Aim: The aim of the present study was to investigate the impact of the COX2 rs5277 polymorphism on early events and treatment response in relation to tumor ER-status and to determine whether any effect is modified by body constitution.

Background: The synonymous COX2 rs5277 polymorphism (306G>C, V102V) has been directly linked to several cancers associated with inflammation. Breast cancer patients with tumors expressing COX-2 have a shorter disease-free survival. It is currently unclear whether the rs5277 genotype is correlated with tumor COX-2 expression. Tumor COX-2 expression may have contrasting effects on breast cancer tumors depending on the tumor's estrogen receptor (ER) status. It has been associated with increased estrogen levels in ER-positive tumors and Akt-pathway activation in ER-negative tumors.

Methods: The present study is based on data collected from 634 patients initiating treatment between October 2002 and October 2008. Risk of early events was assessed for 570 rs5277-genotyped patients. Body measurements and questionnaires were obtained at the pre-operative visit. Clinical data, patient-, and tumor-characteristics were obtained from questionnaires, patients' charts, population registries, and pathology reports.

Results: Among all patients, 70.1% were GG-carriers, 27.5% were GC-carriers, and 2.4% were CC-carriers. Median follow-up was 5.1 years. Median age was 59.6 years (range 25-99 years). No association was seen between the G/G genotype and risk of early events in patients with ER-positive tumors, but this genotype conferred an over 4-fold increased risk in patients with ER-negative tumors (Pinteraction=0.015). G/G-carriers with a larger breast volume who had received chemotherapy had a 9-fold risk of early events irrespective of ER-status. C-allele carriers with ER-positive tumors who had a larger breast volume and had received endocrine-therapy had a 2-fold increased risk of early events.

Conclusion: COX2 genotype, body constitution, and ER-status had a combined effect on the risk of early events and treatment response. The high risk for early events in certain subgroups of patients suggests that COX2 genotype in combination with body measurements may provide a tool for identifying patients in need of more personalized treatment.

Citation Format: Andrea Markkula, Maria Simonsson, Christian Ingvar, Carsten Rose, Helena Jernström. Combined effect of COX2 genotype, ER status, body constitution, and treatment on risk of early events in breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4218. doi:10.1158/1538-7445.AM2014-4218