October 2008

In This Issue

• What Dr. Lee Said About Breast Cancer
• The Breast Cancer Profile: A Conversation with David T. Zava, Ph.D.
• Remembering John...A New Page on Our Site
• Washington Post Admits to Error on Women's Health Initiative Coverage

Welcome to the Hormone Balance Hotline! Because October is Breast Cancer Awareness Month, we are devoting this issue to breast cancer and to the groundbreaking insights that Dr. Lee and his colleagues have brought to the subject. If you or a loved one are struggling with this disease (and with the conventional approaches to treating it), we encourage you to keep reading. There is plenty of hope and good news in what Dr. Lee had to tell women.

Speaking of good news, this issue also describes how your calls and letters convinced the Washington Post to admit to an error it made about natural progesterone earlier this year. You will also be pleased to hear that we have reduced shipping charges for purchases from our web sites. In addition, we are also announcing discounted product packages  for the month of October, so be sure to check them out!

Finally, I want you all to know about a new page on our site entitled "Remembering John" that will contain a growing number of stories from my life with Dr. Lee. If you ever met John (or wish you did), this is my gift to each of you. It is just another way that all of us at the John Lee M.D. Companies want to say "thank you" for your support of my husband's work.

Yours for good health,
Pat Lee

 

 

What Dr. Lee Said About Breast Cancer

For more than 20 years, women and charitable organizations around the world have joined together each October to mark Breast Cancer Awareness Month. Over the last two decades, Breast Cancer Awareness Month has done much to raise money and awareness levels for the disease. In our opinion, however, the event has focused too much attention on promoting the early detection of breast cancer while devoting little energy to preventing women from getting the disease in the first place.

To prevent a disease, one must understand what causes it. This is the truth that Dr. Lee understood. It was Dr. Lee's desire to know the causes behind breast cancer that led him to write his book, What Your Doctor May Not Tell You About Breast Cancer. If you have not read this groundbreaking document, we encourage you to do so this October. Here is an overview of some of the central points he made in the book.

• Despite billions of dollars spent on breast cancer research, a woman's chance of surviving a malignant breast tumor has changed little over the last 50 years. It may come as a shock, but a woman's chance of surviving a malignant breast tumor today is about one in three...roughly the same rate as five decades ago. Research studies on mortality rates have shown that radiation therapy, tamoxifen, and chemotherapy are not saving more lives. At best, they prolong some lives by a few months or years, but often at the expense of painful or even deadly side effects. Moreover, the number of breast cancer cases per thousand women is much higher today than it was 50 or even 30 years ago.

• While breast cancer is rarely caused by a single factor, unopposed estrogens play a central role in the formation of the disease. For decades, researchers have known that excess estrogen (i.e., estrogen that is unopposed by adequate progesterone and other hormones) increases a woman's risk for endometrial cancer. Recent research has revealed that it also plays a key role in breast cancer formation. Unopposed estrogens can break down into quinone estrogens that react with and damage the DNA in breast cells. These damaged cells can become cancer cells if the body's various defense mechanisms do not recognize and destroy them. In addition, unopposed estrogen can activate the Bcl-2 gene that frequently induces cancer-causing cell proliferation.
  
  Unfortunately, it has become common in developed countries for both women and men to have high levels of unopposed estrogens. This condition, which Dr. Lee called estrogen dominance, has been fueled by changes in our diets and lifestyles. Another cause is our growing exposure to the estrogen-like substances–known as xenoestrogens–found in plastics, fertilizers, pesticides, and other manmade products. Unless we address estrogen dominance, breast cancer risks are likely to remain elevated.

• Progesterone plays a critical role in countering the negative effects of unopposed estrogens. In the body, progesterone neutralizes many of the effects of unopposed estrogen that can lead to breast cancer. It decreases the cell proliferation that is induced by estrogen. In addition, it down-regulates the cancer-causing Bcl-2 gene and up-regulates gene p53, a gene that promotes the death (known as apoptosis) of tumor cells.
  
  Given these findings, having adequate progesterone can be critical to preventing breast cancer. Unfortunately, progesterone levels among many women in developed countries are below normal, healthy levels. This is especially the case among older women and those who use conventional hormone replacement therapies (HRT). This is why Dr. Lee recommended natural progesterone supplementation for women suffering from estrogen dominance, not to mention the avoidance of HRT.

• Besides maintaining healthy progesterone levels and avoiding HRT, women should take steps to reduce other breast cancer risk factors. These include reducing our exposure to xenoestrogens, maintaining healthy levels of other hormones such as DHEA and melatonin, reducing our intake of sugars and unhealthy fats, and managing stress levels through exercise and adequate rest.

Throughout his career as a physician and researcher, Dr. Lee was passionate about finding the causes of breast cancer and the other cancers that women face. It is therefore fitting that What Your Doctor May Not Tell You About Breast Cancer was the last book that he completed before he passed away in 2003. The words with which he opens the book speak volumes about his commitment:

"The book is dedicated to all the women who have lost their lives to breast cancer, and to all women currently fighting breast cancer."

To celebrate Breast Cancer Awareness Month, we are offering his book throughout October as part of several discounted product packages. We would encourage you to get one book for yourself and another for your doctor. With your help, we can spread the word that we know enough about the causes of breast cancer to take steps to prevent it, not just detect it.

References

Cavalieri, E.L., et al. "Molecular Origin of Cancer: Catechol Estrogen-3, 4-Quinones as Endogenous Tumor Initiators." Proc Nat Acad Sci USA 94 (1997): 10937-10942.

Cos, S., et al. "Melatonin and Mammary Pathological Growth." Front Neuroendocrinol 21(2) (2000): 133-170.

Early Breast Cancer Trialists' Collaborative Group. "Favourable and Unfavourable Effects on Long-term Survival of Radiotherapy for Early Breast Cancer: An Overview of the Randomized Trials." The Lancet 355 (2000): 1757.

Formby, B., and T.S. Wiley. "Progesterone Inhibits Growth and Induces Apoptosis in Breast Cancer Cells: Inverse Effects on Bcl-2 and p53." Ann Clin Lab Sci 28 (1998): 360-369.

Liehr, J.G. "Catechol Estrogens as Mediators of Estrogen-induced Carcinogenesis." Cancer Res 35 (1994): 704.

Mitchell, G.H., et al. "Weighing the Risks and Benefits of Tamoxifen Treatment for Preventing Breast Cancer." J Nat Cancer Inst 91(21) (1999).

Nagata, C., et al. "Relations of Insulin Resistance and Serum Concentrations of Estradiol and Sex Hormone-binding Globulin to Potential Breast Cancer Risk Factors." Jpn J Cancer Res 91(9) (200): 948-953.

Seer Cancer Statistics Review, 1973-1997.

The Breast Cancer Profile

A Conversation with David T. Zava, Ph.D.

During his life, Dr. Lee was the editor of the John R. Lee, M.D. Medical Letter. Besides featuring Dr. Lee's research, the John R. Lee M.D. Medical Letter published numerous interviews with experts in the field of natural hormone balance. This includes the following interview with Dr. David Zava, the founder of ZRT Laboratory and a co-author with Dr. Lee of What Your Doctor May Not Tell You About Breast Cancer. ZRT Laboratory is a leading provider of hormone testing services.

The following interview with Dr. Zava can be found in the August 2002 issue of the John R. Lee M.D. Medical Letter. In the interview, Dr. Zava explains that women who are diagnosed with breast cancer often have a distinct set of hormonal imbalances which he calls "the breast cancer profile". Women can determine whether their hormones fit this profile through saliva hormone tests that we offer on our web site.

JLML: Dr. Zava, we understand that you've collected some interesting and important data about breast cancer since we wrote the book about breast cancer together.

DTZ: Yes, I call it the breast cancer profile. It relates to the hormone profiles that we look at in saliva. We've been doing some work with Dr. Rebecca Glaser from Ohio. She's a breast surgeon and has been sending us saliva samples from women who have just been diagnosed with breast cancer. In most cases where the diagnosis is infiltrating ductal carcinomas, the hormone profile is quite distinct.

What I see–even in postmenopausal women–is that their estradiol levels are quite high, even if they've had a hysterectomy, and that's very unusual. Their progesterone levels are extremely low–less than 15–which is almost equivalent to zero. Their testosterone levels are high. This has already been well described in the literature on breast cancer patients.

DHEA sulfate [DHEA-S] is very low, which is a hallmark of most cancers. I think that's related to adrenal dysfunction, but is probably also related to the fact that breast tumors produce high levels of the enzyme sulfatase that cleaves the sulfate off of the DHEA-S, making more DHEA, which is converted into estradiol and testosterone. This, I believe, is one of the reasons why the testosterone and the estradiol are high. You've got everything moving in the direction of making estrogen.

The cortisol profile is odd because it tends to be flat. This has recently been described in the literature (Sephton). You don't have the normal diurnal [twice daily] variation, which is that when you wake up in the morning your adrenals are producing a lot of cortisol, and then it drops down to about one-fifth by nightfall. In breast cancer patients, their cortisol is often the same morning and night (which would mean that it's higher than normal at night).

JLML: So to sum up, the breast cancer patient hormone profile you're seeing is high estradiol and testosterone, low progesterone and DHEA-S, and flat cortisol levels, usually created by high night cortisol.

JLML: Do you see this profile often in saliva tests?

DTZ: Rarely in the normal population but frequently in women newly diagnosed with breast cancer. Women with less aggressive intraductal cancers rarely have this profile. And women who have had breast cancer and are in remission tend to have a normal profile, so the profile seems to be something that's happening before or during the time that they are diagnosed with cancer.

I think the hormone profile should, and will, be used in the future as an adjunct to tumor imaging procedures (mammography, sonography, etc.).

JLML: In addition to telling women how their hormones need to be balanced, a saliva test could also potentially tell them that their hormonal milieu is predisposing them to breast cancer. What are your thoughts on how this hormonal profile is created?

DTZ: We're getting a pretty good-sized database now, and most of the breast cancer cases that we've done saliva testing for are associated with 10 to 20 years use of conventional HRT.

JLML: Wow, that's a real indictment.

DTZ: But not surprising, it's what the WHI study found in healthy women using HRT for only five years. Compound this with "not so healthy" women using this form of hormone replacement for a lifetime and it's not so difficult to see the problem.

JLML: What other factors come into play in creating the breast cancer hormone profile that you have noticed?

DTZ: A major stressor that occurs several years prior to discovery of the cancer seems to be common. This is what I believe causes adrenal dysfunction, which in turn suppresses the immune system, sets up an estrogen factory, and allows the expression of a preexisting cancer.

JLML: What role do you see progesterone playing here?

DTZ: Progesterone will counter nearly all biochemical pathways that give the tumor cells a growth advantage, by directly inhibiting cancer cell proliferation, suppressing estrogen receptors, preventing blood vessels from forming around the tumor, and enhancing natural immunity by boosting natural killer cell activity, the first line of defense against all cancers.

JLML: Perhaps this is why Cowan found that women producing higher levels of progesterone had fewer types of all cancers. This underscores the importance of having balanced hormones before breast cancer surgery.

DTZ: Exactly. When you cut through a tumor when the patient is estrogen dominant you're going to have some problems. Natural killer cell function will be suppressed locally because of the excessive estrogen forming around the tumor. That's a setup for poor immune response.

Excess estrogens also encourage blood vessel growth (vascularization) and cause the expansion of the capillaries, allowing small clumps of tumor cells to escape to distant sites (metastasis). To make matters worse, high estrogen enhances blood clotting, and small clots form around clusters of tumor cells, making recognition by the already compromised natural killer cells even more difficult. In other words, the chance of metastasis is much greater under conditions of estrogen dominance.

We should be doing a clinical study to look at the effects of progesterone prior to breast surgery, in order to lower the estrogen burden, to lower the rate of cell proliferation, to increase natural killer cell function, to do all the things that are going to increase the probability that a woman is going to survive the breast cancer. If she's operated on without being protected like that, and she's making loads of estrogen and all these profiles are off, then the probability that the cancer cells are going to escape and set up a metastatic site is much higher.

The Mohr study looked at different phases of the menstrual cycle, and found that women who had high levels of progesterone in their bloodstream at the time of surgery were twice as likely to be alive at 10 to 15 years compared to women who had a low progesterone level. It's surprising to me that we haven't done the obvious–give a woman progesterone for a couple of weeks prior to her surgery, look at what's happening to the cancer cells short term, and follow disease-free and overall survival patterns long term.

From the Chang study we know that 20 to 30 mg of progesterone applied directly to the breasts 10 to 13 days prior to surgery reduces the rate of breast cell proliferation, and we know it helps fibrocystic breasts, which is excessive stimulation by estrogen.

We should be studying this in great detail. There's no question at all that progesterone is protective, but because physicians don't have large-scale clinical studies, they won't use it at a critical time when a woman is having breast surgery. Strange, they have no problems using highly toxic chemotherapy or tamoxifen, but are hesitant to try natural progesterone, which is the body's natural anti-estrogen.

JLML: Do you have any insights to share about the Women's Health Initiative study [WHI], which found higher rates of heart disease, breast cancer and stroke in women using conventional HRT?

DTZ: I think you covered it well in the last issue of the newsletter, but there are several things I'd like to point out. The truth of the WHI is that it created a major selection bias by choosing only healthy women to be in the study. If you had heart disease risk factors such as high blood pressure, diabetes, or obesity, for example, you weren't selected.

You can't extrapolate study results from a population of healthy women to the entire population. If you look at the entire population of women, it only includes a relatively small proportion of very healthy women. An incredible forty-two percent of those healthy women chosen to participate in the WHI fell out of the study in the first couple of years because they didn't like the side effects of the drugs. If all of those women had continued, or if they hadn't limited the study to healthy women, there would have been a much higher rate of all the adverse events (breast cancer, heart attacks, thromboembolism) that they found. The results are actually much worse than they appear to be because of the selection bias.

References

Writing Group for the Women's Health Initiative Investigators, "Risks and benefits of estrogen plus progestin in healthy postmenopausal women," JAMA, July 17, 2002, Vol 288, No. 3.

Chang K-J, Lee TTY, Linares-Cruz G, Fournier S, and de Lignieres, B. "Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo." Fertility and Sterility 1995; 63: 785-791. (Premenopausal women)

Mohr PE, Wang DY, Gregory WM, Richards MA, and Fentiman IS. "Serum progesterone and prognosis in operable breast cancer." British J of Cancer 1996; 73: 1552-1555.

Remembering John...A New Page on Our Site

Over the years, many of you have written or called to tell us how you met Dr. Lee and how he made an enormous personal impact on your lives. Dr. Lee freely gave his time to talk with thousands of women and men on the telephone, at conferences, and anywhere else where he could help people achieve hormone balance naturally.

Because many of you have personal remembrances of Dr. Lee, we know that you will appreciate a new page on his official web site entitled, "Remembering John". On this page, Pat Lee – Dr. Lee's wife and assistant in his work – offers her remembrances of her husband and their many years together. Over the coming months, Pat will add new remembrances to this page, so be sure to visit it often to get an intimate look at the incredible man and physician who remains our inspiration.

Washington Post Admits to Error on Women's Health Initiative Coverage

In our last issue of the Hormone Balance Hotline, we alerted all of you to a serious error that the Washington Post made in its story on the latest study from the Women's Health Initiative (WHI). The study showed that even after women quit taking combination estrogen-progestin pills, they face elevated cancer risks for years afterwards. Unfortunately, the Post reported that the women in the WHI study were taking estrogen and progesterone rather than the progestins they were actually taking. The story had the potential to mislead thousands of women into thinking that progesterone poses a cancer risk. Worse yet, the author of the story refused to issue a correction.

In response to this refusal, we asked all of you to contact the Washington Post and demand that it issue a correction to the article. We are happy to inform you that it did! In her May 11, 2008 column, Washington Post Ombudswoman Deborah Howell admitted that the paper should have issued a correction and quoted Marcia Stefanick, a research professor who chairs the WHI steering committee. Stefanick noted in her statement that the WHI did not use progesterone in its study and that it is "technically wrong" to use the terms "progestin" and "progesterone" interchangeably.

We want to thank all of you who contacted the Post and asked for a correction to their story. With your help, we are dispelling the misinformation about HRT and natural progesterone one woman–and one news organization–at a time. We appreciate your support!