Clinical utility of serine proteases in breast cancer

Abstract

The serine protease uPA and its inhibitor PAI-1 are involved in the degradation of tumor stroma and basement membrane. The independent prognostic value of serine protease urokinase-type plasminogen activator uPA and its inhibitor PAI-1 in breast cancer has been almost uniformly confirmed in numerous individual studies as well as in a meta-analysis, including 18 data sets of more than 8,000 patients. According to these observations, the risk ofrelapse in node negative patients with low levels of uPA and PAI-1 is less then 10%; these patients could be spared from toxic adjuvant systemic therapy.Clinically relevant and even more important is the information that uPA and its inhibitor PAI-1 may also have a predictive value for response to either hormonal or cytotoxic therapy in early breast cancer. According to our data obtained from altogether 460 operable breast cancer patients, uPA and PAI-1 may have a predictive value for the response to hormone therapy, but notto chemotherapy. The high PAI-1 levels were associated with a higher risk of relapse in the patients without adjuvant systemic therapy (HR 2.14; C.I. 95%= 0.48-9.56; p=0.321) and in the patients treated with chemotherapy (RR 2.48; C.1. 95%=1.35-4.57; p=0.003). However, in the patients treated with adjuvant hormone therapy, either alone or in combination with chemotherapy, the prognosric value of uPA and PAI-1 was diminished. Moreover, high levels ofboth uPA and PAI-1 were associated with a lower risk of relapse (HR 0.79; p=0.693 and HR 0.26 p= 0.204, respectively). On the basis of currently available evidence, serine protease uPA and its inhibitor PAI-1 are certainly the markers that improve a proper selection of candidates for adjuvant systemic therapy and may also be the markers that could facilitate treatment decision in each individual patient, which is of utmost importance.

Keywords

Breast Neoplasms;diagnostika;Dojka, novotvorbe;dojke;novotvorbe;Plasminogen Activator Inhibitor 1;Plazminogen aktivator, inhibitor 1;Prognosis;Prognoza;proteaze;Urokinase;zdravljenje

Data

Language:	English
Year of publishing:	2004
Typology:	1.04 - Professional Article
Organization:	OI - Institute of Oncology
Publisher:	Association of Radiology and Oncology
UDC:	616-006
COBISS:	18165977
ISSN:	1318-2099
Parent publication:	Radiology and oncology
Views:	25
Downloads:	3
Average score:	0 (0 votes)
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Other data

Secondary language:	Slovenian
Secondary title:	Klinična uporabnost serinskih proteaz pri raku dojk
Secondary abstract:	Serinska proteaza uPA in njen inhibitor PAI-1 sta udeležena pri razgradnji tumorske strome ter bazalne membrane. Neodvisni napovedni pomen serinske proteaze uPA in njenega inhibitorja PAI-1 pri raku dojke je bil enoznačno potrjen v številnih posameznih raziskavah kot tudi v metaanalizi, v katero je bilo vključenih 18 datotek s podatki več kot 8000 bolnic. Glede na te izsledkeje tveganje za ponovitev bolezni pri bolnicah brez prizadetih pazdušnih bezgavk in nizkimi vrednostmi uPA in PAI-1 v prvotnem tumorju manjšeod 10%. Tem bolnicam lahko prihranimo dopolnilno sistemsko zdravljenje, katerega pogosto spremljajo neželeni učinki. Za vsakodnevno klinično delo pa je še pomembnejše, da prvi izsledki potrjujejo tudi možen napovedni pomen uPA in PAI-1 za odgovor na dopolnilno sistemsko zdravljenje zgodnjega raka dojk. Naša opažanja pri 460 bolnicah z operabilnim rakom dojk potrjujejo napovedni pomen uPA in PAI-1 za odgovor na hormonsko zdravljenje, ne pa za odgovor na citostatsko zdravljenje. Bolnice z visokimi vrednostmi PAI-1 v prvotnem tumorju so imele več kot dvakrat višje tveganje ponovitve bolezni, če niso bile zdravljene z dopolnilno sistemsko terapijo (HR 2.14; C.I. 95%= 0.48-9.56;p=0.321) ali pa so bile zdravljene samo s kemoterapijo (RR 2.48; C.I. 95%=1.354.57; p=0.003). Slab napovedni pomen visokih vrednosti uPA in PAI-1 pa se je povsem izničil pri bolnicah, ki so prejele dopolnilno hormonskozdravljenje, samo ali v kombinaciji z kemoterapijo. Še več, pri bolnicah, ki so prejele hormonsko zdravljenje, je bilo tveganje za ponovitev bolezni celo manjše v primeru visokih vsebnosti uPA ali PAI-1 v prvotnem tumorju (HR 0.79; p=0.693 and HR 0.26 p= 0.204). Serinska proteaza uPA in njeninhibitor PAI-1 sta danes močna napovedna dejavnika poteka raka dojk, ki omogočata ustreznejši izbor bolnic za dopolnilno sistemsko zdravljenje. (Izvleček skrajšan pri 2000 znakih).
Secondary keywords:	Breast Neoplasms;Urokinase;Plasminogen Activator Inhibitor 1;Prognosis;Dojka, novotvorbe;Plazminogen aktivator, inhibitor 1;Prognoza;
Type (COBISS):	Not categorized
Source comment:	BSDOCID107826;
Pages:	str. 85-92
Volume:	ǂLetn. ǂ38
Issue:	ǂšt. ǂ2
Chronology:	June 2004
ID:	22902974