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Clinicopathological and prognostic features of HER2-null and HER2-low advanced breast cancer treated with eribulin or capecitabine. 接受艾瑞布林或卡培他滨治疗的HER2缺失和HER2低下晚期乳腺癌的临床病理和预后特征。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-14 DOI: 10.1007/s12282-024-01617-y
Rui Kitadai, Tatsunori Shimoi, Shu Yazaki, Hitomi Sumiyoshi Okuma, Mai Hoshino, Munehiro Ito, Ayumi Saito, Shosuke Kita, Yuki Kojima, Tadaaki Nishikawa, Kazuki Sudo, Emi Noguchi, Yasuhiro Fujiwara, Masayuki Yoshida, Kan Yonemori

Background: HER2-low populations constitute a heterogeneous group, and the cytotoxic anticancer agent efficacy based on HER2 status remains unclear. This study evaluated the clinicopathological features and outcomes of patients with advanced breast cancer showing HER2-low expression treated with eribulin or capecitabine, two treatment options after anthracycline and taxane treatment.

Methods: We retrospectively evaluated patients who were treated with eribulin or capecitabine between 2011 and 2015. HER2 status was evaluated according to the ASCO/CAP guidelines.

Results: No significant difference was observed in overall survival (OS; eribulin: hazard ratio [HR], 0.66; 95% CI 0.40-1.10; capecitabine: HR, 0.76; 95% CI 0.45-1.30) or progression-free survival (PFS; eribulin: HR, 1.13; 95% CI 0.72-1.78; capecitabine: HR, 0.90; 95% CI 0.56-1.44) between patients receiving eribulin (HER2-null: 35, HER2-low: 44) and those receiving capecitabine (HER2-null: 41, HER2-low: 33). Subgroup analysis revealed no significant differences in OS between the two groups in the hormone-positive and -negative populations for eribulin and capecitabine. HER2-null and HER2-low patients showed objective response rates (ORRs) of 22.5% and 9.1% (p = 0.09) overall, and 32.0% and 10.5% (p = 0.03), respectively, in hormone-positive cases among eribulin-treated patients. No response was observed in hormone-negative patients. Capecitabine treatment in HER2-null and HER2-low patients had overall ORRs of 26.8% and 15.2% (p = 0.23), respectively, with 27.3% and 16.1% (p = 0.28) for hormone-positive cases; and 25.0% and 0% (p = 1.0), respectively, for hormone-negative cases.

Conclusions: Eribulin and capecitabine sensitivity may vary based on HER2 expression in patients with HER2-low and HER2-null breast cancer. Prognosis was similar between the HER2-low and the HER2-null groups.

背景:HER2低表达人群是一个异质性群体,基于HER2状态的细胞毒性抗癌药物疗效仍不明确。本研究评估了HER2低表达晚期乳腺癌患者接受艾瑞布林或卡培他滨治疗后的临床病理特征和预后:我们对2011年至2015年间接受艾瑞布林或卡培他滨治疗的患者进行了回顾性评估。根据ASCO/CAP指南评估HER2状态:总生存率(OS;埃瑞布林:危险比[HR],0.66;95% CI 0.40-1.10;卡培他滨:HR,0.76;95% CI 0.40-1.10)无明显差异:HR,0.76;95% CI,0.45-1.30)或无进展生存期(PFS,埃瑞布林:HR,1.13;95% CI,0.72-1.78;卡培他滨:HR,0.90;95% CI,0.72-1.78)有显著差异:HR,0.90;95% CI,0.56-1.44)之间的差异。亚组分析显示,在激素阳性和阴性人群中,埃瑞布林和卡培他滨两组的OS无明显差异。HER2空值和HER2低值患者的客观反应率(ORR)分别为22.5%和9.1%(P = 0.09),在埃瑞布林治疗的患者中,激素阳性病例的客观反应率(ORR)分别为32.0%和10.5%(P = 0.03)。在激素阴性患者中未观察到反应。HER2-null和HER2-low患者接受卡培他滨治疗的总ORR分别为26.8%和15.2%(p = 0.23),激素阳性病例分别为27.3%和16.1%(p = 0.28);激素阴性病例分别为25.0%和0%(p = 1.0):结论:HER2-低表达和HER2-无效乳腺癌患者对伊瑞布林和卡培他滨的敏感性可能因HER2表达而异。HER2低表达组和HER2无效组的预后相似。
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引用次数: 0
Reply to the Letter to the editor "Does axillary lymph node recurrence breast cancer subtype information matter for prognosis estimation?" 回复致编辑的信 "腋窝淋巴结复发乳腺癌亚型信息对预后评估重要吗?
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-09-01 DOI: 10.1007/s12282-024-01629-8
Hirohito Seki, Shinsuke Sasada, Tadahiko Shien
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引用次数: 0
Breast cancer drugs: FDA approval, development time, efficacy, clinical benefits, innovation, trials, endpoints, quality of life, value, and price. 乳腺癌药物:FDA 批准、开发时间、疗效、临床效益、创新、试验、终点、生活质量、价值和价格。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-09-25 DOI: 10.1007/s12282-024-01634-x
Julia Caroline Michaeli, Thomas Michaeli, Dario Trapani, Sebastian Albers, Dominik Dannehl, Rachel Würstlein, Daniel Tobias Michaeli

Objective: This study analyzes the development, benefits, trial evidence, and price of new breast cancer drugs with US Food and Drug Administration (FDA) approval.

Methods: We identified 26 drugs with 42 FDA-approved indications for early and metastatic breast cancer (2000-2023). Data were collected from FDA labels, clinicaltrials.gov, and Medicare and Medicaid. Overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) and tumor response's relative risk (RR) alongside objective response rate (ORR) were meta-analyzed.

Results: The median development time for breast cancer drugs was 7.8 years (95% CI 6.2-10.8). 26% of treatments were considered innovative ("first-in-indication") with 88% acting via a targeted mechanism. 64% were small molecules, 19% antibodies, and 18% antibody-drug conjugates. 38% were approved for HR + and 31% for HER2 + breast cancer. 6 indications were for early and 36 for metastatic breast cancer. Indications utilized FDA's special programs: orphan (2%), fast track (24%), accelerated approval (19%), priority review (74%), breakthrough therapy (44%). Approval was predominantly supported by phase 3 trials (88%) of randomized controlled design (66%), enrolling a median of 585 patients (IQR 417-752) at 181 centers (IQR 142-223) across 19 countries (IQR 17-20). New drugs' HR were 0.78 for OS (95% CI 0.74-0.82) and 0.59 for PFS (95% CI 0.54-0.64) with a RR for tumor response of 1.61 (95% CI 1.46-1.76). Median improvements of OS were 2.8 months (IQR 1.8-5.8) and PFS were 4.4 months (IQR 2.2-7.1). In single-arm trials, the average ORR was 31% (95% CI 10-53). In meta-regressions, the correlation between OS/PFS was 0.34 (p = 0.031) and OS/response was 0.01 (p = 0.435). 60% of treatments had a 'high-value' ESMO-MCBS score with 14% demonstrating improvements in quality of life. The median price was $16,013 per month (95% CI 13,097-17,617). There was no association between prices and patient benefit. The median value per life year gained was $62,419 (IQR 25,840-86,062).

Conclusions: Over the past two decades, the development of innovative and effective drugs transformed the treatment landscape for breast cancer patients. Yet, investigators and regulators must safeguard that highly-priced new drugs demonstrate improvements in patient-centered clinical endpoints: overall survival and quality of life.

目的:本研究分析了美国食品药品管理局(FDA)批准的乳腺癌新药的开发、效益、试验证据和价格:本研究分析了美国食品和药物管理局(FDA)批准的乳腺癌新药的开发、益处、试验证据和价格:我们确定了 26 种药物,42 种 FDA 批准的早期和转移性乳腺癌适应症(2000-2023 年)。数据收集自 FDA 标签、clinicaltrials.gov 以及 Medicare 和 Medicaid。对总生存期(OS)和无进展生存期(PFS)的危险比(HRs)以及肿瘤反应的相对风险(RR)和客观反应率(ORR)进行了荟萃分析:乳腺癌药物的中位研发时间为 7.8 年(95% CI 6.2-10.8)。26%的治疗药物被认为是创新药物("首个适应症"),88%通过靶向机制发挥作用。64%为小分子药物,19%为抗体药物,18%为抗体药物共轭物。38%被批准用于HR+乳腺癌,31%用于HER2+乳腺癌。6个适应症用于早期乳腺癌,36个用于转移性乳腺癌。适应症采用了 FDA 的特殊计划:孤儿(2%)、快速通道(24%)、加速审批(19%)、优先审查(74%)、突破性治疗(44%)。批准主要由 3 期试验(88%)和随机对照设计(66%)支持,19 个国家(IQR 17-20)的 181 个中心(IQR 142-223)共招募了中位数为 585 名患者(IQR 417-752)。新药的 OS HR 为 0.78(95% CI 0.74-0.82),PFS 为 0.59(95% CI 0.54-0.64),肿瘤反应的 RR 为 1.61(95% CI 1.46-1.76)。OS和PFS的中位改善时间分别为2.8个月(IQR 1.8-5.8)和4.4个月(IQR 2.2-7.1)。在单臂试验中,平均 ORR 为 31% (95% CI 10-53)。在元回归中,OS/PFS之间的相关性为0.34(P = 0.031),OS/应答之间的相关性为0.01(P = 0.435)。60%的治疗获得了ESMO-MCBS "高价值 "评分,14%的治疗改善了生活质量。价格中位数为每月16,013美元(95% CI 13,097-17,617)。价格与患者获益之间没有关联。每延长一生命年的中位值为 62,419 美元(IQR 25,840-86,062 美元):在过去的二十年里,创新有效药物的开发改变了乳腺癌患者的治疗格局。然而,研究人员和监管机构必须确保高价新药能够改善以患者为中心的临床终点:总生存期和生活质量。
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引用次数: 0
Trastuzumab deruxtecan for the treatment of patients with HER2-positive breast cancer with brain and/or leptomeningeal metastases: an updated overall survival analysis using data from a multicenter retrospective study (ROSET-BM). 曲妥珠单抗德鲁司康治疗伴有脑转移和/或脑膜转移的 HER2 阳性乳腺癌患者:利用多中心回顾性研究 (ROSET-BM) 数据进行的最新总生存率分析。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-12 DOI: 10.1007/s12282-024-01614-1
Takahiro Nakayama, Naoki Niikura, Takashi Yamanaka, Mitsugu Yamamoto, Kazuo Matsuura, Kenichi Inoue, Sachiko Takahara, Hironori Nomura, Shosuke Kita, Miki Yamaguchi, Tomoyuki Aruga, Nobuhiro Shibata, Akihiko Shimomura, Yuri Ozaki, Shuji Sakai, Daisuke Takiguchi, Takehiko Takata, Armin Bastanfard, Kazuhito Shiosakai, Junji Tsurutani

We provide updated results (median follow-up duration: 20.4 months) of a retrospective study on the effectiveness of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer with brain metastases (BM) and/or leptomeningeal disease (ROSET-BM). Median progression-free survival (PFS) was 14.6 months. Median overall survival (OS) was not reached (NR); 24-month OS rate was 56.0%. Subgroup analysis showed that median PFS was 13.2 months in patients with analytical active BM, 17.5 months in patients with leptomeningeal carcinomatosis (LMC), and NR in patients with analytical stable BM (24-month PFS rates in patients with analytical active BM, LMC, and analytical stable BM were 32.7%, 25.1%, and 60.8%, respectively). Median OS was 27.0 months in patients with analytical active BM and NR in patients with LMC or analytical stable BM (24-month OS rates in patients with analytical active BM, LMC, and analytical stable BM were 52.0%, 61.6%, and 71.6%, respectively). The most common adverse event leading to discontinuation of T-DXd was interstitial lung disease (ILD; 23.1%); median ILD onset time among patients who discontinued T-DXd treatment due to ILD was 5.3 months. T-DXd has promising effectiveness in heavily pre-treated HER2+ metastatic breast cancer patients with BM and LMC. The incidence and median onset time of ILD were similar to those of Japanese subgroups in previous studies.

我们提供了一项关于曲妥珠单抗德鲁司坦(T-DXd)对人类表皮生长因子受体 2 阳性(HER2+)乳腺癌伴脑转移(BM)和/或脑膜疾病(ROSET-BM)患者疗效的回顾性研究的最新结果(中位随访时间:20.4 个月)。中位无进展生存期(PFS)为14.6个月。中位总生存期(OS)未达到(NR);24个月OS率为56.0%。亚组分析显示,分析性活动性骨髓瘤患者的中位生存期为13.2个月,脑膜外癌(LMC)患者为17.5个月,分析性稳定骨髓瘤患者为NR(分析性活动性骨髓瘤、LMC和分析性稳定骨髓瘤患者的24个月生存率分别为32.7%、25.1%和60.8%)。分析活跃骨髓瘤患者的中位OS为27.0个月,LMC或分析稳定骨髓瘤患者的中位OS为NR(分析活跃骨髓瘤、LMC和分析稳定骨髓瘤患者的24个月OS率分别为52.0%、61.6%和71.6%)。导致停用T-DXd的最常见不良反应是间质性肺病(ILD;23.1%);因ILD而停用T-DXd治疗的患者的中位ILD发病时间为5.3个月。T-DXd对患有BM和LMC的重度预处理HER2+转移性乳腺癌患者具有良好的疗效。ILD的发生率和中位发病时间与之前研究中日本亚组的情况相似。
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引用次数: 0
Does axillary lymph node recurrence breast cancer subtype information matter for prognosis estimation? 腋窝淋巴结复发乳腺癌亚型信息对预后评估有影响吗?
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-20 DOI: 10.1007/s12282-024-01620-3
Kadri Altundag
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引用次数: 0
Utility of a breast biopsy clip and a point marker system in tailored axillary surgery for patients with breast cancer after neoadjuvant chemotherapy. 乳腺活检夹和点标记系统在为新辅助化疗后的乳腺癌患者量身定制腋窝手术中的实用性。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-09-23 DOI: 10.1007/s12282-024-01630-1
Yuka Endo, Haruru Kotani, Nobuko Tamura, Kiyo Tanaka, Chiho Kudo, Masataka Sawaki, Masaya Hattori, Akiyo Yoshimura, Ayumi Kataoka, Kazuki Nozawa, Yuri Ozaki, Ayaka Isogai, Rie Komaki, Akira Nakakami, Nari Kureyama, Maho Kusudo, Waki Hosoda, Hidetaka Kawabata, Hiroji Iwata

Background: Tailored axillary surgery (TAS) is a new approach for selective removal of metastatic lymph nodes. This study evaluated the safety and utility of TAS using a breast biopsy clip inserted into a metastatic lymph node and a point marker consisting of a short hook wire and nylon thread to remove the clipped lymph node.

Methods: Patients with breast cancer and clinically confirmed metastases to one-to-three axillary lymph nodes were included in this study. A breast biopsy clip was inserted into the metastatic lymph nodes before neoadjuvant chemotherapy. TAS was performed in patients with ycN0 disease after neoadjuvant chemotherapy. The lymph nodes containing the clips were removed using a point marker. The success criteria for TAS were the removal of the lymph node into which the clip was inserted using a point marker and the identification of the sentinel lymph node. The false-negative rate was calculated for cases in which TAS and axillary lymph node dissection were performed.

Results: Thirty individuals from two institutions were enrolled between May 2021 and November 2022, of whom 20 underwent TAS. Ten patients had clinically positive axillary lymph nodes and underwent axillary lymph node dissection. No adverse events were observed in any patient using the clips or point markers. TAS was successful in 18 of the 20 patients (90%). Seven patients underwent TAS and axillary lymph node dissection with a false-negative rate of 0%.

Conclusion: The use of clips and point markers to perform TAS is clinically feasible.

背景:定制腋窝手术(TAS)是一种选择性切除转移淋巴结的新方法。本研究评估了TAS的安全性和实用性,TAS使用乳腺活检夹插入转移淋巴结,并使用由短钩丝和尼龙线组成的点标记物切除被剪切的淋巴结:方法:本研究纳入了临床确诊为一至三个腋窝淋巴结转移的乳腺癌患者。在新辅助化疗前,将乳腺活检夹插入转移淋巴结。新辅助化疗后,对ycN0患者进行TAS检查。使用点标记法切除含有夹子的淋巴结。TAS的成功标准是使用点标记去除插入夹子的淋巴结,并确定前哨淋巴结。对进行 TAS 和腋窝淋巴结清扫的病例计算假阴性率:2021年5月至2022年11月期间,来自两家机构的30名患者接受了TAS检查,其中20人接受了TAS检查。10名患者的腋窝淋巴结临床阳性,接受了腋窝淋巴结清扫术。使用夹子或点标记物的患者均未出现不良反应。20 名患者中有 18 名(90%)成功进行了 TAS。7名患者接受了TAS和腋窝淋巴结清扫术,假阴性率为0%:结论:使用夹子和点标记物进行 TAS 在临床上是可行的。
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引用次数: 0
Hub metastatic gene signature and risk score of breast cancer patients with small tumor sizes using WGCNA. 使用 WGCNA 对肿瘤较小的乳腺癌患者进行中枢转移基因特征和风险评分。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-27 DOI: 10.1007/s12282-024-01627-w
Yu-Tien Chang, Zhi-Jie Hong, Hsueh-Han Tsai, An-Chieh Feng, Tzu-Ya Huang, Jyh-Cherng Yu, Kuo-Feng Hsu, Chi-Cheng Huang, Wei-Zhi Lin, Chi-Ming Chu, Chia-Ming Liang, Guo-Shiou Liao

Background: Breast cancer (BC) is the most common cancer in women and accounts for approximately 15% of all cancer deaths among women globally. The underlying mechanism of BC patients with small tumor size and developing distant metastasis (DM) remains elusive in clinical practices.

Methods: We integrated the gene expression of BCs from ten RNAseq datasets from Gene Expression Omnibus (GEO) database to create a genetic prediction model for distant metastasis-free survival (DMFS) in BC patients with small tumor sizes (≤ 2 cm) using weighted gene co-expression network (WGCNA) analysis and LASSO cox regression.

Results: ABHD11, DDX39A, G3BP2, GOLM1, IL1R1, MMP11, PIK3R1, SNRPB2, and VAV3 were hub metastatic genes identified by WGCNA and used to create a risk score using multivariable Cox regression. At the cut-point value of the median risk score, the high-risk score (≥ median risk score) group had a higher risk of DM than the low-risk score group in the training cohort [hazard ratio (HR) 4.51, p < 0.0001] and in the validation cohort (HR 5.48, p = 0.003). The nomogram prediction model of 3-, 5-, and 7-year DMFS shows good prediction results with C-indices of 0.72-0.76. The enriched pathways were immune regulation and cell-cell signaling. EGFR serves as the hub gene for the protein-protein interaction network of PIK3R1, IL1R1, MMP11, GOLM1, and VAV3.

Conclusion: Prognostic gene signature was predictive of DMFS for BCs with small tumor sizes. The protein-protein interaction network of PIK3R1, IL1R1, MMP11, GOLM1, and VAV3 connected by EGFR merits further experiments for elucidating the underlying mechanisms.

背景:乳腺癌(BC)是女性最常见的癌症,约占全球女性癌症死亡人数的15%。在临床实践中,肿瘤体积小的乳腺癌患者发生远处转移(DM)的潜在机制仍然难以捉摸:方法:我们整合了基因表达总库(GEO)数据库中10个RNAseq数据集的BC基因表达,利用加权基因共表达网络(WGCNA)分析和LASSO cox回归建立了小肿瘤(≤2 cm)BC患者无远处转移生存(DMFS)的基因预测模型:结果:ABHD11、DDX39A、G3BP2、GOLM1、IL1R1、MMP11、PIK3R1、SNRPB2和VAV3是WGCNA确定的枢纽转移基因,这些基因通过多变量Cox回归被用于创建风险评分。在中位风险评分的切点值上,在训练队列中,高风险评分(≥中位风险评分)组比低风险评分组有更高的DM风险[危险比(HR)4.51,P 结论:在中位风险评分的切点值上,高风险评分(≥中位风险评分)组比低风险评分组有更高的DM风险]:预后基因特征可预测肿瘤较小的BC的DMFS。由表皮生长因子受体连接的PIK3R1、IL1R1、MMP11、GOLM1和VAV3的蛋白-蛋白相互作用网络值得进一步实验以阐明其潜在机制。
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引用次数: 0
Applying whole-genome and whole-exome sequencing in breast cancer: a review of the landscape. 在乳腺癌中应用全基因组和全外显子组测序:前景综述。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-27 DOI: 10.1007/s12282-024-01628-9
Hetvi Ganatra, Joecelyn Kirani Tan, Ana Simmons, Carola Maria Bigogno, Vatsala Khurana, Aruni Ghose, Adheesh Ghosh, Ishika Mahajan, Stergios Boussios, Akash Maniam, Olubukola Ayodele

Whole-genome sequencing (WGS) and whole-exome sequencing (WES) are crucial within the context of breast cancer (BC) research. They play a role in the detection of predisposed genes, risk stratification, and identification of rare single nucleotide polymorphisms (SNPs). These technologies aid in the discovery of associations between various syndromes and BC, understanding the tumour microenvironment (TME), and even identifying unknown mutations that could be useful in future for personalised treatments. Genetic analysis can find the associated risk of BC and can be used in early screening, diagnosis, specific treatment plans, and prevention in patients who are at high risk of tumour formation. This article focuses on the application of WES and WGS, and how uncovering novel candidate genes associated with BC can aid in treating and preventing BC.

全基因组测序(WGS)和全外显子组测序(WES)在乳腺癌(BC)研究中至关重要。它们在检测易感基因、风险分层和鉴定罕见单核苷酸多态性(SNPs)方面发挥作用。这些技术有助于发现各种综合征与乳腺癌之间的关联,了解肿瘤微环境 (TME),甚至识别未来可能用于个性化治疗的未知突变。基因分析可以发现与 BC 相关的风险,可用于肿瘤形成高风险患者的早期筛查、诊断、特定治疗计划和预防。本文重点介绍 WES 和 WGS 的应用,以及发现与 BC 相关的新型候选基因如何帮助治疗和预防 BC。
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引用次数: 0
Development of a nomogram to predict recurrence scores obtained using Oncotype DX in Japanese patients with breast cancer. 使用 Oncotype DX 预测日本乳腺癌患者复发评分的提名图的开发。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-17 DOI: 10.1007/s12282-024-01616-z
Akio Shibata, Nobuko Tamura, Keiichi Kinowaki, Aya Nishikawa, Kiyo Tanaka, Yoko Kobayashi, Takuya Ogura, Yuko Tanabe, Hidetaka Kawabata

Background: Chemotherapy is crucial for hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, and its survival benefits may outweigh adverse events. Oncotype DX (ODX) assesses this balance; however, it is expensive. Using nomograms to identify cases requiring ODX may be economically beneficial. We aimed to identify clinicopathological variables that correlated with the recurrence score (RS) and develop a nomogram that predicted the RS.

Methods: We included 457 patients with estrogen receptor-positive, HER2-negative breast cancer with metastases in fewer than four axillary lymph nodes who underwent surgery and ODX at our hospital between 2007 and 2023. We developed nomograms and internally validated them in 310 patients who underwent surgery between 2007 and 2021 and validated the model's performance in 147 patients who underwent surgery between 2022 and 2023.

Results: Logistic regression analysis revealed that progesterone receptor (PgR) level, histological grade (HG), and Ki67 index independently predicted the RS. A nomogram was developed using these variables to predict the RS (area under the curve [AUC], 0.870; 95% confidence interval [CI], 0.82-0.92). The nomogram was applied to the model validation group (AUC, 0.877; 95% CI, 0.80-0.95). When the sensitivity of the nomogram was 90%, the model was able to identify 52.3% low-RS and 41.2% high-RS cases not requiring ODX.

Conclusions: This was the first nomogram model developed based on data from a cohort of Japanese women. It may help determine the indications for ODX and the use of nomogram to identify cases requiring ODX may be economically beneficial.

背景:化疗对于激素受体阳性、人表皮生长因子受体 2(HER2)阴性的乳腺癌至关重要,化疗对患者生存的益处可能大于不良反应。Oncotype DX(ODX)可评估这种平衡,但价格昂贵。使用提名图来确定需要进行 ODX 的病例可能会带来经济效益。我们的目的是确定与复发评分(RS)相关的临床病理变量,并开发出一种能预测 RS 的提名图:我们纳入了 457 例雌激素受体阳性、HER2 阴性、腋窝淋巴结转移少于 4 个的乳腺癌患者,这些患者在 2007 年至 2023 年期间在我院接受了手术和 ODX。我们开发了提名图,并在 2007 年至 2021 年期间接受手术的 310 名患者中进行了内部验证,在 2022 年至 2023 年期间接受手术的 147 名患者中验证了模型的性能:逻辑回归分析显示,孕酮受体(PgR)水平、组织学分级(HG)和Ki67指数可独立预测RS。利用这些变量绘制了预测 RS 的提名图(曲线下面积 [AUC],0.870;95% 置信区间 [CI],0.82-0.92)。模型验证组应用了该提名图(AUC,0.877;95% CI,0.80-0.95)。当提名图的灵敏度为 90% 时,该模型能够识别 52.3% 的低 RS 和 41.2% 的高 RS 病例,无需进行 ODX:这是首个基于日本女性队列数据开发的提名图模型。结论:这是首个基于日本妇女队列数据开发的提名图模型,有助于确定 ODX 的适应症,使用提名图来识别需要进行 ODX 的病例可能会带来经济效益。
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引用次数: 0
High-risk pathogenic germline variants in blood relatives of BRCA1/2 negative probands. BRCA1/2 阴性探查者血亲中的高风险致病基因变异。
IF 4 3区 医学 Q1 OBSTETRICS & GYNECOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-13 DOI: 10.1007/s12282-024-01615-0
Reiko Yoshida, Tomoko Kaneyasu, Arisa Ueki, Hideko Yamauchi, Shozo Ohsumi, Shinji Ohno, Daisuke Aoki, Shinichi Baba, Junko Kawano, Naomichi Matsumoto, Masao Nagasaki, Takayuki Ueno, Hitoshi Inari, Yusuke Kobayashi, Junko Takei, Osamu Gotoh, Mitsuyo Nishi, Miki Okamura, Keika Kaneko, Megumi Okawa, Misato Suzuki, Sayuri Amino, Mayuko Inuzuka, Tetsuo Noda, Seiichi Mori, Seigo Nakamura

Background: Tailored, preventive cancer care requires the identification of pathogenic germline variants (PGVs) among potentially at-risk blood relatives (BRs). Cascade testing is carried out for BRs of probands who are positive for PGVs of an inherited cancer but not for negative probands. This study was conducted to examine the prevalence of PGVs for BRs of PGV-negative probands.

Methods: PGV prevalence was assessed for 682 BRs of 281 probands with BRCA1/BRCA2 wild-type hereditary breast and ovarian cancer (HBOC) syndrome.

Results: PGVs were discovered in 22 (45.8%) of the 48 BRs of the PGV-positive probands and in 14 (2.2%) of 634 BRs of the PGV-negative probands. Eleven PGVs on high-risk BRCA1, BRCA2, and TP53 genes were present only in BRs and not in the probands (probands vs BRs in Fisher exact test; p = 0.0104; odds ratio [OR] = 0.000 [0.000-0.5489 of 95% confidence interval]), partly due to the nature of the selection criteria. The enrichment of high-risk PGVs among BRs was also significant as compared with a non-cancer East Asian population (p = 0.0016; OR = 3.0791 [1.5521-5.6694]). PGV prevalence, risk class of gene, and genotype concordance were unaffected by the cancer history among BRs.

Conclusion: These findings imply the necessity to construct a novel testing scheme to complement cascade testing.

背景:量身定制的预防性癌症治疗需要在潜在高危血亲(BRs)中识别致病性种系变异(PGVs)。对于遗传性癌症 PGV 呈阳性的原告的血亲,可进行基因串联检测,而对于阴性原告的血亲,则不进行基因串联检测。本研究的目的是检测 PGV 阴性概率者的血亲中 PGV 的流行率:方法:对281名BRCA1/BRCA2野生型遗传性乳腺癌和卵巢癌(HBOC)综合征(hereditary breast and ovarian cancer,HBOC)患者的682个BR进行了PGV流行率评估:结果:在PGV阳性探查者的48个BR中发现了22个(45.8%)PGV,在PGV阴性探查者的634个BR中发现了14个(2.2%)PGV。高风险 BRCA1、BRCA2 和 TP53 基因上的 11 个 PGV 只出现在 BR 中,而不出现在探针中(费舍尔精确检验中探针与 BR 的比值;P = 0.0104;比值比 [OR] = 0.000 [0.000-0.5489 的 95% 置信区间]),部分原因是选择标准的性质。与非癌症东亚人群相比,BRs 中高风险 PGV 的富集也很显著(p = 0.0016;OR = 3.0791 [1.5521-5.6694])。PGV的流行率、基因的风险等级和基因型的一致性在BR人群中不受癌症病史的影响:这些研究结果表明,有必要建立一种新的检测方案来补充级联检测。
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Breast Cancer
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