Introduction: The relationship between circulating prolactin and invasive breast cancer has been investigated
previously, but the association between prolactin levels and in situ breast cancer risk has received less attention.
Methods: We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer
overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional
logistic regression was used to assess this association in a case-control study nested within the European Prospective
Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched
control subjects.
Results: We found a significant positive association between higher circulating prolactin levels and risk of in situ
breast cancer among all women [pre-and postmenopausal combined, ORlog2 = 1.35 (95% CI 1.04-1.76), Ptrend = 0.03].
No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal
status (Phet = 0.98) or baseline HT use (Phet = 0.20), although the observed association was more pronounced among
postmenopausal women using HT compared to non-users (Ptrend = 0.06 vs Ptrend = 0.35). In subgroup analyses, the
observed positive association was strongest in women diagnosed with in situ breast tumors <4 years compared
to ≥4 years after blood donation (Ptrend = 0.01 vs Ptrend = 0.63; Phet = 0.04) and among nulliparous women compared
to parous women (Ptrend = 0.03 vs Ptrend = 0.15; Phet = 0.07).
Conclusions: Our data extends prior research linking prolactin and invasive breast cancer to the outcome of
in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ
breast cancer.