Linked Life Data

11245445

Source:http://linkedlifedata.com/resource/pubmed/id/11245445

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-3-13
pubmed:abstractText
Thymidylate synthase (TS) is a crucial target for 5-fluorouracil (5-FU) in the de novo pathway of pyrimidine synthesis, which is necessary for DNA synthesis. Thymidine kinase (TK) plays a key role in the complementary or alternative salvage pathway of pyrimidine synthesis in acute or pathological tissue stress. In the present study, the activity levels of TS and TK were determined in 257 primary breast tumors of patients who received tamoxifen as first-line systemic therapy after diagnosis of advanced disease. In 155 (60%) responding patients, the median response duration was 23 months for tumors with low TK activity, 15 months for tumors with intermediate TK activity, and 13 months for tumors with high TK activity (P = 0.003). In Cox multivariate analysis corrected for classical predictive factors including estrogen receptor and progesterone receptor, patients with intermediate and high levels of TK activity in their tumors showed a rapid disease progression (P = 0.0002) and an early death (P = 0.002) after start of tamoxifen treatment. Tumor TS activity levels were not significantly associated with the efficacy of tamoxifen treatment. In 121 patients who became resistant to tamoxifen or additional endocrine treatments and who received 5-FU-containing polychemotherapy, tumor TK activity was not significantly related to the efficacy of chemotherapy. Of the 13 patients with low tumor TS activity, only 1 (8%) responded favorably, whereas 46% (43 of 93) of those with intermediate and 73% (11 of 15) of those with high TS activity responded (P = 0.001). In Cox multivariate regression analysis in which TS was the only significant variable, intermediate and high TS activities were associated with a slow disease progression (P = 0.005) and prolonged survival (P = 0.016) on chemotherapy. In conclusion, for patients with recurrent breast cancer, high tumor TK activity is a significant marker of poor clinical outcome on tamoxifen therapy. Elevated tumor TS activity predicts a favorable outcome for 5-FU-containing polychemotherapy when applied after tumor progression on endocrine therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1421-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11245445-Adult, pubmed-meshheading:11245445-Aged, pubmed-meshheading:11245445-Aged, 80 and over, pubmed-meshheading:11245445-Antineoplastic Agents, Hormonal, pubmed-meshheading:11245445-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:11245445-Breast Neoplasms, pubmed-meshheading:11245445-Cyclophosphamide, pubmed-meshheading:11245445-Disease-Free Survival, pubmed-meshheading:11245445-Doxorubicin, pubmed-meshheading:11245445-Drug Resistance, Neoplasm, pubmed-meshheading:11245445-Epirubicin, pubmed-meshheading:11245445-Female, pubmed-meshheading:11245445-Fluorouracil, pubmed-meshheading:11245445-Humans, pubmed-meshheading:11245445-Methotrexate, pubmed-meshheading:11245445-Middle Aged, pubmed-meshheading:11245445-Neoplasm Recurrence, Local, pubmed-meshheading:11245445-Tamoxifen, pubmed-meshheading:11245445-Thymidine Kinase, pubmed-meshheading:11245445-Thymidylate Synthase
pubmed:year
2001
pubmed:articleTitle
Thymidine kinase and thymidylate synthase in advanced breast cancer: response to tamoxifen and chemotherapy.
pubmed:affiliation
Department of Medical Oncology, Rotterdam Cancer Institute, Daniel den Hoed Kliniek, Academic Hospital Rotterdam, The Netherlands. Foekens@bidh.azr.nl
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, Non-U.S. Gov't