The predictive value of bcl-2, bax, bcl-xL, bag-1, fas, and fasL for chemotherapy response in advanced breast cancer
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/342085
- author
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- in
- 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
- LU publication?
- yes
- id
- eb168e96-dbf9-4da4-90a9-a65fd71ffd6e (old id 342085)
- alternative location
- http://clincancerres.aacrjournals.org/cgi/content/abstract/8/3/811
- date added to LUP
- 2016-04-01 11:59:08
- date last changed
- 2022-04-21 00:41:52
@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 < 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}}, url = {{http://clincancerres.aacrjournals.org/cgi/content/abstract/8/3/811}}, volume = {{8}}, year = {{2002}}, }