A large team of scientists working on multiple continents published a research study that came to startling conclusions about breast cancer and natural progesterone. The team 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.
While this finding is stunning, it is not new. It is one of several conclusions about progesterone that Dr. John R. Lee, M.D. and Dr. David Zava, Ph.D. made more than a decade ago when they co-wrote the book, What Your Doctor May Not Tell You About Breast Cancer. Now that their findings have been confirmed by other scientists, the medical community can no longer assume that natural progesterone promotes breast cancer like progestins do. Progestins are molecularly altered synthetic versions of progesterone.
It’s All About Receptors
For years, breast cancer researchers have known that women whose breast cancers contain both estrogen receptors and progesterone receptors (known as ER positive/PR positive tumors) have better treatment outcomes than women whose tumors do not have these receptors. What researchers have not understood is why this is the case. To find out, scientists at Cancer Research UK and the University of Adelaide in Australia studied the interactions between estrogen and progesterone receptors in breast cancer cells. They published their findings in the July 16, 2015 issue of the scientific journal Nature.
Before we discuss the study, let’s answer the question that many of you may be asking. What are estrogen and progesterone receptors, and what do they do? Estrogen and progesterone receptors are proteins found within many of the cells of our bodies, including cells in the breasts. They are the mechanism that allows estrogen and progesterone to change the behavior of our cells. In the process, they change how many tissues and organs in the body function. Estrogen receptors can only interact with estrogen molecules, while progesterone receptors can only interact with progesterone molecules.
Dr. Lee and Dr. Zava anticipated the conclusions of the latest research study 13 years ago.
When an estrogen or progesterone molecule comes in contact with its respective receptor, the molecule binds to the receptor and activates it. Once this happens, the receptor enters the nucleus of its cell and attaches to specific spots on the chromosomes that contain all of the cell’s genetic coding. When the receptor does this, it “turns on” and “turns off” specific genes that govern the behavior of the cell. So in a real sense, estrogen and progesterone receptors are constantly reprogramming our cells by turning selected genes on and off. However, these receptors can only do their work if the body provides them with estrogen and progesterone to activate them.
For years, scientists have known that when activated by most forms of estrogen, 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. This means that most forms of estrogen – especially estradiol and its metabolites – are potent fuels for breast cancer. That is why oncologists try so hard to reduce estrogen levels in breast cancer patients with drugs such as Tamoxifen, Femara, and Arimidex.
While scientists know how estrogen receptors fuel the growth of cancer cells, they know a lot less about what progesterone receptors do in those same cells. That lack of knowledge is what the latest research study was designed to correct. In the study, scientists took breast cancer cells that were ER positive/PR positive and exposed them to enough estrogen and progesterone to activate both the estrogen and progesterone receptors. They then used new, cutting-edge techniques to examine what the receptors did within the cancer cells. What they found amazed them. When activated by progesterone, the progesterone receptors attached themselves to the estrogen receptors. Once this happened, the estrogen receptors stopped turning on genes that promote the growth of the cancer cells. Instead, they turned on genes that promote the death of cancer cells (known as apoptosis) and the growth of healthy, normal cells!
Since these experiments were only performed on cancer cells in test tubes, the researchers took the next step and 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.
Around two out of three of all breast cancers are hormone receptor-positive. This means that the majority of women suffering from breast cancer may benefit from adding natural progesterone to their treatment plans.
It should be noted that the research team gave the estrogen inhibitor Tamoxifen to some of the mice that had also been treated with natural progesterone. They then compared the tumors of these mice to the tumors of mice that received progesterone but not Tamoxifen. While tumor growth was reduced in both sets of mice, the tumors of the mice treated with both progesterone and Tamoxifen experienced the greatest growth reduction.
This led the research team to advise that doctors combine progesterone with estrogen inhibitors such as Tamoxifen in their patients’ treatment plans. While this advice deserves consideration and further research, Dr. Lee and Dr. Zava point out that Tamoxifen and other estrogen inhibitors have serious side effects that should play a role in any decision about their use.
Taken together, the experiments conducted by the research team led them to a powerful conclusion. When activated by progesterone, progesterone receptors bind to and “reprogram” estrogen receptors, transforming them from agents that turn on cancer-promoting genes to ones that turn on genes which slow down or even reverse the growth of cancer cells. The researchers also pointed out that their conclusions apply to natural, bioidentical progesterone. They rightly observed that many progestins – the synthetic, molecularly altered forms of progesterone found in pharmaceutical drugs – have been clearly shown to increase rather than decrease breast cancer risks.
These findings are incredibly good news for women diagnosed with estrogen receptor positive/progesterone receptor positive breast cancers. If such women have healthy progesterone levels or raise them to those levels through natural progesterone supplementation, they could dramatically improve their treatment outcomes. According to the American Cancer Society, around two out of three of all breast cancers are hormone receptor-positive. This means that the majority of women suffering from breast cancer may benefit from adding natural progesterone to their treatment plans.
How the Latest Study Validates Dr. Lee's & Dr. Zava's Findings
While the scientists behind the Nature study may not know it, Dr. Lee and Dr. Zava came to the same conclusions about natural progesterone and breast cancer 13 years ago. In 2002, the two men reviewed all of the available research on breast cancer in their groundbreaking book, What Your Doctor May Not Tell You About Breast Cancer, and came to the following conclusions:
Women with progesterone levels that are low relative to estrogen levels are more likely to get breast cancer and have poorer treatment outcomes. Dr. Lee coined the term estrogen dominance to identify the hormonal condition of progesterone being low relative to estrogen. Based on available research, he and Dr. Zava 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.
When progesterone is raised to healthy levels relative to estrogen, it turns on genes that can prevent breast cancer from occurring and reduce the size of existing tumors. Dr. Lee and Dr. Zava cited research studies which show that progesterone receptors activate genes such as p53 that promote apoptosis. Apoptosis enables the body to “kill off” many cancer cells before they develop into tumors.
Because progesterone promotes the healthy growth and death of cells, the hormone does two things. First, it can prevent healthy cells in breast tissue from mutating into tumors. Second, it can limit the growth of existing breast tumors or even reduce them in size. Dr. Lee said many times that women with hormone receptor positive breast cancers could especially benefit from natural progesterone supplements because their tumors had progesterone receptors to which the progesterone could bind.
In short, Dr. Lee and Dr. Zava anticipated the conclusions of the latest research study 13 years ago. At the time, many doctors dismissed their statements about the importance of progesterone. To this day, many oncologists refuse to let their breast cancer patients use natural, bioidentical progesterone out of fear that it could fuel tumor growth. Now, thanks to the new study in Nature, the medical community must rethink its position. It turns out that Dr. Lee and Dr. Zava were right all along.
Original of this article was published on ZRT Laboratory Blog.