Study of p16 biomarker after short-period primary endocrinotherapy with tamoxifen and anastrozole in postmenopausal women with breast carcinoma

Abstract

Background: Frequent deletions or mutations of the INK4 gene, which encodes the cyclin-dependent kinase-4 inhibitor p16INK4a, have been documented in various human cancers, but little is known about the role of this tumor suppressor gene in primary breast cancer, and there is a lack of reports in the literature about its expression behavior in neoadjuvant endocrinotherapy with tamoxifen or anastrozole. Objective: To analyze p16INK4a expression in patients with invasive ductal carcinomas (IDC) prior to tamoxifen and anastrozole neoadjuvant treatment and the possible correlation with estrogen receptor (ER) and progesterone receptor (PgR). Methods: We examined p16INK4a expression and its relationship in short period (26 days) neoadjuvant endocrine therapy with tamoxifen and anastrozole in 58 primary breast cancers with palpable HR-positive IDC. They were double-blind randomized in three neoadjuvant treatment groups: Anastrozole 1 mg/day (n = 17), Placebo (n = 25) and Tamoxifen 20 mg/day (n = 15). Biomarkers status (ER, PgR and p16) were obtained by comparing single immunohistochemical evaluation of pre and post-surgery samples using Allred’s method. Results: Variation in p16 was from 22% to 17% in anastrozole group, 8% to 4% in placebo group, but there was no variation in tamoxifen group, standing in 7%. There was no significant statistical difference in p16INK4a expression between groups (p = 0,17). There was no significant statistical correlation between p16 expression and hormonal status (RE and RP). Conclusion: There were no significant differences between the three studied groups. Other biomarkers should be studied to identify early endocrine resistance and specific treatments.