Update Mammakarzinom 2019 Teil 2 – Implementierung neuer Diagnostika und Therapien bei Patientinnen mit fortgeschrittenem Brustkrebs in der klinischen Praxis

Wolfgang Janni; Andreas Schneeweiss; Volkmar Müller; Achim Wöckel; Michael P. Lux; Andreas D. Hartkopf; Naiba Nabieva; Florin-Andrei Taran; Hans Tesch; Friedrich Overkamp; Diana Lüftner; Erik Belleville; Florian Schütz; Peter A. Fasching; Tanja N. Fehm; Hans-Christian Kolberg; Johannes Ettl

doi:10.1055/a-0894-6850

Senologie - Zeitschrift für Mammadiagnostik und -therapie, Table of Contents

Senologie - Zeitschrift für Mammadiagnostik und -therapie 2019; 16(02): 109-122
DOI: 10.1055/a-0894-6850

Wissenschaftliche Arbeit

Update Mammakarzinom 2019 Teil 2 – Implementierung neuer Diagnostika und Therapien bei Patientinnen mit fortgeschrittenem Brustkrebs in der klinischen Praxis

Update breast cancer 2019 part 2 – implementation of novel diagnostics and therapeutics in advanced breast cancer patients in clinical practice

Wolfgang Janni

¹Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm

,

Andreas Schneeweiss

²National Center for Tumor Diseases, Division Gynecologic Oncology, University Hospital Heidelberg, Heidelberg

,

Volkmar Müller

³Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg

,

Achim Wöckel

⁴Department of Gynecology and Obstetrics, University Hospital Würzburg, Würzburg

,

Michael P. Lux

⁵Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University Erlangen-Nuremberg, Erlangen

,

Andreas D. Hartkopf

⁶Department of Obstetrics and Gynecology, University of Tübingen, Tübingen

,

Naiba Nabieva

⁵Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University Erlangen-Nuremberg, Erlangen

,

Florin-Andrei Taran

⁶Department of Obstetrics and Gynecology, University of Tübingen, Tübingen

,

Hans Tesch

⁷Oncology Practice at Bethanien Hospital Frankfurt, Frankfurt

,

Friedrich Overkamp

⁸OncoConsult Hamburg GmbH, Hamburg

,

Diana Lüftner

⁹Charité University Hospital, Campus Benjamin Franklin, Department of Hematology, Oncology and Tumour Immunology, Berlin

,

Erik Belleville

¹⁰ClinSol GmbH & Co KG, Würzburg

,

Florian Schütz

¹¹Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg

,

Peter A. Fasching

⁵Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University Erlangen-Nuremberg, Erlangen

,

Tanja N. Fehm

¹²Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf

,

Hans-Christian Kolberg

¹³Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop

,

Johannes Ettl

¹⁴Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich, Munich

› Author Affiliations

Abstract

Zusammenfassung

Die Behandlung von Patientinnen mit fortgeschrittenem Mammakarzinom hat sich in den letzten Jahren weiterentwickelt. Zusätzlich zum Therapiefortschritt in den etablierten Subgruppen (Hormonrezeptor- und HER2-Status) gibt es nun Therapien, die sich an einzelnen molekularen Charakteristika orientieren, wie zum Beispiel die PARP-Inhibitortherapie bei BRCA-mutierten Patientinnen. Zusätzlich dazu sind Tests in der Entwicklung, die innerhalb von Subgruppen weitere Marker etablieren sollen, um die Wirksamkeit einer Therapie vorherzusagen. Die PI3K-Mutationstestung bei HER2-negativen, hormonrezeptorpositiven Tumoren und die PD‑L1-Testung von Immunzellen bei triple-negativen Tumoren werden voraussichtlich in der klinischen Praxis etabliert, um Patientinnen für die jeweiligen Therapien auszuwählen. Mit neuen Therapieansätzen treten auch neue Nebenwirkungen auf. Das Management dieser Nebenwirkungen ebenso wie das der klassischen Therapien (supportive Therapie) ist mit der Einführung neuer Behandlungen essenziell, um die Lebensqualität der Patientinnen zu erhalten. Das Wissen über Maßnahmen zur Erhaltung und Verbesserung der Lebensqualität hat in den letzten Jahren deutlich zugenommen. Lifestyle-Faktoren sollten dabei ebenso Berücksichtigung finden wie moderne Therapieverfahren. Diese Übersichtsarbeit fasst die neuesten Studien und Veröffentlichungen zusammen und bewertet sie in Bezug auf die Relevanz für die klinische Praxis.

Abstract

The treatment of patients with advanced breast cancer has developed further in recent years. In addition to therapeutic progress in the established subgroups (hormone receptor and HER2 status), there are now therapies which are geared to individual molecular characteristics, such as PARP inhibitor therapy in BRCA-mutated patients. In addition to this, tests are being developed which are intended to establish additional markers within subgroups in order to predict the efficacy of a therapy. PI3K mutation testing in HER2-negative, hormonereceptor-positive tumours and PD‑L1 testing of immune cells in triple-negative tumours are expected to become established in clinical practice in order to select patients for the respective therapies. With new therapeutic approaches, new adverse effects also appear. The management of these adverse effects, just as those of classical therapy (supportive therapy), is essential with the introduction of new treatments in order to preserve patientsʼ quality of life. Knowledge regarding measures to preserve and improve quality of life has significantly increased in recent years. Lifestyle factors should be taken into account, as should modern therapeutic methods. This review summarises the latest studies and publications and evaluates them in regard to the relevance for clinical practice.

Schlüsselwörter

Mammakarzinom - Metastasen - fortgeschritten - PI3K - PD‑L1 - Alpelisib - Atezolizumab - PARP - Supportivtherapie

Key words

breast cancer - metastatic - advanced - PI3K - PD‑L1 - alpelisib - atezolizumab - PARP - supportive therapy

Full Text

References

Literatur
1 Taran FA, Schneeweiss A, Lux MP. et al. Update Breast Cancer 2018 (Part 1) – Primary Breast Cancer and Biomarkers. Geburtsh Frauenheilk 2018; 78: 237-245
2 Schneeweiss A, Lux MP, Janni W. et al. Update Breast Cancer 2018 (Part 2) – Advanced Breast Cancer, Quality of Life and Prevention. Geburtsh Frauenheilk 2018; 78: 246-259
3 Wockel 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
4 Muller V, Wockel A, Lux MP. et al. Update Breast Cancer 2018 (Part 4) – Genomics, Individualized Medicine and Immune Therapies – in the Middle of a New Era: Treatment Strategies for Advanced Breast Cancer. Geburtsh Frauenheilk 2018; 78: 1119-1128
5 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
6 Kassam F, Enright K, Dent R. et al. Survival outcomes for patients with metastatic triple-negative breast cancer: implications for clinical practice and trial design. Clin Breast Cancer 2009; 9: 29-33
7 Kommission Mamma der Arbeitsgemeinschaft Gynäkologische Onkologie e. V. in der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe e. V. sowie in der Deutschen Krebsgesellschaft e. V. Diagnostik und Therapie von Patientinnen mit primärem und metastasiertem Brustkrebs. 2018 Online https://www.ago-online.de/de/infothek-fueraerzte/leitlinienempfehlungen/mamma/ ; Stand: 07.07.2018
8 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
9 Emens LA, Loi S, Rugo HS. et al. IMpassion130: Efficacy in immune biomarker subgroups from the global, randomized, double-blind, placebocontrolled, phase III study of atezolizumab + nab-paclitaxel in patients with treatment-nave, locally advanced or metastatic triple-negative breast cancer. San Antonio Breast Cancer Symposium; 2018 Abstr. GS1-04
10 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
11 Fasching PA, Hu C, Hart SN. et al. Cancer predisposition genes in metastatic breast cancer – Association with metastatic pattern, prognosis, patient and tumor characteristics [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. PD1-02
12 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 Gepar-Quinto Study. J Clin Oncol 2018;
13 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
14 Wunderle M, Gass P, Haberle L. et al. BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients. Breast Cancer Res Treat 2018; 171: 85-94
15 Hoyer J, Vasileiou G, Uebe S. et al. Addition of triple negativity of breast cancer as an indicator for germline mutations in predisposing genes increases sensitivity of clinical selection criteria. BMC Cancer 2018; 18: 926
16 Baselga J, Campone M, Piccart M. et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012; 366: 520-529
17 Tesch H, Stoetzer O, Decker T. et al. Efficacy and safety of everolimus plus exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: Results of the single-arm, phase IIIB 4EVER trial. Int J Cancer 2019; 144: 877-885
18 Banys-Paluchowski M, Krawczyk N, Paluchowski P. Cyclin-dependent kinase 4/6 inhibitors: what have we learnt across studies, therapy situations and substances. Curr Opin Obstet Gynecol 2019; 31: 56-66
19 Turner NC, Slamon DJ, Ro J. et al. Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer. N Engl J Med 2018; 379: 1926-1936
20 Muller V, Nabieva N, Haberle L. et al. Impact of disease progression on health-related quality of life in patients with metastatic breast cancer in the PRAEGNANT breast cancer registry. Breast 2018; 37: 154-160
21 Rugo HS, Dieras V, Gelmon KA. et al. Impact of palbociclib plus letrozole on patient-reported health-related quality of life: results from the PALOMA‑2 trial. Ann Oncol 2018; 29: 888-894
22 Huober J, Fasching PA, Taran FA. et al. Factors associated with first line chemotherapy use in patients with hormone receptor positive, HER2 negative metastatic breast cancer – data from the PRAEGNANT breast cancer registry. Cancer Res 2018;
23 Hartkopf AD, Huober J, Volz B. et al. Treatment landscape of advanced breast cancer patients with hormone receptor positive HER2 negative tumors – Data from the German PRAEGNANT breast cancer registry. Breast 2018; 37: 42-51
24 Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012; 490: 61-70
25 Lux MP, Fasching PA, Schrauder MG. et al. The PI3K Pathway: Background and Treatment Approaches. Breast Care (Basel) 2016; 11: 398-404
26 OʼLeary B, Cutts RJ, Liu Y. et al. The Genetic Landscape and Clonal Evolution of Breast Cancer Resistance to Palbociclib plus Fulvestrant in the PALOMA‑3 Trial. Cancer Discov 2018; 8: 1390-1403
27 André F, Ciruelos E, Rubovszky G. et al. Alpelisib (ALP) + fulvestrant (FUL) for advanced breast cancer (ABC): results of the Phase 3 SOLAR-1 trial. Proceedings of the ESMO Conference 2018. Ann Oncol 2018; Abstr. LBA3_PR
28 Juric D, Ciruelos E, Rubovszky G. et al. Alpelisib + fulvestrant for advanced breast cancer: Subgroup analyses from the phase III SOLAR‑1 trial. San Antonio Breast Cancer Symposium 2018; Abstr. GS3-08
29 Slamon DJ, Clark GM, Wong SG. et al. Human breast cancer: correlation of relapse and survival with amplification of the HER‑2/neu oncogene. Science 1987; 235: 177-182
30 Slamon D, Eiermann W, Robert N. et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 2011; 365: 1273-1283
31 Slamon DJ, Leyland-Jones B, Shak S. et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344: 783-792
32 Connell CM, Doherty GJ. Activating HER2 mutations as emerging targets in multiple solid cancers. ESMO Open 2017; 2: e000279
33 Konecny G, Pauletti G, Pegram M. et al. Quantitative association between HER‑2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst 2003; 95: 142-153
34 Loibl S, von Minckwitz G, Schneeweiss A. et al. PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer. J Clin Oncol 2014; 32: 3212-3220
35 Musolino A, Naldi N, Bortesi B. et al. Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER‑2/neu-positive metastatic breast cancer. J Clin Oncol 2008; 26: 1789-1796
36 Schettini F, Buono G, Cardalesi C. et al. Hormone Receptor/Human Epidermal Growth Factor Receptor 2-positive breast cancer: Where we are now and where we are going. Cancer Treat Rev 2016; 46: 20-26
37 Nuciforo P, Thyparambil S, Aura C. et al. High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti-HER2 therapy. Mol Oncol 2016; 10: 138-147
38 Swain SM, Kim SB, Cortes J. et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 2013; 14: 461-471
39 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
40 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
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 Wockel A, Festl J, Stuber T. et al. Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) – Part 2 with Recommendations for the Therapy of Primary, Recurrent and Advanced Breast Cancer. Geburtsh Frauenheilk 2018; 78: 1056-1088
43 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
44 Lux MP, Nabieva N, Hartkopf AD. et al. Therapy Landscape in Patients with Metastatic HER2-Positive Breast Cancer: Data from the PRAEGNANT Real-World Breast Cancer Registry. Cancers (Basel) 2018;
45 Takegawa N, Nonagase Y, Yonesaka K. et al. DS-8201a, a new HER2-targeting antibody-drug conjugate incorporating a novel DNA topoisomerase I inhibitor, overcomes HER2-positive gastric cancer T‑DM1 resistance. Int J Cancer 2017; 141: 1682-1689
46 Doi T, Shitara K, Naito Y. et al. Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study. Lancet Oncol 2017; 18: 1512-1522
47 Iwata H, Tamura K, Doi T. et al. Trastuzumab deruxtecan (DS-8201a) in subjects with HER2-expressing solid tumors: Long-term results of a large phase 1 study with multiple expansion cohorts. J Clin Oncol 2018;
48 Powell CA, Camidge DR, Gemma A. et al. Characterization, monitoring, and management of interstitial lung disease in patients with metastatic breast cancer: Analysis of data available from multiple studies of DS-8201a, a HER2-targeted antibody drug conjugate with a topoisomerase I inhibitor payload. San Antonio Breast Cancer Symposium 2018; Abstr. P6-17-06
49 Schneeweiss A, Lux MP, Hartkopf AD. et al. Progression free survival (PFS) and overall survival (OS) of patients treated with trastuzumab emtansine (T‑DM1) after previous treatment with pertuzumab in patients with advanced breast cancer (NCT02338167). San Antonio Breast Cancer Symposium 2018; Abstr. P6-17-22
50 Witzel I, Laakmann E, Weide R. et al. Treatment and outcomes of patients in the Brain Metastases in Breast Cancer Network Registry. Eur J Cancer 2018; 102: 1-9
51 Sperduto PW, Kased N, Roberge D. et al. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 2012; 30: 419-425
52 Witzel ID, Riecke K, Laakmann E. et al. Validation of different prognostic scores in breast cancer patients with brain metastases of the BMBC registry (GBG‑79). San Antonio Breast Cancer Symposium 2018; Abstr. P4-08-26
53 Tolaney SM, Sahebjam S, Le Rhun E. et al. A phase 2 study of abemaciclib in patients with leptomeningeal metastases secondary to HR+, HER2-breast cancer. San Antonio Breast Cancer Symposium 2018; Abstr. P1-19-07
54 Braun S, Vogl FD, Naume B. et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 2005; 353: 793-802
55 Trapp E, Janni W, Schindlbeck C. et al. Presence of Circulating Tumor Cells in High-Risk Early Breast Cancer During Follow-Up and Prognosis. J Natl Cancer Inst 2018;
56 Huebner H, Fasching PA, Gumbrecht W. et al. Filtration based assessment of CTCs and CellSearch(R) based assessment are both powerful predictors of prognosis for metastatic breast cancer patients. BMC Cancer 2018; 18: 204
57 Polasik A, Tzschaschel M, Schochter F. et al. Circulating Tumour Cells, Circulating Tumour DNA and Circulating MicroRNA in Metastatic Breast Carcinoma – What is the Role of Liquid Biopsy in Breast Cancer?. Geburtsh Frauenheilk 2017; 77: 1291-1298
58 Janni WJ, Rack B, Terstappen LW. et al. Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer. Clin Cancer Res 2016; 22: 2583-2593
59 Janni W, Rack B, Fasching P. et al. Persistence of circulating tumor cells in high risk early breast cancer patients during follow-up care suggests poor prognosis – Results from the adjuvant SUCCESS A trial. Cancer Res 2016;
60 Rack B, Schindlbeck C, Juckstock J. et al. Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J Natl Cancer Inst 2014;
61 Muller V, Riethdorf S, Rack B. et al. Prognostic impact of circulating tumor cells assessed with the CellSearch System and AdnaTest Breast in metastatic breast cancer patients: the DETECT study. Breast Cancer Res 2012; 14: R118
62 Hosseini H, Obradovic MM, Hoffmann M. et al. Early dissemination seeds metastasis in breast cancer. Nature 2016;
63 Hartkopf AD, Brucker SY, Taran FA. et al. International pooled analysis of the prognostic impact of disseminated tumor cells from the bone marrow in early breast cancer: Results from the PADDY study. San Antonio Breast Cancer Symposium 2018; Abstr. GS5-07
64 Bidard FC, Peeters DJ, Fehm T. et al. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol 2014; 15: 406-414
65 Bidard FC, Jacot W, Dureau S. et al. Clinical utility of circulating tumor cell count as a tool to chose between first line hormone therapy and chemotherapy for ER+ HER2-metastatic breast cancer: Results of the phase III STIC CTC trial. San Antonio Breast Cancer Symposium 2018; Abstr. GS3-07
66 Ganz PA, Yip CH, Gralow JR. et al. Supportive care after curative treatment for breast cancer (survivorship care): resource allocations in lowand middle-income countries. A Breast Health Global Initiative 2013 consensus statement. Breast 2013; 22: 606-615
67 Cardoso F, Bese N, Distelhorst SR. et al. Supportive care during treatment for breast cancer: resource allocations in low- and middle-income countries. A Breast Health Global Initiative 2013 consensus statement. Breast 2013; 22: 593-605
68 Harrison JD, Young JM, Price MA. et al. What are the unmet supportive care needs of people with cancer? A systematic review. Support Care Cancer 2009; 17: 1117-1128
69 Beesley VL, Alemayehu C, Webb PM. A systematic literature review of the prevalence of and risk factors for supportive care needs among women with gynaecological cancer and their caregivers. Support Care Cancer 2018; 26: 701-710
70 Distelhorst SR, Cleary JF, Ganz PA. et al. Optimisation of the continuum of supportive and palliative care for patients with breast cancer in low-income and middle-income countries: executive summary of the Breast Health Global Initiative, 2014. Lancet Oncol 2015; 16: e137-e147
71 Aapro MS, Bohlius J, Cameron DA. et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 2011; 47: 8-32
72 Olver I, Clark-Snow RA, Ballatori E. et al. Guidelines for the control of nausea and vomiting with chemotherapy of low or minimal emetic potential. Support Care Cancer 2011; 19 (Suppl. 01) S33-S36
73 Jordan K, Roila F, Molassiotis A. et al. Antiemetics in children receiving chemotherapy. MASCC/ESMO guideline update 2009. Support Care Cancer 2011; 19 (Suppl. 01) S37-S42
74 Jordan K, Aapro M, Kaasa S. et al. European Society for Medical Oncology (ESMO) position paper on supportive and palliative care. Ann Oncol 2018; 29: 36-43
75 Hesketh PJ, Kris MG, Basch E. et al. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2017; 35: 3240-3261
76 Feyer PC, Maranzano E, Molassiotis A. et al. Radiotherapy-induced nausea and vomiting (RINV): MASCC/ESMO guideline for antiemetics in radiotherapy: update 2009. Support Care Cancer 2011; 19 (Suppl. 01) S5-S14
77 de Wit M, Ortner P, Lipp HP. et al. Management of cytotoxic extravasation – ASORS expert opinion for diagnosis, prevention and treatment. Onkologie 2013; 36: 127-135
78 Bossi P, Antonuzzo A, Cherny NI. et al. Diarrhoea in adult cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2018; 29: iv126-iv142
79 Slamon DJ, Eiermann W, Robert NJ. et al. Ten year follow-up of BCIRG‑006 comparing doxorubicin plus cyclophosphamide followed by docetaxel (AC –> T) with doxorubicin plus cyclophosphamide followed by docetaxel and trastuzumab (AC –> TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2 + early breast cancer. Cancer Res 2016;
80 Janni W, Nitz U, Rack BK. et al. Pooled analysis of two randomized phase III trials (PlanB/SuccessC) comparing six cycles of docetaxel and cyclophosphamide to sequential anthracycline taxane chemotherapy in patients with intermediate and high risk HER2-negative early breast cancer (n = 5,923). J Clin Oncol 2018; 36: 522 . doi:510.1200/ JCO.2018.1236.1215_suppl.1522
81 Munster P, Krischer J, Tamura R. et al. A randomized community-based trial of an angiotensin converting enzyme inhibitor, lisinopril or a beta blocker, carvedilol for the prevention of cardiotoxicity in patients with early stage HER2-positive breast cancer receiving adjuvant trastuzumab. San Antonio Breast Cancer Symposium 2018; Abstr. GS5-01
82 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
83 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
84 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
85 Buser KS, Joss RA, Piquet D. et al. Oral ondansetron in the prophylaxis of nausea and vomiting induced by cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in women with breast cancer. Results of a prospective, randomized, double-blind, placebo-controlled study. Ann Oncol 1993; 4: 475-479
86 Schilling J, Hielscher C, Hanusch C. et al. Efficacy of NEPA as antiemetic prophylaxis in breast cancer patients receiving highly or moderately emetogenic chemotherapy – Interim results of a German prospective, noninterventional study. San Antonio Breast Cancer Symposium 2018; Abstr. P1-11-10
87 Fasching PA, Kollmannsberger B, Strissel PL. et al. Polymorphisms in the novel serotonin receptor subunit gene HTR3C show different risks for acute chemotherapy-induced vomiting after anthracycline chemotherapy. J Cancer Res Clin Oncol 2008; 134: 1079-1086
88 Hammer C, Fasching PA, Loehberg CR. et al. Polymorphism in HTR3D shows different risks for acute chemotherapy-induced vomiting after anthracycline chemotherapy. Pharmacogenomics 2010; 11: 943-950
89 Kollmannsberger B, Lohberg C, Stohlmacher J. et al. Prediction of emesis by polymorphisms in the serotonin receptor subunit gene HTR3C – Rationale for an international prospective pharmacogenomics study Emesis 2 – CINV. Onkologie 2008; 31: 27-28
90 Lopez-Morales P, Flores-Funes D, Sanchez-Migallon EG. et al. Genetic Factors Associated with Postoperative Nausea and Vomiting: a Systematic Review. J Gastrointest Surg 2018; 22: 1645-1651
91 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
92 Wagner LI, Gray RJ, Garcia S. et al. Symptoms and health-related quality of life on endocrine therapy alone (E) versus chemoendocrine therapy (C + E): TAILORx patient-reported outcomes results. San Antonio Breast Cancer Symposium 2018; Abstr. GS6-03
93 Janni W, Rack BK, Friedl TW. et al. Lifestyle Intervention and Effect on Disease-free Survival in Early Breast Cancer Pts: Interim Analysis from the Randomized SUCCESS C Study. San Antonio Breast Cancer Symposium 2018; Abstr. GS5-03
94 Thune I, Husoy A, Frydenberg H. et al. Cardiovascular function and the effect of exercise training during adjuvant breast cancer treatment. Results from The EBBA‑II trial. San Antonio Breast Cancer Symposium 2018; Abstr. GS5-02
95 Hurria A, Magnuson A, Gross CP. et al. Development and validation of a chemotherapy toxicity (Chemo Tox) risk score for older patients (Pts) with breast cancer (BC) receiving adjuvant/neoadjuvant treatment (Adjuvant Tx): A R01 and BCRF funded prospective multicenter study. San Antonio Breast Cancer Symposium 2018; Abstr. GS6-04
96 Schmidt M, Fasching PA, Beckmann MW. et al. Biomarkers in Breast Cancer – An Update. Geburtsh Frauenheilk 2012; 72: 819-832
97 Andre F, Filleron T, Ng C. et al. Genomic characterisation of metastatic breast cancer. San Antonio Breast Cancer Symposium 2018; Abstr. GS1-08
98 Andre F, Bachelot T, Commo F. et al. Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER). Lancet Oncol 2014; 15: 267-274
99 Le Tourneau C, Delord JP, Goncalves A. et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol 2015; 16: 1324-1334
100 Massard C, Michiels S, Ferte C. et al. High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial. Cancer Discov 2017; 7: 586-595
101 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
102 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;
103 Hein A, Gass P, Walter CB. et al. Computerized patient identification for the EMBRACA clinical trial using real-time data from the PRAEGNANT network for metastatic breast cancer patients. Breast Cancer Res Treat 2016; 158: 59-65
104 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