Background Vitamin D has been suggested to prevent and improve the prognosis of several cancers, including breast cancer. We have previously shown a U-shaped association between pre-diagnostic serum levels of vitamin D and risk of breast cancer-related death, with poor survival in patients with the lowest and the highest levels respectively, as compared to the intermediate group. Vitamin D exerts its functions through the vitamin D receptor (VDR), and the aim of the current study was to investigate if the expression of VDR in invasive breast tumors is associated with breast cancer prognosis. Methods VDR expression was evaluated in a tissue microarray of 718 invasive breast tumors. Covariation between VDR expression and established prognostic factors for breast cancer was analyzed, as well as associations between VDR expression and breast cancer mortality. Results We found that positive VDR expression in the nuclei and cytoplasm of breast cancer cells was associated with favorable tumor characteristics such as smaller size, lower grade, estrogen receptor positivity and progesterone receptor positivity, and lower expression of Ki67. In addition, both intranuclear and cytoplasmic VDR expression were associated with a low risk of breast cancer mortality, hazard ratios 0.56 (95% CI 0.34–0.91) and 0.59 (0.30–1.16) respectively. Conclusions This study found that high expression of VDR in invasive breast tumors is associated with favorable prognostic factors and a low risk of breast cancer death. Hence, a high VDR expression is a positive prognostic factor. Electronic supplementary material The online version of this article (10.1186/s13058-019-1169-1) contains supplementary material, which is available to authorized users.

Purpose: To evaluate whether tumor androgen receptor (AR) expression was prognostic and/or predictive for endocrine treatment alone or in combination with estrogen receptor (ER). The AR has been hypothesized to have differential prognostic roles in breast cancer depending on tumor ER status, and to influence endocrine treatment response. Experimental Design: A population-based prospective cohort of 1,026 patients diagnosed with primary invasive breast cancer in Lund, Sweden, between 2002 and 2012 was followed until June 2014. Associations between immunohistochemical AR expression in tumor tissue microarrays, patient and tumor characteristics, and AR genotypes were analyzed. Disease-free survival (DFS) by AR status, and combined ER/AR status was assessed in various treatment groups. Results: AR expression was assessable in 913 tumors. AR+ tumors (85.0%) were associated with higher age (P = 0.036) and favorable tumor characteristics. The AR+ status was a prognostic marker for DFS (LogRank P = 0.025). There was an interaction between AR and ER expression with respect to prognosis (adjusted Pinteraction ≤ 0.024). Tumors with discordant hormone receptor expressions (ER+AR− or ER−AR+) demonstrated worse prognosis compared with concordant tumor expressions (ER+AR+ or ER−AR−) in multivariable models [adjusted HRs (95% confidence intervals); ≥1.99 (1.28–3.10), P ≤ 0.002]. ER+AR− indicated early treatment failure with aromatase inhibitors (AI) among chemonaïve patients aged 50 or older. Conclusions: Prediction of breast cancer prognosis and treatment response was improved by combining AR and ER status. AR negativity predicted early treatment failure with AI but not tamoxifen, a finding that warrants confirmation in a randomized setting. Patients may benefit from anti-androgens or selective AR modulators. Clin Cancer Res; 21(16); 3640–50. ©2015 AACR.

Statins, commonly used to treat hypercholesterolemia, have also been proposed as anti-cancer agents. The identification of a predictive marker is essential. The 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGcR), which is inhibited by statins, might serve as such a marker. thorough antibody validation was performed for four different HMGCR antibodies. Tumor expression of HMGCR (#AMAb90619, CL0260, Atlas Antibodies, Stockholm, Sweden) was evaluated in the Malmö Diet and cancer Study breast cancer cohort. Statin use and cause of death data were retrieved from the Swedish Prescribed Drug Register and Swedish Death Registry, respectively. Breast cancer-specific mortality (BCM) according to statin use and HMGCR expression were analyzed using Cox regression models. Three-hundred-twelve of 910 breast cancer patients were prescribed statins; 74 patients before and 238 after their breast cancer diagnosis. HMGCR expression was assessable for 656 patients; 119 showed negative, 354 weak, and 184 moderate/strong expressions. HMGCR moderate/strong expression was associated with prognostically adverse tumor characteristics as higher histological grade, high Ki67, and eR negativity. HMGcR expression was not associated with BcM. neither was statin use associated with BCM in our study. Among breast cancer patients on statins, no or weak HMGCR expression predicted favorable clinical outcome. these suggested associations need further testing in larger cohorts. Statins are medications most commonly used by patients with cardiovascular diseases and hypercholesterolemia. Cholesterol is produced by the mevalonate pathway, a metabolic pathway that also produces precursors for steroid hormones and isoprenoids 1. Statins exert competitive inhibition of the rate-limiting enzyme of the mevalonate pathway, 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), an enzyme that has been found to be differentially expressed in breast cancer tumors 2. In recent years, attention in cancer research has been drawn to the mevalonate pathway since statins have been found to exert pleiotropic intratumoral effects, suggesting a possible effectiveness in cancer. Examples of these effects are induction of apoptosis and inhibition of proliferation 3 , and immunomodulatory properties, through inhibition of Ras and Rho family GTPases 4-6 , and by decreasing the production of inflammatory cytokines and activating CD8+ T cells 7. In breast cancer, statins have also demonstrated some anti-neoplastic properties in preclinical studies of breast cancer cells 8-11. These findings are supported by epidemiological data showing protective associations between statin use and breast cancer recurrence and thus prognosis 12-14. However, biomarkers for selection of patients that may benefit from statins are needed. Previous studies have explored the correlation between tumor cell expression of HMGCR and breast cancer prognosis, as well as the association with statin treatment. One study found that high levels of HMGCR tumor expression in breast cancer was associated ...