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The predictive value of bcl-2, bax, bcl-xL, bag-1, fas, and fasL for chemotherapy response in advanced breast cancer

Sjostrom, J; Blomqvist, C; von Boguslawski, K; Bengtsson, NO; Mjaaland, I; Malmström, Per LU ; Ostenstadt, B; Wist, E; Valvere, V and Takayama, S, et al. (2002) In Clinical Cancer Research 8(3). p.811-816
Abstract
Purpose: The purpose was to evaluate the utility of some bcl-2 family proteins fas and fasL as predictive indicators for chemotherapy response in advanced breast cancer. Experimental Design: Between October 1994 and October 1997, 283 patients with advanced breast cancer were included in a multicenter randomized study comparing docetaxel (D) to sequential methotrexate and 5-fluorouracil (MF) after anthracycline failure. The response rates (complete response + partial response) were 42 and 21% in the D and MF arms, respectively (P < 0.001). In 126 patients, histological blocks of primary tumors were available for inummohistochemical analysis of bax, bcl-2, bcl-xL, bag-1, fas and fasL. Results: Of the investigated factors, bag-1 correlated... (More)
Purpose: The purpose was to evaluate the utility of some bcl-2 family proteins fas and fasL as predictive indicators for chemotherapy response in advanced breast cancer. Experimental Design: Between October 1994 and October 1997, 283 patients with advanced breast cancer were included in a multicenter randomized study comparing docetaxel (D) to sequential methotrexate and 5-fluorouracil (MF) after anthracycline failure. The response rates (complete response + partial response) were 42 and 21% in the D and MF arms, respectively (P < 0.001). In 126 patients, histological blocks of primary tumors were available for inummohistochemical analysis of bax, bcl-2, bcl-xL, bag-1, fas and fasL. Results: Of the investigated factors, bag-1 correlated positively with bax, bcl-2, and fasL, and fasL correlated positively with fas and bax. None of these apoptosis-related factors was associated with a response to chemotherapy either in the whole patient population or in the D or MF arms. Interestingly, low bcl-2 expression was associated with shorter time to progression (P = 0.02) and shorter overall survival (OS; P = 0.001). High fasL expression showed a trend toward shorter OS. In multivariate backwards stepwise Cox analysis, in which histological grade and estrogen receptor status (ER) were also included, bcl-2 (P = 0.01) and fasL (P = 0.005) remained highly significantly associated with OS, whereas histological grade and ER lost their significance. Conclusions: None of the investigated apoptosis-related factors of primary tumor could predict the later response to either D or MF treatment. However, fasL and bcl-2 were strong prognostic factors. Patients who had tumors with high fasL and low bcl-2 expression had the shortest OS. (Less)
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Clinical Cancer Research
volume
8
issue
3
pages
811 - 816
publisher
American Association for Cancer Research
external identifiers
  • wos:000174403300025
  • scopus:0036300989
ISSN
1078-0432
language
English
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yes
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eb168e96-dbf9-4da4-90a9-a65fd71ffd6e (old id 342085)
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http://clincancerres.aacrjournals.org/cgi/content/abstract/8/3/811
date added to LUP
2007-11-14 12:35:57
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2017-08-20 03:36:11
@article{eb168e96-dbf9-4da4-90a9-a65fd71ffd6e,
  abstract     = {Purpose: The purpose was to evaluate the utility of some bcl-2 family proteins fas and fasL as predictive indicators for chemotherapy response in advanced breast cancer. Experimental Design: Between October 1994 and October 1997, 283 patients with advanced breast cancer were included in a multicenter randomized study comparing docetaxel (D) to sequential methotrexate and 5-fluorouracil (MF) after anthracycline failure. The response rates (complete response + partial response) were 42 and 21% in the D and MF arms, respectively (P &lt; 0.001). In 126 patients, histological blocks of primary tumors were available for inummohistochemical analysis of bax, bcl-2, bcl-xL, bag-1, fas and fasL. Results: Of the investigated factors, bag-1 correlated positively with bax, bcl-2, and fasL, and fasL correlated positively with fas and bax. None of these apoptosis-related factors was associated with a response to chemotherapy either in the whole patient population or in the D or MF arms. Interestingly, low bcl-2 expression was associated with shorter time to progression (P = 0.02) and shorter overall survival (OS; P = 0.001). High fasL expression showed a trend toward shorter OS. In multivariate backwards stepwise Cox analysis, in which histological grade and estrogen receptor status (ER) were also included, bcl-2 (P = 0.01) and fasL (P = 0.005) remained highly significantly associated with OS, whereas histological grade and ER lost their significance. Conclusions: None of the investigated apoptosis-related factors of primary tumor could predict the later response to either D or MF treatment. However, fasL and bcl-2 were strong prognostic factors. Patients who had tumors with high fasL and low bcl-2 expression had the shortest OS.},
  author       = {Sjostrom, J and Blomqvist, C and von Boguslawski, K and Bengtsson, NO and Mjaaland, I and Malmström, Per and Ostenstadt, B and Wist, E and Valvere, V and Takayama, S and Reed, JC and Saksela, E},
  issn         = {1078-0432},
  language     = {eng},
  number       = {3},
  pages        = {811--816},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {The predictive value of bcl-2, bax, bcl-xL, bag-1, fas, and fasL for chemotherapy response in advanced breast cancer},
  volume       = {8},
  year         = {2002},
}