Background: Endocrine therapy has dramatic improvements of prognosis in patients with hormonal receptor positive breast cancer. However, long-term follow up shows that endocrine resistance is still major clinical concern. Although the value of estrogen receptor (ER) level can predict response to endocrine treatment in hormonal receptor positive breast cancers, few markers are available that can predict response to endocrine treatment. We attempted to identify molecular markers, especially progesterone receptor (PR), associated with endocrine failure in breast cancer.

Methods: We reviewed the medical records of 2513 breast cancer patients who underwent breast surgery and endocrine therapy at Samsung Medical Center between March 2007 and July 2011. Patients were compared according to ER and PR expression and to assess the clinical and biological features of ER+positive/PR-negative breast cancers to understand how PR might be a useful marker of these activities. ER and PR expression accessed using Allred score, the ‘positive” was defined that total score is larger than 2.

Results PR negative tumors were found more frequently in postmenopausal women (post- 11.2% vs. pre- 2.5%, P < 0.001) and PR negative tumors were significantly associated with higher grade, higher level of Ki 67 and more expression of EGFR and CK5/6. In Kaplan-Meier analysis and multivariate analysis, PR negativity was significantly poorer prognostic factor of DFS (HR 3.1, 95% CI 1.2-8.2, P = 0.021) and OS (HR 89.8, 95% CI 3.4-2352.3, P = 0.007). Stratified by the menopausal status, there was not shown significant difference of survival between the PR+ and PR- tumor in postmenopausal women (DFS, HR 2.1, 95% CI 0.4-10.8, P = 0.381; OS, HR 10.6, 95% CI 0.6-171.4, P = 0.096). However, PR negative tumors showed an association with poor outcome in premenopausal women (DFS, HR 7.2, 95% CI 2.5-20.6, P <0.001; OS, HR 24.6, 95% CI 2.2-275.6, P = 0.009).

Conclusion: In HR positive breast cancers, PR negative tumors were found more frequently in elderly, postmenopausal women. However, PR negative tumors are shown more aggressive and poorer survival than PR positive tumors despite of endocrine therapy, especially in premenopausal women.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-09-17.