Zielgerichtete Therapien – Quo vadis?

Zielgerichtet wirksame Substanzen sind Medikamente, die ihre Wirkung durch Bindung an definierte Moleküle entfalten. Die derzeit beim Brustkrebs zugelassenen Substanzen richten sich gegen die ungebremste Proliferation und Angiogenese. Neben den endokrinen Therapien unterscheidet man monoklonale Antikörper und Kinase-Inhibitoren. Monoklonale Antikörper binden spezifisch an Antigene auf Tumorzellen oder in deren Umgebung und blockieren relevante Signalwege bzw. induzieren die zellulär-vermittelte Phagozytose. Kinase-Inhibitoren binden an enzymatische Bindungstaschen und hemmen deren katalytische Funktion.

• Literatur

• 1 Wolff AC, Hammond MEH, Schwartz JN et al. American Society of Clinical Oncology / College of American Pathologists Guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J ClinOncol 2007; 25: 118-45
• 2 Gianni L, Eiermann W, Semiglazov V et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet 2010; 375: 377-84
• 3 Burstein HJ. Patients with anti-HER2 responsive disease: definition and adjuvant therapies. Breast 2011; 20 Suppl 3: S132-4
• 4 Telli ML, Hunt SA, Carlson RW et al. Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility. J ClinOncol 2007; 25: 3525-33
• 5 Slamon DJ, Leyland-Jones B, Shak S et al. Use ofchemotherapy plus amonoclonal antibody against HER2 for metastatic breastcancer that overexpresses HER2. N Engl J Med 2001; 344: 783-92
• 6 Marty M, Cognetti F, Maraninchi D et al. Randomized phase II trial of the efficacy andsafety of trastuzumab combined with docetaxel in patients with humanepidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J ClinOncol 2005; 23: 4265-4274
• 7 Kaufman B, Mackey JR et al. Trastuzumab plusanastrozole versus anastrozole alone for the treatment ofpostmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from therandomized phase III TAnDEM Study. J ClinOncol 2009; 27: 5529-5537
• 8 von Minckwitz G, Eidtmann H, Rezai M et al. German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer N Engl J Med 2012; 366: 299-309
• 9 Dawood S, Broglio K, Buzdar AU et al. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J ClinOncol 2010; 28: 92-98
• 10 Spector NL, Blackwell KL. Understanding the mechanisms behind trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer. J ClinOncol 2009; 27: 5838-5847
• 11 Tsang RY, Finn RS. Beyond trastuzumab: novel therapeutic strategies in HER2-positive metastatic breast cancer. Br J Cancer 2012; 106: 6-13
• 12 Cameron D, Casey M, Press M et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat 2008; 112: 533-543
• 13 Blackwell KL, Burstein HJ, Storniolo AM et al. Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J ClinOncol 2010; 28: 1124-1130
• 14 Johnston S, Pippen Jr J, Pivot X et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J ClinOncol 2009; 27: 5538-5546
• 15 Lin NU, Diéras V, Paul D et al. . Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res 2009; 15: 1452-1459
• Weiterführende Literatur bei den Autoren