Cytosolic levels of TFF1/pS2 in breast cancer: Their relationship with clinical-pathological parameters and their prognostic significance

Breast Cancer Res Treat. 2006 Mar;96(1):63-72. doi: 10.1007/s10549-005-9041-7. Epub 2005 Nov 3.

Abstract

Background: The Trefoil Factor 1 (TFF1/pS2), a peptide consisting of 60 amino acids, is the most abundant estrogen-induced messenger RNA present in MCF-7 breast cancer cells. The objective of this work was to evaluate the cytosolic TFF1 content in breast carcinomas, its possible relationship with different clinical-pathological parameters, and its potential prognostic significance and predictive value.

Methods: Cytosolic TFF1 levels were examined by immunoradiometric assay in 1031 patients with invasive breast cancer. The median follow-up period was of 50 months.

Results: There was a wide variability of cytosolic TFF1 levels in tumors (0.9-743.2 ng/mg protein). Statistical analysis showed that TFF1 levels were significantly higher in premenopausal patients (p = 0.001), as well as in tumors showing any of the following characteristics: good differentiation (p = 0.0001), ER and PgR positivity (p = 0.0001 and p = 0.001, respectively), diploidy (p = 0.045) and a high S-phase fraction (p = 0.001). In addition, the presence of high intratumoral TFF1 levels (cut-off: 2 ng/mg protein) was independently associated with a shorter overall survival in the group of patients as a whole (p = 0.001) as well as in the subgroup with node-negative breast cancer (p = 0.0004). Likewise, high intratumoral TFF1 levels were associated with a more prolonged overall survival in patients who received adjuvant tamoxifen (p = 0.004).

Conclusions: In breast cancer patients, intratumoral TFF1 levels are associated with a better clinical outcome, especially in those with node-negative tumors. In addition, TFF1 levels have a low but significant predictive value in regards to response to adjuvant therapy with tamoxifen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / therapy
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / pathology
  • Carcinoma, Lobular / therapy
  • Combined Modality Therapy
  • Cytosol / metabolism*
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Immunoradiometric Assay
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Premenopause
  • Prognosis
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Survival Rate
  • Trefoil Factor-1
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Receptors, Estrogen
  • Receptors, Progesterone
  • TFF1 protein, human
  • Trefoil Factor-1
  • Tumor Suppressor Proteins