Association of Lipid Levels With Breast Cancer Risk in Women With Extensive Mammographic Density
In a nested case-control study reported in Journal of the National Cancer Institute, Martin et al found that higher HDL cholesterol and apolipoprotein A1 (apoA1) levels and lower non-HDL cholesterol and apolipoprotein B (apoB) levels were associated with increased risk of breast cancer in women with extensive mammographic density. The associations were significant only when hormone replacement therapy was not used.
Study Details
The study was conducted within the population of a Canadian randomized dietary intervention trial involving 4,690 women with extensive mammographic density followed for an average of 10 years for breast cancer. The study included lipid measurement in an average of 4.2 blood samples from 279 patients with invasive breast cancer and 558 matched control subjects without breast cancer.
Subaverages of lipids for each subject were calculated based on menopausal status and use of hormone replacement therapy at blood collection, and associations with risk were analyzed using generalized estimating equations. Analysis adjusted for dietary trial group, parity at baseline, smoking status at baseline, first-degree relatives with breast cancer at baseline, study site, age at menarche, age at birth of first child, number of live births, subaverage weight, subaverage age, date of randomization, and menopausal status and hormone replacement therapy use.
Increased Risk
In comparisons of 75th vs 25th percentile levels, higher HDL cholesterol (1.72 vs 1.21 mmol/L, odds ratio [OR] = 1.23, P = .05) and apoA1 (1.9 vs 1.56 g/L, OR = 1.28, P = .02) were associated with increased risk of cancer and higher non-HDL cholesterol (4.29 vs 3.16, OR = 0.81, P = .03) and apoB (1.00 vs 0.75 g/L, OR = 0.78, P = .01) were associated with decreased risk of cancer. No significant associations between these measure and risk were observed when lipids were measured when hormone replacement therapy was used. No significant association with risk was observed for total cholesterol (P = .17) or triglycerides (P = .11).
Analysis by Estrogen Receptor Status
Analysis by estrogen receptor status showed similar results among 210 cases and 420 controls with estrogen receptor–positive disease, with the statistical significance of the association with apoA1 being lost. No significant associations of lipids with risk were observed in the smaller population of 56 cases and 112 controls with estrogen receptor–negative disease.
The investigators concluded: “These results demonstrate that serum lipids are associated with breast cancer risk in women with extensive mammographic density. The possibility that interventions for heart disease prevention, which aim to reduce non-HDL-[cholesterol] or raise HDL-[cholesterol], may have effects on breast cancer risk merits examination.”
Norman F. Boyd, MD, DSc, of Ontario Cancer Institute, is the corresponding author for the Journal of the National Cancer Institute article.
The study was supported by the Ontario Ministry of Health, Medical Research Council of Canada, Canadian Breast Cancer Research Alliance, Canadian Institutes of Health and by the American Institute of Cancer Research and National Institutes of Health.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
