The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells.

Obesity and elevated circulating cholesterol are risk factors for breast cancer recurrence, while the use of statins, cholesterol biosynthesis inhibitors widely used for treating hypercholesterolemia, is associated with improved disease-free survival. Here, we show that cholesterol mediates the metastatic effects of a high-fat diet via its oxysterol metabolite, 27-hydroxycholesterol. Ablation or inhibition of CYP27A1, the enzyme responsible for the rate-limiting step in 27-hydroxycholesterol biosynthesis, significantly reduces metastasis in relevant animal models of cancer. The robust effects of 27-hydroxycholesterol on metastasis requires myeloid immune cell function, and it was found that this oxysterol increases the number of polymorphonuclear-neutrophils and γδ-T cells at distal metastatic sites. The pro-metastatic actions of 27-hydroxycholesterol requires both polymorphonuclear-neutrophils and γδ-T cells, and 27-hydroxycholesterol treatment results in a decreased number of cytotoxic CD8+T lymphocytes. Therefore, through its actions on γδ-T cells and polymorphonuclear-neutrophils, 27-hydroxycholesterol functions as a biochemical mediator of the metastatic effects of hypercholesterolemia.High cholesterol is a risk factor for breast cancer recurrence. Here the authors show that cholesterol promotes breast cancer metastasis via its metabolite 27-hydroxycholesterol (27HC) that acts on immune myeloid cells residing at the distal metastatic sites, thus promoting an immune suppressive environment.

Implementing Trauma-Informed Partner Violence Assessment in Family Planning Clinics.

OBJECTIVE: Intimate partner violence (IPV) and reproductive coercion (RC) are associated with poor reproductive health. Little is known about how family planning clinics implement brief IPV/RC assessment interventions in practice. We describe the uptake and impact of a brief, trauma-informed, universal IPV/RC assessment and education intervention. METHODS: Intervention implementation was evaluated via a mixed methods study among women ages 18 and up receiving care at one of two family planning clinics in greater Baltimore, MD. This mixed methods study entailed a quasi-experimental, single group pretest-posttest study with family planning clinic patients (baseline and exit survey n = 132; 3-month retention n = 68; retention rate = 52%), coupled with qualitative interviews with providers and patients (total n = 35). RESULTS: Two thirds (65%) of women reported receiving at least one element of the intervention on their exit survey immediately following the clinic-visit. Patients reported that clinic-based IPV assessment is helpful, irrespective of IPV history. Relative to those who reported neither, participants who received either intervention element reported greater perceived caring from providers, confidence in provider response to abusive relationships, and knowledge of IPV-related resources at follow-up. Providers and patients alike described the educational card as a valuable tool. Participants described trade-offs of paper versus in-person, electronic medical record-facilitated screening, and patient reluctance to disclose current situations of abuse. CONCLUSION: In real-world family planning clinic settings, a brief assessment and support intervention was successful in communicating provider caring and increasing knowledge of violence-related resources, endpoints previously deemed valuable by IPV survivors. Results emphasize the merit of universal education in IPV/RC clinical interventions over seeking IPV disclosure.

27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology.

Hypercholesterolemia is a risk factor for estrogen receptor (ER)-positive breast cancers and is associated with a decreased response of tumors to endocrine therapies. Here, we show that 27-hydroxycholesterol (27HC), a primary metabolite of cholesterol and an ER and liver X receptor (LXR) ligand, increases ER-dependent growth and LXR-dependent metastasis in mouse models of breast cancer. The effects of cholesterol on tumor pathology required its conversion to 27HC by the cytochrome P450 oxidase CYP27A1 and were attenuated by treatment with CYP27A1 inhibitors. In human breast cancer specimens, CYP27A1 expression levels correlated with tumor grade. In high-grade tumors, both tumor cells and tumor-associated macrophages exhibited high expression levels of the enzyme. Thus, lowering circulating cholesterol levels or interfering with its conversion to 27HC may be a useful strategy to prevent and/or treat breast cancer.