A Mendelian randomization analysis of circulating lipid traits and breast cancer risk.

BACKGROUND: Conventional epidemiologic studies have evaluated associations between circulating lipid levels and breast cancer risk, but results have been inconsistent. As Mendelian randomization analyses may provide evidence for causal inference, we sought to evaluate potentially unbiased associations between breast cancer risk and four genetically predicted lipid traits. METHODS: Previous genome-wide association studies (GWAS) have identified 164 discrete variants associated with high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides and total cholesterol. We used 162 of these unique variants to construct weighted genetic scores (wGSs) for a total of 101 424 breast cancer cases and 80 253 controls of European ancestry from the Breast Cancer Association Consortium (BCAC). Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between per standard deviation increase in genetically predicted lipid traits and breast cancer risk. Additional Mendelian randomization analysis approaches and sensitivity analyses were conducted to assess pleiotropy and instrument validity. RESULTS: Corresponding to approximately 15 mg/dL, one standard deviation increase in genetically predicted HDL-C was associated with a 12% increased breast cancer risk (OR: 1.12, 95% CI: 1.08-1.16). Findings were consistent after adjustment for breast cancer risk factors and were robust in several sensitivity analyses. Associations with genetically predicted triglycerides and total cholesterol were inconsistent, and no association for genetically predicted LDL-C was observed. CONCLUSIONS: This study provides strong evidence that circulating HDL-C may be associated with an increased risk of breast cancer, whereas LDL-C may not be related to breast cancer risk.

How to treat male breast cancer.

The prevalence for breast cancer in males in Europe is estimated to be 1 or less per 100,000. Male breast cancer has a peak incidence at the age of 71 years. There are no randomized data giving information on the optimal therapy for male breast cancer patients, thereby limiting firmer conclusions. The preferred primary surgical therapy is modified radical/simple mastectomy, but breast-conserving surgery has also been used in males. Post-operative radiotherapy should be used on a more routine basis; as males have shorter breast-anatomical distances and males are diagnosed at a later stage compared with females. The so far preferred adjuvant therapy modality has been tamoxifen for patients with endocrine responsive disease. The use of aromatase inhibitors in males is more controversial, since they may not deplete the estradiol levels sufficiently. Different chemotherapy regimens have been used in the adjuvant and metastatic setting. The use of adjuvant therapy has in institutional and review comparisons been demonstrated to result in an improved outcome.