Skip to main content
SpringerLink
Log in

Triple-negative breast cancer

Triple-negativer Brustkrebs

  • Themenschwerpunkt
  • Published:
Wiener Medizinische Wochenschrift Aims and scope Submit manuscript

Zusammenfassung

Rezente molekularbiologische Fortschritte haben zu einem besseren Verständnis der Tumorbiologie beigetragen. Für hormonabhängige und Her2-positive Karzinome stehen heute zielgerichtete Therapieoptionen zur Verfügung, solche Behandlungsmöglichkeiten fehlen jedoch bei triple-negativen Tumoren. Patientinnen mit triple-negativem Brustkrebs haben ein erhöhtes Rückfallsrisiko. Präklinische und frühe klinische Daten zeigen, dass bei dieser Erkrankungsentität Platine die höchste Wirksamkeit aller Zytostatika aufweisen dürften, letztlich fehlen aber Daten prospektiv randomisierter Studien. Bevacizumab, wie auch andere Substanzen, die gegen das Gefäßwachstum gerichtet sind, sind bei allen biologischen Subtypen des Mammakarzinoms potentiell wirksam. Solche Ansätze können also nicht als spezifische zielgerichtete Behandlung triple-negativer Tumore verstanden werden. Ein Teil der triple-negativen und basalzelligen Karzinome zeichnet sich durch Defekte genetischer Reparaturmechanismen aus, wie sie in ähnliche Weise bei Tumoren mit Keimbahnmutationen des BRCA-1 Gens vorliegen. Die medikamentöse Blockade alternativer DNA-Reparaturmechanismen dürfte daher einen der wichtigsten Ansätze zur erfolgreichen Behandlung triple-negativer Tumore darstellen.

Summary

Recent advances in biological characterization of breast cancer have eventually increased our understanding of underlying tumour biology. While for endocrine responsive and Her2-positive disease different molecular targeted therapies are available, up to now no specific targeted approach for triple-negative breast cancer has been developed. Patients with triple-negative disease are at high risk for tumour recurrence. Preclinical and limited clinical data suggest that platinum-based regimens may be the most active conventional chemotherapy, but prospective randomized trials are missing. Bevacizumab and other agents targeting tumour vessel growth have potential activity in all subtypes of breast cancer, and therefore are not considered a targeted approach for triple-negative tumours alone. Due to specific defects in DNA-damage repair, basal-like cancers depend on alternative, more error-prone repair pathways. Currently, scientific interest is focussing on drugs blocking those mechanisms. PARP-1 inhibitors, in conjunction with platinum derivatives, were found to exhibit significant survival benefit over chemotherapy alone even in a relatively small phase II study. For the first time, this approach offers the chance of highly active, specific therapy for triple-negative disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • American Cancer Society Facts and Figures. Available via: http://www.cancer.org/downloads/STT/Global_Facts_and_Figures_2007_rev2.pdf. Cited September 21st 2009

  • Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast cancer. Nature, 406: 747–752, 2000

    Article  CAS  PubMed  Google Scholar 

  • 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, 100: 8418–8423, 2003

    Article  PubMed  Google Scholar 

  • Nielson TO, Hsu FD, Jensen K, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Mod Pathol, 19: 264–271, 2006

    Article  Google Scholar 

  • Cheang MC, Voduc D, Bajdik C, et al. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res, 14: 1368–1376, 2008

    Article  CAS  PubMed  Google Scholar 

  • Rakka EA, Tan DS, Foulkes WD, et al. Are triple-negative tumours and basal-like breast cancer synonymous? Breast Can Res, 9: 404, 2007

    Article  Google Scholar 

  • Tischkowitz M, Brunet JS, Begin LR, et al. Use of immunohistochemistry can refine prognosis in triple negative breast cancer. BMC Cancer, 7: 134, 2007

    Article  PubMed  Google Scholar 

  • Foulkes WD, Stefansson IM, Chappuis PO, et al. Germline BRCA mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst, 95: 1482–1485, 2003

    CAS  PubMed  Google Scholar 

  • Futreal PA, Liu Q, Shattuk-Eidens D, et al. BRCA1 mutations in primary breast and ovarian carcinomas. Science, 266: 120–122, 1994

    Article  CAS  PubMed  Google Scholar 

  • Turner NC, Reis-Filho JS, Russel AM, et al. BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene, 26: 2126–2132, 2007

    Article  CAS  PubMed  Google Scholar 

  • Berger C, Pierce LN, Kruger M, et al. Identification of Id4 as a regulator of BRCA1 expression by using a ribozyme-library-based inverse genomics approach. Proc Natl Acad Sci USA, 98: 130–135, 2001

    Article  Google Scholar 

  • Turner N, Tutt A, Ashworth A. Hallmarks of "BRCAness" in sporadic cancers. Nat Rev Cancer, 4: 814–819, 2004

    Article  CAS  PubMed  Google Scholar 

  • Mullan PB, Quinn JE, Harkin DP. The role of BRCA1 in transcriptional regulation and cell cycle control. Oncogene, 25: 5854–5863, 2006

    Article  CAS  PubMed  Google Scholar 

  • Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA-repair defect in BRCA mutant cells as a therapeutic strategy. Nature, 434: 917–921, 2005

    Article  CAS  PubMed  Google Scholar 

  • Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA, 295: 2492–2502, 2006

    Article  CAS  PubMed  Google Scholar 

  • Fan C, Oh DS, Wessels L, et al. Concordance among gene-expression-based predictors for breast cancer. N Engl J Med, 355: 560–569, 2006

    Article  CAS  PubMed  Google Scholar 

  • Beslija S, Bonneterre J, Burstein H, et al. Third Consensus on medical treatment of metastatic breast cancer. Ann Oncol, 20: 1771–1785, 2009

    Article  CAS  PubMed  Google Scholar 

  • Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res, 13: 4429–4434, 2007

    Article  PubMed  Google Scholar 

  • Morris GJ, Naidu S, Topham AK, et al. Differences in breast carcinoma characteristics in newly diagnosed African–American and Caucasian patients: a single-institution compilation compared with the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer, 110: 876–884, 2007

    Article  PubMed  Google Scholar 

  • Kim MJ, Ro JY, Ahn SH, et al. Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes. Hum Pathol, 37: 1217–1226, 2006

    Article  CAS  PubMed  Google Scholar 

  • Millikan RC, Newman B, Tse CK, et al. Epidemiology of basal-like breast cancer. Breast Cancer Res Treat, 109: 123–139, 2998

    Article  Google Scholar 

  • Liedtke C, Manzouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol, 26: 1275–1281, 2008

    Article  PubMed  Google Scholar 

  • Steger GG, Galid A, Gnant M, et al. Pathologic complete response with six compared with three cycles of neoadjuvant epirubicin plus docetaxel and granulocyte colony-stimulating factor in operable breast cancer: results of ABCSG-14. J Clin Oncol, 25: 2012–2018, 2007

    Article  CAS  PubMed  Google Scholar 

  • Wahl AF, Donaldson KL, Fairchild C, et al. Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis. Nat Med, 2: 72–79, 1996

    Article  CAS  PubMed  Google Scholar 

  • Chabalier C, Lamare C, Racca C, et al. BRCA1 downregulation leads to premature inactivation of spindel checkpoint and confers paclitaxel resistance. Cell Cycle, 5: 1001–1007, 2006

    CAS  PubMed  Google Scholar 

  • Sirohi B, Arnedos M, Popat S, et al. Platinum-based chemotherapy in triple-negative breast cancer. Ann Oncol, 19: 1847–1852, 2009

    Article  Google Scholar 

  • Available via: http://www.clincialtrials.gov. Cited October 21st 2009

  • Frasci G, Comella P, Rinaldo M, et al. Preoperative weekly cisplatin-epirubicin-paclitaxel with G-CSF support in triple-negative operable breast cancer. Ann Oncol, 20: 1185–1192, 2009

    Article  CAS  PubMed  Google Scholar 

  • Byrski T, Huzarski T, Dent R, et al. Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat, 115: 359–363, 2009

    Article  CAS  PubMed  Google Scholar 

  • Diallo-Danebrock R, Ting E, Guz O, et al. Protein expression profiling in high-risk breast cancer patients treated with high-dose or conventional dose-dense chemotherapy. Clin Cancer Res, 13: 488–497, 2007

    Article  CAS  PubMed  Google Scholar 

  • Folkman J, Klagsbrun M. Angiogenic factors. Science, 235: 442–447, 1987

    Article  CAS  PubMed  Google Scholar 

  • Miller KD, Chap LI, Holmes FA, et al. Randomized phase III trial of capecitabine compared with bevacizumab and capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol, 23: 792–799, 2005

    Article  CAS  PubMed  Google Scholar 

  • Casanovas O, Hicklin DJ, Bergers G, et al. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell, 8: 299–309, 2005

    Article  CAS  PubMed  Google Scholar 

  • Miller KD, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med, 357: 2666–2676, 2007

    Article  CAS  PubMed  Google Scholar 

  • Miles D, Chan A, Romieu G, et al. Randomised, double-blind, placebo-controlled phase III study of bevacizumab with docetaxel or docetaxel with placebo as first-line therapy for patients with locally recurrent or metastatic breast cancer: AVADOJ Clin Oncol, 26(Suppl 18): 1008S, 2008

  • Pivot X, Verma S, Thomsen C, et al. Clinical benefit of bevacizumab (BV) plus first-line docetaxel (D) in elderly patients (pts) with locally recurrent (LR) or metastatic breast cancer (mBC): AVADO study. J Clin Oncol, 27(Suppl 15): 64S, 2009

    Google Scholar 

  • Robert N, Dieras V, Glaspy J, et al. RIBBON-1: a randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of HER2-negative locally recurrent or metastatic breast cancer. J Clin Oncol, 27(Suppl 15): 42S, 2009

    Google Scholar 

  • Ebos JM, Lee CR, Kerbel RS. Tumor and host-mediated pathways of resistance and disease progression in response to antiangiogenic therapy. Clin Cancer Res, 15: 5020–5025, 2009

    Article  CAS  PubMed  Google Scholar 

  • Lee JB, Woo OH, Park KH, et al. Bevacizumab for salvage treatment of metastatic breast cancer: a systemic review and meta-analysis of randomized controlled trials. Invest New Drugs, 2009. [Epub ahead of print]

  • Brufsky A, Bondarenko IN, Smirnov V, et al. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of HER2-negative metastatic breast cancer. Cancer Res, 69(Suppl. 3): Abstract Nr 42, 2009

  • Burstein HJ, Elias AD, Rugo HS, et al. Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol, 26: 1810–1816, 2008

    Article  CAS  PubMed  Google Scholar 

  • Moreno-Aspitia A, Morton RF, Hillman DW, et al. Phase II trial of sorafenib in patients with metastatic breast cancer previously exposed to anthracyclines or taxanes: North Central Cancer Treatment Group and Mayo Clinic Trial N0336. J Clin Oncol, 27: 11–15, 2009

    Article  CAS  PubMed  Google Scholar 

  • Baselga J, Segalla JG, Roché H, et al. 3LBA SOLTI-0701: A double-blind, randomized phase 2b study evaluating the efficacy and safety of sorafenib (SOR) compared to placebo (PL) when administered in combination with capecitabine (CAP) in patients (pts) with locally advanced (adv) or metastatic (met) breast cancer (BC). Eur J Cancer, 7(Suppl 2): 3S–4S, 2009

    Google Scholar 

  • Tutt A, Robson M, Garber JE, et al. Phase II trial of the oral PARP inhibitor olaparib in BRCA-deficient advanced breast cancer. J Clin Oncol, 27(Suppl 18): 803S, 2009

    Google Scholar 

  • O'Shaughnessy J, Osborne C, Pippen J, et al. Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): Results of a randomized phase II trial. J Clin Oncol, 27(Suppl 15): 793S, 2009

    Google Scholar 

  • Hoadley KA, Weigman VJ, Fan C, et al. EGFR associated expression profiles vary with breast tumor subtype. BMC Genomics, 8: 258, 2007

    Article  PubMed  Google Scholar 

  • Carey LA, Rugo H, Marcom PK, et al. TBCRC 001: EGFR inhibition with cetuximab added to carboplatin in metastatic triple negative (basal-like) breast cancer. J Clin Oncol, 26(Suppl 15): 43S, 2008

    Google Scholar 

  • Cristofanilli M, Valero V, Mangalik A, et al. A phase II multicenter, double-blind, randomized trial to compare anastrozole plus gefinitib with anastrozole plus placebo in postmenopausal women with hormone receptor-positive (HR+) metastatic breast cancer (MBC). J Clin Oncol, 26(Suppl 15): 44S, 2008

    Google Scholar 

  • O'Shaughnessy J, Weckstein D, Vukelja S, et al. Randomized phase II study of weekly irinotecan/carboplatin with or without cetuximab in patients with metastatic breast cancer. Breast Cancer Res Treat, 106(Suppl 1): 22S–23S, 2007

    Google Scholar 

  • Di Leo A, Gomez HL, Aziz Z, et al. Phase III, double-blind, randomized study comparing lapatinib plus paclitaxel with placebo plus paclitaxel as first-line treatment for metastatic breast cancer. J Clin Oncol, 26: 5544–5552, 2008

    Article  CAS  PubMed  Google Scholar 

  • Johnston S, Pippen 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 Clin Oncol, 2009. [Epub ahead of print]

  • Ozaki K, Kishikawa F, Tanaka M, et al. Histone deacetylase inhibitors enhance the chemosensitivity of tumor cells with cross-resistance to a wide range of DNA-damaging drugs. Cancer Sci, 99: 376–384, 2008

    Article  CAS  PubMed  Google Scholar 

  • Marty B, Maire V, Gravier E, et al. Frequent PTEN genomic alterations and activated phosphatidylinositol 3-kinase pathway in basal-like breast cancer cells. Breast Cancer Res, 10: R101, 2008

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Division of Oncology, Department of Medicine 1 and Cancer Centre, Medical University of Vienna, Vienna, Austria

    Rupert Bartsch, Christoph C. Zielinski & Guenther G. Steger

  2. Department of Medicine 1 (Haematology and Medical Oncology), Academic Teaching Hospital Elisabethinen, Linz, Austria

    Rupert Bartsch & Reinhard Ziebermayr

Authors
  1. Rupert Bartsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Reinhard Ziebermayr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christoph C. Zielinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guenther G. Steger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rupert Bartsch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bartsch, R., Ziebermayr, R., Zielinski, C. et al. Triple-negative breast cancer. Wien Med Wochenschr 160, 174–181 (2010). https://doi.org/10.1007/s10354-010-0773-6

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10354-010-0773-6

Schlüsselwörter

Keywords

Search

Navigation