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Real-world prevalence, treatment and survival of “high risk” early breast cancer, with mandatory testing of gBRCA1/2 mutation according to the OlympiA trial inclusion criteria: Data from a population-based registry 根据奥林匹亚试验纳入标准强制检测 gBRCA1/2 基因突变的 "高风险 "早期乳腺癌的实际发病率、治疗和生存率:来自人口登记处的数据。
IF 5.7 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-08-28 DOI: 10.1016/j.breast.2024.103789
Sylvain Ladoire , Ariane Mamguem Kamga , Loick Galland , Isabelle Desmoulins , Didier Mayeur , Courèche Kaderbhai , Silvia Mihaelia Ilie , Audrey Hennequin , Clementine Jankowski , Juliette Albuisson , Sophie Nambot , Charles Coutant , Laurent Arnould , Manon Reda , Caroline Truntzer , Sandrine Dabakuyo

Background

The results of the OlympiA study led to the approval of a PARP inhibitor (olaparib) as adjuvant treatment for early breast cancer (eBC) at high risk of relapse in patients with a germline BRCA1/2 mutation (gBRCAm). However, the proportion of patients in routine practice who meet the “high-risk” criteria applied in the OlympiA study, and for whom gBRCAm testing would now be mandatory, remains unknown.

Patients and methods

In this population-based study, we use unique data from the French specialized Côte d'Or Breast and Gynecological Cancer Registry, to assess the real-life proportion, and long-term prognosis of patients treated for eBC between 2005 and 2015 with standard treatment, and at “high risk” of relapse according to the OlympiA trial criteria.

Results

We included 3483 patients treated for HER2-negative eBC (N = 380 with ER-, and N = 3103 with ER + tumor). We found N = 62 (1.8 %) patients with gBRCA1/2 mutations. A total of 494 patients (14.2 %) were classified as “high risk” according to the Olympia criteria; 55 % with ER-tumors, and 9.1 % with ER + tumors, respectively. Despite more intensive systemic treatments in “high risk” patients, 10-year overall survival was much worse in these “high risk” patients compared to the others: 60.1 % vs 83.8 % in ER-tumors, and 55.4 % vs 84.1 % in ER + tumors. Our estimates of net survival show an even greater difference.

Conclusion

This study provides real-life insights into the prevalence and prognosis of patients with high-risk eBC, in a context where the approval of adjuvant olaparib requires careful reorganization of care, so as not to overlook a patient with gBRCAm who could benefit from adjuvant olaparib.

背景:奥林匹亚研究(OlympiA)的结果导致一种PARP抑制剂(奥拉帕利)获得批准,可作为具有高复发风险的种系BRCA1/2基因突变(gBRCAm)早期乳腺癌(eBC)患者的辅助治疗药物。然而,在常规治疗中,符合奥林匹亚研究中应用的 "高危 "标准、现在必须接受 gBRCAm 检测的患者比例仍是未知数:在这项以人群为基础的研究中,我们利用法国专业的科特奥尔乳腺癌和妇科癌症登记处的独特数据,评估了2005年至2015年期间接受标准治疗的eBC患者的实际比例,以及根据奥林匹亚试验标准确定的 "高危 "复发患者的长期预后:我们纳入了3483名接受HER2阴性eBC治疗的患者(ER-肿瘤患者380人,ER+肿瘤患者3103人)。我们发现有62例(1.8%)患者存在gBRCA1/2突变。根据奥林匹亚标准,共有 494 名患者(14.2%)被归类为 "高危";其中 55% 患有 ER 肿瘤,9.1% 患有 ER + 肿瘤。尽管 "高危 "患者接受了更多的系统治疗,但与其他患者相比,这些 "高危 "患者的10年总生存率要低得多:ER肿瘤患者的10年总生存率为60.1%对83.8%,ER+肿瘤患者的10年总生存率为55.4%对84.1%。我们对净生存率的估计显示出更大的差异:这项研究提供了有关高危 eBC 患者发病率和预后的真实情况,在奥拉帕利辅助治疗获批的背景下,需要对治疗进行仔细的重组,以免忽视可从奥拉帕利辅助治疗中获益的 gBRCAm 患者。
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引用次数: 0
Locoregional recurrence in studies of primary systemic therapy in early invasive breast cancer 早期浸润性乳腺癌主要系统疗法研究中的局部复发问题
IF 5.7 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-08-27 DOI: 10.1016/j.breast.2024.103791
Luqi Chen , Stuart A. McIntosh , Siddharth Tyagi , David Dodwell

Introduction

The use of primary systemic therapy (PST) in early invasive breast cancer is routine but there are concerns about risk of locoregional recurrence.

Methods

We conducted a systematic literature review to identify studies of locoregional treatment and recurrence in patients with early invasive breast cancer who received non-endocrine PST.

Results

We identified 112 studies (18 prospective trials and 94 non-interventional studies). The use of surgery and radiotherapy after PST was recorded in 65 (58 %) and 50 (45 %) of studies respectively. 66 (59 %) studies reported locoregional recurrence. Cumulative 5-year locoregional recurrence risks varied from 1 % to 23 %. Locoregional recurrence was higher in patients under the age of 40, those who did not achieve a pathological complete remission after PST, had ER-negative or HER2 negative tumours, were recorded to have inoperable disease before PST, and did not have radiotherapy. LRR rates in these studies have not fallen over the overall calendar period of patient enrollment (1999–2016).

Conclusion

The recording of locoregional treatments and outcomes is suboptimal in studies of PST and efforts to improve this are required. In the absence of randomised evidence, our findings may help to inform care and guideline development. We were unable to exclude concern that the use of PST is associated with a higher than desired risk of locoregional recurrence.

方法我们进行了一项系统性文献综述,以确定有关接受非内分泌 PST 的早期浸润性乳腺癌患者的局部治疗和复发的研究。结果我们确定了 112 项研究(18 项前瞻性试验和 94 项非常规研究)。分别有 65 项(58%)和 50 项(45%)研究记录了 PST 后手术和放疗的使用情况。66(59%)项研究报告了局部复发情况。累积 5 年的局部复发风险从 1% 到 23% 不等。40岁以下的患者、PST后未达到病理完全缓解的患者、ER阴性或HER2阴性肿瘤患者、PST前记录为无法手术的患者以及未接受放疗的患者的局部复发率较高。这些研究中的病理完全缓解率在患者入组的整个日历期间(1999-2016 年)并没有下降。结论 PST 研究中对局部治疗和结果的记录不够理想,需要努力改进。在缺乏随机证据的情况下,我们的研究结果可能有助于为护理和指南制定提供参考。我们无法排除使用 PST 会导致局部复发风险高于预期的担忧。
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引用次数: 0
“Perspective: An integrated vision of the quality of life in breast cancer survivorship trajectory” "透视:乳腺癌幸存者生活质量轨迹的综合视角"
IF 5.7 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-08-16 DOI: 10.1016/j.breast.2024.103785
Chiara Marzorati , Marianna Masiero , Gabriella Pravettoni
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引用次数: 0
Meta-analysis of intraoperative electron radiation therapy for partial breast irradiation in early breast cancer 早期乳腺癌术中电子放射治疗乳腺部分照射的 Meta 分析
IF 5.7 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-08-15 DOI: 10.1016/j.breast.2024.103787
Patrick Maisonneuve, Roberto Orecchia
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引用次数: 0
Estimating the risk of major adverse cardiac events following radiotherapy for left breast cancer using a modified generalized Lyman normal-tissue complication probability model 使用改进的广义莱曼正常组织并发症概率模型估算左侧乳腺癌放疗后发生重大心脏不良事件的风险
IF 5.7 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-08-12 DOI: 10.1016/j.breast.2024.103788
Tzu-Yu Lai , Yu-Wen Hu , Ti-Hao Wang , Jui-Pin Chen , Cheng-Ying Shiau , Pin-I Huang , I-Chun Lai , Yu-Ming Liu , Chi-Cheng Huang , Ling-Ming Tseng , Nicole Huang , Chia-Jen Liu

Background

We introduced an adapted Lyman normal-tissue complication probability (NTCP) model, incorporating clinical risk factors and censored time-to-event data, to estimate the risk of major adverse cardiac events (MACE) following left breast cancer radiotherapy (RT).

Materials and methods

Clinical characteristics and MACE data of 1100 women with left-side breast cancer receiving postoperative RT from 2005 to 2017 were retrospectively collected. A modified generalized Lyman NTCP model based on the individual left ventricle (LV) equivalent uniform dose (EUD), accounting for clinical risk factors and censored data, was developed using maximum likelihood estimation. Subgroup analysis was performed for low-comorbidity and high-comorbidity groups.

Results

Over a median follow-up 7.8 years, 64 patients experienced MACE, with higher mean LV dose in affected individuals (4.1 Gy vs. 2.9 Gy). The full model accounting for clinical factors identified D50 = 43.3 Gy, m = 0.59, and n = 0.78 as the best-fit parameters. The threshold dose causing a 50 % probability of MACE was lower in the high-comorbidity group (D50 = 30 Gy) compared to the low-comorbidity group (D50 = 45 Gy). Predictions indicated that restricting LV EUD below 5 Gy yielded a 10-year relative MACE risk less than 1.3 and 1.5 for high-comorbidity and low-comorbidity groups, respectively.

Conclusion

Patients with comorbidities are more susceptible to cardiac events following breast RT. The proposed modified generalized Lyman model considers nondosimetric risk factors and addresses incomplete follow-up for late complications, offering comprehensive and individualized MACE risk estimates post-RT.

背景我们引入了一种改良的莱曼正常组织并发症概率(NTCP)模型,该模型结合了临床风险因素和时间到事件的删减数据,用于估计左侧乳腺癌放疗(RT)后发生重大心脏不良事件(MACE)的风险。材料与方法回顾性收集了2005年至2017年接受术后RT的1100名左侧乳腺癌女性患者的临床特征和MACE数据。使用最大似然估计法建立了基于个体左心室等效均匀剂量(EUD)的改进型广义莱曼NTCP模型,并考虑了临床风险因素和删减数据。结果在中位随访7.8年期间,64名患者发生了MACE,患者的平均左心室剂量较高(4.1 Gy对2.9 Gy)。考虑临床因素的完整模型确定 D50 = 43.3 Gy、m = 0.59 和 n = 0.78 为最佳拟合参数。与低并发症组(D50 = 45 Gy)相比,高并发症组导致 50% MACE 概率的阈值剂量(D50 = 30 Gy)更低。预测表明,将 LV EUD 限制在 5 Gy 以下可使高合并症组和低合并症组的 10 年相对 MACE 风险分别低于 1.3 和 1.5。所提出的改良广义莱曼模型考虑了非计量风险因素,并解决了晚期并发症随访不完全的问题,提供了全面和个性化的乳腺热疗后MACE风险估计。
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引用次数: 0
Non-invasive prediction of axillary lymph node dissection exemption in breast cancer patients post-neoadjuvant therapy: A radiomics and deep learning analysis on longitudinal DCE-MRI data 新辅助治疗后乳腺癌患者腋窝淋巴结清扫豁免的无创预测:对纵向 DCE-MRI 数据进行放射组学和深度学习分析。
IF 5.7 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-08-09 DOI: 10.1016/j.breast.2024.103786
Yushuai Yu , Ruiliang Chen , Jialu Yi , Kaiyan Huang , Xin Yu , Jie Zhang , Chuangui Song

Purpose

In breast cancer (BC) patients with clinical axillary lymph node metastasis (cN+) undergoing neoadjuvant therapy (NAT), precise axillary lymph node (ALN) assessment dictates therapeutic strategy. There is a critical demand for a precise method to assess the axillary lymph node (ALN) status in these patients.

Materials and methods

A retrospective analysis was conducted on 160 BC patients undergoing NAT at Fujian Medical University Union Hospital. We analyzed baseline and two-cycle reassessment dynamic contrast-enhanced MRI (DCE-MRI) images, extracting 3668 radiomic and 4096 deep learning features, and computing 1834 delta-radiomic and 2048 delta-deep learning features. Light Gradient Boosting Machine (LightGBM), Support Vector Machine (SVM), RandomForest, and Multilayer Perceptron (MLP) algorithms were employed to develop risk models and were evaluated using 10-fold cross-validation.

Results

Of the patients, 61 (38.13 %) achieved ypN0 status post-NAT. Univariate and multivariable logistic regression analyses revealed molecular subtypes and Ki67 as pivotal predictors of achieving ypN0 post-NAT. The SVM-based “Data Amalgamation” model that integrates radiomic, deep learning features, and clinical data, exhibited an outstanding AUC of 0.986 (95 % CI: 0.954–1.000), surpassing other models.

Conclusion

Our study illuminates the challenges and opportunities inherent in breast cancer management post-NAT. By introducing a sophisticated, SVM-based “Data Amalgamation” model, we propose a way towards accurate, dynamic ALN assessments, offering potential for personalized therapeutic strategies in BC.

目的:在接受新辅助治疗(NAT)的临床腋窝淋巴结转移(cN+)的乳腺癌(BC)患者中,精确的腋窝淋巴结(ALN)评估决定了治疗策略。目前迫切需要一种精确的方法来评估这些患者的腋窝淋巴结(ALN)状态:我们对福建医科大学附属协和医院接受 NAT 治疗的 160 例 BC 患者进行了回顾性分析。我们分析了基线和两周期再评估动态对比增强核磁共振成像(DCE-MRI)图像,提取了3668个放射学特征和4096个深度学习特征,计算了1834个δ-放射学特征和2048个δ-深度学习特征。采用光梯度提升机(LightGBM)、支持向量机(SVM)、随机森林(RandomForest)和多层感知器(MLP)算法开发风险模型,并使用10倍交叉验证进行评估:61名患者(38.13%)在NAT后达到了ypN0状态。单变量和多变量逻辑回归分析显示,分子亚型和 Ki67 是预测 NAT 后达到 ypN0 的关键因素。基于 SVM 的 "数据整合 "模型整合了放射学、深度学习特征和临床数据,其 AUC 高达 0.986(95 % CI:0.954-1.000),超过了其他模型:我们的研究揭示了 NAT 后乳腺癌管理中固有的挑战和机遇。通过引入复杂的、基于 SVM 的 "数据合并 "模型,我们提出了一种实现准确、动态 ALN 评估的方法,为 BC 的个性化治疗策略提供了潜力。
{"title":"Non-invasive prediction of axillary lymph node dissection exemption in breast cancer patients post-neoadjuvant therapy: A radiomics and deep learning analysis on longitudinal DCE-MRI data","authors":"Yushuai Yu ,&nbsp;Ruiliang Chen ,&nbsp;Jialu Yi ,&nbsp;Kaiyan Huang ,&nbsp;Xin Yu ,&nbsp;Jie Zhang ,&nbsp;Chuangui Song","doi":"10.1016/j.breast.2024.103786","DOIUrl":"10.1016/j.breast.2024.103786","url":null,"abstract":"<div><h3>Purpose</h3><p>In breast cancer (BC) patients with clinical axillary lymph node metastasis (cN+) undergoing neoadjuvant therapy (NAT), precise axillary lymph node (ALN) assessment dictates therapeutic strategy. There is a critical demand for a precise method to assess the axillary lymph node (ALN) status in these patients.</p></div><div><h3>Materials and methods</h3><p>A retrospective analysis was conducted on 160 BC patients undergoing NAT at Fujian Medical University Union Hospital. We analyzed baseline and two-cycle reassessment dynamic contrast-enhanced MRI (DCE-MRI) images, extracting 3668 radiomic and 4096 deep learning features, and computing 1834 delta-radiomic and 2048 delta-deep learning features. Light Gradient Boosting Machine (LightGBM), Support Vector Machine (SVM), RandomForest, and Multilayer Perceptron (MLP) algorithms were employed to develop risk models and were evaluated using 10-fold cross-validation.</p></div><div><h3>Results</h3><p>Of the patients, 61 (38.13 %) achieved ypN0 status post-NAT. Univariate and multivariable logistic regression analyses revealed molecular subtypes and Ki67 as pivotal predictors of achieving ypN0 post-NAT. The SVM-based “Data Amalgamation” model that integrates radiomic, deep learning features, and clinical data, exhibited an outstanding AUC of 0.986 (95 % CI: 0.954–1.000), surpassing other models.</p></div><div><h3>Conclusion</h3><p>Our study illuminates the challenges and opportunities inherent in breast cancer management post-NAT. By introducing a sophisticated, SVM-based “Data Amalgamation” model, we propose a way towards accurate, dynamic ALN assessments, offering potential for personalized therapeutic strategies in BC.</p></div>","PeriodicalId":9093,"journal":{"name":"Breast","volume":"77 ","pages":"Article 103786"},"PeriodicalIF":5.7,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0960977624001176/pdfft?md5=6038c7edb2a3b27da76fa99d12532300&pid=1-s2.0-S0960977624001176-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy and safety of oncoplastic breast-conserving surgery versus conventional breast-conserving surgery: An updated meta-analysis 肿瘤整形保乳手术与传统保乳手术的疗效和安全性对比:最新荟萃分析。
IF 5.7 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-08-05 DOI: 10.1016/j.breast.2024.103784
Rui Tian , Yu Zheng , Ruikang Liu , Chen Jiang , Hongmei Zheng

Introduction

Breast cancer is the most common cancer among women. The surgical treatment of breast cancer has transitioned progressively from radical mastectomy to breast-conserving surgery. In this meta-analysis, we are aiming to compare oncoplastic breast-conserving surgery (OS) with conventional breast-conserving surgery (BCS) in terms of efficacy and safety.

Methods

We searched Medline, Web of Science, Embase, Cochrane databases, Clinicaltrial.gov, and CNKI until April 30, 2024. Data from cohort studies and randomized controlled trials (RCTs) were included. Outcomes included primary outcomes (re-excision, local recurrence, positive surgical margin, mastectomy), secondary outcomes and safety outcomes. The Cochrane Risk of Bias Assessment Tool and Newcastle-Ottawa Scale were used to evaluate the quality of outcomes.

Results

Our study included 52 studies containing 46,835 patients. Primary outcomes comprise re-excision, local recurrence, positive surgical margin, and mastectomy, there were significant differences favoring OS over BCS (RR 0.68 [0.56, 0.82], RR 0.62 [0.47, 0.82], RR 0.76 [0.59, 0.98], RR 0.66 [0.44, 0.98] respectively), indicating superior efficacy of OS. Additionally, OS demonstrated significant aesthetic benefits (RR 1.17 [1.03, 1.33] and RR 1.34 [1.18, 1.52]). While total complications were significantly fewer in the OS group (RR 0.70 [0.53, 0.94]), the differences in specific complications were not significant. Furthermore, subgroup analyses were conducted based on nationality, sample size, quality, and type.

Conclusion

OS demonstrates either superior or at least comparable outcomes across various aspects when compared to BCS.

导言乳腺癌是女性最常见的癌症。乳腺癌的外科治疗已从根治性乳房切除术逐步过渡到保乳手术。在这项荟萃分析中,我们旨在比较肿瘤整形保乳手术(OS)与传统保乳手术(BCS)的疗效和安全性:我们检索了 Medline、Web of Science、Embase、Cochrane 数据库、Clinicaltrial.gov 和 CNKI,直至 2024 年 4 月 30 日。纳入了队列研究和随机对照试验(RCT)的数据。结果包括主要结果(再次切除、局部复发、手术切缘阳性、乳房切除)、次要结果和安全性结果。采用 Cochrane 偏倚风险评估工具和纽卡斯尔-渥太华量表评估结果的质量:我们的研究包括 52 项研究,涉及 46,835 名患者。主要结果包括再次切除、局部复发、手术切缘阳性和乳房切除,与 BCS 相比,OS 有显著差异(分别为 RR 0.68 [0.56, 0.82]、RR 0.62 [0.47, 0.82]、RR 0.76 [0.59, 0.98]、RR 0.66 [0.44, 0.98]),表明 OS 的疗效更优。此外,OS 还具有明显的美观效果(RR 1.17 [1.03, 1.33] 和 RR 1.34 [1.18, 1.52])。虽然 OS 组的总并发症明显较少(RR 0.70 [0.53, 0.94]),但具体并发症的差异并不明显。此外,还根据国籍、样本大小、质量和类型进行了亚组分析:结论:与 BCS 相比,OS 在各个方面都显示出更优越或至少相当的结果。
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引用次数: 0
Use of tamoxifene-controlled ovarian hyperstimulation for fertility preservation before breast cancer treatment: A prospective cohort study with a 5-year follow-up 在乳腺癌治疗前使用他莫昔芬控制的卵巢过度刺激来保留生育能力:一项为期 5 年的前瞻性队列研究
IF 5.7 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-08-03 DOI: 10.1016/j.breast.2024.103776
A. Dezellus , S. Mirallie , F. Leperlier , B. Sauterey , P.-E. Bouet , A. Dessaint , S. Duros , A.S. Gremeau , M.-A. Mouret-Reynier , L.M. Durand , L. Venat , P. De Blay , M. Robert , T. Freour , M. Campone , A. Blanc-Lapierre , V. Bordes

Purpose

Fertility issues are of great concern for young women undergoing treatment for breast cancer (BC). Fertility preservation (FP) protocols using controlled ovarian stimulation (COS) with letrozole have been widely used with overall good results. However, letrozole cannot be used in every country in this context. This study aimed to assess the efficacy of tamoxifen for COS in women with early BC undergoing FP.

Methods

This multicentric prospective study included patients aged 18–40, diagnosed with stage I, II and III invasive BC, undergoing tamoxifen-COS before adjuvant or neoadjuvant chemotherapy (NAC). The primary endpoint was the efficacy of tamoxifen-COS protocol evaluated by the number of oocytes collected and vitrified. Secondary endpoints included the time interval before chemotherapy, breast cancer (BC) recurrence rates, and reproductive outcomes.

Results

Ninety-five patients were included between 2014 and 2017, aged 31.5 ± 4 years on average. 37.9 % received NAC and 62.1 % received adjuvant chemotherapy. FP procedure was successful in 89.5 % of the cycles. The mean number of collected and vitrified oocytes was 12.8 ± 7.9 and 9.8 ± 6.2, respectively. The mean duration of COS was 10.4 ± 1.9 days. Median time before chemotherapy initiation was 3.6 weeks (IQR 3.1; 4.1) for women receiving NAC. Five-year relapse-free and overall survival rates were in-line with those expected in this population. Twenty-one women had spontaneous full-term pregnancies, while 5 underwent IVF cycles with frozen-thawed oocytes, without pregnancy.

Conclusion

Tamoxifen-COS protocols appear to be feasible before adjuvant or NAC treatment in young BC patients and efficient in terms of oocyte yield.

目的对于接受乳腺癌(BC)治疗的年轻女性来说,生育问题是一个非常令人担忧的问题。来曲唑控制性卵巢刺激(COS)的生育力保留(FP)方案已被广泛使用,总体效果良好。然而,来曲唑并非在每个国家都能使用。这项多中心前瞻性研究纳入了年龄在18-40岁、确诊为I、II和III期浸润性BC、在辅助化疗或新辅助化疗(NAC)前接受他莫昔芬-COS治疗的患者。主要终点是他莫昔芬-COS方案的疗效,通过收集和玻璃化的卵母细胞数量进行评估。次要终点包括化疗前的时间间隔、乳腺癌(BC)复发率和生殖结果。结果2014年至2017年期间纳入了95名患者,平均年龄为(31.5±4)岁。37.9%的患者接受了新农合,62.1%的患者接受了辅助化疗。89.5%的周期成功进行了FP手术。采集和玻璃化卵母细胞的平均数量分别为(12.8±7.9)个和(9.8±6.2)个。COS 的平均持续时间为 10.4 ± 1.9 天。接受 NAC 的女性化疗开始前的中位时间为 3.6 周(IQR 3.1; 4.1)。五年无复发率和总生存率符合该人群的预期。21名妇女自然足月妊娠,5名妇女用冷冻解冻的卵母细胞进行了体外受精周期,但未怀孕。
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引用次数: 0
Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study 奥拉帕利(Olaparib)联合曲妥珠单抗治疗 HER2 阳性、BRCA1/2 基因突变的晚期乳腺癌患者:OPHELIA 2 期研究。
IF 5.7 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-08-02 DOI: 10.1016/j.breast.2024.103780
José Enrique Alés-Martínez , Judith Balmaña , Pedro Sánchez-Rovira , Francisco Javier Salvador Bofill , Jose Ángel García Sáenz , Isabel Pimentel , Serafín Morales , María Fernández-Abad , Ainhara Lahuerta Martínez , Neus Ferrer , Pilar Zamora , Begoña Bermejo , Tamara Díaz-Redondo , María Helena López-Ceballos , María Galán , Jhudit Pérez-Escuredo , Laura Calabuig , Miguel Sampayo , José Manuel Pérez-Garcia , Javier Cortés , Antonio Llombart-Cussac

Purpose

To evaluate the efficacy and safety of the combination of olaparib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC) and germinal BRCA mutations (gBRCAm).

Methods

OPHELIA (NCT03931551) was a single-arm, open-label, phase 2 clinical trial. Patients aged ≥18 years diagnosed with HER2-positive ABC with germinal deleterious mutations in BRCA1 or BRCA2 who had received at least one prior systemic regimen for advanced disease were enrolled. Patients received olaparib plus trastuzumab until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was investigator-assessed clinical benefit rate for at least 24 weeks as per RECIST v.1.1. Key secondary endpoints included overall response rate (ORR) and safety profile.

Results

A total of 68 pre-treated HER2-positive ABC patients were screened. Due to slow accrual the trial was stopped after enrolling 5 patients instead of the planned sample size of 20. Four patients achieved clinical benefit (80.0 %, 95 % CI; 28.4–99.5, p < 0.001) and the primary endpoint was met. The ORR was 60.0 % (95 % CI; 14.7–94.7), including one complete response. Four (80.0 %) patients experienced at least one treatment-related treatment-emergent adverse event (TEAE). Most TEAEs were grade 1 or 2. There were no treatment-related deaths and no new safety signals were identified.

Conclusions

This study suggests that the combination of olaparib plus trastuzumab may be effective and safe in pre-treated patients with HER2-positive gBRCAm ABC. This ABC patient population should be further studied and not be pre-emptively excluded from clinical trials of targeted therapy for BRCA1/2-driven cancers.

目的:评估奥拉帕利联合曲妥珠单抗治疗HER2阳性晚期乳腺癌(ABC)和BRCA基因突变(gBRCAm)患者的有效性和安全性:OPHELIA(NCT03931551)是一项单臂、开放标签的2期临床试验。入组患者年龄≥18岁,确诊为HER2阳性ABC且BRCA1或BRCA2存在生殖毒性突变,既往至少接受过一种治疗晚期疾病的系统疗法。患者接受奥拉帕利联合曲妥珠单抗治疗,直至疾病进展、出现不可接受的毒性或同意退出治疗。根据RECIST v.1.1标准,主要终点是研究者评估的至少24周临床获益率。主要次要终点包括总体反应率(ORR)和安全性:共筛选出68名经前期治疗的HER2阳性ABC患者。由于进展缓慢,试验在招募了 5 名患者后停止,而不是计划的 20 名样本量。四名患者获得了临床获益(80.0%,95% CI;28.4-99.5,P 结论:该研究表明,联合使用奥拉西泮治疗 HER2 阳性 ABC 患者的疗效显著:这项研究表明,奥拉帕利联合曲妥珠单抗可能对HER2阳性gBRCAm ABC预处理患者有效且安全。应进一步研究这一ABC患者群体,而不应将其预先排除在BRCA1/2驱动癌症靶向治疗的临床试验之外。
{"title":"Olaparib plus trastuzumab in HER2-positive advanced breast cancer patients with germline BRCA1/2 mutations: The OPHELIA phase 2 study","authors":"José Enrique Alés-Martínez ,&nbsp;Judith Balmaña ,&nbsp;Pedro Sánchez-Rovira ,&nbsp;Francisco Javier Salvador Bofill ,&nbsp;Jose Ángel García Sáenz ,&nbsp;Isabel Pimentel ,&nbsp;Serafín Morales ,&nbsp;María Fernández-Abad ,&nbsp;Ainhara Lahuerta Martínez ,&nbsp;Neus Ferrer ,&nbsp;Pilar Zamora ,&nbsp;Begoña Bermejo ,&nbsp;Tamara Díaz-Redondo ,&nbsp;María Helena López-Ceballos ,&nbsp;María Galán ,&nbsp;Jhudit Pérez-Escuredo ,&nbsp;Laura Calabuig ,&nbsp;Miguel Sampayo ,&nbsp;José Manuel Pérez-Garcia ,&nbsp;Javier Cortés ,&nbsp;Antonio Llombart-Cussac","doi":"10.1016/j.breast.2024.103780","DOIUrl":"10.1016/j.breast.2024.103780","url":null,"abstract":"<div><h3>Purpose</h3><p>To evaluate the efficacy and safety of the combination of olaparib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC) and germinal <em>BRCA</em> mutations (<em>gBRCAm)</em>.</p></div><div><h3>Methods</h3><p>OPHELIA (NCT03931551) was a single-arm, open-label, phase 2 clinical trial. Patients aged ≥18 years diagnosed with HER2-positive ABC with germinal deleterious mutations in <em>BRCA1</em> or <em>BRCA2</em> who had received at least one prior systemic regimen for advanced disease were enrolled. Patients received olaparib plus trastuzumab until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was investigator-assessed clinical benefit rate for at least 24 weeks as per RECIST v.1.1. Key secondary endpoints included overall response rate (ORR) and safety profile.</p></div><div><h3>Results</h3><p>A total of 68 pre-treated HER2-positive ABC patients were screened. Due to slow accrual the trial was stopped after enrolling 5 patients instead of the planned sample size of 20. Four patients achieved clinical benefit (80.0 %, 95 % CI; 28.4–99.5, p &lt; 0.001) and the primary endpoint was met. The ORR was 60.0 % (95 % CI; 14.7–94.7), including one complete response. Four (80.0 %) patients experienced at least one treatment-related treatment-emergent adverse event (TEAE). Most TEAEs were grade 1 or 2. There were no treatment-related deaths and no new safety signals were identified.</p></div><div><h3>Conclusions</h3><p>This study suggests that the combination of olaparib plus trastuzumab may be effective and safe in pre-treated patients with HER2-positive g<em>BRCA</em>m ABC. This ABC patient population should be further studied and not be pre-emptively excluded from clinical trials of targeted therapy for <em>BRCA1/2</em>-driven cancers.</p></div>","PeriodicalId":9093,"journal":{"name":"Breast","volume":"77 ","pages":"Article 103780"},"PeriodicalIF":5.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0960977624001115/pdfft?md5=20d3f93336a801c524354de317ea6580&pid=1-s2.0-S0960977624001115-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Women's views on using artificial intelligence in breast cancer screening: A review and qualitative study to guide breast screening services 妇女对在乳腺癌筛查中使用人工智能的看法:指导乳腺癌筛查服务的回顾与定性研究。
IF 5.7 2区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-07-31 DOI: 10.1016/j.breast.2024.103783
Stacy M. Carter , Diana Popic , M. Luke Marinovich , Lucy Carolan , Nehmat Houssami

As breast screening services move towards use of healthcare AI (HCAI) for screen reading, research on public views of HCAI can inform more person-centered implementation. We synthesise reviews of public views of HCAI in general, and review primary studies of women's views of AI in breast screening. People generally appear open to HCAI and its potential benefits, despite a wide range of concerns; similarly, women are open towards AI in breast screening because of the potential benefits, but are concerned about a wide range of risks. Women want radiologists to remain central; oversight, evaluation and performance, care, equity and bias, transparency, and accountability are key issues; women may be less tolerant of AI error than of human error. Using our recent Australian primary study, we illustrate both the value of informing participants before collecting data, and women's views. The 40 screening-age women in this study stipulated four main conditions on breast screening AI implementation: 1) maintaining human control; 2) strong evidence of performance; 3) supporting familiarisation with AI; and 4) providing adequate reasons for introducing AI. Three solutions were offered to support familiarisation: transparency and information; slow and staged implementation; and allowing women to opt-out of AI reading. We provide recommendations to guide both implementation of AI in healthcare and research on public views of HCAI. Breast screening services should be transparent about AI use and share information about breast screening AI with women. Implementation should be slow and staged, providing opt-out options if possible. Screening services should demonstrate strong governance to maintain clinician control, demonstrate excellent AI system performance, assure data protection and bias mitigation, and give good reasons to justify implementation. When these measures are put in place, women are more likely to see HCAI use in breast screening as legitimate and acceptable.

随着乳腺筛查服务逐渐使用医疗人工智能(HCAI)进行屏幕阅读,有关公众对 HCAI 的看法的研究可以为更加以人为本的实施提供参考。我们综述了公众对 HCAI 的总体看法,并回顾了有关妇女对乳腺筛查中人工智能看法的主要研究。人们普遍对 HCAI 及其潜在益处持开放态度,尽管存在各种顾虑;同样,由于潜在益处,女性对乳腺筛查中的人工智能持开放态度,但对各种风险表示担忧。女性希望放射科医生仍然是核心;监督、评估和绩效、护理、公平和偏见、透明度和问责制是关键问题;女性对人工智能错误的容忍度可能低于对人为错误的容忍度。我们利用最近在澳大利亚进行的初步研究,说明了在收集数据前告知参与者的价值以及女性的观点。在这项研究中,40 名适龄女性对乳腺筛查人工智能的实施提出了四个主要条件:1) 保持人为控制;2) 有力的绩效证据;3) 支持熟悉人工智能;4) 提供引入人工智能的充分理由。为支持熟悉人工智能提供了三种解决方案:透明度和信息;缓慢和分阶段实施;允许妇女选择不阅读人工智能。我们为在医疗保健领域实施人工智能和研究公众对 HCAI 的看法提供了指导建议。乳腺筛查服务机构应透明人工智能的使用情况,并与妇女分享有关乳腺筛查人工智能的信息。实施过程应缓慢且分阶段进行,并在可能的情况下提供退出选项。筛查服务机构应表现出强大的管理能力,以保持临床医生的控制权,展示人工智能系统的卓越性能,确保数据保护和减少偏差,并提供充分的理由证明实施的合理性。当这些措施落实到位时,妇女更有可能认为在乳腺筛查中使用 HCAI 是合法且可接受的。
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引用次数: 0
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