Das tripelnegative/basale Mammakarzinom

Zusammenfassung

Das Mammakarzinom wird zunehmend als eine heterogene Gruppe individueller Mammakarzinomsubtypen verstanden. Diese Subgruppen unterscheiden sich sowohl (molekular-)pathologisch als auch klinisch. Der basale/tripelnegative Subtyp zeichnet sich durch eine fehlende Expression des Östrogenrezeptors (estrogen receptor, ER), des Progesteronrezeptors (PR) und des Her-2-Onkoproteins aus. Patientinnen mit einem tripelnegativen Mammakarzinom sind gekennzeichnet durch eine schlechte Prognose trotz einer hohen Ansprechrate gegenüber der systemischen Chemotherapie. Insbesondere Patientinnen, die nach der Primärtherapie ein Rezidiv erleiden, haben eine äußerst schlechte Überlebensprognose, nicht zuletzt aufgrund mangelnder Therapiealternativen. Vor diesem Hintergrund ist die Optimierung bestehender Therapieformen sowie die Entwicklung neuer systemischer Therapien für Patientinnen dieses Mammakarzinomsubtyps von besonderer Wichtigkeit.

Abstract

Breast cancer is increasingly understood as a heterogeneous mixture of individual subtypes which differ with regard to molecular, pathological and clinical features. The basal/triple negative subtype is characterized by the lack of expression of the estrogen receptor (ER), the progesterone receptor (PR) and the Her-2 oncogene. Patients bearing this unfavorable subtype suffer from an unfavorable prognosis despite increased response to systemic chemotherapy. Particularly those patients experiencing disease recurrence following primary therapy of their triple negative primary breast cancer have a poor prognosis, which is largely due to limited therapeutic options. In order to improve the prognosis of these individuals, clinical and basic research efforts should aim for an optimization of current treatments as well as the implementation of new therapies.

Mammakarzinom - tripelnegativ - basal - neoadjuvante Chemotherapie - gezielte Therapie

breast cancer - triple negative - basal - neoadjuvant chemotherapy - targeted therapy

Literatur

• 1 Forbes J F, Cuzick J, Buzdar A. et al. . Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial.  Lancet Oncol. 2008;  9 45-53
• 2 Carey L A, Dees E C, Sawyer L. et al . The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes.  Clin Cancer Res. 2007;  13 2329-2334
• 3 Carey L A, Perou C M, Livasy C A. et al . Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study.  JAMA. 2006;  295 2492-2502
• 4 Dent R, Trudeau M, Pritchard K I. et al . Triple-negative breast cancer: Clinical features and patterns of recurrence.  Clin Cancer Res. 2007;  13 4429-4434
• 5 Early Breast Cancer Trialists' Collaborative Group (EBCTCG) . Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials.  Lancet. 2005;  365 1687-1717
• 6 Farmer H, McCabe N, Lord C J. et al . Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy.  Nature. 2005;  434 917-921
• 7 Fernández-Sánchez M, Gamboa-Dominguez A, Uribe N. et al . Clinical and pathological predictors of the response to neoadjuvant anthracycline chemotherapy in locally advanced breast cancer.  Med Oncol. 2006;  23 171-183
• 8 Finn R S, Dering J, Ginther C. et al . Dasatinib, an orally active small molecule inhibitor of both the src and abl kinases, selectively inhibits growth of basal-type/“triple-negative” breast cancer cell lines growing in vitro.  Breast Cancer Res Treat. 2007;  105 319-326
• 9 Gluz O, Nitz U A, Harbeck N. et al. . Triple-negative high-risk breast cancer drives particular benefit from dose intensification of adjuvant chemotherapy: results of WSG AM‐01 trial.  Ann Oncol. 2008;  19 861-870
• 10 Goldhirsch A, Wood W C, Gelber R D. et al. . Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007.  Ann Oncol. 2007;  18 1133-1144
• 11 Haffty B G, Yang Q, Reiss M. et al . Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer.  J Clin Oncol. 2006;  24 5652-5657
• 12 Hayes D F, Thor A D, Dressler L G. et al. . HER2 and response to paclitaxel in node-positive breast cancer.  N Engl J Med. 2007;  357 1496-1506
• 13 Hess K R, Pusztai L, Buzdar A U. et al . Estrogen receptors and distinct patterns of breast cancer relapse.  Breast Cancer Res Treat. 2003;  78 105-118
• 14 Hoadley K A, Weigman V J, Fan C. et al . EGFR associated expression profiles vary with breast tumor subtype.  BMC Genomics. 2007;  8 258
• 15 Imkampe A, Bendall S, Bates T. The significance of the site of recurrence to subsequent breast cancer survival.  Eur J Surg Oncol. 2007;  33 420-423
• 16 Kennedy R D, Quinn J E, Mullan P B. et al . The role of BRCA1 in the cellular response to chemotherapy.  J Natl Cancer Inst. 2004;  96 1659-1668
• 17 Liedtke C, Mazouni C, Hess K R. et al . Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer.  J Clin Oncol. 2008;  26 1275-1281
• 18 Miller K, Wang M, Gralow J. et al . Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer.  N Engl J Med. 2007;  357 2666-2676
• 19 Millikan R C, Newman B, Tse C K. et al . Epidemiology of basal-like breast cancer.  Breast Cancer Res Treat. 2008;  109 123-139
• 20 Perou C M, Sørlie T, Eisen M B. et al . Molecular portraits of human breast tumours.  Nature. 2000;  406 747-752
• 21 Piccart-Gebhart M J, Procter M, Leyland-Jones B. et al. . Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.  N Engl J Med. 2005;  353 1659-1672
• 22 Rastogi P, Anderson S J, Bear H D. et al . Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B‐18 and B‐27. J Clin Oncol 2008; 26: 778–785.  Erratum in: J Clin Oncol. 2008;  26 2793
• 23 Romond E H, Perez E A, Bryant J. et al . Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.  N Engl J Med. 2005;  353 1673-1684
• 24 Rouzier R, Perou C M, Symmans W F. et al . Breast cancer molecular subtypes respond differently to preoperative chemotherapy.  Clin Cancer Res. 2005;  11 5678-5685
• 25 Ruckhäberle E, Rody A, Kaufmann M. Kongressbericht zur 44. Jahrestagung der American Society of Clinical Oncology, Chicago 30.5.–3.6.2008. Onkologische Therapie im Wandel – gerät die Chemotherapie an ihre Grenzen?.  Geburtsh Frauenheilk. 2008;  68 889-895
• 26 Slamon D J, 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
• 27 Sørlie T, Perou C M, Tibshirani R. et al . Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications.  Proc Natl Acad Sci USA. 2001;  98 10869-10874
• 28 Sørlie T, Tibshirani R, Parker J. et al . Repeated observation of breast tumor subtypes in independent gene expression data sets.  Proc Natl Acad Sci USA. 2003;  100 8418-8423