Vitamin D and Breast Cancer in Obesity: Therapeutic Trials
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: For women, being overweight or obese (we use the term obese for the combined group) is a well-known risk factor for developing breast cancer (BCa) and for having a worse prognosis. The BCa-associated hazards are: (1) inability to respond to insulin normally (insulin resistance) causing elevated levels of insulin and growth factors, (2) increased estrogen formation by the breast fat, and (3) influx of inflammatory cells into the breast that further stimulate estrogen formation and growth. Obese women are frequently vitamin D deficient. Vitamin D exerts many anti-cancer actions to reduce cancer growth but is especially useful to treat BCa because it suppresses the obesity-induced hazards.
 
 
 
 
 
 
 
 First, we will study the effect of vitamin D in mouse models of human breast cancer. In previous work we have shown that these tumors respond to estrogens and that vitamin D suppresses this activity. For the present studies we will use an innovative mouse model of estrogen receptor positive (ER+) BCa induced by stem cells injected into the mouse mammary fat pads. The cells will contain a gene allowing quantitative, continuous assessment of tumor growth. We will monitor tumor growth and possible metastases using state of the art bioluminescent imaging. The study will compare normal and obese mice generated by a dietary-induced obesity regimen and assess the chemo-preventive activity of vitamin D to delay or prevent the development or progression of BCa.
 
 
 
 
 
 
 
 In parallel work we will validate the beneficial actions of vitamin D by assaying biomarkers in women with newly diagnosed BCa. We will assess the women’s blood and the profile of activated genes in BCa tissue specimens. For these studies, we will recruit 60 BCa volunteers, half of whom will be obese, 40 will receive high dose (10,000 IU) vitamin D and 20 will receive a minimal dose (400 IU) as a control group. The vitamin D is given orally in the interval between the diagnostic biopsy and the surgery several weeks later. We use advanced molecular methods to study blood biomarkers and tissue genes that predict disease prognosis. We will compare the ability of vitamin D to improve the hazards of insulin resistance, inflammation and increased estrogen formation and to change the biomarkers and genes from a pattern that predicts poor prognosis to one that indicates an improved outcome.
 
 
 
 
 
 
 
 Taken together, our findings will indicate to physicians and the BCa community the importance of avoiding vitamin D deficiency and the need to screen for and treat deficiency when it is found. We expect that the benefit of high dose vitamin D will be more dramatic in obese women but that there will be a benefit to all subjects including African Americans who are especially at increased risk for vitamin D deficiency and BCa. We envision that vitamin D will be routinely added to other therapies to enhance their activity by inhibiting estrogen formation in the breast and protecting bones from osteoporosis. These findings will provide the basis for a large clinical trial that will show compelling evidence for the value of avoiding vitamin D deficiency as well as the benefit of vitamin D therapy in women with BCa. The Breast Cancer Connections (BCC), advocacy group in Palo Alto, will advise us and assist in recruitment, development of educational materials; especially in the outreach efforts to underserved and minority women.