medwireNews: A Finnish population-based study has found that the inverse association between statin use after breast cancer diagnosis and breast cancer mortality may be mediated by the underlying cholesterol levels.
Specifically, postdiagnosis statin use correlated with a reduced risk for breast cancer death only among women whose cholesterol levels decreased after initiating statins, note Mika Murto (Hatanpää Hospital, Tampere, Finland) and colleagues.
They suggest that the heterogeneous results of previous studies investigating the impact of statins on breast cancer mortality could perhaps be explained by the failing to account for “simultaneous cholesterol levels or changes due to statin use.”
The team drew on national registries to identify 13,378 women newly diagnosed with breast cancer between 1995 and 2013 who had available hormone receptor data and at least one cholesterol measurement. Of these, 40.7% had ever used statins.
Multivariable analysis showed that prediagnosis statin use was associated with a significantly increased risk for breast cancer death after adjustment for a raft of factors including total cholesterol levels, at a hazard ratio (HR) of 1.22.
By contrast, postdiagnosis statin use appeared to reduce the risk, with a borderline significant HR for breast cancer death of 0.85. But the association was statistically significant only among participants who experienced a decrease in cholesterol levels after starting statins, at an HR of 0.49, and not those without a reduction in cholesterol (nonsignificant HR=0.69).
Statin use before diagnosis was also associated with a significantly increased risk for overall mortality (HR=1.28), where once again postdiagnosis use was associated with a significantly reduced risk (HR=0.80).
Discussing the findings in JAMA Network Open, the researchers say that “[t]he beneficial role of cholesterol reduction is plausible given that in epidemiological studies, dietary cholesterol and hypercholesterolemia have been associated with increased risk of [breast cancer].”
They continue: “The primary cholesterol metabolite activates the [estrogen receptor], subsequently increasing [breast cancer] cellular proliferation and tumor growth. Cholesterol is also a precursor for biosynthesis of estrogen, which in high levels is considered to be a mammary gland carcinogen.”
Murto et al outline some limitations of the study, including “the lack of information on lifestyle factors, such as smoking, obesity, and physical activity, that are known to be associated with the risk of [breast cancer] mortality,” as well as the possibility of residual bias since statin use was not randomized.
And they conclude: “All analyses were exploratory and should be considered as hypothesis generating. Confirmation of the results is needed from prospective randomized clinical trials.”
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