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Apolipoprotein D expression does not predict breast cancer recurrence among tamoxifen-treated patients

Background Apolipoprotein D (ApoD) has been proposed as a predictor of breast cancer recurrence among estrogen receptor-positive (ER+), tamoxifen-treated patients. Methods We conducted a population-based case-control study nested in a population of 11,251 women aged 35–69 years at diagnosis with Stage I–III breast cancer between 1985 and 2001 on Denmark’s Jutland Peninsula and registered with the Danish Breast Cancer Cooperative Group. We identified 541 recurrent or contralateral breast cancers cases among women with ER+ disease treated with tamoxifen for at least 1 year and 300 cases in women with ER– disease never treated with tamoxifen. We matched one control subject per case and assessed ApoD expression in the tumor cell nucleus and cytoplasm using tissue microarray immunohistochemistry. We computed the odds ratio (OR) associating ApoD expression with recurrence and adjusted for potential confounding using logistic regression. Results Cytoplasmic ApoD expression was seen in 68% of ER+ tumors, in 66% of ER– tumors, and in 66% of controls across both groups. In women with ER+ tumors, the associations of cytoplasmic ApoD expression with recurrence (OR = 1.0; 95% CI = 0.7 to 1.4) and increasing cytoplasmic expression with recurrence (OR = 1.0; 95% CI = 0.996 to 1.003) were null, as were those for women with ER– tumors. Associations for nuclear ApoD expression and combined nuclear and cytoplasmic expression were similarly near-null. Conclusion ApoD expression is likely not a predictor of recurrence in tamoxifen-treated patients. Impact This study eliminates the previously suggested marker ApoD as a predictor of recurrence among tamoxifen-treated women.