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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

2400 - Germline mutation status and therapy response in patients with triple-negative breast cancer (TNBC): Results of the GeparOcto study

Date

22 Oct 2018

Session

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

Topics

Genetic Testing and Counselling;  Genetic and Genomic Testing

Tumour Site

Breast Cancer

Presenters

Esther Pohl

Citation

Annals of Oncology (2018) 29 (suppl_8): viii58-viii86. 10.1093/annonc/mdy270

Authors

E. Pohl1, A. Schneeweiss2, J. Hauke1, V. Moebus3, J. Furlanetto4, C. Denkert5, P.A. Fasching6, C. Hanusch7, H. Tesch8, N. Weber-Lassalle1, V. Müller9, K. Rhiem1, M. Untch10, K. Luebbe11, B. Lederer4, C. Jackisch12, V. Nekljudova4, R.K. Schmutzler1, E. Hahnen1, S. Loibl4

Author affiliations

  • 1 Center For Familial Breast And Ovarian Cancer And Center For Integrated Oncology (cio), Medical Faculty, University of Cologne and University Hospital Cologne, 50931 - Cologne/DE
  • 2 National Center For Tumor Diseases, University of Heidelberg, 69115 - Heidelberg/DE
  • 3 Department Of Gynecology And Obstetrics, Klinikum Frankfurt Höchst, Academic Hospital of the Goethe University Frankfurt, Frankfurt/DE
  • 4 Gbg, German Breast Group Forschungs GmbH, 63263 - Neu-Isenburg/DE
  • 5 Institute Of Pathology, Charité - Universitätsmedizin Berlin, 10117 - Berlin/DE
  • 6 Department Of Gynecology And Obstetrics, University Hospital Erlangen, 91054 - Erlangen/DE
  • 7 Frauenklinik, Rotkreuzklinikum, Munich/DE
  • 8 Hämatologisch-onkologische Gemeinschaftspraxis, Bethanien-Krankenhaus, Frankfurt/DE
  • 9 Department Of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg/DE
  • 10 Department Of Gynecology And Obstetrics, Helios Klinikum Berlin-Buch, Berlin/DE
  • 11 Breast Center, Diakovere Henriettenstift, Hannover/DE
  • 12 Department Of Obstetrics And Gynecology, Sana Klinikum Offenbach GmbH, 63069 - Offenbach/DE

Resources

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Abstract 2400

Background

The phase III neoadjuvant GeparOcto trial (NCT02125344) randomized patients with triple negative breast cancer (TNBC) to receive treatment with intensified dose-dense epirubicin (E), paclitaxel (P), and cyclophosphamide (C; iddEPC) or weekly paclitaxel/liposomal doxorubicin (PM), plus carboplatin (Cb). Data on germline mutational analysis of patients with TNBC and the correlation with pathological complete response (pCR ypT0/is ypN0) were analysed.

Methods

NGS-based germline mutational analysis of BRCA1/2 and further 16 BC predisposition or candidate predisposition genes was carried out in 393 patients (iddEPC n = 194, PMCb n = 199). Deleterious (IARC class 4/5) variants were validated by Sanger sequencing. Detection of copy number variations (CNV) was carried out using an in-house CNV detection tool and established open access tools. Validation of CNVs was performed by either multiplex ligation-dependent probe amplification or real-time PCR.

Results

Overall, 69 of 393 (17.6%) patients carry pathogenic mutations in the BRCA1/2 genes. In 324 BRCA1/2-negative patients, 30 patients carry mutations in at least one of the 16 further analysed genes (9.3%). Of those, two patients carry mutations in two genes (ATM/CHEK2, PALB2/XRCC2) and 28 carry mutations in one gene (n = 2 BARD1, n = 5 BRIP1, n = 1 CHEK2, n = 9 FANCM, n = 1 NBN, n = 8 PALB2, n = 1 RAD50, n = 1 RAD51C); no mutations were found in CDH1, MRE11A, PTEN, RAD51D, STK11, and TP53). Overall patients with a BRCA1/2 mutation had a pCR of 69.6% vs 46.0% without a mutation (p < 0.001). In the iddETC group, patients with a BRCA1/2 mutation had a pCR of 64.7% vs 45.0% without a mutation (p = 0.040); in the PMCb arm, patients with a BRCA1/2 mutation had a pCR of 74.3% vs 47.0% without a mutation (p = 0.005).

Conclusions

Our data confirm that BRCA1/2 germline mutations represent a predictive biomarker for the achievement of pCR following neoadjuvant anthracycline-taxane-containing chemotherapy for TNBC.

Clinical trial identification

NCT02125344.

Legal entity responsible for the study

German Breast Group (GBG).

Funding

German Breast Group (GBG).

Editorial Acknowledgement

Disclosure

A. Schneeweiss: Honoraria: Roche, Celgene, AstraZeneca, Novartis, and Pfizer during the past 2 years. C. Hanusch: Consulting or advisory role: Novartis, Roche, Amgen, and Celgene during the past 2 years; Speakers’ bureau: Novartis, Roche, Amgen, Pfizer, and Celgene during the past 2 years. V. Müller: Honoraria: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, Novartis, Roche, and Teva during the past two years; Consulting or advisory role: Hexal, Roche, Pfizer, Amgen, Daiichi Sankyo, Nektar, and Eisai during the past 2 years; Travel, accommodation, or other expenses paid or reimbursed: Roche and Pfizer during the past 2 years. K. Luebbe: Consulting or advisory role: Roche and Novartis during the past 2 years. S. Loibl: Honoraria: Pfizer and Roche during the past 2 years (institution); Consulting or advisory role: Novartis, Pfizer, Roche, and SeaGen during the past 2 years (institution); Research project funding: Abbvie, Amgen, AstraZeneca, Celgene Novartis, Pfizer, Roche, SeaGen, Teva, and Vifor during the past 2 years (institution). All other authors have declared no conflicts of interest.

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