A pilot study of Pi-class glutathione S-transferase expression in breast cancer: Correlation with estrogen receptor expression and prognosis in node-negative breast cancer

Purpose and Methods: Previous studies have indicated that RNA levels for pi-class glutathione S-transferase (GSTtπ), a phase II, drug-metabolizing enzyme, were inversely related to estrogen receptor (ER) and progesterone receptor (PR) levels in human breast tumors. Because GSTπ also is expressed in normal breast epithelium, an immunohistochemical assay that uses affinity-purified polyclonal antibodies to GSTπ was developed to examine the possible relationship between GSTπ expression in breast cancer cells and hormone receptor expression, as well as prognosis, in patients with primary breast cancer. Results: A strong inverse correlation between GSTπ expression and ER (two-sided P [P₂] = .002) and PR status (P₂ = .023) was found in our study of 189 patients with primary breast cancer. GSTπ expression was not related to tumor size, nodal metastasis, nuclear grade, histology, or age of the patient. In node-negative breast cancer (n = 72), increased GSTπ expression was associated with decreased disease-free survival (DFS) and overall survival (OS). When GSTπ expression was divided into categories of negative (no GSTπ-positive tumor cells), intermediate (1% to 70% GSTπ-positive tumor cells), and high (> 70% GSTπ-positive tumor cells), the relative risk of tumor recurrence in patients with node-negative breast cancer was increased 3.39-fold for each successive category of expression (P₂ = .0045; 95% confidence interval, 1.46 to 7.87) and the relative risk of death was increased 4.49-fold for each successive category (P₂ = .0003; 95% confidence interval, 2.02 to 10.42). The actuarial 5-year OS was 100%, 79%, and 51%, and the DFS was 94%, 77%. and 44%, for the negative, intermediate, and high tumor groups, respectively. Among the factors studied in multivariate analysis (ER status, PR status, nuclear grade, and tumor size), GSTπ expression was the factor that most accurately predicted shorter DFS and OS in node-negative patients. Conclusion; GSTπ expression is inversely related to hormone receptor status in breast cancer. This pilot study also suggests that increased GSTπ expression may be an important predictor of early recurrence and death in node-negative breast cancer patients that merits additional investigation.