Purpose@#This study investigated the
association of
insulin,
metformin, and
statin use with
survival and whether the
association was modified by the
hormone receptor status of the
tumor in
patients with
breast cancer. @*Materials and
Methods@#We studied 7,452
patients who had undergone
surgery for
breast cancer at
Seoul National
University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded
prescription of each
drug within 12 months before the
diagnosis of
breast cancer. @*Results@#
Patients with prior
insulin or
statin use were more likely to be older than 50 years at
diagnosis and had a higher
comorbidity index than those without it (p < 0.01 for both). The
hazard ratio (HR) for
death with
insulin use was 5.7 (p < 0.01), and the effect was attenuated with both
insulin and
metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened
risk of
death with
insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-
administration of
metformin with an HR of 1.3 (p=0.67) in
patients with
estrogen receptor (ER)–negative
breast cancer.
Statin use was associated with increased overall
mortality only in
patients with ER-positive
breast cancer with HR for
death of 1.5 (p=0.05). @*Conclusion@#
Insulin or
statin use before the
diagnosis of
breast cancer was associated with an increase in all-cause
mortality. Subsequent analyses suggested that
metformin or
statin use may have been protective in
patients with ER-negative
disease, which warrants further studies.