Circulating gamma-glutamyl transferase and development of specific breast cancer subtypes: findings from the Apolipoprotein Mortality Risk (AMORIS) cohort

Background: Different etiological pathways may precede development of specific breast cancer subtypes and impact prevention or treatment strategies. We investigated the association between gamma-glutamyl transferase (GGT) and development of specific breast cancer subtypes based on oestrogen receptor (ER), progesterone receptor (PR) and HER2 status. Methods: We included 231,283 cancer-free women in a Swedish cohort. Associations between GGT and breast cancer subtypes were investigated with nested case-control and case-case analyses. We used logistic regression models to assess serum GGT in relation to breast cancer subtype, based on individual and combined receptor status. Results: Positive associations were found between serum GGT and development of ER+, ER-and PR+ breast cancers compared to controls (odds ratio (OR) 1.14 (95% confidence interval (CI) 1.08-1.19), 1.11 (1.01-1.23) and 1. 18 (1.12-1.24), respectively) and of ER+/PR+ tumours. We found inverse associations between GGT levels and PR-breast cancers compared to PR+ (OR 0.87 (0.80-0.95)), between ER+/PR-tumours compared to ER+/PR+ tumours and between ER-/PR-/HER+ compared to ER+/HER2 or PR+/HER2 tumours (OR 0.55 (95% CI 0.34-0.90). Conclusion: The observed associations between pre-diagnostic serum GGT and different breast cancer subtypes may indicate distinct underlying pathways and require further investigations to tease out their clinical implications.