Prognostic importance of thymidylate synthase expression in early breast cancer

B. C. Pestalozzi, H. F. Peterson, R. D. Gelber, A. Goldhirsch, B. A. Gusterson, H. Trihia, J. Lindtner, H. Cortés-Funes, E. Simmoncini, M. J. Byrne, R. Golouh, C. M. Rudenstam, M. Castiglione-Gertsch, C. J. Allegra, P. G. Johnston

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Abstract

Purpose: To assess the prognostic importance of thymidylate synthase (TS) expression in breast tumors of patients with early-stage breast cancer, and to determine whether the benefit of chemotherapy (CT) is associated with TS expression. Patients and Methods: The level of TS expression was evaluated in 210 node-negative and 278 node-positive patients enrolled onto Trial V of the International Breast Cancer Study Group ([IBCSG] formerly the Ludwig Breast Cancer Study Group) with a median follow-up time of 8.5 years. TS expression was assessed using the immunohistochemical method with the monoclonal antibody TS 106 on paraffin-embedded tissue specimens. Results: High TS expression was associated with a significantly worse prognosis in node-positive but not in node-negative breast cancer patients. Twenty-seven percent of node-positive patients with high TS expression were disease-free at 10 years, compared with 44% of node-positive patients with low TS expression (P = .03). Forty-one percent of patients with node-positive high- TS-expressing tumors were alive after 10 years, compared with 49% of those with low TS expression (P = .06). The association between TS and disease- free survival (DFS) and overall survival (OS) was independent of other prognostic factors such as tumor size, tumor grade, nodal status, vessel invasion, estrogen receptor (ER)/progestin receptor (PR) status, c-erb B-2, or Ki-67 expression. In node-positive patients, six cycles of standard adjuvant cyclophosphamide, methotrexate, and fluorouracil ([5-FU] CMF) CT improved DFS and OS compared with one cycle of perioperative CMF therapy. The magnitude of this benefit was greatest in patients whose tumors had high TS expression (P <.01 for DFS; P <.01 for OS). Node-negative patients demonstrated no difference in outcome to CT based on TS expression; however, the power to detect differences was limited by the small number of events in this group. Conclusion: In early-stage breast cancer, high TS expression is associated with a significantly worse prognosis in node-positive patients. Node-positive patients with high TS levels demonstrate the most significant improvement in DFS and OS when treated with six cycles of conventional adjuvant CMF therapy.

Original languageEnglish
Pages (from-to)1923-1931
Number of pages9
JournalJournal of Clinical Oncology
Volume15
Issue number5
Publication statusPublished - May 1997

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Thymidylate Synthase
Breast Neoplasms
Disease-Free Survival
Survival
Drug Therapy
Fluorouracil
Neoplasms
Progesterone Receptors
Methotrexate
Estrogen Receptors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pestalozzi, B. C., Peterson, H. F., Gelber, R. D., Goldhirsch, A., Gusterson, B. A., Trihia, H., ... Johnston, P. G. (1997). Prognostic importance of thymidylate synthase expression in early breast cancer. Journal of Clinical Oncology, 15(5), 1923-1931.

Prognostic importance of thymidylate synthase expression in early breast cancer. / Pestalozzi, B. C.; Peterson, H. F.; Gelber, R. D.; Goldhirsch, A.; Gusterson, B. A.; Trihia, H.; Lindtner, J.; Cortés-Funes, H.; Simmoncini, E.; Byrne, M. J.; Golouh, R.; Rudenstam, C. M.; Castiglione-Gertsch, M.; Allegra, C. J.; Johnston, P. G.

In: Journal of Clinical Oncology, Vol. 15, No. 5, 05.1997, p. 1923-1931.

Research output: Contribution to journalArticle

Pestalozzi, BC, Peterson, HF, Gelber, RD, Goldhirsch, A, Gusterson, BA, Trihia, H, Lindtner, J, Cortés-Funes, H, Simmoncini, E, Byrne, MJ, Golouh, R, Rudenstam, CM, Castiglione-Gertsch, M, Allegra, CJ & Johnston, PG 1997, 'Prognostic importance of thymidylate synthase expression in early breast cancer', Journal of Clinical Oncology, vol. 15, no. 5, pp. 1923-1931.
Pestalozzi BC, Peterson HF, Gelber RD, Goldhirsch A, Gusterson BA, Trihia H et al. Prognostic importance of thymidylate synthase expression in early breast cancer. Journal of Clinical Oncology. 1997 May;15(5):1923-1931.
Pestalozzi, B. C. ; Peterson, H. F. ; Gelber, R. D. ; Goldhirsch, A. ; Gusterson, B. A. ; Trihia, H. ; Lindtner, J. ; Cortés-Funes, H. ; Simmoncini, E. ; Byrne, M. J. ; Golouh, R. ; Rudenstam, C. M. ; Castiglione-Gertsch, M. ; Allegra, C. J. ; Johnston, P. G. / Prognostic importance of thymidylate synthase expression in early breast cancer. In: Journal of Clinical Oncology. 1997 ; Vol. 15, No. 5. pp. 1923-1931.
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title = "Prognostic importance of thymidylate synthase expression in early breast cancer",
abstract = "Purpose: To assess the prognostic importance of thymidylate synthase (TS) expression in breast tumors of patients with early-stage breast cancer, and to determine whether the benefit of chemotherapy (CT) is associated with TS expression. Patients and Methods: The level of TS expression was evaluated in 210 node-negative and 278 node-positive patients enrolled onto Trial V of the International Breast Cancer Study Group ([IBCSG] formerly the Ludwig Breast Cancer Study Group) with a median follow-up time of 8.5 years. TS expression was assessed using the immunohistochemical method with the monoclonal antibody TS 106 on paraffin-embedded tissue specimens. Results: High TS expression was associated with a significantly worse prognosis in node-positive but not in node-negative breast cancer patients. Twenty-seven percent of node-positive patients with high TS expression were disease-free at 10 years, compared with 44{\%} of node-positive patients with low TS expression (P = .03). Forty-one percent of patients with node-positive high- TS-expressing tumors were alive after 10 years, compared with 49{\%} of those with low TS expression (P = .06). The association between TS and disease- free survival (DFS) and overall survival (OS) was independent of other prognostic factors such as tumor size, tumor grade, nodal status, vessel invasion, estrogen receptor (ER)/progestin receptor (PR) status, c-erb B-2, or Ki-67 expression. In node-positive patients, six cycles of standard adjuvant cyclophosphamide, methotrexate, and fluorouracil ([5-FU] CMF) CT improved DFS and OS compared with one cycle of perioperative CMF therapy. The magnitude of this benefit was greatest in patients whose tumors had high TS expression (P <.01 for DFS; P <.01 for OS). Node-negative patients demonstrated no difference in outcome to CT based on TS expression; however, the power to detect differences was limited by the small number of events in this group. Conclusion: In early-stage breast cancer, high TS expression is associated with a significantly worse prognosis in node-positive patients. Node-positive patients with high TS levels demonstrate the most significant improvement in DFS and OS when treated with six cycles of conventional adjuvant CMF therapy.",
author = "Pestalozzi, {B. C.} and Peterson, {H. F.} and Gelber, {R. D.} and A. Goldhirsch and Gusterson, {B. A.} and H. Trihia and J. Lindtner and H. Cort{\'e}s-Funes and E. Simmoncini and Byrne, {M. J.} and R. Golouh and Rudenstam, {C. M.} and M. Castiglione-Gertsch and Allegra, {C. J.} and Johnston, {P. G.}",
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T1 - Prognostic importance of thymidylate synthase expression in early breast cancer

AU - Pestalozzi, B. C.

AU - Peterson, H. F.

AU - Gelber, R. D.

AU - Goldhirsch, A.

AU - Gusterson, B. A.

AU - Trihia, H.

AU - Lindtner, J.

AU - Cortés-Funes, H.

AU - Simmoncini, E.

AU - Byrne, M. J.

AU - Golouh, R.

AU - Rudenstam, C. M.

AU - Castiglione-Gertsch, M.

AU - Allegra, C. J.

AU - Johnston, P. G.

PY - 1997/5

Y1 - 1997/5

N2 - Purpose: To assess the prognostic importance of thymidylate synthase (TS) expression in breast tumors of patients with early-stage breast cancer, and to determine whether the benefit of chemotherapy (CT) is associated with TS expression. Patients and Methods: The level of TS expression was evaluated in 210 node-negative and 278 node-positive patients enrolled onto Trial V of the International Breast Cancer Study Group ([IBCSG] formerly the Ludwig Breast Cancer Study Group) with a median follow-up time of 8.5 years. TS expression was assessed using the immunohistochemical method with the monoclonal antibody TS 106 on paraffin-embedded tissue specimens. Results: High TS expression was associated with a significantly worse prognosis in node-positive but not in node-negative breast cancer patients. Twenty-seven percent of node-positive patients with high TS expression were disease-free at 10 years, compared with 44% of node-positive patients with low TS expression (P = .03). Forty-one percent of patients with node-positive high- TS-expressing tumors were alive after 10 years, compared with 49% of those with low TS expression (P = .06). The association between TS and disease- free survival (DFS) and overall survival (OS) was independent of other prognostic factors such as tumor size, tumor grade, nodal status, vessel invasion, estrogen receptor (ER)/progestin receptor (PR) status, c-erb B-2, or Ki-67 expression. In node-positive patients, six cycles of standard adjuvant cyclophosphamide, methotrexate, and fluorouracil ([5-FU] CMF) CT improved DFS and OS compared with one cycle of perioperative CMF therapy. The magnitude of this benefit was greatest in patients whose tumors had high TS expression (P <.01 for DFS; P <.01 for OS). Node-negative patients demonstrated no difference in outcome to CT based on TS expression; however, the power to detect differences was limited by the small number of events in this group. Conclusion: In early-stage breast cancer, high TS expression is associated with a significantly worse prognosis in node-positive patients. Node-positive patients with high TS levels demonstrate the most significant improvement in DFS and OS when treated with six cycles of conventional adjuvant CMF therapy.

AB - Purpose: To assess the prognostic importance of thymidylate synthase (TS) expression in breast tumors of patients with early-stage breast cancer, and to determine whether the benefit of chemotherapy (CT) is associated with TS expression. Patients and Methods: The level of TS expression was evaluated in 210 node-negative and 278 node-positive patients enrolled onto Trial V of the International Breast Cancer Study Group ([IBCSG] formerly the Ludwig Breast Cancer Study Group) with a median follow-up time of 8.5 years. TS expression was assessed using the immunohistochemical method with the monoclonal antibody TS 106 on paraffin-embedded tissue specimens. Results: High TS expression was associated with a significantly worse prognosis in node-positive but not in node-negative breast cancer patients. Twenty-seven percent of node-positive patients with high TS expression were disease-free at 10 years, compared with 44% of node-positive patients with low TS expression (P = .03). Forty-one percent of patients with node-positive high- TS-expressing tumors were alive after 10 years, compared with 49% of those with low TS expression (P = .06). The association between TS and disease- free survival (DFS) and overall survival (OS) was independent of other prognostic factors such as tumor size, tumor grade, nodal status, vessel invasion, estrogen receptor (ER)/progestin receptor (PR) status, c-erb B-2, or Ki-67 expression. In node-positive patients, six cycles of standard adjuvant cyclophosphamide, methotrexate, and fluorouracil ([5-FU] CMF) CT improved DFS and OS compared with one cycle of perioperative CMF therapy. The magnitude of this benefit was greatest in patients whose tumors had high TS expression (P <.01 for DFS; P <.01 for OS). Node-negative patients demonstrated no difference in outcome to CT based on TS expression; however, the power to detect differences was limited by the small number of events in this group. Conclusion: In early-stage breast cancer, high TS expression is associated with a significantly worse prognosis in node-positive patients. Node-positive patients with high TS levels demonstrate the most significant improvement in DFS and OS when treated with six cycles of conventional adjuvant CMF therapy.

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