Literature DB >> 29791287

BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study.

Peter A Fasching1, Sibylle Loibl1, Chunling Hu1, Steven N Hart1, Hermela Shimelis1, Raymond Moore1, Christian Schem1, Hans Tesch1, Michael Untch1, Jörn Hilfrich1, Mahdi Rezai1, Bernd Gerber1, Serban Dan Costa1, Jens-Uwe Blohmer1, Tanja Fehm1, Jens Huober1, Cornelia Liedtke1, Richard M Weinshilboum1, Liewei Wang1, James N Ingle1, Volkmar Müller1, Valentina Nekljudova1, Karsten E Weber1, Brigitte Rack1, Matthias Rübner1, Gunter von Minckwitz1, Fergus J Couch1.   

Abstract

Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane-containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3% of patients with TNBC. Overall, patients with mutations had a pCR rate of 50%, compared with 31.5% in patients without a mutation (odds ratio [OR], 2.17; 95% CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5% for BRCA1/2 mutation carriers and 35.6% for those without mutations (OR, 2.90; 95% CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95% CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95% CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane-based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations.

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Year:  2018        PMID: 29791287      PMCID: PMC6067803          DOI: 10.1200/JCO.2017.77.2285

Source DB:  PubMed          Journal:  J Clin Oncol        ISSN: 0732-183X            Impact factor:   44.544


  30 in total

1.  dbSNP: the NCBI database of genetic variation.

Authors:  S T Sherry; M H Ward; M Kholodov; J Baker; L Phan; E M Smigielski; K Sirotkin
Journal:  Nucleic Acids Res       Date:  2001-01-01       Impact factor: 16.971

2.  Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial.

Authors:  Harry D Bear; Gong Tang; Priya Rastogi; Charles E Geyer; Qing Liu; André Robidoux; Luis Baez-Diaz; Adam M Brufsky; Rita S Mehta; Louis Fehrenbacher; James A Young; Francis M Senecal; Rakesh Gaur; Richard G Margolese; Paul T Adams; Howard M Gross; Joseph P Costantino; Soonmyung Paik; Sandra M Swain; Eleftherios P Mamounas; Norman Wolmark
Journal:  Lancet Oncol       Date:  2015-08-10       Impact factor: 41.316

3.  Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes.

Authors:  Gunter von Minckwitz; Michael Untch; Jens-Uwe Blohmer; Serban D Costa; Holger Eidtmann; Peter A Fasching; Bernd Gerber; Wolfgang Eiermann; Jörn Hilfrich; Jens Huober; Christian Jackisch; Manfred Kaufmann; Gottfried E Konecny; Carsten Denkert; Valentina Nekljudova; Keyur Mehta; Sibylle Loibl
Journal:  J Clin Oncol       Date:  2012-04-16       Impact factor: 44.544

Review 4.  Hypoxia-induced genetic instability--a calculated mechanism underlying tumor progression.

Authors:  L Eric Huang; Ranjit S Bindra; Peter M Glazer; Adrian L Harris
Journal:  J Mol Med (Berl)       Date:  2006-12-20       Impact factor: 4.599

5.  Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial.

Authors:  Michael Untch; Sibylle Loibl; Joachim Bischoff; Holger Eidtmann; Manfred Kaufmann; Jens-Uwe Blohmer; Jörn Hilfrich; Dirk Strumberg; Peter A Fasching; Rolf Kreienberg; Hans Tesch; Claus Hanusch; Bernd Gerber; Mahdi Rezai; Christian Jackisch; Jens Huober; Thorsten Kühn; Valentina Nekljudova; Gunter von Minckwitz
Journal:  Lancet Oncol       Date:  2012-01-17       Impact factor: 41.316

6.  Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy.

Authors:  Tomasz Byrski; Jacek Gronwald; Tomasz Huzarski; Ewa Grzybowska; Magdalena Budryk; Malgorzata Stawicka; Tomasz Mierzwa; Marek Szwiec; Rafal Wisniowski; Monika Siolek; Rebecca Dent; Jan Lubinski; Steven Narod
Journal:  J Clin Oncol       Date:  2009-12-14       Impact factor: 44.544

7.  Neo-adjuvant doxorubicin and cyclophosphamide followed by paclitaxel in triple-negative breast cancer among BRCA1 mutation carriers and non-carriers.

Authors:  Shani Paluch-Shimon; Eitan Friedman; Raanan Berger; Moshe Papa; Maya Dadiani; Neil Friedman; Moshe Shabtai; Dov Zippel; Mordechai Gutman; Talia Golan; Ady Yosepovich; Raphael Catane; Tami Modiano; Bella Kaufman
Journal:  Breast Cancer Res Treat       Date:  2016-04-25       Impact factor: 4.872

8.  Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44-GeparQuinto)†.

Authors:  G von Minckwitz; S Loibl; M Untch; H Eidtmann; M Rezai; P A Fasching; H Tesch; H Eggemann; I Schrader; K Kittel; C Hanusch; J Huober; C Solbach; C Jackisch; G Kunz; J U Blohmer; M Hauschild; T Fehm; V Nekljudova; B Gerber
Journal:  Ann Oncol       Date:  2014-09-15       Impact factor: 32.976

9.  Germline Mutation Status, Pathological Complete Response, and Disease-Free Survival in Triple-Negative Breast Cancer: Secondary Analysis of the GeparSixto Randomized Clinical Trial.

Authors:  Eric Hahnen; Bianca Lederer; Jan Hauke; Sibylle Loibl; Sandra Kröber; Andreas Schneeweiss; Carsten Denkert; Peter A Fasching; Jens U Blohmer; Christian Jackisch; Stefan Paepke; Bernd Gerber; Sherko Kümmel; Christian Schem; Guido Neidhardt; Jens Huober; Kerstin Rhiem; Serban Costa; Janine Altmüller; Claus Hanusch; Holger Thiele; Volkmar Müller; Peter Nürnberg; Thomas Karn; Valentina Nekljudova; Michael Untch; Gunter von Minckwitz; Rita K Schmutzler
Journal:  JAMA Oncol       Date:  2017-10-01       Impact factor: 31.777

10.  CSN and CAVA: variant annotation tools for rapid, robust next-generation sequencing analysis in the clinical setting.

Authors:  Márton Münz; Elise Ruark; Anthony Renwick; Emma Ramsay; Matthew Clarke; Shazia Mahamdallie; Victoria Cloke; Sheila Seal; Ann Strydom; Gerton Lunter; Nazneen Rahman
Journal:  Genome Med       Date:  2015-07-28       Impact factor: 11.117

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  31 in total

1.  Reply to the Correspondence by Untch et al. "Concerning Dediu M, Zielinski C: A Proposal to Redefine Pathologic Complete Remission as Endpoint following Neoadjuvant Chemotherapy in Early Breast Cancer" [Breast Care 2019; DOI 10.1159/000500624].

Authors:  Mircea Dediu; Christoph Zielinski
Journal:  Breast Care (Basel)       Date:  2019-08-29       Impact factor: 2.860

2.  Phase II Trial of Neoadjuvant Carboplatin and Nab-Paclitaxel in Patients with Triple-Negative Breast Cancer.

Authors:  Yuan Yuan; Jin Sun Lee; Susan E Yost; Sierra Min Li; Paul H Frankel; Christopher Ruel; Daniel Schmolze; Kim Robinson; Aileen Tang; Norma Martinez; Daphne Stewart; James Waisman; Laura Kruper; Veronica Jones; Andrea Menicucci; Sahra Uygun; Erin Yoder; Bastiaan van der Baan; John H Yim; Christina Yeon; George Somlo; Joanne Mortimer
Journal:  Oncologist       Date:  2020-11-08

3.  Mutations in BRCA1/2 and Other Panel Genes in Patients With Metastatic Breast Cancer -Association With Patient and Disease Characteristics and Effect on Prognosis.

Authors:  Peter A Fasching; Siddhartha Yadav; Chunling Hu; Marius Wunderle; Lothar Häberle; Steven N Hart; Matthias Rübner; Eric C Polley; Kun Y Lee; Rohan D Gnanaolivu; Peyman Hadji; Hanna Hübner; Hans Tesch; Johannes Ettl; Friedrich Overkamp; Michael P Lux; Arif B Ekici; Bernhard Volz; Sabrina Uhrig; Diana Lüftner; Markus Wallwiener; Volkmar Müller; Erik Belleville; Michael Untch; Hans-Christian Kolberg; Matthias W Beckmann; André Reis; Arndt Hartmann; Wolfgang Janni; Pauline Wimberger; Florin-Andrei Taran; Tanja N Fehm; Diethelm Wallwiener; Sara Y Brucker; Andreas Schneeweiss; Andreas D Hartkopf; Fergus J Couch
Journal:  J Clin Oncol       Date:  2021-03-29       Impact factor: 44.544

4.  Dynamic contrast-enhanced breast MRI features correlate with invasive breast cancer angiogenesis.

Authors:  Jennifer Xiao; Habib Rahbar; Daniel S Hippe; Mara H Rendi; Elizabeth U Parker; Neal Shekar; Michael Hirano; Kevin J Cheung; Savannah C Partridge
Journal:  NPJ Breast Cancer       Date:  2021-04-16

5.  Breast MRI texture analysis for prediction of BRCA-associated genetic risk.

Authors:  Georgia Vasileiou; Maria J Costa; Christopher Long; Iris R Wetzler; Juliane Hoyer; Cornelia Kraus; Bernt Popp; Julius Emons; Marius Wunderle; Evelyn Wenkel; Michael Uder; Matthias W Beckmann; Sebastian M Jud; Peter A Fasching; Alexander Cavallaro; André Reis; Matthias Hammon
Journal:  BMC Med Imaging       Date:  2020-07-29       Impact factor: 1.930

6.  Update Breast Cancer 2018 (Part 3) - Genomics, Individualized Medicine and Immune Therapies - in the Middle of a New Era: Prevention and Treatment Strategies for Early Breast Cancer.

Authors:  Achim Wöckel; Michael P Lux; Wolfgang Janni; Andreas D Hartkopf; Naiba Nabieva; Florin-Andrei Taran; Friedrich Overkamp; Peyman Hadji; Hans Tesch; Johannes Ettl; Diana Lüftner; Volkmar Müller; Manfred Welslau; Erik Belleville; Sara Y Brucker; Florian Schütz; Peter A Fasching; Tanja N Fehm; Andreas Schneeweiss; Hans-Christian Kolberg
Journal:  Geburtshilfe Frauenheilkd       Date:  2018-11-26       Impact factor: 2.915

Review 7.  Optimal Systemic Treatment for Early Triple-Negative Breast Cancer.

Authors:  Jenny Furlanetto; Sibylle Loibl
Journal:  Breast Care (Basel)       Date:  2020-06-02       Impact factor: 2.860

Review 8.  Triple-negative breast cancer: new treatment strategies in the era of precision medicine.

Authors:  Song-Yang Wu; Hai Wang; Zhi-Ming Shao; Yi-Zhou Jiang
Journal:  Sci China Life Sci       Date:  2020-08-11       Impact factor: 6.038

9.  Protein Signature Predicts Response to Neoadjuvant Treatment With Chemotherapy and Bevacizumab in HER2-Negative Breast Cancers.

Authors:  Mads H Haugen; Ole Christian Lingjærde; Ingrid Hedenfalk; Øystein Garred; Elin Borgen; Niklas Loman; Thomas Hatschek; Anne-Lise Børresen-Dale; Bjørn Naume; Gordon B Mills; Gunhild M Mælandsmo; Olav Engebraaten
Journal:  JCO Precis Oncol       Date:  2021-01-28

10.  Influence of Family History of Breast or Ovarian Cancer on Pathological Complete Response and Long-Term Prognosis in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

Authors:  Marius Wunderle; Lothar Häberle; Alexander Hein; Sebastian M Jud; Michael P Lux; Carolin C Hack; Julius Emons; Felix Heindl; Naiba Nabieva; Christian R Loehberg; Rüdiger Schulz-Wendtland; Arndt Hartmann; Matthias W Beckmann; Peter A Fasching; Paul Gass
Journal:  Breast Care (Basel)       Date:  2020-07-01       Impact factor: 2.268

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