Update Mammakarzinom 2019 Teil 4 – diagnostische und therapeutische Herausforderungen neuer personalisierter Therapien für Patientinnen mit frühem Mammakarzinom

Zusammenfassung

Die Weiterentwicklung der Therapien für Frauen mit einem frühen Mammakarzinom schreitet deutlich langsamer voran als bei Patientinnen mit fortgeschrittenem Mammakarzinom und ist zudem zeitlich versetzt zu Entwicklungen beim metastasiertem Mammakarzinom. Trotzdem konnten in letzter Zeit deutliche Fortschritte verzeichnet werden. Diese Übersichtsarbeit fasst die jüngsten Entwicklungen vor dem Hintergrund der neuesten Publikationen und Fachkongresse zusammen. Für hormonrezeptorpositive Patientinnen sind neue Aspekte für die Dauer der Antihormontherapie und in Bezug auf den Nutzen von Multigentests veröffentlicht worden. Bei HER2-positiven Patientinnen wird der Stellenwert einer post-neoadjuvanten Therapie und eine Deeskalation der Therapie diskutiert. Bei Patientinnen mit tripel-negativem Mammakarzinom stellt sich die Frage, ob das Wissen um den biologischen Hintergrund einer Defizienz der homologen Rekombination (HRD) dabei hilft, neue Therapien für diesen Subtyp zu entwickeln. Insbesondere die „Nutzung“ einer BRCA1/2-Mutation oder des biologischen Merkmals HRD als potenzielles Therapiemotiv spielen dabei eine Rolle, den Stellenwert der Platintherapie und einer Therapie mit PARP-Inhibitoren zu spezifizieren.

Schlüsselwörter

Mammakarzinom - adjuvant - neoadjuvant - Chemotherapie - Antihormontherapie - Multigentests

• References/Literatur

• 1 Couch FJ, Hart SN, Sharma P. et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol 2015; 33: 304-311
• 2 Couch FJ, Kuchenbaecker KB, Michailidou K. et al. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer. Nat Commun 2016; 7: 11375
• 3 Couch FJ, Shimelis H, Hu C. et al. Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer. JAMA Oncol 2017; 3: 1190-1196
• 4 Garcia-Closas M, Couch FJ, Lindstrom S. et al. Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nat Genet 2013; 45: 392-398 398e1–398e2
• 5 Ghoussaini M, Fletcher O, Michailidou K. et al. Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nat Genet 2012; 44: 312-318
• 6 Michailidou K, Beesley J, Lindstrom S. et al. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer. Nat Genet 2015; 47: 373-380
• 7 Michailidou K, Hall P, Gonzalez-Neira A. et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet 2013; 45: 353-361 361e1–361e2
• 8 Michailidou K, Lindstrom S, Dennis J. et al. Association analysis identifies 65 new breast cancer risk loci. Nature 2017; 551: 92-94
• 9 Milne RL, Kuchenbaecker KB, Michailidou K. et al. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nat Genet 2017; 49: 1767-1778
• 10 Shimelis H, LaDuca H, Hu C. et al. Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing. J Natl Cancer Inst 2018;
• 11 Wu L, Shi W, Long J. et al. A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer. Nat Genet 2018;
• 12 Wunderle M, Olmes G, Nabieva N. et al. Risk, Prediction and Prevention of Hereditary Breast Cancer – Large-Scale Genomic Studies in Times of Big and Smart Data. Geburtsh Frauenheilk 2018; 78: 481-492
• 13 Stevens KN, Fredericksen Z, Vachon CM. et al. 19p13.1 is a triple-negative-specific breast cancer susceptibility locus. Cancer Res 2012; 72: 1795-1803
• 14 Stevens KN, Vachon CM, Lee AM. et al. Common breast cancer susceptibility loci are associated with triple-negative breast cancer. Cancer Res 2011; 71: 6240-6249
• 15 Vachon CM, Scott CG, Tamimi RM. et al. Joint association of mammographic density adjusted for age and body mass index and polygenic risk score with breast cancer risk. Breast Cancer Res 2019; 21: 68
• 16 Rudolph A, Song M, Brook MN. et al. Joint associations of a polygenic risk score and environmental risk factors for breast cancer in the Breast Cancer Association Consortium. Int J Epidemiol 2018;
• 17 Muranen TA, Greco D, Blomqvist C. et al. Genetic modifiers of CHEK2*1100delC-associated breast cancer risk. Genet Med 2017; 19: 599-603
• 18 Brouckaert O, Rudolph A, Laenen A. et al. Reproductive profiles and risk of breast cancer subtypes: a multi-center case-only study. Breast Cancer Res 2017; 19: 119
• 19 Barrdahl M, Rudolph A, Hopper JL. et al. Gene-environment interactions involving functional variants: Results from the Breast Cancer Association Consortium. Int J Cancer 2017; 141: 1830-1840
• 20 Schmidt MK, Hogervorst F, van Hien R. et al. Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers. J Clin Oncol 2016; 34: 2750-2760
• 21 Vachon CM, Pankratz VS, Scott CG. et al. The contributions of breast density and common genetic variation to breast cancer risk. J Natl Cancer Inst 2015;
• 22 Rudolph A, Milne RL, Truong T. et al. Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors. Int J Cancer 2015; 136: E685-E696
• 23 Rudolph A, Fasching PA, Behrens S. et al. A comprehensive evaluation of interaction between genetic variants and use of menopausal hormone therapy on mammographic density. Breast Cancer Res 2015; 17: 110
• 24 Mavaddat N, Pharoah PD, Michailidou K. et al. Prediction of breast cancer risk based on profiling with common genetic variants. J Natl Cancer Inst 2015;
• 25 Jamshidi M, Fagerholm R, Khan S. et al. SNP-SNP interaction analysis of NF-kappaB signaling pathway on breast cancer survival. Oncotarget 2015; 6: 37979-37994
• 26 Milne RL, Herranz J, Michailidou K. et al. A large-scale assessment of two-way SNP interactions in breast cancer susceptibility using 46,450 cases and 42,461 controls from the breast cancer association consortium. Hum Mol Genet 2014; 23: 1934-1946
• 27 Nickels S, Truong T, Hein R. et al. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors. PLoS Genet 2013; 9: e1003284
• 28 Milne RL, Gaudet MM, Spurdle AB. et al. Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study. Breast Cancer Res 2010; 12: R110
• 29 Vachon CM, Scott CG, Fasching PA. et al. Common breast cancer susceptibility variants in LSP1 and RAD51L1 are associated with mammographic density measures that predict breast cancer risk. Cancer Epidemiol Biomarkers Prev 2012; 21: 1156-1166
• 30 Mavaddat N, Michailidou K, Dennis J. et al. Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes. Am J Hum Genet 2018;
• 31 Wöckel A, Lux MP, Janni W. et al. 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. Geburtsh Frauenheilk 2018; 78: 1110-1118
• 32 Hartkopf AD, Müller V, Wöckel A. et al. Update Breast Cancer 2019 Part 1 – Implementation of Study Results of Novel Study Designs in Clinical Practice in Patients with Early Breast Cancer. Geburtsh Frauenheilk 2019; 79: 256-267
• 33 Heusinger K, Jud SM, Haberle L. et al. Association of mammographic density with the proliferation marker Ki-67 in a cohort of patients with invasive breast cancer. Breast Cancer Res Treat 2012; 135: 885-892
• 34 Heusinger K, Jud SM, Haberle L. et al. Association of mammographic density with hormone receptors in invasive breast cancers: results from a case-only study. Int J Cancer 2012; 131: 2643-2649
• 35 Sigl V, Owusu-Boaitey K, Joshi PA. et al. RANKL/RANK control Brca1 mutation. Cell Res 2016; 26: 761-774
• 36 Sigl V, Owusu-Boaitey K, Joshi PA. et al. RANKL/RANK control Brca1 mutation-driven mammary tumors. Cell Res 2016; 26: 761-774
• 37 Sigl V, Jones LP, Penninger JM. RANKL/RANK: from bone loss to the prevention of breast cancer. Open Biol 2016;
• 38 ABCSG. Schon drei Frauen randomisiert! 2019. Online: https://wwwabcsgorg/abcsg-50-brca-p-schon-drei-frauen-randomisiert/ last access: 24.07.2019
• 39 Fasching PA, Hartkopf AD, Gass P. et al. Efficacy of neoadjuvant pertuzumab in addition to chemotherapy and trastuzumab in routine clinical treatment of patients with primary breast cancer: a multicentric analysis. Breast Cancer Res Treat 2019; 173: 319-328
• 40 Gianni L, Pienkowski T, Im YH. et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012; 13: 25-32
• 41 Verma S, Miles D, Gianni L. et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012; 367: 1783-1791
• 42 von Minckwitz G, Huang CS, Mano MS. et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med 2018;
• 43 Hurvitz SA, Martin M, Symmans WF. et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol 2018; 19: 115-126
• 44 Hurvitz SA, Martin M, Jung KH. et al. Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study. J Clin Oncol 2019;
• 45 Bergh JCS, Andersson A, Bjohle J. et al. Docetaxel, trastuzumab, pertuzumab versus trastuzumab emtansine as neoadjuvant treatment of HER2-positive breast cancer: Results from the Swedish PREDIX HER2 trial identifying a new potential de-escalation standard?. J Clin Oncol 2019;
• 46 Fasching PA, Gass P, Hein A. Neoadjuvant Treatment of Breast Cancer – Advances and Limitations. Breast Care (Basel) 2016; 11: 313-314
• 47 Fernandez-Gonzalez S, Falo C, Pla MJ. et al. The Shift From Sentinel Lymph Node Biopsy Performed Either Before or After Neoadjuvant Systemic Therapy in the Clinical Negative Nodes of Breast Cancer Patients. Results, and the Advantages and Disadvantages of Both Procedures. Clin Breast Cancer 2018; 18: 71-77
• 48 Fasching PA, Heusinger K, Haeberle L. et al. Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer 2011; 11: 486
• 49 Robertson JFR, Dowsett M, Bliss JM. et al. Peri‐operative Aromatase Inhibitor treatment in determining or predicting Longterm Outcome in Early Breast Cancer-the POETIC* Trial (CRUK/07/015) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5–9; San Antonio, TX Philadelphia (PA): AACR. Cancer Res 2018; 78: Abstr.. GS1-03
• 50 von Minckwitz G, Untch M, Blohmer JU. et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 2012; 30: 1796-1804
• 51 Cortazar P, Zhang L, Untch M. et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014; 384: 164-172
• 52 Schneeweiss A, Chia S, Hickish T. et al. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer 2018; 89: 27-35
• 53 Untch M, Fasching PA, Konecny GE. et al. Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol 2011; 29: 3351-3357
• 54 Schneeweiss A, Loibl S, Mamounas EP. et al. Patient-reported outcomes (PROs) from KATHERINE: A phase III study of adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab (H) in patients (pts) with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer. J Clin Oncol 2019;
• 55 Liedtke C, Jackisch C, Thill M. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2018. Breast Care (Basel) 2018; 13: 196-208
• 56 Thill M, Liedtke C, Muller V. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Advanced and Metastatic Breast Cancer: Update 2018. Breast Care (Basel) 2018; 13: 209-215
• 57 Davies C, Pan H, Godwin J. et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 2013; 381: 805-816
• 58 Gnant M, Steger G, Greil R. et al. A prospective randomized multi-center phase-III trial of additional 2 versus additional 5 years of Anastrozole after initial 5 years of adjuvant endocrine therapy – results from 3,484 postmenopausal women in the ABCSG-16 trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5–9; San Antonio, TX Philadelphia (PA): AACR. Cancer Res 2018; 78: Abstr.. GS3-01
• 59 Del Mastro L, Mansutti M, Bisagni G. et al. Benefit from letrozole as extended adjuvant therapy after sequential endocrine therapy: A randomized, phase III study of Gruppo Italiano Mammella (GIM). J Clin Oncol 2019;
• 60 Bartlett J, Sgroi D, Treuner K. et al. Trans-aTTom: Breast Cancer Index for prediction of endocrine benefit and late distant recurrence (DR) in patients with HR+ breast cancer treated in the adjuvant tamoxifen–To offer more? (aTTom) trial. J Clin Oncol 2019;
• 61 Stearns V. Adjuvant Endocrine Therapy: Selecting the Optimal Path. 2019 ASCO Annual Meeting, Chicago 2019. Online: https://meetinglibrary.asco.org/record/175033/video last access: 30.06.2019
• 62 Sparano JA, Gray RJ, Makower DF. et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med 2018; 379: 111-121
• 63 Sparano JA, Gray RJ, Makower DF. et al. Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. N Engl J Med 2015; 373: 2005-2014
• 64 Sparano JA, Gray RJ, Makower DF. et al. Impact of clinical risk category on prognosis and prediction of chemotherapy benefit in early breast cancer (EBC) by age and the 21-gene recurrence score (RS) in TAILORx. J Clin Oncol 2019;
• 65 Fasching PA, Schneeweiss A, Kolberg HC. et al. Translational highlights in breast cancer research and treatment: recent developments with clinical impact. Curr Opin Obstet Gynecol 2019; 31: 67-75
• 66 Im SA, Lu YS, Bardia A. et al. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med 2019;
• 67 Novartis. Novartis Kisqali significantly prolongs life in women with HR+/HER2- advanced breast cancer now in two distinct Phase III trials. Novartis Press Release; 2019 Online: https://www.novartis.com/news/media-releases/novartis-kisqali-significantly-prolongs-life-women-hrher2-advanced-breast-cancer-now-two-distinct-phase-iii-trials last access: 03.08.2019
• 68 Slamon DJ, Neven P, Chia S. et al. Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3. J Clin Oncol 2018;
• 69 Nabieva N, Kellner S, Fehm T. et al. Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients. Ann Oncol 2018; 29: 186-192
• 70 Nabieva N, Fehm T, Haberle L. et al. Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study. Eur J Cancer 2018; 96: 82-90
• 71 Basch EM, Deal AM, Dueck AC. et al. Overall survival results of a randomized trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. J Clin Oncol 2017; 35 (Suppl.) Abstr.. LBA2
• 72 Hartkopf AD, Graf J, Simoes E. et al. Electronic-Based Patient-Reported Outcomes: Willingness, Needs, and Barriers in Adjuvant and Metastatic Breast Cancer Patients. JMIR Cancer 2017; 3: e11
• 73 Tresp V, Overhage JM, Bundschus M. et al. Going Digital: A Survey on Digitalization and Large-Scale Data Analytics in Healthcare. P IEEE 2016; 104: 2180-2206
• 74 Wallwiener M, Matthies L, Simoes E. et al. Reliability of an e-PRO Tool of EORTC QLQ-C30 for Measurement of Health-Related Quality of Life in Patients With Breast Cancer: Prospective Randomized Trial. J Med Internet Res 2017; 19: e322
• 75 Katzorke N, Rack BK, Haeberle L. et al. Prognostic value of HER2 on breast cancer survival. J Clin Oncol 2013;
• 76 Untch M, Jackisch C, Schneeweiss A. et al. NAB-Paclitaxel Improves Disease-Free Survival in Early Breast Cancer: GBG 69-GeparSepto. J Clin Oncol 2019;
• 77 Wurfel F, Erber R, Huebner H. et al. TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients – First Results on the Influence of Tumor-Infiltrating Lymphocytes. Breast Care (Basel) 2018; 13: 8-14
• 78 Schneeweiss A, Jackisch C, Schmatloch S. et al. Survival analysis of the prospectively randomized phase III GeparSepto trial comparing neoadjuvant chemotherapy with weekly nab-paclitaxel with solvent-based paclitaxel followed by anthracycline-cyclosphosphamide for patients with early breast cancer – GBG69 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5–9; San Antonio, TX Philadelphia (PA): AACR. Cancer Res 2018; 78: Abstr.. GS3-05
• 79 Gass P, Lux MP, Rauh C. et al. Prediction of pathological complete response and prognosis in patients with neoadjuvant treatment for triple-negative breast cancer. BMC Cancer 2018; 18: 1051
• 80 Hahnen E, Lederer B, Hauke J. et al. Germline Mutation Status, Pathological Complete Response, and Disease-Free Survival in Triple-Negative Breast Cancer: Secondary Analysis of the GeparSixto Randomized Clinical Trial. JAMA Oncol 2017; 3: 1378-1385
• 81 Untch M, von Minckwitz G, Konecny GE. et al. PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer–outcome on prognosis. Ann Oncol 2011; 22: 1999-2006
• 82 Untch M, Fasching PA, Konecny GE. et al. PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel and CMF versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel ± darbepoetin alfa in primary breast cancer–results at the time of surgery. Ann Oncol 2011; 22: 1988-1998
• 83 Fasching PA, Loibl S, Hu C. et al. 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. J Clin Oncol 2018;
• 84 Sikov WM, Polley M-Y, Twohy E. et al. CALGB (Alliance) 40603: Long-term outcomes (LTOs) after neoadjuvant chemotherapy (NACT) +/- carboplatin (Cb) and bevacizumab (Bev) in triple-negative breast cancer (TNBC). J Clin Oncol 2019;
• 85 von Minckwitz G, Schneeweiss A, Loibl S. et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol 2014; 15: 747-756
• 86 Sikov WM, Berry DA, Perou CM. et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol 2015; 33: 13-21
• 87 Loibl S, OʼShaughnessy J, Untch M. et al. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol 2018; 19: 497-509
• 88 Scully R, Panday A, Elango R. et al. DNA double-strand break repair-pathway choice in somatic mammalian cells. Nature Reviews Molecular Cell Biology 2019;
• 89 Sharma P, Barlow WE, Godwin AK. et al. Impact of homologous recombination deficiency biomarkers on outcomes in patients with triple-negative breast cancer treated with adjuvant doxorubicin and cyclophosphamide (SWOG S9313). Ann Oncol 2018; 29: 654-660
• 90 Mayer EL, Abramson VG, Jankowitz RC. et al. TBCRC030: A randomized phase II study of preoperative cisplatin versus paclitaxel in TNBC–Evaluating the homologous recombination deficiency (HRD) biomarker. J Clin Oncol 2019; 37 (Suppl.) Abstr.. 507
• 91 Loibl S, Weber KE, Timms KM. et al. Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response – final results from GeparSixto. Ann Oncol 2018;
• 92 Tutt A, Tovey H, Cheang MCU. et al. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med 2018; 24: 628-637
• 93 Fasching P, Jackisch C, Rhiem K. et al. GeparOLA: A randomized phase II trial to assess the efficacy of paclitaxel and olaparib in comparison to paclitaxel/carboplatin followed by epirubicin/cyclophosphamide as neoadjuvant chemotherapy in patients (pts) with HER2-negative early breast cancer (BC) and homologous recombination deficiency (HRD). J Clin Oncol 2019; 37 (Suppl.) Abstr.. 506
• 94 Denkert C, von Minckwitz G, Darb-Esfahani S. et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol 2018; 19: 40-50
• 95 Schmid P, Adams S, Rugo HS. et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med 2018; 379: 2108-2121
• 96 Merck. Merckʼs KEYTRUDA® (pembrolizumab) in Combination with Chemotherapy Met Primary Endpoint of Pathological Complete Response (pCR) in Pivotal Phase 3 KEYNOTE-522 Trial in Patients with Triple-Negative Breast Cancer (TNBC). 2019. Online: https://www.mrknewsroom.com/news-release/oncology/mercks-keytruda-pembrolizumab-combination-chemotherapy-met-primary-endpoint-pa last access: 29.07.2019
• 97 Schmid P, Cortes J, Bergh JCS. et al. KEYNOTE-522: Phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs. placebo + chemo as neoadjuvant therapy followed by pembro vs. placebo as adjuvant therapy for triple-negative breast cancer (TNBC). J Clin Oncol 2018;
• 98 Clinicaltrials.gov. Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs. Placebo Plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs. Placebo as Adjuvant Therapy in Participants With Triple Negative Breast Cancer (TNBC) (MK-3475-522/KEYNOTE-522). Online: https://clinicaltrialsgov/ct2/show/NCT03036488%202019 last access: 24.07.2019
• 99 ABCSG. ABCSG 50/BRCA-P Übersicht. Online: https://www.abcsg.org/abcsg-studien/abcsg-studien-open/abcsg-studien-mammakarzinom-status-open/abcsg-50-brca-p/abcsg-50-brca-p-uebersicht/ last access: 24.07.2019