MaltSci 麦伴科研

Appearance

文献精选 > 近年高分"脑机接口"研究（IF≥30，近5年）

Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen-To Offer More? (aTTom) trial. ​

文献信息 ​

DOI10.1093/annonc/mdz289
PMID31504126
期刊Annals of oncology : official journal of the European Society for Medical Oncology
影响因子65.4
JCR 分区Q1
发表年份2019
被引次数85
关键词BCI、早期乳腺癌、内分泌益处、分子特征、预测性生物标志物
文献类型Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
ISSN0923-7534
页码1776-1783
期号30(11)
作者J M S Bartlett, D C Sgroi, K Treuner, Y Zhang, I Ahmed, T Piper, R Salunga, E F Brachtel, S J Pirrie, C A Schnabel, D W Rea

一句话小结 ​

本研究探讨了乳腺癌指数（BCI）在预测早期激素受体阳性（HR+）乳腺癌患者延长内分泌治疗获益中的作用，发现高H/I表达的BCI能够显著识别出从10年对比5年他莫昔芬治疗中获益的患者。研究结果为BCI作为预测生物标志物的有效性提供了强有力的证据，具有重要的临床应用意义。

在麦伴科研 (maltsci.com) 搜索更多文献 ​

BCI · 早期乳腺癌 · 内分泌益处 · 分子特征 · 预测性生物标志物

摘要 ​

背景
延长辅助内分泌治疗的时间可以降低一部分早期激素受体阳性（HR+）乳腺癌女性患者复发的风险。经过验证的内分泌反应预测生物标志物可以显著改善扩展治疗的患者选择。乳腺癌指数（BCI）[HOXB13/IL17BR比例（H/I）]被评估用于预测在之前参与“辅助他莫昔芬-更多选择？”（aTTom）试验的患者中延长内分泌治疗的获益。

患者与方法
Trans-aTTom是一项多中心的前瞻性-回顾性研究，研究对象为可获得福尔马林固定的石蜡嵌入的原发肿瘤切块的患者。BCI检测以及通过免疫组织化学法对雌激素受体（ER）和孕激素受体（PR）状态的中央判定均在不知临床结果的情况下进行。生存终点使用Kaplan-Meier分析和Cox回归进行评估，以无复发生存期（RFI）作为主要终点。扩展内分泌治疗与BCI（H/I）之间的相互作用使用似然比检验进行评估。

结果
在分析的583名HR+、N+患者中，49%被归类为BCI（H/I）高组，这部分患者从10年对比5年的他莫昔芬治疗中获得了显著获益[风险比（HR）：0.35；95%置信区间（CI）0.15-0.86；基于RFI的绝对风险降低10.2%，P=0.027]。BCI（H/I）低组患者未显示出从扩展内分泌治疗中获得显著获益（HR：1.07；95% CI 0.69-1.65；绝对风险降低-0.2%；P=0.768）。持续的BCI（H/I）水平预测了从扩展他莫昔芬中获益的大小，而集中测定的ER和PR没有。扩展他莫昔芬治疗与BCI（H/I）之间的相互作用在统计上显著（P=0.012），并调整了临床病理因素。

结论
高H/I表达的BCI预测了内分泌反应，并识别出一部分从10年对比5年他莫昔芬治疗中获得显著获益的HR+、N+患者。这些数据进一步验证了与之前MA.17数据的一致性，为BCI作为扩展内分泌治疗获益的预测生物标志物建立了1B级证据。

试验注册
ISRCTN17222211；NCT00003678。

英文摘要 ​

BACKGROUND Extending the duration of adjuvant endocrine therapy reduces the risk of recurrence in a subset of women with early-stage hormone receptor-positive (HR+) breast cancer. Validated predictive biomarkers of endocrine response could significantly improve patient selection for extended therapy. Breast cancer index (BCI) [HOXB13/IL17BR ratio (H/I)] was evaluated for its ability to predict benefit from extended endocrine therapy in patients previously randomized in the Adjuvant Tamoxifen-To Offer More? (aTTom) trial.

PATIENTS AND METHODS Trans-aTTom is a multi-institutional, prospective-retrospective study in patients with available formalin-fixed paraffin-embedded primary tumor blocks. BCI testing and central determination of estrogen receptor (ER) and progesterone receptor (PR) status by immunohistochemistry were carried out blinded to clinical outcome. Survival endpoints were evaluated using Kaplan-Meier analysis and Cox regression with recurrence-free interval (RFI) as the primary endpoint. Interaction between extended endocrine therapy and BCI (H/I) was assessed using the likelihood ratio test.

RESULTS Of 583 HR+, N+ patients analyzed, 49% classified as BCI (H/I)-High derived a significant benefit from 10 versus 5 years of tamoxifen treatment [hazard ratio (HR): 0.35; 95% confidence interval (CI) 0.15-0.86; 10.2% absolute risk reduction based on RFI, P = 0.027]. BCI (H/I)-low patients showed no significant benefit from extended endocrine therapy (HR: 1.07; 95% CI 0.69-1.65; -0.2% absolute risk reduction; P = 0.768). Continuous BCI (H/I) levels predicted the magnitude of benefit from extended tamoxifen, whereas centralized ER and PR did not. Interaction between extended tamoxifen treatment and BCI (H/I) was statistically significant (P = 0.012), adjusting for clinicopathological factors.

CONCLUSION BCI by high H/I expression was predictive of endocrine response and identified a subset of HR+, N+ patients with significant benefit from 10 versus 5 years of tamoxifen therapy. These data provide further validation, consistent with previous MA.17 data, establishing level 1B evidence for BCI as a predictive biomarker of benefit from extended endocrine therapy.

TRIAL REGISTRATION ISRCTN17222211; NCT00003678.

麦伴智能科研服务 ​

智能阅读回答你对文献的任何问题，帮助理解文献中的复杂图表和公式
定位观点定位某个观点在文献中的蛛丝马迹
加入知识库完成数据提取，报告撰写等更多高级知识挖掘功能

主要研究问题 ​

  1. BCI在不同类型的乳腺癌患者中的预测能力是否存在差异？
  2. 除了BCI，还有哪些生物标志物可以用于预测乳腺癌患者对延长内分泌治疗的反应？
  3. 研究中提到的风险降低10.2%是否在临床实践中具有实际意义？
  4. 对于BCI (H/I)-低的患者，是否有其他治疗方案可以考虑？
  5. 该研究结果对未来乳腺癌治疗指南的影响是什么？

核心洞察 ​

研究背景和目的 ​

本研究旨在评估乳腺癌指数（BCI）在预测接受延长内分泌治疗的早期激素受体阳性（HR+）乳腺癌患者中的效用。延长内分泌治疗可以降低某些女性乳腺癌复发的风险，而有效的预测生物标志物可以显著改善患者的治疗选择。

主要方法/材料/实验设计 ​

本研究为多中心的前瞻性-回顾性研究，纳入了来自“辅助他莫昔芬——提供更多?”（aTTom）试验的患者。具体方法如下：

  1. 患者选择：

    • 选择在aTTom试验中随机分配的、具有可用的福尔马林固定石蜡包埋（FFPE）肿瘤标本的患者。
    • 排除标准包括缺乏侵袭性肿瘤或组织样本不足。

  2. BCI测试：

    • 采用RT-PCR技术对FFPE样本进行基因表达分析，评估HOXB13/IL17BR比率（H/I）作为预测生物标志物。

  3. 激素受体状态确定：

    • 通过免疫组化（IHC）对ER和PR状态进行中心化评估，评估时盲法进行。

  4. 统计分析：

    • 使用Kaplan-Meier分析和Cox回归分析评估复发无事件间隔（RFI）作为主要终点。
    • 通过似然比检验评估延长内分泌治疗与BCI（H/I）之间的相互作用。
Mermaid diagram

关键结果和发现 ​

  • 在583名HR+、N+患者中，49%被分类为BCI（H/I）高表达组，显示出显著的延长治疗益处（HR: 0.35，P=0.027），相较于5年治疗，10年治疗的绝对风险降低为10.2%。
  • BCI（H/I）低表达组则未显示显著益处（HR: 1.07，P=0.768）。
  • BCI（H/I）水平与延长他莫昔芬治疗的益处成正相关。

主要结论/意义/创新性 ​

BCI（H/I）高表达组患者在延长内分泌治疗中获益显著，表明BCI作为预测生物标志物的有效性。这项研究为BCI在内分泌治疗中的临床应用提供了进一步的验证，强调了个体化治疗的重要性。

研究局限性和未来方向 ​

  • 本研究仅报告了N+患者的亚组数据，整体队列的样本收集仍在进行中。
  • 虽然研究中仅包含接受他莫昔芬治疗的绝经后女性，但BCI在其他抗雌激素治疗背景下的预测活性也得到验证。

未来的研究应继续探索BCI在不同治疗背景下的预测能力，以进一步优化乳腺癌患者的治疗选择。

参考文献 ​

  1. Comparison of the Performance of 6 Prognostic Signatures for Estrogen Receptor-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. - Ivana Sestak;Richard Buus;Jack Cuzick;Peter Dubsky;Ralf Kronenwett;Carsten Denkert;Sean Ferree;Dennis Sgroi;Catherine Schnabel;Frederick L Baehner;Elizabeth Mallon;Mitch Dowsett - JAMA oncology (2018)
  2. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. - E Senkus;S Kyriakides;S Ohno;F Penault-Llorca;P Poortmans;E Rutgers;S Zackrisson;F Cardoso; - Annals of oncology : official journal of the European Society for Medical Oncology (2015)
  3. Breast cancer index identifies early-stage estrogen receptor-positive breast cancer patients at risk for early- and late-distant recurrence. - Yi Zhang;Catherine A Schnabel;Brock E Schroeder;Piiha-Lotta Jerevall;Rachel C Jankowitz;Tommy Fornander;Olle Stål;Adam M Brufsky;Dennis Sgroi;Mark G Erlander - Clinical cancer research : an official journal of the American Association for Cancer Research (2013)
  4. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. - Hongchao Pan;Richard Gray;Jeremy Braybrooke;Christina Davies;Carolyn Taylor;Paul McGale;Richard Peto;Kathleen I Pritchard;Jonas Bergh;Mitch Dowsett;Daniel F Hayes; - The New England journal of medicine (2017)
  5. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. - Paul E Goss;James N Ingle;Silvana Martino;Nicholas J Robert;Hyman B Muss;Martine J Piccart;Monica Castiglione;Dongsheng Tu;Lois E Shepherd;Kathleen I Pritchard;Robert B Livingston;Nancy E Davidson;Larry Norton;Edith A Perez;Jeffrey S Abrams;David A Cameron;Michael J Palmer;Joseph L Pater - Journal of the National Cancer Institute (2005)
  6. Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial. - Mitch Dowsett;Craig Allred;Jill Knox;Emma Quinn;Janine Salter;Chris Wale;Jack Cuzick;Joan Houghton;Norman Williams;Elizabeth Mallon;Hugh Bishop;Ian Ellis;Denis Larsimont;Hironobu Sasano;Pauline Carder;Antonio Llombart Cussac;Fiona Knox;Valerie Speirs;John Forbes;Aman Buzdar - Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2008)
  7. Clinical use of biomarkers in breast cancer: Updated guidelines from the European Group on Tumor Markers (EGTM). - M J Duffy;N Harbeck;M Nap;R Molina;A Nicolini;E Senkus;F Cardoso - European journal of cancer (Oxford, England : 1990) (2017)
  8. Predictive value and clinical utility of centrally assessed ER, PgR, and Ki-67 to select adjuvant endocrine therapy for premenopausal women with hormone receptor-positive, HER2-negative early breast cancer: TEXT and SOFT trials. - Meredith M Regan;Olivia Pagani;Prudence A Francis;Gini F Fleming;Barbara A Walley;Roswitha Kammler;Patrizia Dell'Orto;Leila Russo;János Szőke;Franco Doimi;Laura Villani;Stefano Pizzolitto;Christian Öhlschlegel;Fausto Sessa;Vicente Peg Cámara;José Luis Rodríguez Peralto;Gaëtan MacGrogan;Marco Colleoni;Aron Goldhirsch;Karen N Price;Alan S Coates;Richard D Gelber;Giuseppe Viale; - Breast cancer research and treatment (2015)
  9. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. - Eleftherios P Mamounas;Jong-Hyeon Jeong;D Lawrence Wickerham;Roy E Smith;Patricia A Ganz;Stephanie R Land;Andrea Eisen;Louis Fehrenbacher;William B Farrar;James N Atkins;Eduardo R Pajon;Victor G Vogel;Joan F Kroener;Laura F Hutchins;André Robidoux;James L Hoehn;James N Ingle;Charles E Geyer;Joseph P Costantino;Norman Wolmark - Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2008)
  10. Adjuvant ovarian suppression in premenopausal breast cancer. - Prudence A Francis;Meredith M Regan;Gini F Fleming;István Láng;Eva Ciruelos;Meritxell Bellet;Hervé R Bonnefoi;Miguel A Climent;Gian Antonio Da Prada;Harold J Burstein;Silvana Martino;Nancy E Davidson;Charles E Geyer;Barbara A Walley;Robert Coleman;Pierre Kerbrat;Stefan Buchholz;James N Ingle;Eric P Winer;Manuela Rabaglio-Poretti;Rudolf Maibach;Barbara Ruepp;Anita Giobbie-Hurder;Karen N Price;Marco Colleoni;Giuseppe Viale;Alan S Coates;Aron Goldhirsch;Richard D Gelber; ; - The New England journal of medicine (2015)

引用本文的文献 ​

  1. Update Breast Cancer 2019 Part 4 - Diagnostic and Therapeutic Challenges of New, Personalised Therapies for Patients with Early Breast Cancer. - Florian Schütz;Peter A Fasching;Manfred Welslau;Andreas D Hartkopf;Achim Wöckel;Michael P Lux;Wolfgang Janni;Johannes Ettl;Diana Lüftner;Erik Belleville;Hans-Christian Kolberg;Friedrich Overkamp;Florin-Andrei Taran;Sara Y Brucker;Markus Wallwiener;Hans Tesch;Tanja N Fehm;Andreas Schneeweiss;Volkmar Müller - Geburtshilfe und Frauenheilkunde (2019)
  2. Breast cancer: are long-term and intermittent endocrine therapies equally effective? - Jutta Engel;Gabriele Schubert-Fritschle;Rebecca Emeny;Dieter Hölzel - Journal of cancer research and clinical oncology (2020)
  3. The Clinical Relevance and Function of Krüppel-Like Factor 16 in Breast Cancer. - Soyeon Bang;Junhong Li;Meiqin Zhang;Renjie Cui;Xingwen Wu;Zhaochen Xin;Duan Ma;Jin Zhang;Hongwei Zhang - Cancer management and research (2020)
  4. Endocrine Therapy in Early Breast Cancer. - Katja Krauss;Elmar Stickeler - Breast care (Basel, Switzerland) (2020)
  5. Prognostic and predictive parameters in breast pathology: a pathologist's primer. - Kimberly H Allison - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (2021)
  6. Clinical Implications of Serum 25-Hydroxyvitamin D Status after 5-Year Adjuvant Endocrine Therapy for Late Recurrence of Hormone Receptor-positive Breast Cancer. - Seung Taek Lim;Ye Won Jeon;Hongki Gwak;Young Jin Suh - Journal of breast cancer (2020)
  7. Epigenetics in Breast Cancer Therapy-New Strategies and Future Nanomedicine Perspectives. - Verona Buocikova;Ivan Rios-Mondragon;Eleftherios Pilalis;Aristotelis Chatziioannou;Svetlana Miklikova;Michal Mego;Karlis Pajuste;Martins Rucins;Naouale El Yamani;Eleonora Marta Longhin;Arkadij Sobolev;Muriel Freixanet;Victor Puntes;Aiva Plotniece;Maria Dusinska;Mihaela Roxana Cimpan;Alena Gabelova;Bozena Smolkova - Cancers (2020)
  8. The role of capecitabine-based neoadjuvant and adjuvant chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis. - Xingfa Huo;Jinming Li;Fuxing Zhao;Dengfeng Ren;Raees Ahmad;Xinyue Yuan;Feng Du;Jiuda Zhao - BMC cancer (2021)
  9. Genomic Assays in Node Positive Breast Cancer Patients: A Review. - Maroun Bou Zerdan;Maryam Ibrahim;Clara El Nakib;Rayan Hajjar;Hazem I Assi - Frontiers in oncology (2020)
  10. Advanced Approaches to Breast Cancer Classification and Diagnosis. - M Zubair;S Wang;N Ali - Frontiers in pharmacology (2020)

... (75 更多 篇文献)

© 2025 MaltSci 麦伴科研 - 我们用人工智能技术重塑科研