The Wisdom of Menopause
Page 68
Though no one has done a definitive long-term clinical trial of bioidentical progesterone, my clinical experience and that of many of my colleagues, including the late John Lee, M.D., a pioneer in bioidentical hormone research, has led me to believe that bioidentical progesterone can benefit many women, especially if used during peri-menopause, and will very likely be found to decrease the risk for breast and other estrogen-responsive cancers that may well get their start during this time of life.
Progesterone Preparations and
Progesterone-Receptor-Positive Breast Cancer
One of the questions I’m frequently asked is whether a woman whose breast cancer has tested positive for progesterone receptors can safely take progesterone. There is a great deal of confusion about what it means to have a breast biopsy that shows that the tumor is positive for progesterone receptors, especially in those women who have been using bioidentical progesterone at the time of their diagnosis.
Here are the facts. All breast cancers that are positive for progesterone receptors are also estrogen-receptor-positive. Because estrogen is known to stimulate growth of these types of cancer cells, many people automatically assume that progesterone must do the same. Just the opposite is true. Positive progesterone receptors indicate that a cancer is receptive to the balancing and anticancer effects of progesterone.
To understand this apparent paradox, remember that hormones in the bloodstream and the fluid surrounding cells work by uniting with receptors on the surface of the cell. The hormone fits the receptor like a key in a lock. If the right receptor is there, the hormone message makes its way to the chromosomes and turns on the appropriate gene to produce a specific cellular effect. Progesterone signals the cell to stop multiplying, while estrogen signals the opposite. For that reason, bioidentical progesterone is probably beneficial for women with progesterone-receptor-positive breast cancer.
In general, women with estrogen-and progesterone-receptor-positive breast tumors have the best prognosis, since the presence of both these receptors means that the tumor is well differentiated and slower-growing than more poorly differentiated tumors.
Though I’m convinced that bioidentical progesterone is safe and even beneficial for women with estrogen-and progesterone-receptor-positive breast cancers, this is a controversial area. Use your inner guidance and consult with your doctor.
My Advice About Progesterone
~ If you are currently perimenopausal and using a progesterone cream or another form of bioidentical progesterone such as Prometrium or Crinone, you are helping your body create hormonal balance that may well protect your breasts from overstimulation by estrogen and androgen. I recommend that you continue to use it until after menopause, unless your inner guidance tells you otherwise.
~ If you are at risk for estrogen or androgen dominance, consider adding bioidentical progesterone. Conditions associated with estrogen dominance are the following: irregular periods, body fat percentage greater than 28 percent, sedentary lifestyle, polycystic ovary syndrome, fibroid tumors of the uterus, breast tenderness, a low-fiber diet high in refined carbohydrates, heavy menstrual periods, and hormone therapy with estrogen only. Androgen dominance is associated with acne, polycystic ovary syndrome, and male pattern baldness.
~ Though not all women’s health experts agree on the progesterone question, I personally would recommend that every woman who is concerned about her breast health avail herself of the substantial benefits of bioidentical progesterone, especially during the perimenopausal period, when it is well known that she is likely to start skipping ovulations and therefore to have low progesterone levels. Substantial doses of soy protein, or the phytoestrogen found in Pueraria mirifica (see PUERARIA MIRIFICA (PM):), would be a reasonable alternative to progesterone. Use progesterone for two to three weeks out of the month and then take a week off. This is the most beneficial and physiological way to use it. If you are postmenopausal, get a blood or saliva test done to be sure you’re not converting progesterone to estrogen.
What About Testosterone?
Androgens such as testosterone and even DHEA can be converted into estrogen in the body, which means that taking testosterone could theoretically increase your risk for breast cancer. Use the lowest dose that gives you the results you need, or try alternatives first.
Here’s the bottom line: it is in our best interest to make the wisest choices we can if we opt for hormone therapy—which means using bioidentical, individualized HT regimens when needed at the lowest doses that give us the results we want. Once we’ve done that, we simply have to let go of our illusion of control and realize that there are no perfect solutions. We all do the best we can with the information we have at the time. But that information, like us, keeps evolving and changing. This year’s best solution may differ from next year’s. Nevertheless, most of the time our bodies and our cells maintain their health—which is why the vast majority of women, either on or off hormone therapy, do not get breast cancer.
THE TAMOXIFEN DILEMMA
Tamoxifen (trade name Nolvadex) is commonly prescribed to women with certain types of breast cancer and also to prevent breast cancer in high-risk women. It is one of a class of drugs called selective estrogen receptor modulators (SERMs). Other SERMs include raloxifene (Evista), which is used to prevent and treat osteoporosis and is also now recommended as an alternative to tamoxifen in postmenopausal women. Tamoxifen’s antiestrogenic effect on breast tissue has been shown to prolong the disease-free interval and overall survival rate in women with estrogen-receptor-positive breast cancer. It has been prescribed for hundreds of thousands of women, making it the most commonly used anticancer drug in the United States. Tamoxifen became a generic drug in the early part of this century, thus reducing its cost and the profits made from it. As a result, attention has turned to newer, more expensive drugs.
Tamoxifen has significant risks, sometimes due to its estrogenic properties, other times due to its antiestrogenic effects. Some researchers are concerned that its antiestrogenic effects on brain tissue may put women at increased risk for dementia or depression.125 It has been my experience that many women who are taking tamoxifen suffer from depression but don’t tell their doctors because they don’t want to bother them. This is particularly true for women who no longer have periods. In its estrogenic mode, tamoxifen results in changes in the endometrial lining of the uterus, ranging from atypical hyperplasia (abnormal thickening) and polyps to invasive cancer. The longer you’re on it, the greater the risk.126 This means that any woman on tamoxifen needs to have regular uterine screenings by ultrasound or other means to make sure she doesn’t develop uterine cancer. Another problem with tamoxifen is that if a woman continues to take it beyond five years, it may stop acting like an antiestrogen in her breasts and start to act more like an estrogen.127 In other words, a woman may develop resistance to it, and, if she does get breast cancer again, it may even increase the chance of the cancer being resistant to treatment.128 Tamoxifen is also associated with increased risk for stroke, cataracts, and blood clots.
Tamoxifen for Breast Cancer Prevention
Although placebo-controlled, randomized clinical trials have never been done, tamoxifen is currently approved for and marketed to healthy women considered at increased risk for breast cancer. In a highly publicized study done by the National Cancer Institute, the drug reduced the rate of expected breast cancers in a group of 13,000 women in the United States and Canada from 1 in 130 women to 1 in 236 women. Statistically, this represented a 50 percent reduction in the risk of breast cancer in those women who took tamoxifen prophylactically—a figure that certainly got everyone’s attention. Though two other studies, done in Europe, did not show any breast-cancer-decreasing benefits, the drug was approved for prevention of breast cancer in women at high risk for the disease.129
After its approval for prevention in 1998, many ads for Nolvadex appeared in mainstream magazines. One read, “If you care about breast cancer, care more about being a 1.7 than a 36B. Know
your breast cancer risk assessment number. You can call 1-800-898-8423 to learn more about Nolvadex and the Breast Cancer Risk Assessment test.”
The NCI tamoxifen prevention trial included women with a 1.7 percent risk. This “risk number” is based on what is known as the Gail model, which was developed by a group of statisticians at the National Cancer Institute in the late 1980s. Its purpose was to try to assess the theoretical risk of breast cancer using data developed on only 28,000 white women. Those who came up with this assessment tool admitted that it represented only a “best guess,” not the last word in scientific proof.130 The updated Gail risk assessment that was developed to promote tamoxifen has been controversial from the start, with critics contending that it tended to overstate risk. Even the original creators of the Gail model cited “three major sources of uncertainty” about their risk model. However, these uncertainties, as well as the risks of the drug itself, tended to be underplayed.
For example, women taking tamoxifen for prevention are two to three times more likely to develop uterine cancer or blood clots in the lung and legs than controls. Stroke, cataracts, and cataract surgery are more common with the drug, too. Most postmenopausal women also experienced hot flashes and bothersome vaginal discharge. Quite a few healthy women knew intuitively that the risks outweighed the benefits and decided to take their chances without tamoxifen. And it turns out that their inner wisdom was correct.
In 2006, a study reported in the journal Cancer showed that women at the lower end of the risk range did not, in fact, live longer as a result of taking tamoxifen. The study, which was based on a hypothetical population model of a group of fifty-year-old women considered at high risk (1.7 percent or higher), took into account the calculated incidence of breast and endometrial cancers, end-result statistics, and non-cancer-related outcomes of those on tamoxifen. Researchers found that tamoxifen actually increased mortality in women with a uterus whose risk was under 2.1 percent. For those with a very high risk number, 3 percent or more, however, there was a potential benefit in terms of decreased mortality. This beneficial effect was especially strong in women who’d had hysterectomies.131
The pendulum has now swung back to center when it comes to SERMs and breast cancer prevention. In an article on Medscape news, V. Craig Jordan, Ph.D. (dubbed “the father of tamoxifen” by the media), the scientific director for the medical science division at Fox Chase Cancer Center in Philadelphia, said, “This drug has got to be used very specifically. It is not one that should be added to the water supply, and it calls for a huge amount of physician discretion.”132 I couldn’t agree more.
In 2009, a study of more than a thousand women with ER-positive breast cancer clearly showed that women who take tamoxifen for at least five years after having a lumpectomy or mastectomy more than quadruple their risk of developing ER-negative breast cancer—a rare but more aggressive and more difficult-to-treat cancer—in their healthy breast.133 Using tamoxifen for less than five years was not linked to the ER-negative breast cancer, but because women don’t get the full benefit of tamoxifen until they’ve taken it for five years, that finding didn’t do much to assuage anxiety about the drug.
The bottom line is that while most women with breast cancer will lower the risk of cancer recurring by taking tamoxifen, 25 percent of them will actually increase their risk of getting an even more deadly form of breast cancer. I’m not at all comfortable with those odds, especially because of the added risk of blood clots, stroke, and uterine cancer associated with tamoxifen.
My Advice on Tamoxifen and Other SERMs
~ If you are already on tamoxifen, feel good about it, and are having no side effects, then I’d recommend that you stick with it for up to five years.
~ If taking tamoxifen reduces your fear of breast cancer significantly and brings you peace, then by all means take it. This is especially true if you’ve watched your sister or mother die of breast cancer. In this case, the overall benefits of tamoxifen—including the sense that you are doing something to protect yourself—may well outweigh the risks.
~ If you’re offered raloxifene, remember that it is a “same doll, different dress” drug. Though it is touted as having a lower incidence of serious side effects than tamoxifen, they are still significant. Remember, too, that it is recommended only for postmenopausal women.
~ If you’ve had breast cancer, discuss with your doctor whether your type of cancer has shown a response to tamoxifen, and, if so, how long you should take it. Remember that neither tamoxifen nor raloxifene decreases your risk for breast cancer that is estrogen-receptor-negative—the type of breast cancer that tends to be more aggressive.
~ If you are at increased risk for breast cancer, decrease that risk by following the suggestions I’ve given earlier in this chapter. Discuss taking a SERM with your doctor if your risk is 3 percent or greater, but let your inner guidance have a voice in your decision.
~ If you opt to take tamoxifen or raloxifene, get regular medical care, including screening for endometrial abnormalities and cataracts.
~ You can decrease some of the side effects of tamoxifen by taking soy or Pueraria mirifica, using supplements, and following the dietary guidelines given on pages 516–526.
~ Don’t take tamoxifen for longer than five years unless you and your doctor feel strongly that your individual situation warrants it.
THE NEWEST DRUGS FOR FIGHTING BREAST CANCER:
HERCEPTIN (TRASTUZUMAB) AND ARIMIDEX
(AROMATASE INHIBITORS)
Two extremely promising drug treatments for breast cancer are helping us to make great strides against this disease. One, the antibody trastuzumab (the generic name for the drug Herceptin), specifically targets a protein called HER-2/neu that is present in 20 to 30 percent of breast cancer patients. In effect, this drug blocks the ability of the cancer cells to receive chemical signals telling the cells to grow, thereby slowing or stopping the growth of the cancer. It also works by alerting the immune system to destroy the cancer cells the drug attaches to. Although traditionally reserved for treating women with advanced breast cancer, trastuzumab has been proven to delay the growth and spread of tumors in women who are in the early stages of the disease as well. Evidence presented at the May 2005 meeting of the American Society of Clinical Oncology showed that trastuzumab reduced the risk of breast cancer recurrence in this group by about 50 percent and the risk of death by about 33 percent. (The FDA recently approved this drug in combination with chemotherapy for treating advanced HER-2/neu-positive stomach cancer as well.) Yet this drug is not a silver bullet—it was also associated with a small but real increase in the risk of developing weakening of the heart muscle. It is the first of what researchers hope will be other more targeted drugs. If you have breast cancer, your tumor should have been tested for this HER-2/neu gene.
Aromatase Inhibitors
The aromatase inhibitors are another class of drug (including anastrozole, the generic name for Arimidex; letrozole, the generic name for Femara; and exemestane, the generic name for Aromasin). These drugs inhibit the adrenal glands, fat stores, and breast and other tissues from converting precursor steroids into estrogen, thereby lowering estrogen levels in the body. When given to postmenopausal women with early-stage breast cancer, these drugs reduce the rate of cancer recurrence and lengthen the time between bouts for those who do have recurrences. In one of the early trials, Arimidex delayed tumor progression for an average of 11.1 months (tamoxifen delayed tumor progression for only 5.6 months). While initial evidence showed that aromatase inhibitors cause an increased incidence of heart problems, joint pain, and broken bones, as well as osteoporosis, a 2010 study showed that side effects were worse than previously believed (which has certainly been borne out by my discussions with women who are on these drugs). The study, presented at the annual conference of the American Association for Cancer Research, showed that women taking these drugs were five times more likely to report having hot flashes, breast sensitivity, and chest pain; four times more like
ly to report night sweats, cold sweats, and hair loss; and about three times more likely to report leg cramps, weight gain, sleep disturbance, tendency to take naps, and forgetfulness than healthy women.134 However, the side effects may turn out to be good news for some. A 2008 study done in London of almost 4,000 breast cancer patients showed that women who developed joint symptoms within the first three months of taking anastrozole were 10 percent less likely to suffer from a recurrence of the cancer, while those who reported vasomotor (hot flash) symptoms were 6 percent less likely to have their cancer return.135 Women who reported both joint symptoms and vasomotor symptoms within three months of starting the drug were 11 percent less likely to have a recurrence. Additional research has also shown that these drugs are indeed effective against DCIS, but since 98 percent of DCIS doesn’t become invasive cancer, the risk of the drugs may be worse than the risk of breast cancer.
In conclusion, please realize that the problem of breast cancer can’t be solved only at the physical level. Don’t be fooled into believing that you must always take a drug to help your body stay well. To create healthy breast tissue, each of us needs to be willing to participate in creating a life that is healthy in mind and spirit as well as body. We need to learn how to fully receive as well as give. We must open our hearts and learn how to bring more sustainable pleasure into our lives on a daily basis. Yes, sometimes we may need drugs or surgery; at other times we need only the natural strategies I’ve emphasized in this chapter and throughout this book—eating healthfully, getting exercise, stopping smoking, cutting down on or eliminating alcohol, expressing your feelings, loving, and allowing yourself to be loved.