Abstract A55: Regional differences in breast cancer biomarkers in American Indian and Alaska Native women

Abstract

Introduction: Breast cancer is a major cause of cancer mortality in American Indian and Alaska Native (AIAN) women. However regional differences are striking with lowers rates in Arizona and highest in Alaska with almost a three-fold difference in incidence and mortality between the two states. These differences may be due in part to varying levels of biologic tumor aggressiveness. To evaluate this, we compared a panel of biomarkers on consecutively diagnosed AIAN breast cancer cases from AZ (N=53) and AK (N=42). Methods: Retrospective analysis of tissue blocks measured expression levels for the following panel of biomarkers: ER and PR (ordinally coded as positive vs. negative); her2, BCL-2, and EGFR (coded 0.1.2. and 3+) and P53, MIB-1 and cyclin D (continuous percent of cells stained). Distributions of biomarker values were compared across state of residence using t-tests for continuous and ordinally scaled markers and chi-square tests of significance for binary markers. Age adjusted analyses were also carried out using linear and logistic regression models as appropriate to account for possible differences in age at diagnosis across states. Chart reviews recorded demographics and treatment characteristics. Results: The following demographics were observed with 95 cases of AIAN women with breast cancer analyzed. Average age at diagnosis was similar in the two states (mean, 58.4 for AZ vs. 56.1 for AK, t-test p value=0.45). 74% presented with a palpable mass. 32% had lumpectomy and axillary node dissection. 28% were premenopausal. 8% had a first-degree relative with breast cancer. 46% received adjuvant chemotherapy. 54% received adjuvant hormonal therapy. Cases from AK had higher levels of p53 staining (40.3 vs. 18.5, p=0.004) and lower levels of both EGFR (mean ordinal scaling 0.15 vs. 0.53, p=0.02) and Her2 (mean ordinal scaling 0.81 vs. 1.32, p=0.02) tan those from AZ. No differences in distribution were observed for MIB-1, Cyclin D, BCL-2, ER or PR. When examined together, the triple negative combination of ER/PR/Her2 also did not differ across states (12% for AK vs.13%forAZ, p=0.85). Conclusions: Our findings indicate that regional differences in biomarker expression levels of P53, EGFR and Her2 may exist in AIAN women. Further research is needed to confirm our results and determine to what extent these differences may explain the observed differences in mortality. Genetic testing for BRCA1,2 or other genetic associations with breast cancer have not been done in these populations and may also be useful to examine the reasons for differences in incidence and mortality. In addition, AIAN women are more likely to present with palpable masses representing higher risk stages of breast cancer. Outreach activities in this population continue to be highly important to change mortality. Supported in part by NCI U01 114609 Spirit of Eagles Community Network Program Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A55.