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Predictors of pneumonitis in patients treated with systemic therapy and radiotherapy for localized triple negative or HER2 positive breast cancer 局部三阴性或HER2阳性乳腺癌患者接受全身治疗和放疗后肺炎的预测因素
IF 7.9 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-19 DOI: 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。
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引用次数: 0
Pleomorphic and florid lobular carcinoma in situ of the Breast: A systematic review of current evidence and knowledge gaps 乳腺多形性和花状小叶原位癌:当前证据和知识空白的系统回顾。
IF 7.9 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-31 DOI: 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.
多形性(PLCIS)和花型(FLCIS)小叶原位癌是一种罕见的肿瘤,其特征是明显的结构扭曲和细胞异型性。其罕见性提出了三个关键的临床挑战:诊断变异性,组织学升级和局部复发风险(LR)。目前还没有标准化的管理指南。本系统综述提供了迄今为止关于P/FLCIS的临床、放射学、病理和分子特征的最全面的综合证据,并评估了不同治疗策略的相关结果。方法:系统检索截至2025年6月的主要生物医学数据库的文献。符合条件的研究是报告P/FLCIS主要数据的原始病例系列。结果:从5402份筛选记录中,纳入38项研究,共629例:411例PLCIS, 98例FLCIS, 120例LCIS具有多型或非经典特征。合并升级率为35.3% (PLCIS为35.1%,FLCIS为33.3%,p = 0.843),以浸润性癌为主(28.8%)。258例可随访的纯P/FLCIS患者(中位,50个月),总LR率为12.4% (PLCIS 13.1%, FLCIS 9.1%, P = 0.618),侵袭性复发占多数(62.5%,P = 0.04)。切缘状态与LR风险显著相关(切缘阳性38.2%,切缘闭合)。结论:考虑到P/FLCIS的高升级率和显著的LR风险,强烈建议切缘阴性的完全手术切除以确保明确诊断并减少未来的乳房事件。辅助治疗的作用仍然不清楚,强调迫切需要标准化的多中心研究来指导最佳的临床管理。
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引用次数: 0
Patient-reported outcomes from the randomized ALICE trial evaluating the addition of atezolizumab to anthracycline-based chemotherapy in metastatic triple-negative breast cancer 随机ALICE试验评估了转移性三阴性乳腺癌在蒽环类药物化疗中添加atezolizumab的患者报告的结果。
IF 7.9 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-19 DOI: 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.
背景:ALICE试验表明,在蒽环类免疫调节化疗中加入atezolizumab可改善转移性三阴性乳腺癌(mTNBC)患者的无进展生存期(PFS),包括pd - l1阴性肿瘤患者。在这里,我们报告了患者报告的结果测量(PROMs)。方法:患者随机接受化疗加阿特唑单抗(atezo-chemo)或化疗加安慰剂(安慰剂-chemo)。在基线和第9、17、25和49周使用EORTC QLQ-C15-PAL、Chalder疲劳问卷(CFQ)和疼痛数值评定量表(NRS)收集prom。结果:68例患者中64例获得PROMs。在第9周,在所有QLQ-C15-PAL结构域、CFQ评分和NRS疼痛强度方面,从基线开始的平均变化有利于atezo-chemo组。恶化时间分析也倾向于atezo-chemo,总体生活质量(QoL; HR 0.24)、情绪功能(HR 0.30)和疼痛(HR 0.20)的风险比具有统计学意义。疼痛-预先指定的主要症状-在atezo化疗组在所有时间点都有所改善。在12个月时,PROMs显示持续耐受性。更好的基线PROM评分与改善的PFS和总生存期相关,特别是在接受atezolizumab治疗的患者中。基线生活质量中位数评分为>的患者在接受阿特唑单抗治疗后,PFS得到改善(HR 0.25),而生活质量中位数评分≤的患者则没有改善(HR 1.02)。结论:在mTNBC的化疗研究中加入atezolizumab可改善PFS和患者报告的生活质量、情绪健康和症状控制。这些发现支持了这种联合治疗方案的持续发展,并表明基线生活质量可以作为免疫治疗获益的有用预测指标。试验注册:NCT03164993, 2017年5月24日;https://clinicaltrials.gov/ct2/show/record/NCT03164993。
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引用次数: 0
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 CDK4/6抑制剂在一线HR+/HER2转移性乳腺癌中的表观遗传学和基于片段的分析对magnetic1研究的辅助分析。
IF 7.9 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-27 DOI: 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.
背景:CDK4/6抑制剂(CDK4/6i)联合内分泌治疗(ET)是激素受体阳性、HER2阴性(HR+/HER2-)转移性乳腺癌(MBC)患者的标准治疗方法。然而,没有直接比较palbociclib、ribociclib和abemaciclib的头对头随机试验。此外,对CDK4/6i耐药的预测性生物标志物在很大程度上仍未确定。本研究旨在评估基于循环肿瘤DNA (ctDNA)的表观遗传学和片段组学生物标志物作为CDK4/6i治疗患者反应和耐药的潜在预测因子。方法:我们在前瞻性、多中心的magnetics 1研究中进行了一项生物标志物驱动分析,纳入了149例接受一线内分泌治疗和CDK4/6抑制剂治疗的HR+/HER2- MBC患者。在基线和治疗期间(3个月和6个月)收集血浆样本。采用微滴数字PCR技术评估ESR1启动子甲基化和ACTB片段组谱。评估无进展生存期(PFS)和总生存期(OS),并比较治疗组间的分子动力学。结果:中位随访34.8个月后,尽管核糖环尼与帕博西尼治疗患者的PFS更长,生存率更高,但在PFS或OS方面,核糖环尼与帕博西尼治疗患者无统计学差异。在分子水平上,帕博西尼治疗的特点是在第一次评估时ESR1启动子甲基化短暂增加,6个月时actb短片段水平相对于基线出现反弹。这些动态模式在接受核糖西尼的患者中没有观察到。结论:基于ctdna的甲基化和片段组学分析揭示了探索性的、治疗特异性的分子动力学,突出了CDK4/6抑制剂之间的生物学差异。这些发现支持了在这种情况下基于液体活检的生物标志物研究的可行性,尽管其潜在的临床相关性仍处于初步阶段,需要在更早、更细粒度的治疗时间点上进行更大规模的队列验证。
{"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 ,&nbsp;Lorenzo Foffano ,&nbsp;Fabiola Giudici ,&nbsp;Elisabetta Molteni ,&nbsp;Alessandra Franzoni ,&nbsp;Martina Tessitori ,&nbsp;Linda Cucciniello ,&nbsp;Silvia Bolzonello ,&nbsp;Lucia Da Ros ,&nbsp;Lucia Bortot ,&nbsp;Elena Scudeler ,&nbsp;Brenno Pastò ,&nbsp;Giulia Cudia ,&nbsp;Serena Della Rossa ,&nbsp;Marta Bonotto ,&nbsp;Alessandro Marco Minisini ,&nbsp;Giuseppe Damante ,&nbsp;Barbara Belletti ,&nbsp;Lorenzo Gerratana ,&nbsp;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}
引用次数: 0
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 基线18F-FDG PET/CT定义的腋窝病变程度对临床淋巴结阳性乳腺癌新辅助全身治疗后腋窝手术分期准确性的影响
IF 7.9 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-31 DOI: 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.
背景:在临床淋巴结阳性患者中,前哨淋巴结活检(SLNB)、放射性碘种子标记腋窝淋巴结(MARI)和SLNB/MARI联合(risas程序)可以替代新辅助全身治疗后的腋窝淋巴结清扫(ALND)。手术分期结果可结合18F-FDG PET/CT的基线腋窝疾病。本研究评估了18F-FDG PET/CT基线腋窝疾病是否会影响分期程序的准确性。其次,当分期程序检测到残留病变时,评估18F-FDG PET/CT基线腋窝病变是否影响完成ALND (cALND)时剩余阳性淋巴结的概率。方法:纳入了基线18F-FDG PET/CT在RISAStrial (NCT02800317)的患者。患者接受risas手术,然后进行cALND。假阴性率根据局限性或晚期基线腋窝疾病分层(1-3 vs.≥4个高代谢淋巴结)。当分期程序检测到残留疾病时,cALND剩余阳性淋巴结的概率根据基线腋窝疾病分层。结果:185例患者中,116例为局限性腋窝疾病,69例为晚期基线腋窝疾病。分期程序在有限的情况下比晚期基线腋窝疾病有更高的准确性。当risas检测到残留疾病时,cALND剩余阳性淋巴结的概率在有限范围内低于基线腋窝疾病晚期(44.9% vs. 91.5%,p 88.4%),无论基线腋窝疾病如何。结论:在基线18F-FDG PET/CT上,分期程序对局限性腋窝疾病患者比晚期腋窝疾病患者具有更高的准确性。当分期检查发现残留病变时,cALND剩余阳性淋巴结的概率仍然很高。
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引用次数: 0
Risk factors for breast fibrosis and unfavorable cosmetic outcomes after breast conserving therapy in the contemporary treatment era: a systematic review 当代治疗时代保乳治疗后乳腺纤维化的危险因素和不良美容结果:系统回顾。
IF 7.9 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-20 DOI: 10.1016/j.breast.2026.104707
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

Background

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。
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引用次数: 0
Toward genomic personalization of breast cancer radiotherapy: foundations, challenges, and a roadmap for clinical integration 乳腺癌放疗的基因组个性化:基础、挑战和临床整合的路线图
IF 7.9 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2026-04-01 Epub Date: 2026-02-11 DOI: 10.1016/j.breast.2026.104733
Pierre Loap , Irene Buvat , Gilles Crehange , Youlia Kirova
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.
个性化乳腺癌放疗剂量仍然是一个主要的未满足的需求,因为目前的治疗范例依赖于统一的处方,忽视了患者内在放射敏感性的差异。在过去的十年中,基于转录组的生物标志物,如放射敏感性指数(RSI)及其放射生物学延伸,基因组调整辐射剂量(GARD),已经成为能够量化这种生物异质性并将其与预期治疗效果联系起来的有前途的工具。对不同乳腺癌队列的回顾性临床研究一致表明,RSI和GARD与局部区域控制相关,确定了可能受益于剂量递增的放射耐药亚组,并揭示了可以安全地探索剂量递增的放射敏感肿瘤。这些发现挑战了辐射反应在组织学或分子亚型中是均匀的假设,并强调了生物定制剂量的机会。然而,尽管有早期证据,但将其转化为临床实践仍然有限。主要障碍包括缺乏前瞻性验证,RNA测序和RSI计算的异构分析管道,新辅助时代最佳生物标志物时间的不确定性,以及大量转录组学分析对空间和微环境异质性的敏感性。应对这些挑战需要标准化,就临床意义的GARD阈值达成共识,并协调国际努力,确定方法和监管途径。放射组学、数字病理学和多模态人工智能的新兴方法可能会进一步完善放射敏感性评估,减少对侵入性采样的依赖。随着该领域的发展,放射治疗的基因组个性化有可能改变乳腺癌的管理,用生物学上知情的剂量适应取代一刀切的处方,旨在最大限度地控制肿瘤,同时最大限度地减少毒性。
{"title":"Toward genomic personalization of breast cancer radiotherapy: foundations, challenges, and a roadmap for clinical integration","authors":"Pierre Loap ,&nbsp;Irene Buvat ,&nbsp;Gilles Crehange ,&nbsp;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}
引用次数: 0
Identifying premenopausal patients with early-stage hormone receptor–positive breast cancer at minimal risk of distant recurrence by breast cancer index 通过乳腺癌指数确定绝经前早期激素受体阳性乳腺癌患者远处复发风险最小。
IF 7.9 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-29 DOI: 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)。
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引用次数: 0
Letter to the Editor "Adjuvant ovarian function suppression and aromatase inhibitors in premenopausal patients with hormone receptor-positive, HER2-positive breast cancer". 致编辑的信“激素受体阳性、her2阳性乳腺癌绝经前患者的辅助卵巢功能抑制和芳香酶抑制剂”。
IF 7.9 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-31 DOI: 10.1016/j.breast.2026.104716
Akshat Verma, Dileep Ramesh Hoysal, Amar Deshpande, Rajendra A Badwe
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引用次数: 0
Global mammographic asymmetry and short-term breast cancer risk by breast density: a nationwide screening cohort of 5.5 million women 全球乳房x线摄影不对称与乳房密度的短期乳腺癌风险:一项涵盖550万妇女的全国筛查队列
IF 7.9 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2026-04-01 Epub Date: 2026-01-21 DOI: 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。
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引用次数: 0
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