
A large team of scientists have determined that unlike synthetic progestins which increase breast cancer risks,
natural progesterone has the potential to slow the growth of many breast cancer tumors or even shrink them. It has long been known that tumors with estrogen receptors (ER) and progesterone receptors (PR) (ER/PR double positive) have the best clinical outcome, but the interplay between the two proteins has remained elusive. Both are transcription factors, which means they are both involved in switching genes on and off. In a study published in Nature, July 2015, researchers from prestigious institutions including the Cancer Research UK Cambridge Institute; University of Adelaide, Australia; University of Texas, Southwestern Medical Center at Dallas; and University of North Carolina at Chapel Hill explain why double positive breast cancer patients have the best chance of survival. The finding could benefit up to half of all breast cancer patients.
Scientists know that when activated by most forms of estrogen - especially estradiol and its metabolites, estrogen receptors turn on genes within cancerous cells that program those cells to multiply rapidly and stay alive rather than die off as normal, healthy cells do. When activated by progesterone, progesterone receptors attach themselves to estrogen receptors. Once this happens, estrogen receptors stop turning on genes that promote the growth of the cancer cells. Instead, they turn on genes that promote the death of cancer cells (apoptosis) and stimulate the growth of healthy, normal cells.
Jason Carroll and colleagues of Cancer Research UK's Cambridge Research Institute grew breast cancer cells that displayed both ER and PR in the laboratory, and made sure the cells had enough estrogen and progesterone to bind to the receptors. They found that the receptor bound to different regions of DNA depending on whether progesterone was present. In other words, the PR (that had bound to progesterone) was changing the genes that the ER was switching on or off. In addition, the researchers saw that progesterone was associated with slowing cancer cell growth.
Following in vitro testing, the researchers ran tests on breast cancer tumors in live mice. After embedding ER positive/PR positive breast tumors in a number of mice, they exposed some of the mice to estrogen only, others to both estrogen and progesterone, and others to no hormones at all. After 25 days, the team found that while the tumors in the mice that received only estrogen grew, the tumors in the mice that received both estrogen and progesterone decreased in size.
Progesterone inhibited estrogen-mediated growth of ERα+ cell line xenografts and primary ERα+ breast tumor explants, and had increased anti-proliferative effects when coupled with an ERα antagonist. These findings indicate that PR functions as a molecular rheostat to control ERα chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions.
The researchers pointed out that only natural, bio-identical progesterone slows the growth of breast cancer. Conversely, synthetic progestins (molecularly altered forms of progesterone) have been shown to increase rather than decrease breast cancer risks.
This is exciting news for women who are diagnosed with ER/PR positive breast cancers. If such women have healthy progesterone levels, or when progesterone levels are increased through natural progesterone supplementation, treatment outcomes may improve significantly. In their book What Your Doctor May Not Tell You About Breast Cancer, John R. Lee, M.D. and David Zava, Ph.D. noted that
women with progesterone levels that are low relative to estrogen levels are more likely to get breast cancer and have poorer treatment outcomes. They concluded that estrogen dominance causes estrogen receptors to activate genes such as Bcl-2 that are known to promote the rapid growth of cancer cells. They theorized that chronic states of estrogen dominance contribute to high rates of breast cancer, and their theory has been validated with this latest research.
Hormonal imbalances have reached epidemic proportions in most developed countries over the last several decades. Due to poor diets, lack of exercise, a rise in obesity levels, the widespread use of hormone-altering chemicals, and other factors, many women suffer from chronically higher than normal estrogen levels and much lower than normal progesterone levels.
Ask our compounding pharmacist for more information about natural progesterone and the benefits of topical therapy. We work together with physicians and other practitioners and their patients to customize medications in the proper dosage to meet each patient's specific needs.
ReferencesJohn R. Lee, M.D.; David Zava, Ph.D.; and Virginia Hopkins.
"What Your Doctor May Not Tell You About Breast Cancer." 2002