Abstract P3-10-10: Progesterone Receptor-Negative Status Predicts Poorer Outcomes in Estrogen Receptor-Positive Patients Treated with Selective Estrogen Receptor Modulators
Introduction: While estrogen receptor (ER) status has been used as the primary factor influencing the use of selective estrogen receptor modulators (SERMs), a number of ER-positive patients will relapse on this therapy. It has been postulated that SERM-resistance may be modulated by aberrant growth factor signaling, for which progesterone receptor (PR) status may be a surrogate. PR status, however, is frequently not considered as a strong prognostic or predictive marker in ER-positive patients. We sought to define the effect of PR-status on outcomes in such patients treated with SERMs. Methods: The North American Fareston versus Tamoxifen Adjuvant (NAFTA) Trial is an investigator-initiated, multicenter, prospective trial that randomized patients with resected hormone-receptor positive breast cancers to receive either adjuvant tamoxifen (20 mg po daily) or toremifene (60 mg po daily) for five years. Between July 1998 and December 2002, 1692 ER-positive positive patients were randomized. PR was missing for 15 patients. The remaining 1677 (1424 PR-positive and 253 PR-negative) patients formed the cohort of interest for this analysis. The impact of PR status on overall (OS) and disease-free survival (DFS) was assessed using Kaplan Meier and Cox Proportional Hazards modeling. Results: The median patient age was 67 (range; 41-100) with a median tumor size of 1.2 cm (range; 0.01-14.00 cm). PR-positive status was correlated with node-negative disease (91.3% vs. 87.0%, p=0.035) and low grade tumors (34.9% vs. 27.7%, p=0.009), but was not associated with tumor size (p=0.533) or patient age (p=0.067). With a median follow-up of 59 months, the 5-year actuarial OS and DFS of PR-negative patients was significantly worse than that of PR-positive patients (88.5% vs. 94.3%, p=0.009 and 86.1% vs. 92.5%, p=0.003, respectively). Controlling for tumor size, grade and lymph node status, PR-negative status continued to predict worse DFS (OR=1.561; 95% CI: 1.013-2.406, p=0.043), although it lost significance in terms of OS (OR=1.619; 95% CI: 0.980-2.674, p=0.060). Conclusion: PR-negative status is an independent predictor of worse DFS in ER-positive patients treated with SERMs. These data support the hypothesis that PR-negative status may signal a higher rate of SERM-resistance, and should be considered in adjuvant therapy decisionmaking. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-10.