Linda Vona Davis
Department of Surgery and Breast Cancer Research Program,
West Virginia University Robert C. Byrd Health Sciences Center,
Morgantown, United States
Dr. Linda Vona-Davis is an associate professor at the department of surgery of West Virginia University and at the Mary Babb Randolph Cancer Center in West Virginia, USA. She completed her Bachelor of Science in education, Masters in animal science then a PhD in animal nutrition. She taught many basic science and biology subjects at the West Virginia University. She is the president of the Association for Women in Science, West Virginia, in addition to many senior positions in academic and scientific committees. Dr. Vona-Davis is an invited speaker to many national and international scientific meetings. In addition to multiple publications, she is the author of numerous books and book chapters.
Abstract 1: Breast cancer pathology, receptor status, and patterns of metastasis in a rural appalachian population
Background: Breast cancer patients in rural Appalachia have a high prevalence of obesity and poverty, together with excessive expression of the triple-negative phenotype. Methods: Clinical records for 687 patients provided data which included tumor receptor status and time to distant metastasis. Breast cancers with the triple-negative phenotype were compared with other receptor combinations. Body mass index, tumor size, grade, nodal status, and receptor status, were related to metastatic patterns. Results: Ninety-five of 687 patients, (13.8%) developed metastases to bone (n=42) or visceral sites (n=53). Metastases to viscera occurred within five years, a latent period which was shorter than that for bone (P = 0.042). Significantly more women with visceral metastasis presented with grade 3 tumors compared with the bone and non-metastatic groups (P = 0.0002). There were 135/574 women (23.5%) with triple-negative breast cancer, who presented with lymph node involvement and visceral metastases (68.2% versus 24.3%; P = 0.033). Triple-negative tumors that metastasized to visceral sites were significantly larger (P = 0.007). Although the probability of developing a visceral metastasis within 10 years was higher among women with triple-negative tumors, this relationship was not influenced by increasing body mass index. Conclusions: For all breast cancer receptor subtypes, the probability of remaining distant metastasis-free was greater for brain and liver than for lung. The excess risk of metastatic spread to visceral organs in triple-negative breast cancers, even in the absence of positive nodes, was combined with the burden of larger and more advanced tumors.
Abstract 2: Effects of high-fat diet feeding on mammary tumor growth and metastasis in an er-negative mouse model
Epidemiological studies indicate that overweight and obesity are associated with poor outcomes in several cancers. In the present study, we determined whether a chronic consumption of high-fat diet increases solid tumor growth and metastasis in the ER-negative, MMTV-PyMT mammary cancer mouse model. Four-week old, female mice (n=40) were provided ad libitum access to water and randomized to diets at 60% kcal% fat (HF) or 7.0 % fat (control) for 8 weeks. Body weights were obtained weekly, and at that time, mice were imaged for mammary tumor volumes in the 4th and 5th mammary glands by 3D ultrasound. Tumor burden was collected during hyperplastic, early and late stages, weighed and fixed for immunohistochemical staining. Blood and tissue from the liver, lung, and mesenteric fat were also collected. Rates of body weight gain were higher (P<0.0001) in mice consuming the HF diet while their food intakes were lower (P<0.05) compared to controls. Average mammary tumor volumes measured by ultrasound were significantly larger in mice fed the HF diet compared to the controls 19.0±3.9 vs 38.0±8.5mm3 respectively (P<0.0001). Average tumor burdens were 2.7±0.4gm for control diet and 3.9±0.8gm for HF (P=0.056). Immunohistochemical evaluation of tissues revealed the presence of lung metastases in all MMTV-PyMT mice, regardless of diet. Mice consuming the HF diet showed an increased the number of metastases to the lung by 2-fold. In addition to higher tumor burdens and rates of metastases, mice fed a high fat diet showed elevated levels of adipocyte derived monocyte chemoattractant protein-1 (MCP-1) in the blood. We hypothesized that diet-induced obesity promotes mammary carcinogenesis by inducing an inflammatory and tumor-supportive microenvironment. We further compared chow fed lean MMTV(PyMT) mice with those fed 45.0% (w/w) high fat (HF) to investigate the impact of body adiposity and dietary nutrient overload on levels of MCP-1 in tissue, tumor associated macrophages (TAMs) and for the degree of microvessel density. We analyzed early and late carcinoma stage tumors together with adipose tissue from mice fed HF and control diets in order to identify possible sources of MCP-1 production. MCP-1 levels in tumors of mice differed significantly by cancer stage and diet, with late stage tumors showing more MCP-1 (P<0.05). Moreover, MCP-1 production was elevated in adipose tissue of obese mice compared to lean mice. Tumors and adjacent adipose were stained with CD68 and the numbers of TAMs were quantified. Significantly more TAMs (P<0.05) were found within tumor beds and more crown-like structures were evident in adipose tissue surrounding the tumor beds from obese mice at both early and late stage carcinoma. Tumor beds also showed increased microvessel density when stained with CD31. The increased angiogenesis resulting from consuming a HF diet most probably contributes to increased tumor growth and metastasis and may explain, in part, the aggressive growth of some ER-negative tumors. In summary, diet-induced obesity increased levels of MCP-1 in tumors and adipose with more macrophage infiltration and greater vascular density evident in mammary tumor beds. Taken together, these findings suggest that high body adiposity caused by diet-induced changes promote an inflammatory and tumor-supportive microenvironment in breast cancer. NIH P20 RR016440, P30 R032138/GM103488, and P20 RR016477