Avtor/Urednik		Harbeck, Nadia; Čufer, Tanja; Borštnar, Simona
Naslov		Ten-year analysis of the prospective multicentre Chemo-N0 trial validates American Society of Clinical Oncology (ASCO)-recommended biomarkers uPA and PAI-1 for therapy decision making in node-negative breast cancer patients
Tip		članek
Vol. in št.		Letnik 49, št. 8
Leto izdaje		2013
Obseg		str. 1825-1835
ISSN		0959-8049 - European journal of cancer (Oxford, England : 1990)
Jezik		eng
Abstrakt		Aim: Final 10-year analysis of the prospective randomised Chemo-N0 trial ispre- sented. Based onthe Chemo-N0 interim results and anEuropean Organisation for Research and Treatment of Cancer (EORTC)pooled analysis (n = 8377),American Society ofClinical Oncology (ASCO) and Arbeitsgemeinschaft Gyna kologische Onkologie (AGO) guidelines recommend invasion and metastasis markers urokinase-type plasminogen activator (uPA)/ plasminogen activator inhibitor-1 (PAI-1)for risk assessment and treatment decision in node-negative (N0) breast cancer (BC). Methods: The final Chemo-N0 trial analysis (recruitment19931998; n = 647;12centres)com- prises 113 (5-167) months ofmedian follow-up.Patients with low-uPA and PAI-1 tumour tissue levels (n = 283)were observed.External quality assurance guaranteed uPA/PAI-1 enzyme-linked immunosorbent assay (ELISA)standardisation.Of364 high uPA and/or PAI- 1 patients,242 agreed torandomisation for CMF chemotherapy (n = 117)versus observation (n = 125). Results: Actuarial 10-year recurrence rate (withoutany adjuvant systemic therapy)for high-uPA/PAI-1 observation group patients (randomised and non-randomised)was 23.0%,in contrast to only 12.9%for low-uPA/PAI-1 patients (plog-rank = 0.011).High-risk patients randomised to cyclophosphamide-methotrexate-5-fluorouracil(CMF)therapy had a26.0% lower estimated probability of disease recurrence than those randomised for observation (inten- tion-to-treat (ITT)-analysis: hazard ratio (HR)0.74 (0.441.27); plog-ran k = 0.28).Per-protocol analysis demonstrated significanttreatment benefit:HR0.48 (0.260.88), p = 0.019,disease-free survival (DFS) Cox regression,adjusted for tumour stage and grade. Conclusions: Chemo-N0 is the firstprospective biomarker-based therapy trial inearly BC defining patients reaching good long-term DFS without adjuvant systemic therapy.Using a standardised uPA/PAI-1 ELISA, almost half ofN0-patients could bespared chemotherapy, while high-risk patients benefit from adjuvant chemotherapy.These 10-year results validate the long-term prognostic impact ofuPA/PAI-1 and the benefitfrom adjuvant chemotherapy in the high-uPA/PAI-1 group athighest level ofevidence.They thus support the guideline-based routine use ofuPA/PAI-1 for risk-adapted individualised therapy decisions inN0breast cancer.
Proste vsebinske oznake		rak dojke tumorski označevalci adjuvantna kemoterapija breast cancer cancer biomarkers adjuvant chemotherapy