Das Medizinportal



Nebenwirkungsmanagement beim Hormonrezeptor-positiven Mammakarzinom

(S. 28–34)
M. Dieterich, J. Stubert, A. Stachs


  1.  RKI: Robert Koch-Institut: Evaluation of cancer incidence in Germany 2007-2010. (http://www.rki.de/DE/Home/homepage_node.html) Zugegriffen: 5. August 2017
  2. Interdisziplinäre S3-Leitlinie für die Diagnostik, Therapie und Nachsorge des Mammakarzinoms. Langversion 3.0, Aktualisierung 2012, AWMF-Register-Nummer: 032 – 045OL, Leitlinie (Langversion). 2012
  3. Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 2003; 349: 1793–1802
  4. Howell A. The 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) Trial: a step forward in the treatment of early breast cancer. Rev Recent Clin Trials 2006; 1: 207–215
  5. Morden JP, Alvarez I, Bertelli G, Coates AS, Coleman R, Fallowfield L, et al. Long-Term Follow-Up of the Intergroup Exemestane Study. J Clin Oncol 2017; 35: 2507–2514
  6. Early Breast Cancer Trialists' Collaborative G; Davies C, Godwin J, Gray R, Clarke M, Cutter D, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011; 378: 771–784
  7. van de Water W, Bastiaannet E, Hille ET, Meershoek-Klein Kranenbarg EM, Putter H, et al. Age-specific nonpersistence of endocrine therapy in postmenopausal patients diagnosed with hormone receptor-positive breast cancer: a TEAM study analysis. Oncologist 2012; 17: 55–63
  8. Murphy CC, Bartholomew LK, Carpentier MY, Bluethmann SM, Vernon SW. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat 2012; 134: 459–478
  9. Niravath P. Aromatase inhibitor-induced arthralgia: a review. Ann Oncol 2013; 24: 1443–1449
  10. Crew KD, Greenlee H, Capodice J, Raptis G, Brafman L, Fuentes D, Sierra A, Hershman DL. Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol 2007; 25: 3877–3883
  11. Henry NL, Giles JT, Ang D, Mohan M, Dadabhoy D, Robarge J, et al. Prospective characterization of musculoskeletal symptoms in early stage breast cancer patients treated with aromatase inhibitors. Breast Cancer Res Treat 2008; 111: 365–372
  12. Irwin ML, Cartmel B, Gross CP, Ercolano E, Li F, Yao X, et al: Randomized exercise trial of aromatase inhibitor-induced arthralgia in breast cancer survivors. J Clin Oncol 2015; 33: 1104–1111
  13. Thorne C. Management of arthralgias associated with aromatase inhibitor therapy. Curr Oncol 2007; 14: 11–19
  14. Beuth J. Evidence-based complementary oncology: innovative approaches to optimise standard therapy strategies. Anticancer Res 2010; 30: 1767–1771
  15. Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 2004; 350: 1081–1092
  16. Eastell R, Hannon R. Long-term effects of aromatase inhibitors on bone. J Steroid Biochem Mol Biol 2005; 95: 151–154
  17. Gnant M, Pfeiler G, Dubsky PC, Hubalek M, Greil R, Jakesz R, et al. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 2015; 386: 433–443
  18. Early Breast Cancer Trialists' Collaborative G; Coleman R, Powles T, Paterson A, Gnant M, Anderson S, et al. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet 2015; 386: 1353–1361
  19. Prague JK, Roberts RE, Comninos AN, Clarke S, Jayasena CN, Nash Z, et al. Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet 2017; 389: 1809–1820
  20. Desai K, Mao JJ, Su I, Demichele A, Li Q, Xie SX, Gehrman PR. Prevalence and risk factors for insomnia among breast cancer patients on aromatase inhibitors. Support Care Cancer 2013; 21: 43–51.
  21. Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, et al. MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. J Clin Oncol 2017; 35: 3638–3646
  22. Beck JT, Hortobagyi GN, Campone M, Lebrun F, Deleu I, Rugo HS, et al. Everolimus plus exemestane as first-line therapy in HR(+), HER2(-) advanced breast cancer in BOLERO-2. Breast Cancer Res Treat 2014; 143: 459–467
  23. Saggar V, Wu S, Dickler MN, Lacouture ME. Alopecia with endocrine therapies in patients with cancer. Oncologist 2013; 18: 1126–1134
  24. Donders G, Neven P, Moegele M, Lintermans A, Bellen G, Prasauskas V, et al. Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor((R))) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhibitors: pharmacokinetic, safety, and efficacy phase I clinical study. Breast Cancer Res Treat 2014; 145: 371–379


Bedeutung des Hospiz- und Palliativgesetzes für Krankenhäuser (S. 39–42)
Marianne Kloke

  1. Bundesgesetzblatt Teil 1 Nr. 48 vom 07.12.2015, Seite 2114. Gesetz zur Verbesserung der Hospiz- und Palliativversorgung in Deutschland
  2. www.charta-zur-betreuung-sterbender.de (2017) Charta zur Betreuung schwerkranker und sterbender Menschen in Deutschland
  3. Leitlinienprogramm Onkologie der AWMF (2015) S3-Leitlinie Palliativmedizin für Patienten mit einer nicht heilbaren Krebserkrankung, Kapitel 11 Versorgungstrukturen: 172–225, Kohlhammer-Verlag 2015
  4. Council of Europe (2003) Recommendation Rec 24 of the Committee of Ministers to member states on the organisation of palliative care
  5. Deutsches Institut für Medizinische Dokumentation und Information DIMDI im Auftrag des Bundesministeriums für Gesundheit (BMG)(2017). http://www.icd-code.de/suche/ops/code/8-982.html?sp=S8-982
  6. ClarCert (2018). clarcert.com/systeme/zertifizierung-und-anerkennung-von-palliativstationen/system.html
  7. Deutsches Institut für Medizinische Dokumentation und Information DIMDI im Auftrag des Bundesministeriums für Gesundheit (BMG)(2017). http://www.icd-code.de/ops/code/8-98h.html
  8. Deutsche Gesellschaft für Palliativmedizin (2016) www.dgpalliativmedizin.de/images/Informationen_zum_krankenhausindividuellen_Zusatzentgelt_-_OPS_8-98h.pdf
  9. Earle CC, Landrum MB, Souza JM, Neville BA, Weeks JC, Ayanian JZ. Aggressiveness of Cancer Care Near the End of Life: Is It a Quality-of-Care Issue? J Clin Oncol 2008; 26(23): 3860–3866


Genetische Krebsprädispositionssyndrome (S. 44–53)
Christina M. Dutzmann, Kristian W. Pajtler, Stefan M. Pfister, Christian P. Kratz,
Beate B. Dörgeloh

  1. Zhang J, Nichols K, Downing J. Germline Mutations in Predisposition Genes in Pediatric Cancer. N Engl J Med 2016; 374(14): 1391–1391
  2. Ripperger T, Bielack SS, Borkhardt A, Brecht IB, Burkhardt B, Calaminus G, et al. Childhood cancer predisposition syndromes-A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology. Am J Med Genet A 2017 Apr; 173(4): 1017–1037
  3. Li FP, Fraumeni JF, Mulvihill JJ, Blattner WA, Dreyfus MG, Tucker MA, et al. A cancer family syndrome in twenty-four kindreds. Cancer Res 1988; 48(18): 5358–5362
  4. Malkin D, Friend SH, Li FP, Strong LC. Germ-line mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms. N Engl J Med 1997; 336(10): 734–734
  5. Malkin D, Li FP, Strong LC, Fraumeni JF, Nelson CE, Kim DH, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 1990; 250(4985): 1233–1238
  6. Chompret A, Brugières L, Ronsin M, Gardes M, Dessarps Freichey F, Abel A, et al. P53 germline mutations in childhood cancers and cancer risk for carrier individuals. Br J Cancer 2000; 82(12): 1932–1937
  7. Achatz M, Zambetti G. The Inherited p53 Mutation in the Brazilian Population. Cold Spring Harb Perspect Med 2016; 6(12)
  8. Mai P, Best A, Peters J, DeCastro R, Khincha P, Loud J, et al. Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort. Cancer 2016; 122(23): 3673–3681
  9. Bougeard G, Renaux-Petel M, Flaman J, Charbonnier C, Fermey P, Belotti M, et al. Revisiting Li-Fraumeni Syndrome From TP53 Mutation Carriers. JCO 2015 07/20; 2017/08; 33(21): 2345–2352
  10. Grobner SN, Worst BC, Weischenfeldt J, Buchhalter I, Kleinheinz K, Rudneva VA, et al. The landscape of genomic alterations across childhood cancers. Nature 2018 Mar 15; 555(7696): 321–327
  11. Li FP, Fraumeni JF. Rhabdomyosarcoma in children: epidemiologic study and identification of a familial cancer syndrome. J Natl Cancer Inst 1969; 43(6): 1365–1373
  12. Chompret A, Abel A, Stoppa Lyonnet D, Brugiéres L, Pagés S, Feunteun J, et al. Sensitivity and predictive value of criteria for p53 germline mutation screening. J Med Genet 2001; 38(1): 43–47
  13. Tinat J, Bougeard G, Baert Desurmont S, Vasseur S, Martin C, Bouvignies E, et al. 2009 version of the Chompret criteria for Li Fraumeni syndrome. J Clin Oncol 2009; 27(26): e108-9; author reply e110
  14. Rausch T, Jones DT, Zapatka M, Stutz AM, Zichner T, Weischenfeldt J, et al. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell 2012 Jan 20; 148(1-2): 59–71
  15. Waszak SM et al. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort. Lancet Oncol. 2018 May 9. pii: S1470–2045(18)30242-0. doi: 10.1016/S1470-2045(18)30242-0. [Epub ahead of print]
  16. Holmfeldt L, Wei L, Diaz-Flores E, Walsh M, Zhang J, Ding L, et al. The genomic landscape of hypodiploid acute lymphoblastic leukemia. Nat Genet 2013 Mar; 45(3): 242–252
  17. Kool M, Jones DT, Jager N, Northcott PA, Pugh TJ, Hovestadt V, et al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell 2014 Mar 17; 25(3): 393–405
  18. Zhukova N, Ramaswamy V, Remke M, Pfaff E, Shih DJ, Martin DC, et al. Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma. J Clin Oncol 2013 Aug 10; 31(23): 2927–2935
  19. Mirabello L, Yeager M, Mai PL, Gastier-Foster JM, Gorlick R, Khanna C, et al. Germline TP53 variants and susceptibility to osteosarcoma. J Natl Cancer Inst 2015 Apr 20; 107(7): 10.1093/jnci/djv101. Print 2015 Jul
  20. Hof J, Krentz S, van Schewick C, Korner G, Shalapour S, Rhein P, et al. Mutations and deletions of the TP53 gene predict nonresponse to treatment and poor outcome in first relapse of childhood acute lymphoblastic leukemia. J Clin Oncol 2011 Aug 10; 29(23): 3185–3193
  21. Villani A, Shore A, Wasserman JD, Stephens D, Kim RH, Druker H, et al. Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study. The Lancet Oncology 2016 Sep ; 17(9): 1295–1305
  22. Kratz C, Achatz M, Brugières L, Frebourg T, Garber J, Greer M, et al. Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome. Clin Cancer Res 2017; 23(11): e38–e45
  23. Ricciardone MD, Ozcelik T, Cevher B, Ozdag H, Tuncer M, Gurgey A, et al. Human MLH1 deficiency predisposes to hematological malignancy and neurofibromatosis type 1. Cancer Res 1999 Jan 15; 59(2): 290–293
  24. Wang Q, Lasset C, Desseigne F, Frappaz D, Bergeron C, Navarro C, et al. Neurofibromatosis and early onset of cancers in hMLH1-deficient children. Cancer Res 1999 Jan 15; 59(2): 294–297
  25. Ripperger T, Beger C, Rahner N, Sykora KW, Bockmeyer CL, Lehmann U, et al. Constitutional mismatch repair deficiency and childhood leukemia/lymphoma--report on a novel biallelic MSH6 mutation. Haematologica 2010 May; 95(5): 841–844
  26. Ligtenberg MJ, Kuiper RP, Chan TL, Goossens M, Hebeda KM, Voorendt M, et al. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1. Nat Genet 2009 Jan; 41(1): 112–117
  27. Wimmer K, Kratz CP. Constitutional mismatch repair-deficiency syndrome. Haematologica 2010 May; 95(5): 699–701
  28. Wimmer K, Kratz CP, Vasen HF, Caron O, Colas C, Entz-Werle N, et al. Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium 'care for CMMRD' (C4CMMRD). J Med Genet 2014 Jun; 51(6): 355–365
  29. Lavoine N, Colas C, Muleris M, Bodo S, Duval A, Entz-Werle N, et al. Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort. J Med Genet 2015 Nov; 52(11): 770–778
  30. Tabori U, Hansford JR, Achatz MI, Kratz CP, Plon SE, Frebourg T, et al. Clinical Management and Tumor Surveillance Recommendations of Inherited Mismatch Repair Deficiency in Childhood. Clin Cancer Res 2017 Jun 1; 23(11): e32–e37
  31. Jiricny J. The multifaceted mismatch-repair system. Nat Rev Mol Cell Biol 2006 May; 7(5): 335–346
  32. Karran P, Attard N. Thiopurines in current medical practice: molecular mechanisms and contributions to therapy-related cancer. Nat Rev Cancer 2008 Jan; 8(1): 24–36
  33. Attarbaschi A, Carraro E, Abla O, Barzilai-Birenboim S, Bomken S, Brugieres L, et al. Non-Hodgkin lymphoma and pre-existing conditions: spectrum, clinical characteristics and outcome in 213 children and adolescents. Haematologica 2016 Dec; 101(12): 1581–1591
  34. Bouffet E, Larouche V, Campbell BB, Merico D, de Borja R, Aronson M, et al. Immune Checkpoint Inhibition for Hypermutant Glioblastoma Multiforme Resulting From Germline Biallelic Mismatch Repair Deficiency. J Clin Oncol 2016 Jul 1; 34(19): 2206–2211
  35. Vasen HF, Ghorbanoghli Z, Bourdeaut F, Cabaret O, Caron O, Duval A, et al. Guidelines for surveillance of individuals with constitutional mismatch repair-deficiency proposed by the European Consortium "Care for CMMR-D" (C4CMMR-D). J Med Genet 2014 May; 51(5): 283–293
  36. Durno C, Boland CR, Cohen S, Dominitz JA, Giardiello FM, Johnson DA, et al. Recommendations on Surveillance and Management of Biallelic Mismatch Repair Deficiency (BMMRD) Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2017 May; 152(6): 1605–1614
  37. Elbracht M, Prawitt D, Nemetschek R, Kratz C, Eggermann T. [Beckwith-Wiedemann Syndrome (BWS) Current Status of Diagnosis and Clinical Management: Summary of the First International Consensus Statement]. Klin Padiatr 2018
  38. Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, et al. Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol 2018 Apr; 14(4): 229–249
  39. Foulkes WD, Priest JR, Duchaine TF. DICER1: mutations, microRNAs and mechanisms. Nat Rev Cancer 2014 Oct; 14(10): 662–672
  40. Doros L, Schultz KA, Stewart DR, Bauer AJ, Williams G, Rossi CT, et al. DICER1-Related Disorders. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, et al, editors. GeneReviews((R)) Seattle (WA): University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved; 1993
  41. Schultz KAP, Williams GM, Kamihara J, Stewart DR, Harris AK, Bauer AJ, et al. DICER1 and Associated Conditions: Identification of At-risk Individuals and Recommended Surveillance Strategies. Clin Cancer Res 2018 Jan 17
  42. Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, et al. DICER1 mutations in familial pleuropulmonary blastoma. Science 2009 Aug 21; 325(5943): 965
  43. Messinger YH, Stewart DR, Priest JR, Williams GM, Harris AK, Schultz KA, et al. Pleuropulmonary blastoma: a report on 350 central pathology-confirmed pleuropulmonary blastoma cases by the International Pleuropulmonary Blastoma Registry. Cancer 2015 Jan 15; 121(2): 276–285
  44. Schneider DT, Calaminus G, Wessalowski R, Pathmanathan R, Harms D, Gobel U. Therapy of advanced ovarian juvenile granulosa cell tumors. Klin Padiatr 2002 Jul-Aug; 214(4): 173–178
  45. Jongmans MCJ, Loeffen JLCM, Waanders E, Hoogerbrugge P, Ligtenberg MJL, Kuiper R, et al. Recognition of genetic predisposition in pediatric cancer patients: An easy-to-use selection tool. Eur J Med Genet 2016; 59(3): 116–125
  46. Druker H, Zelley K, McGee RB, Scollon SR, Kohlmann WK, Schneider KA, et al. Genetic Counselor Recommendations for Cancer Predisposition Evaluation and Surveillance in the Pediatric Oncology Patient. Clin Cancer Res 2017 Jul 1; 23(13): e91–e97