Breast Cancer Prevention (cont.)
What are breast cancer prevention treatments?
Selective estrogen
receptor modulator (SERM) and its effect of estrogen on breast cell growth
A selective estrogen receptor
modulator (SERM) is a chemical that is designed
to act like estrogen in certain tissue such as the bones and not like estrogen
in other tissue such as the breast. The use of SERMs takes advantage of the
benefits of estrogen while trying to avoid the risks associated with estrogen. Two SERMs, Tamoxifen and Raloxifene, have been used as preventive treatment. The advantages and disadvantages of each are discussed in more detail below.
Tamoxifen
Tamoxifen (Nolvadex) is the first SERM to receive
approval by the United States Food and Drug Administration in the treatment of breast cancer. Some
breast cancer cells are "estrogen sensitive," meaning they possess so-called
estrogen receptors and need estrogen to grow and divide. But estrogen has to
bind to the receptors of these cancer cells in order to stimulate them. Binding
of estrogen to the receptors is analogous to fitting a key into a lock.
Tamoxifen blocks the action of estrogen on the cancer cells by occupying the
receptors (the locks), thus preventing estrogen (the keys) from fitting into the
receptors. Blocking estrogen from the estrogen-sensitive cancer cells stops the
growth and multiplication of these cells. Tamoxifen (in higher than usual doses)
may also possess other properties that cause the death of breast cancer cells
that are not estrogen sensitive.
Tamoxifen has been used to treat both advanced and early
stage breast
cancers. This drug has also proven valuable to women who have had cancer in one
breast in reducing the chances of developing cancer in the second breast.
Even though tamoxifen behaves like an anti-estrogen agent in breast tissue,
it acts like a weak estrogen in the bones. Thus, tamoxifen may have some benefit
in preventing osteoporosis fractures in postmenopausal women.
Tamoxifen also decreases cysts and lumps in the breasts, especially among
younger women. Fewer cysts and lumps make early detection by breast examinations
and mammograms easier. This use of the drug would only be in extreme situations
and is not an approved use.
Aromatase inhibitors
Primary prevention of breast cancer with tamoxifen
The term "primary prevention" means trying to reduce the risks of developing
breast cancer in women without a prior history of breast cancer. Tamoxifen not
only blocks the action of estrogen on estrogen-sensitive cancer cells, but it
also blocks estrogen from acting on cells that are not cancerous. Therefore, by
reducing the growth and division of normal breast cells, tamoxifen decreases the
population of cells that can develop cancer-causing DNA damage.
In the National Surgical Adjuvant Breast and Bowel
Project (NSABP) P-1, more
than 13,000 women considered at high risk for developing breast cancer were
given either tamoxifen or a placebo for
five years. The women receiving tamoxifen
developed 49% fewer breast cancers than women receiving the placebo. A further
study, the International Breast Cancer Intervention Study (IBIS-I) in Europe,
also confirmed a reduction in the rate of breast-cancer development in high-risk
women.
The United States Food and Drug Administration (FDA) has
approved the use of tamoxifen for primary prevention in women at high risk for
developing breast cancer. There is no evidence to suggest that tamoxifen can
reduce breast cancer incidence in women considered to have a normal risk for the development of
breast cancer.
Risks and side effects of tamoxifen
The risk of tamoxifen is the development of uterine
cancer. Although the
overall risk of developing uterine cancer is small (probably less than 1%), in
the NSABP-P1 trial, more women on tamoxifen developed uterine cancer than women
taking the placebo.
Additionally, women over 50 years of age on tamoxifen have a slightly
heightened chance of developing blood clots in the veins of the lower
extremities. These blood clots can occasionally break off and travel to cause
blockage of blood vessels in the lungs (a process called pulmonary embolism).
Symptoms of pulmonary embolism include shortness of breath, chest pain, and
sometimes shock. Some studies have also reported an increased risk of stroke in
patients taking tamoxifen.
The other side effects of tamoxifen include weight gain,
hot flashes, irregular periods, vaginal dryness or discharge, and a slightly enhanced risk of
cataracts.
Many of these side effects also depend on the age group being studied.
Raloxifene (Evista)
Raloxifene is the second SERM to be approved by the FDA. It has been approved
for use in preventing osteoporosis in postmenopausal women. Data suggest that
raloxifene, like tamoxifen, can reduce the chance of developing breast cancer in
high-risk women. Unlike tamoxifen, raloxifene does not stimulate cells of the
uterus, and is not believed
to increase the risk of uterine cancer.
Studies that examined the effects of both tamoxifen and raloxifene (including
the STAR trial, which studied over 19,000 postmenopausal women at high risk for
developing breast cancer) showed that both drugs lowered the incidence of breast
cancer in a similar manner. While both tamoxifen and raloxifene increased a
woman's risk of blood clots, the observed increase was smaller with raloxifene.
Raloxifene was also associated with a lower risk of uterine cancer and
hysterectomy for noncancerous reasons than tamoxifen. However, some data
suggested that raloxifene might not be as effective in preventing the
development of early, noninvasive cancers as tamoxifen.
Data are not available on the effects of raloxifene in premenopausal women,
and it is a potential teratogen, meaning that it may cause harm to the
developing fetus. Therefore, raloxifene is limited to use by postmenopausal
women and not used in women of childbearing age.
Controversies or other concerns about the use of tamoxifen or raloxifene
as a primary prevention for patients at high risk
The data from studies of raloxifene and tamoxifen are encouraging. But there
are still unresolved issues such as:
- Do women treated with tamoxifen or
raloxifene for primary prevention have a higher long-term survival rate than
women who received the placebo do?
- Does tamoxifen or raloxifene really prevent breast cancer, or do they only suppress the growth of existing breast cancer, thus delaying detection?
- If tamoxifen is offered to healthy, young women, what are the long-term side effects? Does breast-cancer reduction translate into better long-term survival and quality of life?
- How many years should patients be kept on the medication?
Select groups of high-risk women for whom a preventive medication such as tamoxifen or raloxifene should considered for use as primary prevention.
A specific model has been developed to assist doctors in predicting breast cancer risks for their patients. This model was used in the NSABP tamoxifen trial and is available to help evaluate patients considering this question. Some doctors would consider recommending tamoxifen to perimenopausal (the years around menopause) or raloxifene to postmenopausal patients with several first-degree relatives who have had breast cancer if the patient has had biopsies with abnormal, but not yet cancerous cell changes (atypical hyperplasia) or a type of localized breast cancer (lobular carcinoma in situ). This recommendation would be even stronger if the patient has had a hysterectomy.
Studies are also ongoing to determine whether tamoxifen or raloxifene are effective in preventing breast cancer in women with inherited BRCA1 or BRCA2 genes.
Aromatase inhibitors
Other medications, known collectively as aromatase inhibitors, are also used to block the effects of estrogen. Their main activity is to inhibit (block) the action of a particular enzyme (aromatase) that creates estrogen from other normally circulating hormones.
Tamoxifen and aromatase inhibitors, therefore, act differently and have different side effects. Studies are under way to compare their use as breast-cancer preventive drugs together and in sequence.
Surgical measures to prevent breast cancer
Preventive or prophylactic
mastectomy is the surgical removal of one or both breasts in women who have
moderate to high risk of developing breast cancer. Studies have shown that this
technique reduces a woman's chance of developing breast cancer by up to 90%.
Since small amounts of breast tissue can remain on the chest wall, in the
underarm, or even in the abdomen following a mastectomy,
it is impossible to completely prevent development of breast cancer by
prophylactic mastectomy. Women often chose to have surgical reconstruction of
the breasts at the time of surgery.
It is very important for a woman considering preventive mastectomy to have a
frank discussion with her physician concerning her cancer risk, other available
treatments, and the potential complications and implications of the surgery
before making a decision.
Next: Are there other breast cancer prevention measures? »
- tamoxifen, Nolvadex -
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