Progesterone, Inflammation and Breast Cancer

progesterone_inflammation.jpgA study from Michigan State University (MSU) has created some controversy about progesterone, inflammation and breast cancer. The study was ostensibly set up to learn more about differences in how the two primary progesterone receptors, A and B, affect breast cancer. To biochemists involved in this particular microcosm, it’s an intriguing study, and the authors should have left it at that. Instead, they created a press release aimed at you and me, that has been widely circulated in the media, that is misleading and inaccurate.

Genetically Tweaked Mice and Cell Cultures
Here’s a layperson’s brief overview of how the study was conducted: A specialized strain of genetically tweaked female mice, some at puberty, some adult, had their ovaries removed, then were injected with saline or progesterone. Their mammary glands were collected and then in culture were exposed to either a control substance, a synthetic progestin, progesterone or angiostenin. The cells from these cultures were examined for morphological (form and structure) changes and proliferation (growth), and their RNA was extracted and analyzed.

The Press Release to the Media
The issues surrounding this study aren’t with the study in and of itself, which did not make any outlandish declarations, but with the authors’ statements to the media. The MSU press release headline is, “Progesterone leads to inflammation, a breast cancer risk factor.” The press release declares that, “Exposure to progesterone in normal amounts and in normal circumstances causes inflammation, which promotes breast development.” Well, no it really doesn’t. That’s a misleading misstatement—something like saying that adding eggs to a cake mix causes the cake to collapse in the oven.

Then the press release goes on to say, “However, exposure to progesterone in menopausal hormone therapy is known to increase breast cancer risk.” This is an inaccurate statement. There is no evidence that progesterone increases breast cancer risk. There is plenty of evidence that synthetic progestins increase breast cancer risk. There’s a big difference.

The Microcosm vs. the Macrocosm
This results of this study can’t be accurately applied directly to the big picture because it would be difficult to have cells further removed from the reality of what occurs in a human woman. Breast tissues and genes continually interact with hundreds of substances, including all of the hormones, the immune system, nutrients and blood factors.

Furthermore, the theorized association of progesterone with one biochemical linked indirectly to inflammation, is one small piece of this study, and to pull it out of dozens of pieces of information and declare it evidence that progesterone is a “…key factor in increasing the risk of breast cancer,” is puzzling to say the least. This study should have been left in the microcosm of arcane breast cancer biochemistry where it belongs.

Another Point of View
Just for the sake of comparison and to illustrate the point, here is the conclusion of another arcane but interesting piece of breast cancer biochemistry research done at University of Texas Southwestern Medical Center and published in 2007: “Collectively, these findings suggest that PR [progesterone receptor] plays an important antiinflammatory [emphasis mine] role in breast cancer cells via ligand-dependent and ligand-independent mechanisms.”

References

Santosa SJ, Aupperleea MD, Xiea J et al, “Progesterone receptor A-regulated gene expression in mammary organoid cultures,” Journal of Steroid Biochemistry & Molecular Biology 115 (2009) 161–172.

Hardy DB, Bethan A, Janowski CC et al, “Progesterone Receptor Inhibits Aromatase and Inflammatory Response Pathways in Breast Cancer Cells via Ligand-Dependent and Ligand-Independent Mechanisms,” Molecular Endocrinology 22 (8): 1812-1824.