Akt2 expression is associated with good long-term prognosis in oestrogen receptor positive breast cancer

Abstract

IntroductionAkt is a signalling modulator for many cellular processes, including metabolism, cell proliferation, cell survival and cell growth. Three isoforms of Akt have been identified, but only a few studies have concerned the isoform-specific roles in the prognosis of breast cancer patients. The aim of this study was to investigate the prognostic value of v-akt murine thymoma viral oncogene homologue 1 (Akt1) and v-akt murine thymoma viral oncogene homologue 2 (Akt2) in oestrogen receptor positive (ER+) and oestrogen receptor negative (ER–) breast cancer with long-term follow-up. Material and methodsThe expression of Akt in tumour tissue was analysed with immunohistochemistry in a cohort of 272 postmenopausal patients with stage II breast cancer. The median follow-up time was 19years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox’s proportional hazards model. ResultsThe risk of distant recurrence was reduced for patients with ER+ tumours expressing Akt2 compared to patients with no Akt2 expression (HR=0.49, 95% CI 0.29–0.82, p=0.007). When adjusting for important clinical tumour characteristics and treatment, Akt2 was still an independent prognostic factor (HR=0.38, 95% CI 0.21–0.68, p=0.001) and the association remained long-term. The prognostic value of Akt2 increased with higher oestrogen receptor levels from no effect among patients with ER– tumours to 68% risk reduction for the group with high ER-levels (P for trend=0.042). Akt1 showed no significant prognostic information. ConclusionOur results indicate that Akt2 expression is associated with a lower distant recurrence rate for patients with ER+ tumours and that this association remains long-term. The prognostic value of Akt2 increases with higher oestrogen receptor expression, motivating further mechanistic studies on the role of Akt2 in ER+ breast cancer.