 0.25), while patients with ≤median QoL score did not (HR 1.02).
Conclusions
Adding atezolizumab to the study-chemotherapy in mTNBC improves both PFS and patient-reported quality of life, emotional well-being and symptom control. These findings support continued development of this combination regimen and suggest that baseline quality of life may serve as a useful predictor of immunotherapy benefit.
Trial registration
NCT03164993, May 24th 2017; https://clinicaltrials.gov/ct2/show/record/NCT03164993.
{"title":"Patient-reported outcomes from the randomized ALICE trial evaluating the addition of atezolizumab to anthracycline-based chemotherapy in metastatic triple-negative breast cancer","authors":"K.G. Svalheim , N.K. Andresen , C. Bjerre , B. Gilje , E.H. Jakobsen , R.S. Falk , B. Naume , S. Kaasa , J.A. Kyte","doi":"10.1016/j.breast.2026.104704","DOIUrl":"10.1016/j.breast.2026.104704","url":null,"abstract":"<div><h3>Background</h3><div>The ALICE trial demonstrated that adding atezolizumab to anthracycline-based immunomodulatory chemotherapy improved progression-free survival (PFS) in patients with metastatic triple-negative breast cancer (mTNBC), including those with PD-L1–negative tumors. Here, we report the patient-reported outcome measures (PROMs).</div></div><div><h3>Methods</h3><div>Patients were randomized to receive chemotherapy plus atezolizumab (atezo-chemo) or chemotherapy plus placebo (placebo-chemo). PROMs were collected at baseline and weeks 9, 17, 25, and 49 using the EORTC QLQ-C15-PAL, Chalder Fatigue Questionnaire (CFQ), and Numeric Rating Scale (NRS) for pain.</div></div><div><h3>Results</h3><div>PROMs were available from 64 of 68 patients. At week 9, mean changes from baseline favored the atezo-chemo arm across all QLQ-C15-PAL domains, CFQ scores, and NRS pain intensity. Time-to-deterioration analyses also favored atezo-chemo, with statistically significant hazard ratios for global quality of life (QoL; HR 0.24), emotional functioning (HR 0.30), and pain (HR 0.20). Pain—a pre-specified cardinal symptom—improved in the atezo-chemo group at all time points. At 12 months, PROMs indicated sustained tolerability. Better baseline PROM scores were associated with improved PFS and overall survival, especially among patients treated with atezolizumab. Patients with >median QoL score at baseline recorded improved PFS when treated with atezolizumab (HR 0.25), while patients with ≤median QoL score did not (HR 1.02).</div></div><div><h3>Conclusions</h3><div>Adding atezolizumab to the study-chemotherapy in mTNBC improves both PFS and patient-reported quality of life, emotional well-being and symptom control. These findings support continued development of this combination regimen and suggest that baseline quality of life may serve as a useful predictor of immunotherapy benefit.</div></div><div><h3>Trial registration</h3><div>NCT03164993, May 24<sup>th</sup> 2017; <span><span>https://clinicaltrials.gov/ct2/show/record/NCT03164993</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":9093,"journal":{"name":"Breast","volume":"86 ","pages":"Article 104704"},"PeriodicalIF":7.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-27DOI: 10.1016/j.breast.2026.104703
Claudia Noto , Lorenzo Foffano , Fabiola Giudici , Elisabetta Molteni , Alessandra Franzoni , Martina Tessitori , Linda Cucciniello , Silvia Bolzonello , Lucia Da Ros , Lucia Bortot , Elena Scudeler , Brenno Pastò , Giulia Cudia , Serena Della Rossa , Marta Bonotto , Alessandro Marco Minisini , Giuseppe Damante , Barbara Belletti , Lorenzo Gerratana , Fabio Puglisi
Background
CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) represent the standard of care for hormone receptor–positive, HER2-negative (HR+/HER2–) metastatic breast cancer (MBC) patients. However, no head-to-head randomized trials have directly compared palbociclib, ribociclib, and abemaciclib. Moreover, predictive biomarkers of resistance to CDK4/6i remain largely undefined. This study aimed to evaluate circulating tumor DNA (ctDNA)-based epigenetic and fragmentomic biomarkers as potential predictors of response and resistance in patients receiving CDK4/6i.
Methods
We conducted a biomarker-driven analysis within the prospective, multicenter MAGNETIC.1 study, enrolling 149 patients with HR+/HER2– MBC treated with first-line endocrine therapy and a CDK4/6 inhibitor. Plasma samples were collected at baseline and during treatment (3 and 6 months). Droplet digital PCR was used to assess ESR1 promoter methylation and ACTB fragmentomic profiles. Progression-free survival (PFS) and overall survival (OS) were evaluated, and molecular dynamics were compared between treatment groups.
Results
After a median follow-up of 34.8 months, no statistically significant differences in PFS or OS were observed between ribociclib and palbociclib treated patients, although ribociclib was associated with numerically longer PFS and higher survival rates. At the molecular level, palbociclib treatment was characterized by transient increases in ESR1 promoter methylation at the first evaluation and a rebound in ACTBshort fragment levels at six months relative to baseline. These dynamic patterns were not observed among patients receiving ribociclib.
Conclusions
ctDNA-based methylation and fragmentomic profiling revealed exploratory, treatment specific molecular dynamics, highlighting biological differences between CDK4/6 inhibitors. These findings support the feasibility of liquid biopsy–based biomarker studies in this setting, although their potential clinical relevance remains preliminary and requires validation in larger cohorts with earlier and more granular on-treatment timepoints.
{"title":"Epigenetic and fragment-based profiling across CDK4/6 inhibitors in first-line HR+/HER2– metastatic breast cancer. An ancillary analysis of the MAGNETIC.1 study","authors":"Claudia Noto , Lorenzo Foffano , Fabiola Giudici , Elisabetta Molteni , Alessandra Franzoni , Martina Tessitori , Linda Cucciniello , Silvia Bolzonello , Lucia Da Ros , Lucia Bortot , Elena Scudeler , Brenno Pastò , Giulia Cudia , Serena Della Rossa , Marta Bonotto , Alessandro Marco Minisini , Giuseppe Damante , Barbara Belletti , Lorenzo Gerratana , Fabio Puglisi","doi":"10.1016/j.breast.2026.104703","DOIUrl":"10.1016/j.breast.2026.104703","url":null,"abstract":"<div><h3>Background</h3><div>CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) represent the standard of care for hormone receptor–positive, HER2-negative (HR+/HER2–) metastatic breast cancer (MBC) patients. However, no head-to-head randomized trials have directly compared palbociclib, ribociclib, and abemaciclib. Moreover, predictive biomarkers of resistance to CDK4/6i remain largely undefined. This study aimed to evaluate circulating tumor DNA (ctDNA)-based epigenetic and fragmentomic biomarkers as potential predictors of response and resistance in patients receiving CDK4/6i.</div></div><div><h3>Methods</h3><div>We conducted a biomarker-driven analysis within the prospective, multicenter MAGNETIC.1 study, enrolling 149 patients with HR+/HER2– MBC treated with first-line endocrine therapy and a CDK4/6 inhibitor. Plasma samples were collected at baseline and during treatment (3 and 6 months). Droplet digital PCR was used to assess <em>ESR1</em> promoter methylation and <em>ACTB</em> fragmentomic profiles. Progression-free survival (PFS) and overall survival (OS) were evaluated, and molecular dynamics were compared between treatment groups.</div></div><div><h3>Results</h3><div>After a median follow-up of 34.8 months, no statistically significant differences in PFS or OS were observed between ribociclib and palbociclib treated patients, although ribociclib was associated with numerically longer PFS and higher survival rates. At the molecular level, palbociclib treatment was characterized by transient increases in <em>ESR1</em> promoter methylation at the first evaluation and a rebound in <em>ACTB</em><sub>short</sub> fragment levels at six months relative to baseline. These dynamic patterns were not observed among patients receiving ribociclib.</div></div><div><h3>Conclusions</h3><div>ctDNA-based methylation and fragmentomic profiling revealed exploratory, treatment specific molecular dynamics, highlighting biological differences between CDK4/6 inhibitors. These findings support the feasibility of liquid biopsy–based biomarker studies in this setting, although their potential clinical relevance remains preliminary and requires validation in larger cohorts with earlier and more granular on-treatment timepoints.</div></div>","PeriodicalId":9093,"journal":{"name":"Breast","volume":"86 ","pages":"Article 104703"},"PeriodicalIF":7.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-31DOI: 10.1016/j.breast.2026.104718
Cornelis M. de Mooij , Janine M. Simons , Florien J.G. van Amstel , Cristina Mitea , Paul J. van Diest , Patty J. Nelemans , Felix M. Mottaghy , Carmen C. van der Pol , Ernest J.T. Luiten , Linetta B. Koppert , Marjolein L. Smidt , Thiemo J.A. van Nijnatten
Background
In clinically node-positive patients, sentinel lymph node biopsy (SLNB), marking axillary lymph node with radioactive iodine seed (MARI), and combined SLNB/MARI (RISAS-procedure) can replace axillary lymph node dissection (ALND) after neoadjuvant systemic therapy. Surgical staging outcome can be combined with baseline axillary disease on 18F-FDG PET/CT. This study assessed whether baseline axillary disease on 18F-FDG PET/CT affects the accuracy of staging-procedures. Second, when staging-procedures detected residual disease, it was assessed whether baseline axillary disease on 18F-FDG PET/CT affected the probability of remaining positive nodes at completion ALND (cALND).
Method
Included were patients with baseline 18F-FDG PET/CT within the RISAStrial (NCT02800317). Patients underwent the RISAS-procedure followed by cALND. False negative rates were stratified by limited or advanced baseline axillary disease (1-3 vs. ≥4 hypermetabolic lymph nodes). When staging-procedures detected residual disease, the probability of remaining positive nodes at cALND was stratified by baseline axillary disease.
Results
Of 185 patients, 116 had limited and 69 had advanced baseline axillary disease. Staging-procedures had higher accuracy in limited than advanced baseline axillary disease. When the RISAS-procedure detected residual disease, the probability of remaining positive nodes at cALND was lower in limited than advanced baseline axillary disease (44.9% vs. 91.5%,p < .001). When SLNB or MARI detected residual disease, the probability of remaining positive nodes at cALND was >88.4%, irrespective of baseline axillary disease.
Conclusion
Staging-procedures had higher accuracy in patients with limited than advanced axillary disease on baseline 18F-FDG PET/CT. When staging-procedures detected residual disease, the probability of remaining positive nodes at cALND remained high.
{"title":"Impact of axillary disease extent defined by baseline 18F-FDG PET/CT on the accuracy of axillary surgical staging after neoadjuvant systemic therapy in clinically node-positive breast cancer","authors":"Cornelis M. de Mooij , Janine M. Simons , Florien J.G. van Amstel , Cristina Mitea , Paul J. van Diest , Patty J. Nelemans , Felix M. Mottaghy , Carmen C. van der Pol , Ernest J.T. Luiten , Linetta B. Koppert , Marjolein L. Smidt , Thiemo J.A. van Nijnatten","doi":"10.1016/j.breast.2026.104718","DOIUrl":"10.1016/j.breast.2026.104718","url":null,"abstract":"<div><h3>Background</h3><div>In clinically node-positive patients, sentinel lymph node biopsy (SLNB), marking axillary lymph node with radioactive iodine seed (MARI), and combined SLNB/MARI (RISAS-procedure) can replace axillary lymph node dissection (ALND) after neoadjuvant systemic therapy. Surgical staging outcome can be combined with baseline axillary disease on <sup>18</sup>F-FDG PET/CT. This study assessed whether baseline axillary disease on <sup>18</sup>F-FDG PET/CT affects the accuracy of staging-procedures. Second, when staging-procedures detected residual disease, it was assessed whether baseline axillary disease on <sup>18</sup>F-FDG PET/CT affected the probability of remaining positive nodes at completion ALND (cALND).</div></div><div><h3>Method</h3><div>Included were patients with baseline <sup>18</sup>F-FDG PET/CT within the RISAStrial (NCT02800317). Patients underwent the RISAS-procedure followed by cALND. False negative rates were stratified by limited or advanced baseline axillary disease (1-3 vs. ≥4 hypermetabolic lymph nodes). When staging-procedures detected residual disease, the probability of remaining positive nodes at cALND was stratified by baseline axillary disease.</div></div><div><h3>Results</h3><div>Of 185 patients, 116 had limited and 69 had advanced baseline axillary disease. Staging-procedures had higher accuracy in limited than advanced baseline axillary disease. When the RISAS-procedure detected residual disease, the probability of remaining positive nodes at cALND was lower in limited than advanced baseline axillary disease (44.9% vs. 91.5%,p < .001). When SLNB or MARI detected residual disease, the probability of remaining positive nodes at cALND was >88.4%, irrespective of baseline axillary disease.</div></div><div><h3>Conclusion</h3><div>Staging-procedures had higher accuracy in patients with limited than advanced axillary disease on baseline <sup>18</sup>F-FDG PET/CT. When staging-procedures detected residual disease, the probability of remaining positive nodes at cALND remained high.</div></div>","PeriodicalId":9093,"journal":{"name":"Breast","volume":"86 ","pages":"Article 104718"},"PeriodicalIF":7.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This systematic review aimed to identify risk factors for fibrosis and unfavorable cosmetic outcomes after breast conserving therapy (BCT) for breast cancer in the light of contemporary oncoplastic surgery and 3D-radiotherapy techniques.
Methods
The systematic literature search was carried out in Embase, Ovid Medline, Cochrane Central Register of Controlled Trials, and CINAHL. Studies published after 2005, reporting two or more risk factors for fibrosis or unfavorable cosmetic outcomes as primary outcomes were eligible for inclusion. Only prospective studies with 100 or more patients analyzed were included. The Quality In Prognosis Studies tool and Cochrane risk-of-bias tool were used to assess risk of bias. Patient, tumor, and treatment-related predictors were identified.
Results
Twelve papers investigating 12.118 patients were identified. Risk factors for both the development of fibrosis and unfavorable cosmetic outcomes were increasing age, larger tumor size, re-resection, poor early cosmetic outcomes before the start of radiotherapy, high boost dose, boost volume per 10 cc, homogeneity-index, dose whole breast irradiation, and adjuvant chemotherapy. No specific risk factors in the setting of BCT with complex oncoplastic surgery techniques or ultra-hypo fractionated radiotherapy were identified in this review.
Conclusion
The risk factors identified in this review are largely similar to those found in 2D-radiotherapy studies; dose homogeneity was additionally identified. Administering chemotherapy before radiotherapy should be considered for patients requiring both treatments. However, the lack of sufficient high-quality data regarding BCT with (complex) oncoplastic surgery techniques and ultra-hypo fractionated radiotherapy schedules address the need for large, multidisciplinary prospective studies with long-term follow-up.
背景:本系统综述旨在根据当代肿瘤整形手术和3d放疗技术,确定乳腺癌保乳治疗(BCT)后纤维化和不良美容结果的危险因素。方法:在Embase、Ovid Medline、Cochrane Central Register of Controlled Trials和CINAHL中进行系统文献检索。2005年以后发表的将两个或两个以上纤维化风险因素或不良美容结局作为主要结局的研究符合纳入标准。仅纳入了100例或更多患者的前瞻性研究。使用预后质量研究工具和Cochrane风险偏倚工具评估偏倚风险。确定了患者、肿瘤和治疗相关的预测因素。结果:共收录12篇论文,共12.118例患者。发生纤维化和不良美容结果的危险因素包括年龄增加、肿瘤大小增大、再切除、放疗开始前早期美容结果不佳、高增强剂量、每10cc增强体积、均匀性指数、全乳照射剂量和辅助化疗。在本综述中,没有发现复杂肿瘤整形手术技术或超低分割放疗的BCT设置的特定危险因素。结论:本综述中发现的危险因素与2d放疗研究中发现的危险因素基本相似;另外还确定了剂量均匀性。对于同时需要化疗和放疗的患者,应考虑在放疗前进行化疗。然而,缺乏足够高质量的BCT(复杂)肿瘤整形手术技术和超低分割放疗计划的数据,需要进行大规模、多学科、长期随访的前瞻性研究。
{"title":"Risk factors for breast fibrosis and unfavorable cosmetic outcomes after breast conserving therapy in the contemporary treatment era: a systematic review","authors":"M.C.A.W. Notenboom , W.D. Heemsbergen , M. Franckena , L.B. Koppert , M.A.M. Mureau , R.A. Nout , M.B.E. Menke-Pluijmers , F.E. Froklage","doi":"10.1016/j.breast.2026.104707","DOIUrl":"10.1016/j.breast.2026.104707","url":null,"abstract":"<div><h3>Background</h3><div>This systematic review aimed to identify risk factors for fibrosis and unfavorable cosmetic outcomes after breast conserving therapy (BCT) for breast cancer in the light of contemporary oncoplastic surgery and 3D-radiotherapy techniques.</div></div><div><h3>Methods</h3><div>The systematic literature search was carried out in Embase, Ovid Medline, Cochrane Central Register of Controlled Trials, and CINAHL. Studies published after 2005, reporting two or more risk factors for fibrosis or unfavorable cosmetic outcomes as primary outcomes were eligible for inclusion. Only prospective studies with 100 or more patients analyzed were included. The Quality In Prognosis Studies tool and Cochrane risk-of-bias tool were used to assess risk of bias. Patient, tumor, and treatment-related predictors were identified.</div></div><div><h3>Results</h3><div>Twelve papers investigating 12.118 patients were identified. Risk factors for both the development of fibrosis and unfavorable cosmetic outcomes were increasing age, larger tumor size, re-resection, poor early cosmetic outcomes before the start of radiotherapy, high boost dose, boost volume per 10 cc, homogeneity-index, dose whole breast irradiation, and adjuvant chemotherapy. No specific risk factors in the setting of BCT with complex oncoplastic surgery techniques or ultra-hypo fractionated radiotherapy were identified in this review.</div></div><div><h3>Conclusion</h3><div>The risk factors identified in this review are largely similar to those found in 2D-radiotherapy studies; dose homogeneity was additionally identified. Administering chemotherapy before radiotherapy should be considered for patients requiring both treatments. However, the lack of sufficient high-quality data regarding BCT with (complex) oncoplastic surgery techniques and ultra-hypo fractionated radiotherapy schedules address the need for large, multidisciplinary prospective studies with long-term follow-up.</div></div>","PeriodicalId":9093,"journal":{"name":"Breast","volume":"86 ","pages":"Article 104707"},"PeriodicalIF":7.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Personalizing radiotherapy dose in breast cancer remains a major unmet need, as current treatment paradigms rely on uniform prescriptions that overlook interpatient variability in intrinsic radiosensitivity. Over the past decade, transcriptome-based biomarkers such as the Radiosensitivity Index (RSI) and its radiobiological extension, the Genomic-Adjusted Radiation Dose (GARD), have emerged as promising tools capable of quantifying this biological heterogeneity and linking it to expected therapeutic effectiveness. Retrospective clinical studies across diverse breast cancer cohorts have consistently demonstrated that RSI and GARD correlate with locoregional control, identify radioresistant subgroups that may benefit from dose escalation, and reveal radiosensitive tumors for which de-escalation may be safely explored. These findings challenge the assumption that radiation response is uniform within histological or molecular subtypes and highlight the opportunity for biologically tailored dosing. Yet despite early evidence, translation into clinical practice remains limited. Key barriers include the absence of prospective validation, heterogeneous analytic pipelines for RNA sequencing and RSI computation, uncertainty regarding optimal biomarker timing in the neoadjuvant era, and sensitivity of bulk transcriptomic assays to spatial and microenvironmental heterogeneity. Addressing these challenges will require standardization, consensus on clinically meaningful GARD thresholds, and coordinated international efforts to define methodological and regulatory pathways. Emerging approaches in radiomics, digital pathology, and multimodal artificial intelligence may further refine radiosensitivity assessment and reduce reliance on invasive sampling. As the field progresses, genomic personalization of radiotherapy has the potential to transform breast cancer management by replacing one-size-fits-all prescriptions with biologically informed dose adaptation aimed at maximizing tumor control while minimizing toxicity.
{"title":"Toward genomic personalization of breast cancer radiotherapy: foundations, challenges, and a roadmap for clinical integration","authors":"Pierre Loap , Irene Buvat , Gilles Crehange , Youlia Kirova","doi":"10.1016/j.breast.2026.104733","DOIUrl":"10.1016/j.breast.2026.104733","url":null,"abstract":"<div><div>Personalizing radiotherapy dose in breast cancer remains a major unmet need, as current treatment paradigms rely on uniform prescriptions that overlook interpatient variability in intrinsic radiosensitivity. Over the past decade, transcriptome-based biomarkers such as the Radiosensitivity Index (RSI) and its radiobiological extension, the Genomic-Adjusted Radiation Dose (GARD), have emerged as promising tools capable of quantifying this biological heterogeneity and linking it to expected therapeutic effectiveness. Retrospective clinical studies across diverse breast cancer cohorts have consistently demonstrated that RSI and GARD correlate with locoregional control, identify radioresistant subgroups that may benefit from dose escalation, and reveal radiosensitive tumors for which de-escalation may be safely explored. These findings challenge the assumption that radiation response is uniform within histological or molecular subtypes and highlight the opportunity for biologically tailored dosing. Yet despite early evidence, translation into clinical practice remains limited. Key barriers include the absence of prospective validation, heterogeneous analytic pipelines for RNA sequencing and RSI computation, uncertainty regarding optimal biomarker timing in the neoadjuvant era, and sensitivity of bulk transcriptomic assays to spatial and microenvironmental heterogeneity. Addressing these challenges will require standardization, consensus on clinically meaningful GARD thresholds, and coordinated international efforts to define methodological and regulatory pathways. Emerging approaches in radiomics, digital pathology, and multimodal artificial intelligence may further refine radiosensitivity assessment and reduce reliance on invasive sampling. As the field progresses, genomic personalization of radiotherapy has the potential to transform breast cancer management by replacing one-size-fits-all prescriptions with biologically informed dose adaptation aimed at maximizing tumor control while minimizing toxicity.</div></div>","PeriodicalId":9093,"journal":{"name":"Breast","volume":"86 ","pages":"Article 104733"},"PeriodicalIF":7.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146185280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-29DOI: 10.1016/j.breast.2026.104714
Ruth M. O'Regan , Yue Ren , Yi Zhang , Gini F. Fleming , Prudence A. Francis , Olivia Pagani , Barbara A. Walley , Roswitha Kammler , Patrizia Dell’Orto , Giuseppe Viale , Sherene Loi , Marco Colleoni , Kai Treuner , Meredith M. Regan
Background
An adjusted Breast Cancer Index (BCI) model with an additional cutpoint identified postmenopausal women with hormone-receptor-positive node-negative disease at minimal (<5%) risk of distant recurrence (DR) within 10 years.
Methods
2025 premenopausal patients with hormone-receptor-positive node-negative breast cancer, randomized to adjuvant endocrine therapy in SOFT and TEXT (35.6% and 40.4% received adjuvant chemotherapy, respectively), previously had BCI assessed. The additional BCI cutpoint re-classified a subset of the low-risk group into minimal-risk; those in intermediate- or high-risk groups were unchanged. The 10-year DR was estimated by Kaplan-Meier method.
Results
The adjusted BCI model re-classified 17.8 % and 19.6 % of node-negative disease in SOFT and TEXT into BCI minimal-risk groups; 43.2 % and 38.3 % remained classified in low-risk groups, respectively. In SOFT, the estimated 10-year DR was 2.3 % (95 %CI 0.9–6.0 %) and 4.1 % (95 %CI 2.6–6.5 %) in the minimal-risk and revised low-risk groups, respectively. In TEXT, the estimated 10-year DR was 2.0 % (95 %CI 0.7–6.2 %) and 4.6 % (95 %CI 2.8–7.7 %) in the minimal- and low-risk groups, respectively.
Conclusions
This study confirmed prognostic ability of the minimal-risk BCI cutpoint to classify patients estimated to have minimal-risk of distant recurrence within 10 years among premenopausal patients treated for hormone-receptor-positive node-negative breast cancer, providing relevant information for personalizing adjuvant endocrine therapy.
Soft
(clinicaltrials.gov NCT00066690)
Text
(clinicaltrials.gov NCT00066703)
背景:调整后的乳腺癌指数(BCI)模型增加了一个额外的临界点,以最小限度地确定患有激素受体阳性淋巴结阴性疾病的绝经后妇女(方法:2025例绝经前激素受体阳性淋巴结阴性乳腺癌患者,在SOFT和TEXT中随机分配到辅助内分泌治疗组(分别为35.6%和40.4%接受辅助化疗),之前进行过BCI评估。额外的脑机接口切点将低风险组的一个子集重新分类为最低风险;中等或高危人群则没有变化。用Kaplan-Meier法估计10年DR。结果:调整后的BCI模型将SOFT和TEXT患者中17.8%和19.6%的淋巴结阴性疾病重新划分为BCI低危组;43.2%和38.3%的人仍然被划分为低风险组。在SOFT中,在最小风险组和修正的低风险组中,估计的10年DR分别为2.3% (95% CI 0.9- 6.0%)和4.1% (95% CI 2.6- 6.5%)。在TEXT中,最低风险组和低风险组的估计10年DR分别为2.0% (95% CI 0.7- 6.2%)和4.6% (95% CI 2.8- 7.7%)。结论:本研究证实了最小风险BCI切点对绝经前激素受体阳性淋巴结阴性乳腺癌患者10年内远处复发风险最小的患者进行分类的预后能力,为个性化辅助内分泌治疗提供了相关信息。软:(clinicaltrials.gov NCT00066690)文本:(clinicaltrials.gov NCT00066703)。
{"title":"Identifying premenopausal patients with early-stage hormone receptor–positive breast cancer at minimal risk of distant recurrence by breast cancer index","authors":"Ruth M. O'Regan , Yue Ren , Yi Zhang , Gini F. Fleming , Prudence A. Francis , Olivia Pagani , Barbara A. Walley , Roswitha Kammler , Patrizia Dell’Orto , Giuseppe Viale , Sherene Loi , Marco Colleoni , Kai Treuner , Meredith M. Regan","doi":"10.1016/j.breast.2026.104714","DOIUrl":"10.1016/j.breast.2026.104714","url":null,"abstract":"<div><h3>Background</h3><div>An adjusted Breast Cancer Index (BCI) model with an additional cutpoint identified postmenopausal women with hormone-receptor-positive node-negative disease at minimal (<5%) risk of distant recurrence (DR) within 10 years.</div></div><div><h3>Methods</h3><div>2025 premenopausal patients with hormone-receptor-positive node-negative breast cancer, randomized to adjuvant endocrine therapy in SOFT and TEXT (35.6% and 40.4% received adjuvant chemotherapy, respectively), previously had BCI assessed. The additional BCI cutpoint re-classified a subset of the low-risk group into minimal-risk; those in intermediate- or high-risk groups were unchanged. The 10-year DR was estimated by Kaplan-Meier method.</div></div><div><h3>Results</h3><div>The adjusted BCI model re-classified 17.8 % and 19.6 % of node-negative disease in SOFT and TEXT into BCI minimal-risk groups; 43.2 % and 38.3 % remained classified in low-risk groups, respectively. In SOFT, the estimated 10-year DR was 2.3 % (95 %CI 0.9–6.0 %) and 4.1 % (95 %CI 2.6–6.5 %) in the minimal-risk and revised low-risk groups, respectively. In TEXT, the estimated 10-year DR was 2.0 % (95 %CI 0.7–6.2 %) and 4.6 % (95 %CI 2.8–7.7 %) in the minimal- and low-risk groups, respectively.</div></div><div><h3>Conclusions</h3><div>This study confirmed prognostic ability of the minimal-risk BCI cutpoint to classify patients estimated to have minimal-risk of distant recurrence within 10 years among premenopausal patients treated for hormone-receptor-positive node-negative breast cancer, providing relevant information for personalizing adjuvant endocrine therapy.</div></div><div><h3>Soft</h3><div>(<span><span>clinicaltrials.gov</span><svg><path></path></svg></span> NCT00066690)</div></div><div><h3>Text</h3><div>(<span><span>clinicaltrials.gov</span><svg><path></path></svg></span> NCT00066703)</div></div>","PeriodicalId":9093,"journal":{"name":"Breast","volume":"86 ","pages":"Article 104714"},"PeriodicalIF":7.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-31DOI: 10.1016/j.breast.2026.104716
Akshat Verma, Dileep Ramesh Hoysal, Amar Deshpande, Rajendra A Badwe
{"title":"Letter to the Editor \"Adjuvant ovarian function suppression and aromatase inhibitors in premenopausal patients with hormone receptor-positive, HER2-positive breast cancer\".","authors":"Akshat Verma, Dileep Ramesh Hoysal, Amar Deshpande, Rajendra A Badwe","doi":"10.1016/j.breast.2026.104716","DOIUrl":"10.1016/j.breast.2026.104716","url":null,"abstract":"","PeriodicalId":9093,"journal":{"name":"Breast","volume":" ","pages":"104716"},"PeriodicalIF":7.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-04-01Epub Date: 2026-01-21DOI: 10.1016/j.breast.2026.104708
Sangjun Lee , Soyeoun Kim
Global mammographic asymmetry (GA) is generally considered benign, and its association with subsequent breast cancer risk is unclear. We examined whether GA on screening mammography predicts short-term and long-term breast cancer and whether this varies by Breast Imaging Reporting and Data System (BI-RADS) breast density. In this retrospective cohort study using the Korean National Health Insurance Service screening programme, we included women aged ≥40 years who underwent screening mammography in 2009–2010 and had no prior breast cancer. GA and BI-RADS density were recorded on baseline mammograms; incident invasive breast cancer through December 31, 2019 was ascertained from insurance claims. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) for breast cancer associated with GA overall and by BI-RADS density and follow-up interval (<1, 1–2 and ≥2 years), adjusting for demographic, reproductive and lifestyle factors. Among 5,475,113 women, GA was present in 4.0 %. Overall, GA was associated with a modestly increased breast cancer risk (aHR 1.15; 95 % CI 1.11–1.19), strongest within 1 year of screening (aHR 1.90; 95 % CI 1.70–2.12). In women with BI-RADS 1 breasts, GA doubled overall risk (aHR 2.03) and quadrupled short-term risk (<1 year: aHR 4.14), whereas in BI-RADS 4 breasts GA did not increase overall risk (aHR 0.94). GA is uncommon but identifies women at substantially elevated short-term breast cancer risk, particularly those with non-dense breasts, and has limited long-term prognostic value in extremely dense breasts. These findings support consideration of short-interval follow-up or supplemental imaging when GA is reported in non-dense breasts.
乳房x线摄影不对称(GA)通常被认为是良性的,其与随后的乳腺癌风险的关系尚不清楚。我们研究了筛查乳房x线摄影的GA是否能预测短期和长期乳腺癌,以及这是否因乳房成像报告和数据系统(BI-RADS)乳腺密度而异。在这项使用韩国国民健康保险服务筛查项目的回顾性队列研究中,我们纳入了年龄≥40岁、在2009-2010年接受乳房x光筛查且既往无乳腺癌的女性。在基线乳房x线照片上记录GA和BI-RADS密度;从保险索赔中确定了截至2019年12月31日的侵袭性乳腺癌事件。Cox比例风险模型通过BI-RADS密度和随访间隔(1年、1年- 2年和≥2年)来估计与GA相关的乳腺癌的调整风险比(aHRs),并对人口统计学、生殖和生活方式因素进行了调整。在5,475,113名女性中,4.0%存在GA。总体而言,GA与适度增加的乳腺癌风险相关(aHR 1.15; 95% CI 1.11-1.19),在筛查后1年内最强(aHR 1.90; 95% CI 1.70-2.12)。在BI-RADS 1型乳房的女性中,GA的总风险增加了一倍(aHR 2.03),短期风险增加了四倍(1年:aHR 4.14),而BI-RADS 4型乳房的GA没有增加总风险(aHR 0.94)。GA并不常见,但可以识别出短期乳腺癌风险显著升高的女性,特别是那些乳房不致密的女性,而对于极致密的乳房,GA的长期预后价值有限。这些发现支持在非致密乳腺中报告GA时考虑短间隔随访或补充成像。
{"title":"Global mammographic asymmetry and short-term breast cancer risk by breast density: a nationwide screening cohort of 5.5 million women","authors":"Sangjun Lee , Soyeoun Kim","doi":"10.1016/j.breast.2026.104708","DOIUrl":"10.1016/j.breast.2026.104708","url":null,"abstract":"<div><div>Global mammographic asymmetry (GA) is generally considered benign, and its association with subsequent breast cancer risk is unclear. We examined whether GA on screening mammography predicts short-term and long-term breast cancer and whether this varies by Breast Imaging Reporting and Data System (BI-RADS) breast density. In this retrospective cohort study using the Korean National Health Insurance Service screening programme, we included women aged ≥40 years who underwent screening mammography in 2009–2010 and had no prior breast cancer. GA and BI-RADS density were recorded on baseline mammograms; incident invasive breast cancer through December 31, 2019 was ascertained from insurance claims. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) for breast cancer associated with GA overall and by BI-RADS density and follow-up interval (<1, 1–2 and ≥2 years), adjusting for demographic, reproductive and lifestyle factors. Among 5,475,113 women, GA was present in 4.0 %. Overall, GA was associated with a modestly increased breast cancer risk (aHR 1.15; 95 % CI 1.11–1.19), strongest within 1 year of screening (aHR 1.90; 95 % CI 1.70–2.12). In women with BI-RADS 1 breasts, GA doubled overall risk (aHR 2.03) and quadrupled short-term risk (<1 year: aHR 4.14), whereas in BI-RADS 4 breasts GA did not increase overall risk (aHR 0.94). GA is uncommon but identifies women at substantially elevated short-term breast cancer risk, particularly those with non-dense breasts, and has limited long-term prognostic value in extremely dense breasts. These findings support consideration of short-interval follow-up or supplemental imaging when GA is reported in non-dense breasts.</div></div>","PeriodicalId":9093,"journal":{"name":"Breast","volume":"86 ","pages":"Article 104708"},"PeriodicalIF":7.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}