Quantitative progesterone receptor expression and efficacy of anti-estrogen therapy in breast cancer

The central role of estrogen receptor (ER) presence in predicting which breast cancer patients are likely to benefit from anti-estrogen therapies is well-established, but the added benefit of progesterone receptor (PR) and in particular low levels of PR is less well understood. The objective of this study was to determine the quantitative relationship between borderline levels of PR and subsequent benefit from anti-estrogen therapy. We examined data from 447 patients, age 50 or older. ER and PR levels were quantitated by conventional ligand binding assay and Scatchard plot analysis or by enzyme-linked immunoassay. Comparison of clinical outcome in relation with ER and PR status was calculated using Kaplan-Meier actuarial survival analysis and the log-rank test. Subpopulation treatment effect pattern plot (STEPP) analysis was used to explore the interaction between treatment effects and ER or PR levels for the 409 patients with ER values greater than 0. For anti-estrogen treated patients, when the ER and PR positivity cut-off was set at 1.0 fmole/mg protein, there was a statistically significant advantage for patients with ER+PR+ over ER+ PR- tumors for both breast cancer-free interval (BCFI) and overall survival (OS). STEPP analysis found no overall interaction between treatment outcome (5 year survival probability) and levels of hormone receptor. However, patients with borderline PR levels did not appear to benefit from anti-estrogen therapy. PR levels above borderline in addition to the presence of ER predicts an increased probability of benefit from anti-estrogen therapy in breast cancer patients.