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DOI: 10.1055/s-0043-122885
Update Breast Cancer 2017 – Implementation of Novel Therapies
Article in several languages: English | deutschPublication History
received 04 November 2017
revised 13 November 2017
accepted 13 November 2017
Publication Date:
18 December 2017 (online)
![](https://www.thieme-connect.de/media/gebfra/201712/lookinside/thumbnails/10-1055-s-0043-122885_gf5099452_en-1.jpg)
Abstract
In recent years, numerous new therapy options for patients with breast cancer have been developed in clinical studies, with some options already approved for routine treatment. As the speed at which innovations are introduced increases, the importance of conferences also increases, as conferences are where the data underpinning new therapies are usually presented for the first time. This review looks at publications of the ASCO (American Society of Clinical Oncology) and ESMO (European Society of Medical Oncology) conferences in 2017, summarizes them and evaluates them in the context of existing data. The focus is on new insights for neoadjuvant therapy and new treatment options in the metastatic setting, such as the use of CDK4/6 inhibitors or PARP inhibitors. The first results of treatments with checkpoint inhibitors are presented. With the patent expiry of trastuzumab, a number of study results for trastuzumab biosimilars have also been published. The digitization of patient care provides the first results on quality of life and prognosis of patients with advanced cancer. Digital communications between patients and physicians are being evaluated in several studies in Germany. As the discussion about patient-relevant endpoints for patients in the metastatic setting continues, overall survival rates from studies of big endocrine-based therapies are urgently needed. Preliminary analyses of small study cohorts offer initial insights. In the context of improving patient care, in the coming years, questions will center on which patients particularly benefit from certain therapies and which patients need particular protection from specific side effects. Questions about these predictors are raised in many scientific projects as attention increasingly focuses on this topic.
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References/Literatur
- 1 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
- 2 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
- 3 Paluch-Shimon S, Friedman E, Berger R. et al. Neo-adjuvant doxorubicin and cyclophosphamide followed by paclitaxel in triple-negative breast cancer among BRCA1 mutation carriers and non-carriers. Breast Cancer Res Treat 2016; 157: 157-165
- 4 Huober JB, McCormick Holmes E, Baselga J. et al. Survival outcomes of the NeoALTTO study: updated results of a randomized multicenter phase III neoadjuvant trial. J Clin Oncol 2017; 35 (Suppl.) Abstr.. 512
- 5 Baselga J, Bradbury I, Eidtmann H. et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 2012; 379: 633-640
- 6 Untch M, Loibl S, Bischoff J. et al. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol 2012; 13: 135-144
- 7 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
- 8 Untch M, Schneeweiss A, Salat C. et al. Long-term survival analysis of the randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative (TNBC) and HER2-positive early breast cancer (GeparSixto). Ann Oncol 2017; 28 (Suppl. 05) v43-v67 Abstr. 163PD
- 9 Schneeweiss A, Moebus V, Tesch H. et al. A randomised phase III trial comparing two dose-dense, dose-intensified approaches (EPC and PM(Cb)) for neoadjuvant treatment of patients with high-risk early breast cancer (GeparOcto). J Clin Oncol 2017; 35 (Suppl.) Abstr.. 518
- 10 Loibl S, Werutsky G, Nekljudova V. et al. Impact in delay of start of chemotherapy and surgery on pCR and survival in breast cancer: a pooled analysis of individual patient data from six prospectively randomized neoadjuvant trials. J Clin Oncol 2017; 35 (Suppl.) Abstr.. 571
- 11 Fasching PA, Blohmer JU, Burchardi N. et al. 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 with HER2-negative early breast cancer and homologous recombination deficiency (HRD): GeparOLA. J Clin Oncol 2016; 34 (Suppl.) Abstr.. TPS1096
- 12 von Minckwitz G, Procter MJ, De Azambuja E. et al. APHINITY trial (BIG 4-11): a randomized comparison of chemotherapy (C) plus trastuzumab (T) plus placebo (Pla) versus chemotherapy plus trastuzumab (T) plus pertuzumab (P) as adjuvant therapy in patients (pts) with HER2-positive early breast cancer (EBC). J Clin Oncol 2017; 35 (Suppl.) Abstr. LBA500
- 13 von Minckwitz G, Procter M, de Azambuja E. et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med 2017; 377: 122-131
- 14 Baselga J, Cortes J, Kim SB. et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012; 366: 109-119
- 15 Swain SM, Baselga J, Kim SB. et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 2015; 372: 724-734
- 16 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
- 17 Chan A, Delaloge S, Holmes FA. et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2016; 17: 367-377
- 18 Martin M, Holmes FA, Ejlertsen B. et al. Neratinib after trastuzumab (T)-based adjuvant therapy in early-stage HER2+ breast cancer (BC): 5-year analysis of the phase III ExteNET trial. Ann Oncol 2017; 28 (Suppl. 05) v43-v67 Abstr. 149O
- 19 Finn RS, Crown JP, Lang I. et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 2015; 16: 25-35
- 20 Finn RS, Martin M, Rugo HS. et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med 2016; 375: 1925-1936
- 21 Turner NC, Ro J, Andre F. et al. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med 2015; 373: 209-219
- 22 Hortobagyi GN, Stemmer SM, Burris HA. et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med 2016; 375: 1738-1748
- 23 Goetz MP, Toi M, Campone M. et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol 2017; DOI: 10.1200/JCO.2017.75.6155.
- 24 Sledge jr. GW, Toi M, Neven P. et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol 2017; 35: 2875-2884
- 25 Sledge jr. GW, Toi M, Neven P. et al. MONARCH 2: abemaciclib in combination with fulvestrant in patients with HR+/HER2- advanced breast cancer who progressed on endocrine therapy. J Clin Oncol 2017; 35 (Suppl.) Abstr. 1000
- 26 Di Leo A, Toi M, Campone M. et al. MONARCH 3: abemaciclib as initial therapy for patients with HR+/HER2- advanced breast cancer. Ann Oncol 2017; 28 (Suppl. 05) v74-v108 Abtr. 236O
- 27 Finn RS, Crown J, Lang I. et al. Overall survival results from the randomized phase II study of palbociclib (P) in combination with letrozole (L) vs. letrozole alone for frontline treatment of ER+/HER2- advanced breast cancer (PALOMA-1; TRIO-18). J Clin Oncol 2017; 35 (Suppl.) Abstr. 1001
- 28 Hortobagyi GN, Stemmer SM, Burris HA. et al. Updated results from MONALEESA-2, a phase 3 trial of first-line ribociclib + letrozole in hormone receptor-positive (HR+), HER2-negative (HER2–), advanced breast cancer (ABC). J Clin Oncol 2017; 35 (Suppl.) Abstr. 1038
- 29 Dickler MN, Barry WT, Cirrincione CT. et al. Phase III trial evaluating letrozole as first-line endocrine therapy with or without bevacizumab for the treatment of postmenopausal women with hormone receptor-positive advanced-stage breast cancer: CALGB 40503 (Alliance). J Clin Oncol 2016; 34: 2602-2609
- 30 Martin M, Loibl S, von Minckwitz G. et al. Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: the letrozole/fulvestrant and avastin (LEA) study. J Clin Oncol 2015; 33: 1045-1052
- 31 Walsh CS. Two decades beyond BRCA1/2: homologous recombination, hereditary cancer risk and a target for ovarian cancer therapy. Gynecol Oncol 2015; 137: 343-350
- 32 Robson M, Im SA, Senkus E. et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 2017; 377: 523-533
- 33 Robson ME, Im S-A, Senkus E. et al. OlympiAD: Phase III trial of olaparib monotherapy versus chemotherapy for patients (pts) with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm). J Clin Oncol 2017; 35 (Suppl.) Abstr. LBA4
- 34 Delaloge S, Conte PF, Im S-A. et al. OlympiAD: Further efficacy outcomes in patients with HER2-negative metastatic breast cancer and a germline BRCA mutation receiving olaparib monotherapy vs. standard single-agent chemotherapy treatment of physicianʼs choice. Ann Oncol 2017; 28 (Suppl. 05) v74-v108 Abstr. 243PD
- 35 Turner NC, Telli ML, Rugo HS. et al. Final results of a phase 2 study of talazoparib (TALA) following platinum or multiple cytotoxic regimens in advanced breast cancer patients (pts) with germline BRCA1/2 mutations (ABRAZO). J Clin Oncol 2017; 35 (Suppl.) Abstr. 1007
- 36 Geyer CE, OʼShaughnessy J, Untch M. et al. Phase 3 study evaluating efficacy and safety of veliparib (V) plus carboplatin (Cb) or Cb in combination with standard neoadjuvant chemotherapy (NAC) in patients (pts) with early stage triple-negative breast cancer (TNBC). J Clin Oncol 2017; 35 (Suppl.) Abstr. 520
- 37 Couch FJ, Shimelis H, Hu C. et al. Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol 2017; 3: 1190-1196
- 38 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
- 39 Michailidou K, Lindstrom S, Dennis J. et al. Association analysis identifies 65 new breast cancer risk loci. Nature 2017; 551: 92-94
- 40 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
- 41 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
- 42 Purrington KS, Slager S, Eccles D. et al. Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer. Carcinogenesis 2014; 35: 1012-1019
- 43 Milne RL, Kuchenbaecker KB, Michailidou K. et al. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nat Genet 2017; DOI: 10.1038/ng.3785.
- 44 Schmid P, Park YH, Muñoz-Couselo E. et al. Pembrolizumab (pembro) + chemotherapy (chemo) as neoadjuvant treatment for triple negative breast cancer (TNBC): preliminary results from KEYNOTE-173. J Clin Oncol 2017; 35 (Suppl.) Abstr. 556
- 45 Adams A, Loi S, Toppmeyer D. et al. Phase 2 study of pembrolizumab as first-line therapy for PD-L1–positive metastatic triple-negative breast cancer (mTNBC): preliminary data from KEYNOTE-086 cohort B. J Clin Oncol 2017; 35 (Suppl.) Abstr. 1088
- 46 Stebbing J, Baranau YV, Baryash V. et al. Double-blind, randomized phase III study to compare the efficacy and safety of CT-P6, trastuzumab biosimilar candidate versus trastuzumab as neoadjuvant treatment in HER2 positive early breast cancer (EBC). J Clin Oncol 2017; 35: 510
- 47 Pivot XB, Bondarenko I, Dvorkin M. et al. A randomized, double-blind, phase III study comparing SB3 (trastuzumab biosimilar) with originator trastuzumab in patients treated by neoadjuvant therapy for HER2-positive early breast cancer. J Clin Oncol 2017; 35 (Suppl.) Abstr. 509
- 48 Pegram M, Tan-Chiu E, Freyman A. et al. A randomized, double-blind study of PF-05280014 (a potential trastuzumab biosimilar) vs. trastuzumab, both in combination with paclitaxel, as first-line treatment for HER2-positive metastatic breast cancer. Ann Oncol 2017; 28 (Suppl. 05) v74-v108 Abstr. 238PD
- 49 Lammers PE, Dank M, Masetti R. et al. A randomized, double-blind study of PF-05280014 (a potential biosimilar) vs. trastuzumab, both given with docetaxel (D) and carboplatin (C), as neoadjuvant treatment for operable human epidermal growth factor receptor 2-positive (HER21) breast cancer. Ann Oncol 2017; 28 (Suppl. 05) v43-v67 Abstr. 154PD
- 50 Pivot X, Bondarenko IM, Nowecki Z. et al. One-year safety, immunogenicity, and survival results from a phase III study comparing SB3 (a proposed trastuzumab biosimilar) and originator trastuzumab in HER2-positive early breast cancer treated with neoadjuvant-adjuvant treatment. Ann Oncol 2017; 28 (Suppl. 05) v43-v67 153PD
- 51 Esteva FJ, Baranau Y, Baryash V. et al. Double-blind, randomized phase III study to compare the efficacy and safety of trastuzumab and its biosimilar candidate CT-P6 in HER2 positive early breast cancer (EBC). Ann Oncol 2017; 28 (Suppl. 05) v43-v67 152PD
- 52 von Minckwitz G, Ponomarova O, Morales S. et al. Efficacy and safety of biosimilar ABP 980 compared with trastuzumab in HER2 positive early breast cancer. Ann Oncol 2017; 28 (Suppl. 05) v43-v67 Abstr. 151PD
- 53 Hadji P, Blettner M, Harbeck N. et al. The Patientʼs Anastrozole Compliance to Therapy (PACT) Program: a randomized, in-practice study on the impact of a standardized information program on persistence and compliance to adjuvant endocrine therapy in postmenopausal women with early breast cancer. Ann Oncol 2013; 24: 1505-1512
- 54 Hadji P, Jackisch C, Bolten W. et al. COMPliance and Arthralgia in Clinical Therapy: the COMPACT trial, assessing the incidence of arthralgia, and compliance within the first year of adjuvant anastrozole therapy. Ann Oncol 2014; 25: 372-377
- 55 Nabieva N, Kellner S, Fehm T. et al. Patient and tumor characteristics and their influence on early therapy persistence with letrozole in postmenopausal patients with early breast cancer. Ann Oncol 2017; DOI: 10.1093/annonc/mdx630.
- 56 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
- 57 Henry NL, Azzouz F, Desta Z. et al. Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer. J Clin Oncol 2012; 30: 936-942
- 58 Chirgwin JH, Giobbie-Hurder A, Coates AS. et al. Treatment adherence and its impact on disease-free survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence. J Clin Oncol 2016; 34: 2452-2459
- 59 ClinicalTrials.gov. Impact of eHealth-support on quality of life in metastatic breast cancer patients treated with palbociclib and endocrine therapy (PRECYCLE). 2017 Online: https://clinicaltrials.gov/ct2/show/NCT03220178 Stand: 03.11.2017
- 60 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
- 61 Wallwiener M, Heindl F, Brucker SY. et al. Implementation and feasibility of electronic Patient-Reported Outcome (ePRO) data entry in the PRAEGNANT real-time advanced and metastatic breast cancer registry. Geburtsh Frauenheilk 2017; 77: 870-878
- 62 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
- 63 Fasching PA, Brucker SY, Fehm TN. et al. Biomarkers in patients with metastatic breast cancer and the PRAEGNANT study network. Geburtsh Frauenheilk 2015; 75: 41-50
- 64 Fasching PA, Lux MP, Häberle L. et al. SERAPHINA – Safety, Efficacy and patient Reported outcomes of Advanced breast cancer Patients: tHerapy management wIth NAb-paclitaxel in daily routine (a non-interventional study). Senologie 2016; 13: A24A