2009/01/01 by Håvard Søiland, Ivar Skaland, Jan Erik Varhaug +5 · 2 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Estrogen and related hormone effects #Cancer, Lipids, and Metabolism #Cancer, Stress, Anesthesia, and Immune Response #Medicine #Breast cancer #Internal medicine #Oncology #Estrogen receptor #Tamoxifen #Immunohistochemistry #Hazard ratio #Cancer #Estrogen
paper · pdf · doi:10.1080/02841860802620613
openalex publication_date 2009/01/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/05
BACKGROUND: Estrogen receptor-alpha (ERalpha) is an important prognostic and predictive marker in breast cancer. ERalpha signaling normally down-regulates expression of Apolipoprotein D (ApoD), a lipocalin that binds, transports or chelates lipophilic ligands, including tamoxifen (TAM). Hence, the co-expression of ApoD may therefore identify clinical relevant subgroups of ERalpha positive breast cancer patients. MATERIAL AND METHODS: ApoD, ERalpha, and progesterone receptor (PR) protein expressions were determined by immunohistochemistry (IHC) in primary tumors of 290 patients with operable breast cancer. The median follow-up was 12 years. Patients were stratified according to age, nodal stage and the expression of ERalpha and the combined cytoplasm and nuclear staining of ApoD (ApoD(CN)). RESULTS: In elderly women (> or =70 years) (n = 76), ApoD(CN) expression identified different prognostic subgroups in ERalpha positive patients (Trend: p < 0.0001). Multivariate analysis in this age group (n = 72), showed that the ERalpha-positive /ApoD(CN)-negative subgroup had a better breast cancer specific survival (BCSS) compared with the ERalpha-positive/ApoD(CN)-positive group (hazard ratio (HR) = 4.3; 95% CI = 1.6-11.9; p = 0.005). This difference was predominantly seen in the node positive patients (n = 30) (HR = 10.5; 95% CI = 2.3-47.6; p = 0.002). In a subset of postmenopausal ERalpha-positive/node positive patients (n = 60) previously enrolled in a trial on 2 year adjuvant TAM 20 mg vs. placebo, a better BCSS was observed in ApoD(CN) negative patients compared to placebo (p = 0.02). In ApoD(CN) positive patients, adjuvant TAM did not provide any survival benefit. DISCUSSION: ERalpha and ApoD(CN) co-expression seems to be of prognostic importance in node positive elderly patients with operable breast cancer. In addition, we hypothesize that ApoD(CN) expression may be a novel marker and/or mechanism of TAM resistance in postmenopausal node positive patients. Thus, when targeting the ERalpha pathway in these patients, the ApoD status of the tumor may be of clinical relevance.