Geburtshilfe Frauenheilkd 2016; 76(05): 503-506
DOI: 10.1055/s-0042-102003
Aktuell diskutiert
Onkologie / Mammakarzinom
Georg Thieme Verlag KG Stuttgart · New York

Immuntherapien beim Mammakarzinom – Wie hängen Immunsystem und Krebs zusammen und woran arbeitet die Forschung?

Katrin Almstedt
,
Marcus Schmidt
Further Information

Publication History

Publication Date:
19 May 2016 (online)

Das Mammakarzinom stellt eine sehr heterogene Erkrankung dar. Zum aktuellen Zeitpunkt fungiert die St. Gallener Konsensusempfehlung der sogenannten intrinsischen Subtypen als Basis zur Erhebung molekular-biologischer prädiktiver und prognostischer Faktoren [1]. Weitere biologische Einflussgrößen, die als prognostische oder prädiktive Faktoren dienen könnten, werden im Rahmen von translationalen Arbeiten untersucht. Hier ist das Ziel, Übertherapien und unnötige Nebenwirkungen zu vermeiden und die Prognose zu verbessern. Neben genetischen Alterationen als Ursache für maligne Zelltransformationen gilt das Tumorstroma als zentrale Einflussgröße für maligne Prozesse und das Ansprechen auf onkologische Therapien. Ein besseres Verständnis über das Zusammenspiel zwischen dem primär gegen den Tumor wirkenden endogenen Immunsystem und bestehenden immunsuppressiven, tumorstimulierenden Mechanismen bietet die Möglichkeit zu neuen Therapieoptionen in der Behandlung des Mammakarzinoms.

 
  • Literatur

  • 1 Goldhirsch A, Winer EP, Coates AS et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 2013; 24: 2206-2223
  • 2 Di Paola M, Angelini L, Bertolotti A et al. Host resistance in relation to survival in breast cancer. BMJ 1974; 4: 268-270
  • 3 Schmidt M, Bohm D, von Torne C et al. The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res 2008; 68: 5405-5413
  • 4 Rody A, Holtrich U, Pusztai L et al. T-cell metagene predicts a favorable prognosis in estrogen receptor-negative and HER2-positive breast cancers. BCR 2009; 11: R15
  • 5 Loi S, Sirtaine N, Piette F et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02–98. J Clin Oncol 2013; 31: 860-867
  • 6 Adams S, Gray RJ, Demaria S et al. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol 2014; 32: 2959-2966
  • 7 Ibrahim EM, Al-Foheidi ME, Al-Mansour MM et al. The prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancer: a meta-analysis. Breast Cancer Res Treat 2014; 148: 467-476
  • 8 Loi S, Michiels S, Salgado R et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol 2014; 25: 1544-1550
  • 9 Perez EA, Ballman KV, Tenner KS et al. Association of Stromal Tumor-Infiltrating Lymphocytes With Recurrence-Free Survival in the N9831 Adjuvant Trial in Patients With Early-Stage HER2-Positive Breast Cancer. JAMA Oncol 2015; 1-9 DOI: 10.1001/jamaoncol.2015.3239.
  • 10 Denkert C, Loibl S, Noske A et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol 2010; 28: 105-113
  • 11 Denkert C, von Minckwitz G, Brase JC et al. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol 2015; 33: 983-991
  • 12 West NR, Milne K, Truong PT et al. Tumor-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer. BCR 2011; 13: R126
  • 13 Ono M, Tsuda H, Shimizu C et al. Tumor-infiltrating lymphocytes are correlated with response to neoadjuvant chemotherapy in triple-negative breast cancer. Breast Cancer Res Treat 2012; 132: 793-805
  • 14 Yamaguchi R, Tanaka M, Yano A et al. Tumor-infiltrating lymphocytes are important pathologic predictors for neoadjuvant chemotherapy in patients with breast cancer. Hum Pathol 2012; 43: 1688-1694
  • 15 Salgado R, Denkert C, Demaria S et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol 2015; 26: 259-271
  • 16 Romond EH, Perez EA, Bryant J et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. The New England journal of medicine 2005; 353: 1673-1684
  • 17 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
  • 18 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
  • 19 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
  • 20 Schneeweiss A, Chia S, Hickish T et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 2013; 24: 2278-2284
  • 21 Postow MA, Callahan MK, Wolchok JD. Immune Checkpoint Blockade in Cancer Therapy. J Clin Oncol 2015; 33: 1974-1982
  • 22 Keir ME, Butte MJ, Freeman GJ et al. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008; 26: 677-704
  • 23 Muenst S, Soysal SD, Gao F et al. The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat 2013; 139: 667-676
  • 24 Gatalica Z, Snyder C, Maney T et al. Programmed cell death 1 (PD-1) and its ligand (PD-L1) in common cancers and their correlation with molecular cancer type. Cancer Epidemiol Biomarkers Prev 2014; 23: 2965-2970
  • 25 Wimberly H, Brown JR, Schalper K et al. PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer. Cancer Immunol Res 2015; 3: 326-332
  • 26 Schalper KA, Velcheti V, Carvajal D et al. In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas. Clin Cancer Res 2014; 20: 2773-2782
  • 27 Mittendorf EA, Philips AV, Meric-Bernstam F et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res 2014; 2: 361-370
  • 28 Nanda R, Chow LQ, Dees EC et al. Abstract S1–09: A phase Ib study of pembrolizumab (MK-3475) in patients with advanced triple-negative breast cancer. Cancer Res 2015; 75 S1–109-S01–09
  • 29 Wolchok JD, Hoos A, O‘Day S et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 2009; 15: 7412-7420
  • 30 Mittendorf EA, Clifton GT, Holmes JP et al. Final report of the phase I / II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients. Ann Oncol 2014; 25: 1735-1742
  • 31 Martin SD, Coukos G, Holt RA et al. Targeting the undruggable: immunotherapy meets personalized oncology in the genomic era. Ann Oncol 2015; 26: 2367-2374
  • 32 Rizvi NA, Hellmann MD, Snyder A et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science (New York, NY) 2015; 348: 124-128
  • 33 Kreiter S, Diken M, Selmi A et al. Tumor vaccination using messenger RNA: prospects of a future therapy. Curr Opin Immunol 2011; 23: 399-406
  • 34 Kreiter S, Vormehr M, van de Roemer N et al. Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature 2015; 520: 692-696