CYR61 Confers the Sensitivity to Aromatase Inhibitor Letrozole in ER Positive Breast Carcinoma

Background: Studies have demonstrated that cysteine-rich 61 (CYR61) may be involved in tumor proliferation and invasion. However, the role of CYR61 plays in endocrine therapy response is largely unknown. Patients and Methods: We tested the levels of CYR61 expression of 36 primary breast cancer patients who received neo-adjuvant endocrine therapy for at least 3 months by immunohistochemistry staining before and after administrating letrozole, an oral non-steroidal aromatase inhibitor (AI) for the treatment of hormone-responsive breast cancer. The expression levels of CYR61 and ki67 were compared between pre-treatment and post-treatment samples by using the paired t test. Chi-square test was used to determine the relationship between baseline CYR61 expression and clinical response. Results: In the clinical case series analysis, a positive correlation was observed between baseline CYR61 expression and clinical outcomes (p=0.02). CYR61 expression was significantly increased in the residual tumors after treatment (indicating insensitivity to endocrine therapy) compared with that in the baseline biopsy samples, which was irrespective of the efficacy of primary endocrine treatment. In addition, the ki67 level was significantly decreased after neo-adjuvant endocrine therapy, compared with that in the baseline samples. Conclusion: This study provides evidence that CYR61 may confer the sensitivity to letrozole treatment and may offer an opportunity to target CYR61 to improve endocrine resistance in ER-positive breast cancer.