The January 21, 2013 issue of The Journal of Cell Biology published a report by Susana Gonzalo at Saint Louis University and her associates that indicates a possible benefit for vitamin D in triple-negative breast cancer, one of the more treatment-resistant forms of the disease. Triple negative cancers have reduced receptors for estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2), which makes them unresponsive to hormone-targeted therapies.

Dr Gonzalo's research discovered a molecular pathway in women with triple negative breast cancer and mutations in a tumor suppressor gene known as BRCA1. Loss of BRCA1 function impairs the cells' ability to repair DNA double-strand breaks and halt the proliferation of damaged cells.

It was recently discovered that the loss of another DNA repair factor known as 53BP1 enables the proliferation of BRCA1-deficient cells. Dr Gonzalo's team discovered that the protease cathepsin L degrades 53BP1, and that vitamin D restores it. "It's a new pathway that explains how breast cancer cells lose 53BP1," stated Dr Gonzalo, who is an assistant professor of biochemistry and molecular biology at Saint Louis University. She added, however, that the mechanism behind the increase in cancer cells' nuclear cathepsin L has not been defined.

In further research utilizing tissue samples from breast cancer patients with BRCA1 mutations or triple-negative breast cancer, the team found high levels of nuclear cathepsin L and decreased levels of 53BP1 and vitamin D receptor. These markers identify which populations might best benefit from cathepsin inhibitors or vitamin D therapy.

An important aspect in any reproductive cancer is whether the tumor growth is hormonally driven. Often breast tumors require hormones for growth, i.e., hormonally responsive tumor. The hormones attach to their receptor sites and promote cell proliferation. Hormone receptor-positive tumors consist of cancer cells with receptor sites for estrogen, progesterone, or both. The receptor status of a tumor is determined by testing tissue removed during a biopsy. Breast cancer can be categorized by its receptor status, which can be estrogen receptor-positive (ER+), estrogen receptor-negative (ER -), progesterone receptor-positive (PR+), progesterone receptor-negative (PR-) or any combination thereof. Both estrogen and progesterone are naturally occurring hormones that the body produces in varying amounts throughout one's lifetime. These hormones are essential for many other physiological functions, such as bone integrity.

Vitamin A and vitamin D3 inhibit breast cancer cell division and can induce cancer cells to differentiate into mature, noncancerous cells. Vitamin D3 works synergistically with tamoxifen (and melatonin) to inhibit breast cancer cell proliferation. The vitamin D3 receptor as a target for breast cancer prevention was examined. Preclinical studies demonstrated that vitamin D compounds could reduce breast cancer development in animals. Furthermore, human studies indicate that both vitamin D status and genetic variations in the vitamin D3 receptor (VDR) may affect breast cancer risk. Findings from cellular, molecular and population studies suggest that the VDR is a nutritionally modulated growth-regulatory gene that may represent a molecular target for chemoprevention of breast cancer (Welsh et al. 2003).