Association of Breast Tumour Expression of Cannabinoid Receptors CBR1 and CBR2 with Prognostic Factors and Survival in Breast Cancer Patients.

ABSTRACT

Cannabinoid receptors (CBR) are potential therapeutic targets for breast cancer. However, the role of CBR in breast cancer survival remains poorly understood. Data from a prospective cohort of 522 women diagnosed with invasive breast cancer between 2010 and 2012 were analysed. Clinical and pathological features were retrieved from electronic medical records. CBR expression was measured by immunohistochemistry. Adjusted partial Spearman correlations and multivariate Cox models were used to estimate associations with breast cancer prognostic factors and survival, respectively. The median follow-up was 92.0 months (range 7.0-114.0). CBR expression was heterogenous in tumours. Cytoplasmic expression of CBR1 was positively correlated with lymph node invasion (rs = 0.110; p = 0.0155) and positive status of the human epidermal growth factor receptor 2 (HER2) (rs = 0.168; p = 0.0002), while nuclear CBR2 was negatively correlated with grade (rs = -0.171; p = 0.0002) and positively correlated with oestrogen receptor and progesterone receptor-positive status (rs = 0.173; p = 0.0002 and rs = 0.121; p = 0.0084, respectively). High cytoplasmic expression of CBR2 was associated, with 13% higher locoregional and distant recurrences (HR = 1.13 [0.97-1.33]), though this association did not reach statistical significance. Although the few events occurring during follow-up may have limited the detection of significant associations, these results indicate that CBR expression in breast cancer deserves further investigation.