Consumption of walnuts has slowed breast cancer growth and/or reduced the risk of mammary cancer in mice. The benefit against cancer was associated with altered expression of genes for cancer growth and survival. We hypothesized that walnut consumption would alter gene expression in pathologically confirmed breast cancers of women in a direction that would be expected to decrease breast cancer growth and survival, as was seen in mice. The study was a nonplacebo, 2-arm, clinical trial. Women with breast lumps large enough for research and pathology biopsies were recruited and randomized to walnut consuming or control groups. Immediately after biopsy collection, women in the walnut group began to consume 2 oz of walnuts per day until follow-up surgery. Pathological studies confirmed that lumps were breast cancer in all women who remained in the trial. At surgery, about 2 weeks after biopsy, additional specimens were taken from the breast cancers. Changes in gene expression in the surgical specimen compared to baseline were determined in each individual woman in walnut-consuming (n = 5) and control (n = 5) groups. RNA sequencing expression profiling revealed that expression of 456 identified genes was significantly changed in the tumor due to walnut consumption. Ingenuity Pathway Analysis showed activation of pathways that promote apoptosis and cell adhesion, and inhibition of pathways that promote cell proliferation and migration. These results support the hypothesis that, in humans, walnut consumption could suppress growth and survival of breast cancers.

This article contains supporting data for the research paper entitled: 'Dietary walnut altered gene expressions related to tumor growth, survival, and metastasis in breast cancer patients: a pilot clinical trial' [1] Hardman et al., 2019. Included are tables for all mapped genes and all unmapped loci identifications that were significantly changed in breast cancers by consumption of walnut for about 2 weeks. All gene networks that were identified by Ingenuity Pathway Analyses as modified are shown in table 3. Files containing the raw reads, along with a shell script describing the complete data analysis pipeline, were deposited to the Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) and can be obtained via accession number GSE111073. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE111073.

Breast cancer is the most common cancer in women with multiple risk factors including smoking, genetics, environmental factors, and obesity. Smoking and obesity are the top two risk factors for the development of breast cancer. The effect of obesity on adipose tissue mediates the pathogenesis of breast cancer in the context of obesity. Triple-negative breast cancer (TNBC) is a breast cancer subtype within which the cells lack estrogen, progesterone, and HER2 receptors. TNBC is the deadliest breast cancer subtype. The 5-year survival rates for patients with TNBC are 8–16% lower than the 5-year survival rates for patients with estrogen-receptor-positive breast tumors. In addition, TNBC patients have early relapse rates (3–5 years after diagnosis). Obesity is associated with an increased risk for TNBC, larger TNBC tumors, and increased breast cancer metastasis compared with lean women. Thus, novel therapeutic approaches are warranted to treat TNBC in the context of obesity. In this paper, we show that peritumor breast adipose-derived secretome (ADS) from patients with a high (>30) BMI is a stronger inducer of TNBC cell invasiveness and JAG1 expression than peritumor breast ADS from patients with low (<30) BMI. These findings indicate that patient BMI-associated changes in peritumor AT induce changes in peritumor ADS, which in turn acts on TNBC cells to stimulate JAG1 expression and cancer cell invasiveness.