MEDICATIONS: GET THE FACTS: HORMONES AND BREAST CANCER

Every day, you make choices that affect your health — the food you eat, the exercise you get, the amount you sleep. One of the biggest choices facing women with severe symptoms during menopause is what to do when hormone levels begin to drop and symptoms develop.

Hormones are substances formed in a type of body organ called a gland. A hormone is then carried to another organ or tissue where it has a specific effect. As levels of estrogen and progesterone, which are made in a woman's ovaries, drop off, your monthly periods eventually stop.

Most of the problems a woman has during early menopause are related to the fall in estrogen levels in her body. A woman has a choice of many non-hormone therapies to treat specific symptoms, or she can begin hormone therapy (HT) or estrogen therapy (ET).

HT replaces the estrogen and progesterone that ovaries no longer make in large amounts. Synthetic progesterone is called progestin. Estrogen and progestin use has been linked with breast cancer, however, so you need to understand the risks involved in taking estrogen.

Replacing your hormones with laboratory-made or natural forms of hormones may help you overcome some of the symptoms of early menopause, particularly hot flashes, problems sleeping, mood swings and vaginal dryness. HT can help to relieve symptoms that are uncomfortable and problems that can be dangerous, such as weakened bones. HT also reduces the rate of bone loss, which is faster during the first few years after menopause.

HT may not be the best treatment for all women, however. Because each woman has a unique health history and set of risk factors, you should discuss the benefits and risks of taking hormones with your doctor. Other therapies, such as medications to treat bone loss and high cholesterol levels, may be helpful.

How Hormones Can Affect You

Estrogen can cause breast tissue to grow faster. Cancer usually appears in fast-growing tissue. This is one of the ways that scientists believe that estrogen may be related to developing breast cancer.

Another idea is that breast tissue breaks down estrogen into chemicals that can bind to DNA (genetic material) and damage it. Damage to DNA is a common cause of cancer. At this time, we don't know exactly why estrogen might cause breast cancer and what role it does play in breast cancer growth.

Taking estrogen by itself has been shown to cause cancer of the lining of the uterus (the endometrium). Scientists have discovered that the combination of a form of progesterone taken with estrogen prevents this effect. Progesterone combined with estrogen blocks the cancer-causing effect that estrogen taken alone has on the uterus. The combination of two hormones reduces the risk of uterine cancer almost to the level of not taking hormones at all.

Laboratory-made progesterone, called progestin, also can stimulate breast tissue to grow. When estrogen and progestin are combined in HT, the chance of breast cancer developing increases, particularly among thin women. Nevertheless, most doctors believe that some form of progesterone should be taken with estrogen to reduce the risk of cancer of the uterus.

For women who have had their uterus removed (an operation called a hysterectomy), estrogen alone may be taken. Estrogen therapy alone is known as ET.

To increase your sex drive, which may fall off as your female hormone levels drop, your doctor may recommend low doses of androgens, which are male hormones.

Estrogen and Breast Cancer: Are They Connected?

Many clinical trials have been conducted to study the link between taking estrogen and developing breast cancer. Three of the largest studies have shown that longtime use of estrogen (more than five years) seems to be related to developing breast cancer. A large, recent study (The Million Women) from the U.K. also indicates that there was a slight increased risk of developing breast cancer.

A grouped analysis (meta-analysis) of several of the smaller studies also shows a risk of cancer. The average of these data shows a slightly increased risk of a woman developing breast cancer. Two recent studies (the Women's Health Initiative and the Million Women study) suggest that estrogen plus progestin increases the risk of breast cancer to a greater extent than estrogen alone.

The major evidence that links breast cancer to estrogen comes from studies of breast cancer in women with both ovaries removed by surgery before age 35. Estrogen is produced mostly in the ovaries. These women were followed for 20 to 40 years and were matched to a control group of women who had only one ovary removed. Breast cancer developed 75 percent less often in women without any ovaries.

Eight studies have compared women who had never used HT to those using HT at the time of diagnosis of their breast cancer. The good, surprising news is that every one of those previous studies reported a lower chance of dying for women receiving HT at the time their breast cancer was discovered. However, the recent update from the WHI raised caution since breast cancers diagnosed in women while receiving HT were larger and had spread to a greater extent regionally than in women not receiving HT.

In a recent study of nurses' health, women receiving estrogens lived longer than those not taking them. Survival improved by about 50 percent. Even women with breast cancer lived longer, probably because it was diagnosed at a time when the cancer was easier to treat.

In a study published in the Journal of the National Cancer Institute in May 2001, Ellen O'Meara and colleagues found that women taking HT after a diagnosis of breast cancer had both a lower risk of death and lower rates of recurrence (cancer returning). The results suggested that HT after breast cancer has no adverse impact on recurrence and death rate. This conclusion, however, needs further study.

What all this means is that some clinical studies point to the possibility of taking hormones after you've had breast cancer. Most doctors, however, would not prescribe estrogen for breast cancer survivors at this time.

What are My Chances of Getting Breast Cancer?

It is easy to get confused about your actual risk of getting breast cancer if you take estrogen. You might read in the newspaper that taking estrogen over a five to 10 year period raises your risk of breast cancer by 20 percent to 50 percent. This does not mean you have a 20 percent to 50 percent chance of getting breast cancer. It means that the risk of getting cancer increases by that much.

For example, a 50-year-old woman has two chances in 100 of developing breast cancer by the time she is 60. If she takes estrogen over those 10 years, her chances go up to 2.1 chances in 100 of developing breast cancer. If she is thin and takes estrogen with progestin (HT), her chances go up to 2.8 in 100 that she will develop breast cancer.

What the Experts Say About Estrogen Risk

Estrogen Use If You Have Had Breast Cancer
Most physicians today believe that estrogens should not be given to breast cancer survivors. Estrogen might stimulate the growth of small, hidden tumors in the body or cause a second breast cancer. It is impossible to know for sure how many women still harbor these hidden cells, called micrometastases. A recent study did suggest, however, that the rate of cancer occurrence is not higher in women who received HT after breast cancer treatment.

Estrogen Use If You Have Family History of Breast Cancer
No one knows yet whether women who are at risk for breast cancer because of family history of that cancer are more at risk if they take estrogen. Most physicians would be very cautious in recommending estrogens if your mother, sister or daughter have had breast cancer.

What Other Risk Factors Exist?
Women probably should not take estrogen if they have: a history of breast cancer, a recent diagnosis of uterine cancer, liver disease, a history of blood clots, undiagnosed vaginal bleeding, or existing heart disease.

What Else Do I Need to Know to Make the Best Decision?
You and your doctor should take several aspects into consideration. First, what is your risk of getting breast cancer? Is it higher than average? Women who go through menopause later have a higher risk of breast cancer. Weight gain also increases cancer risk. Surprisingly, while weight gain also increases risk, this risk does not appear to increase with use of HT.

The situation is difficult for women who have survived breast cancer and want the benefits that estrogen provides. Many women may want to accept the risks, known and unknown, that come with taking estrogen. Others may not want to accept any risk at all. Each woman must decide for herself, with input from her doctor, the best course of action. Both patient and doctor should be comfortable with the decision to take HT or to pursue other treatments.

Mammograms and Hormone Use

In a recent report from the WHI study, HT changes the look of a breast on a mammogram (a breast X-ray). Estrogen use can make the X-ray harder to read because it increases the thickness of the breast tissue in about half of women. This can cause new and thicker areas on the mammogram, which can be confused with cancer. For women who have had breast cancer, hormone use may make it more difficult to diagnose another cancer in a mammogram.

A practical way to use HT and still get a good image on your mammogram is to stop taking HT for two to four weeks before your mammogram. One study showed that a short break from HT reversed the breast changes and helped women avoid biopsies. Biopsies (taking tissue out with a small cut into the flesh) are done when doctors suspect cancer. Biopsies are needed to tell the difference between a benign (not harmful) area and a malignant condition (cancer).

Hormones Before, During and After Menopause

Many different symptoms can occur during the process of menopause. As estrogen levels first drop in early menopause, common symptoms include:

· Frequent or intense hot flashes and problems sleeping

· Mood swings and depressed moods

· Vaginal dryness, which affects a woman during intercourse, and a lowered sex drive

Several diseases begin to affect women during this time of life. Menopause increases the risk of bone loss and bone disease (the severe form of bone disease is called osteoporosis). The risk of heart disease increases after menopause. Recent studies have shown that estrogen should not be taken to prevent heart disease because it is not effective. The HERS and WHI studies showed that hormone therapy did not reduce the risk of subsequent heart disease in women with or without pre-existing heart disease, and may have actually slightly increased the risk. Very few doctors prescribe HT or ET only for the purpose of preventing heart disease, although many felt that it was an added benefit, as previous observational epidemiologic studies indicated that this was the case.

Likewise, although estrogen has been shown in some studies to help prevent eye (retina) degeneration and colon cancer, it should not be taken only to prevent these conditions. We need more studies designed specifically to study the effects of estrogen replacement on the development of these diseases.

Previous studies indicated that HT or ET might lower the risk of Alzheimer's disease and other types of dementia. One of the largest of these studies was performed in younger women who had been on estrogen therapy for ten years or more, and had no signs of dementia before starting hormonal therapy. However, a recent report from the WHI study, which evaluated women 65 years or older taking HT for five years or less, indicated that dementia was not reduced and might have been increased. In addition to dementia, this study also evaluated mild cognitive impairment, which also showed no improvement.

With so many health concerns and so many treatments available, what is the best course of action?

A New Approach to Managing Menopause

The Hormone Foundation, the public education affiliate of The Endocrine Society, supports a new approach to menopause. Every woman is affected in different ways — no two women have the same pattern of symptoms and changes. A woman should remember that she is a partner with her health care provider. Input from both you and your provider will help reach the treatment decisions that are right for you.

Four Principles Should Be Followed When Managing Menopause:

First: According to several studies, changes in lifestyle have benefited many women. In some women, lifestyle changes alone may be sufficient and drug therapy may not be necessary. Adopt a healthy lifestyle, with a diet that includes 1500 mg of calcium daily and low amounts of saturated and partially hydrogenated fat. You should try to exercise regularly at least 30 minutes, three times a week. If you smoke, try to cut down and quit; if you drink alcohol, drink moderately. If you are overweight, use a lower calorie, nutritionally balanced diet to lose weight. Have your doctor examine your breasts each year. Your doctor may order an annual mammogram (breast X-ray). Recent information from a clinical trial has called into question the benefit of mammograms on cancer survival rates, but these images can help to detect tumors.

Second: Treat your symptoms during early menopause. Taking hormones may be a good idea for some symptoms like hot flashes and vaginal dryness, if you are at low risk for breast cancer. HT should be used only for a sufficient period to minimize severe symptoms. Other treatment options are available.

Third: Assess your breast cancer risk and risks for other diseases. Before you decide about which medications you might want to take for your menopausal symptoms, you and your doctor need to evaluate your risk for breast cancer. You also need to learn your risk for bone loss and heart disease. You can learn whether you are at high, intermediate or low risk for various diseases by talking to your doctor about your personal history and family history of disease.

Fourth: Women should be treated in two phases. In the first phase, prevention of osteoporosis may begin, along with treatment of specific menopause symptoms, including hot flashes and vaginal dryness. After the short-term therapy, usually a period of five years or less, you should discuss the risks and benefits of continuing hormone therapy with your doctor. Remember that short-term goals of treatment are different from long-term goals. Short-term therapy is designed to relieve symptoms. Long-term therapy helps to prevent osteoporosis. If a woman has an increased risk of developing breast cancer, she will need to take different medications than a woman who is not at risk.

What Should I Take?

Depending on your age and risk factors, various choices may be available for you. However, if you are at moderate or high risk for breast cancer, many physicians feel you should not take estrogen. Other choices are available.

Most of the treatments listed in the tables that follow will need to be prescribed by your doctor. Tamoxifen and raloxifene are relatively new drugs, known as "designer estrogens." These drugs have been developed to act beneficially as estrogens on some tissues and as estrogen-blockers (anti-estrogens) on other tissues. These drugs also are known by the more technical name Selective Estrogen Receptor Modulators or SERMs.

Tamoxifen blocks the effect of estrogen on the breast and is used both to prevent breast cancer in women at high risk and treat breast cancer. Like estrogen, it increases the risk of blood clots, particularly during the first six months to one year. Tamoxifen acts like an estrogen on the uterus, increasing the risk of uterine cancer. It has the ability to lower levels of bad cholesterol, which can clog blood vessels and may lead to heart disease.

Raloxifene is a designer estrogen that acts beneficially on bone and lowers levels of bad cholesterol. Raloxifene blocks the harmful effects of estrogen on the breast and uterus, and four-year data suggest that it may reduce the risk of breast cancer.

The bisphosphonate family of drugs, similar to estrogen and SERMs, blocks the breakdown of bone and results in an increased amount of bone when taken for six months or longer. Commonly prescribed bisphosphonates include risedronate and alendronate.

Cholesterol-lowering drugs to prevent heart disease need to be prescribed by your doctor, depending on the various cholesterol and other fat levels found in your blood. These drugs are called the "statin" drugs, such as lovostatin, simvastatin and pravastatin. These drugs should only be taken if your risk of heart and blood vessel disease is increased. Otherwise, you should try to lower your cholesterol by eating foods low in cholesterol and other fats.

Pros and Cons for Treatment of Menopause Symptoms

Symptom: Hot Flashes

Sources: Women's Health Initiative, NIH/DHHS/NHLBI, www.nhlbi.nih.gov/whi; Susan G. Komen Foundation, www.breastcancerinfo.com/bhealth/html/tamoxifen.asp; Evista.com (raloxifene); North American Menopause Society, www.menopause.org/edumaterials/guidebook/guidebook.html; National Institute on Aging, Age Page on Osteoporosis, www.nia.nih.gov/health/agepages/osteo.htm; MEDLINEplus Drug Information Service, www.nlm.nih.gov/medlineplus/druginformation.html.

Other Menopause Treatments

Talk to your doctor about all of the choices of drug treatments to decide what is right for you. Clonidine is a blood-pressure-lowering drug that is also used to reduce the frequency and severity of hot flashes. Megestrol acetate, a progesterone-type drug, is used to treat hot flashes.

The SSRI (Selective-Serotonin Reuptake Inhibitor) drugs are useful in two ways — treating depression and treating hot flashes. Counseling or support groups also can help you to handle sad, depressed or confusing feelings you may be having as your body changes.

For vaginal tissue thinning and dryness, you might want to try vaginal lubricants. Low dose vaginal estrogen, such as estrogen-containing vaginal rings, is generally a safe way to take estrogen to solve these problems.

Other treatments for bone loss and osteoporosis (severe loss of bone) include calcium tablets and vitamin D, taken separately or combined in a pill. Prescription treatments include calcitonin (a hormone sprayed in the nose), bisphosphonates and raloxifene.

What Form of Hormone Treatment Is Best for Me?

If you and your doctor decide that hormone treatments will be a safe and effective way of managing your symptoms of menopause, then you have choices about the type of HT to take. Different combinations of hormones can affect women in different ways. You may need to try more than one form to find the one that suits you best. The following table shows how many choices are available.

Progesterone and progestins (a form of progesterone) can stimulate breast tissue to grow, which may be considered a risk. At this time, we still don't know whether progesterone or progestins cause breast cancer, but we do know that they protect the uterus. Most doctors say that a woman who still has her uterus should take a form of progesterone along with estrogen.

Two studies show that in thin women particularly, progestins taken with estrogen may increase the risk of breast cancer compared with estrogen alone. Other treatments can be considered for these women.

If a woman has had her uterus removed, however, she does not need to take a progestin with estrogen. Estrogen alone might be a good solution.

Low-dose estrogen, in the form of a vaginal pill, vaginal cream or vaginal ring may help you relieve vaginal dryness.

Some progesterone forms taken alone can help to relieve hot flashes. Megestrol acetate is prescribed for that use.

The U.S. Food and Drug Administration (FDA) has directed certain products to carry new labeling and is asking all manufacturers to update their labeling with the results of the Women's Health Initiative because all estrogen and progestin products may have similar risks.

For hot flashes and symptoms of vulvar and vaginal atrophy, these products still are the most effective approved therapies. Estrogens and progestins should be used at the lowest doses for the shortest duration to reach treatment goals, although it is not known at what dose there may be less risk of serious side effects.

Estrogen Therapy (ET) (Estrogen only)

Sources: Food and Drug Administration, Office of Women's Health, www.fda.gov; New England Journal of Medicine, www.nejm.org; Doctor's Guide, personal edition: HRT (search keyword "HRT"), www.docguide.com; Project Aware (Association of Women for the Advancement of Research and Education), Managing Menopause page, HRT link, www.project-aware.org; North American Menopause Society, www.menopause.org; Menopause Online, www.menopause-online.com; Women's Health America, www.womenshealth.com; Wyeth Pharmaceuticals, www.wyeth.com; Premarin, www.premarin.com; Prempro, www.prempro.com.

Herbal Medicines

You may have read articles in the press about herbal remedies to treat menopause symptoms. Some, like St. John's Wort to treat depression, are proving to be helpful. Others are still not well studied. The manufacturing quality of herbal products often is a problem. Information about their safety and effectiveness do not have to be reported to any government agencies.

Please tell your doctors if you are taking any herbal products. It is important to discuss the use of dietary supplements, herbs, and alternative approaches or combinations of medicines to relieve menopause symptoms. These drugs may interact in harmful ways or cause harmful effects, including cancer.

Glossary

Anti-estrogen: A drug that blocks the harmful effects of estrogen on certain tissues like the breast.

Clinical Trial: When physicians want to learn if a therapy or medication works, they create a clinical trial to learn what will happen when patients are treated in a certain way. They closely examine what happens in groups of patients studied and followed over a period of time. Usually one group is given one drug and a second group another drug. Often a drug is compared with a sugar pill (placebo).

Designer Estrogens: Drugs have been developed that act as estrogens on some tissues and as estrogen blockers (anti-estrogens) on others. An example is the drug raloxifene, which blocks the effect of estrogen on the breast and uterus, but acts as an estrogen on the bone. Another designer estrogen is tamoxifen.

Estradiol: A naturally occurring form of estrogen, which is made primarily in the ovaries.

Estrogen: The major female hormone that causes the breasts to develop in young girls and causes development of the uterus. This hormone also can stimulate the growth of breast cancer tissue.

Estrogen Therapy (ET): A hormonal treatment with estrogen alone.

Hormone: A substance formed in a type of organ in the body called a gland. The hormone is then carried to another organ or tissue where it has a specific effect.

Hormone Therapy (HT): This treatment is estrogen plus progestin. Estrogen therapy (ET) is estrogen alone.

Hot Flashes: A sudden flow of the blood through the skin, which makes a woman feel a hot flush and a sensation of warmth.

Hysterectomy: A surgical operation that removes the uterus. The uterus expands as a fetus grows during pregnancy. The lining of the uterus is shed each month during the monthly period (menstruation) when a woman is not pregnant.

Lymph Node: Lymph nodes are tissues that act like filters to stop the spread of infection to areas nearby. When cancer has spread to lymph nodes, the risk of having the disease return is higher and the chance for a cure is lower. The greater the number of lymph nodes that contain cancer, the worse the chance for a cure.

Mammography: Process of taking an X-ray picture of the breast, which is called a mammogram.

Menopause: Time of life when the ovaries stop making estrogen and the monthly (menstrual) periods stop. Menopausal is an adjective that describes this time of life.

Meta-Analysis: This is a way to evaluate the results of several similar trials by analyzing the results from all of the trials and reaching a conclusion. The idea is that if one clinical trial gives an answer and many trials evaluated together give the same answer, it is likely that the answer is correct.

Micrometastasis: This refers to when a tumor has spread to other parts of the body. These metastases (distant tumor deposits) can either be very small (micro in size or micrometastases) or large and easily detectable (macrometastases or detectable metastases).

Nodal Status: Nodal status refers to the number of lymph nodes that contain cancer. Breast cancer spreads from the breast tissue to the lymph nodes under the armpit. Lymph nodes are tissues that act like filters to stop the spread of infection to areas nearby. When cancer has spread to lymph nodes, the risk of having the disease return is higher and the chance for a cure is lower.

Node-negative: An adjective that means that the lymph nodes are clear of cancer and chances of survival are higher.

Node-positive: An adjective that means that cancer has spread to the lymph nodes.

Osteoporosis: This is a condition of very low amounts of bone. With this problem, there is a high frequency of broken bones, especially the hip and the spine. As osteoporosis progresses, a woman becomes shorter because the vertebrae (bones in the spine) collapse, and the spine curves in the chest area ("dowager's hump").

Ovary: One of a pair of female glands that produce eggs and the sex hormones, estrogen and progesterone. It also produces male-type hormones, called androgens.

Progesterone: A female hormone that acts on the uterus to prepare it for receiving an egg following fertilization by a sperm from a man. When progesterone levels drop each month, this causes the bleeding associated with menstrual periods.

Progestin: This is a synthetic form of progesterone. This class of drugs was originally developed to allow absorption by mouth for use in birth control pills. Progestin means that these medications work like progesterone in the body. Progestin is sometimes called "progestogen."

Tumor: A growth of cells that can be cancerous (malignant) or non-cancerous (benign).

Urinary and Genital Atrophy; Urogenital Atrophy: This refers to two separate problems. One is genital atrophy and the other is atrophy of the urinary system. Genital atrophy means that the tissues of the vagina become thinner because of the lack of estrogen. This results in itching, pain during sexual intercourse, and a greater frequency of vaginal infection. Atrophy of the urinary system means that the tissues of the bladder (sac that holds urine) and urethra (tube through which urine drains) become thinner. This results in more frequent release of urine (urinating), incontinence (sudden, unexpected loss of urine), and frequent urinary system infections.

Uterus; Uterine (adjective): The organ in which a baby grows inside of a woman. The uterus is also called the womb and the tissue that lines the uterus is called the endometrium.

Vagina: The canal through which babies are born; it leads from the woman's outer sex organs to the uterus.