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Breast Cancer Prevention Studies
Key Points
- Breast cancer
prevention
studies are clinical
trials involving women who have not had cancer,
but are at high risk of developing the disease (see Question
1).
- In the Breast Cancer Prevention Trial (BCPT), the women who received
tamoxifen
had a lower incidence
of breast cancer than women who did not receive the drug.
Initial results of this study were published in 1998 (see Question
2).
- Another trial, the Study of Tamoxifen and Raloxifene
(STAR), found that tamoxifen and another drug
called raloxifene are equally effective in reducing breast cancer risk
in postmenopausal
women who are at increased risk of the disease (see Question
3).
- Other breast cancer prevention studies are in progress (see Question
4).
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- What are breast cancer prevention studies?
Breast cancer prevention studies are clinical trials (research studies)
that explore ways of reducing the risk, or chance, of developing breast
cancer. These studies usually involve women who have not had breast cancer
but are at high risk of developing the disease. For example, it is clear
that breast cancer occurs more often in women over the age of 60 years;
so, these women have a higher risk of developing breast cancer than younger
women. Other factors associated with increased risk include a personal or
family
history of breast cancer and changes in certain genes,
such as BRCA1
and BRCA2.
Most breast cancer prevention research is based on evidence linking the
development of this disease, in many cases, with exposure to the hormone
estrogen.
The focus of several breast cancer prevention studies has been on
testing the effectiveness of drugs called selective
estrogen receptor modulators (SERMs). SERMs are drugs that have some
antiestrogen
properties and some estrogen-like properties. Their antiestrogen activity
may help reduce the risk of breast cancer by blocking the effects of estrogen
on breast tissue.
Their estrogen-like properties may help prevent the loss of bone
density in postmenopausal women; however, SERMs may cause bone loss
in premenopausal
women.
- What is the Breast Cancer Prevention
Trial (BCPT)?
The Breast Cancer Prevention Trial (BCPT) was funded by the National
Cancer Institute (NCI), a part of the National
Institutes of Health, and conducted by the National Surgical Adjuvant
Breast and Bowel
Project (NSABP). The BCPT was designed to see whether tamoxifen (Nolvadex®),
a SERM, could prevent breast cancer in women who are at an increased risk
of developing this disease. The study began recruiting participants in April
1992 and closed to enrollment in September 1997. In the study, 13,388 premenopausal
and postmenopausal women were enrolled at more than 300 centers across the
United States and Canada and randomly assigned to receive tamoxifen or a
placebo
orally
each day for 5 years.
Initial results of the BCPT were published in September 1998 (1). Among
the women randomly assigned to take tamoxifen, there were 49 percent fewer
diagnoses
of invasive
breast cancer than among the women randomly assigned to take the placebo.
Women on tamoxifen also had 49 percent fewer diagnoses of noninvasive breast
tumors,
such as ductal
carcinoma in situ (DCIS) or lobular
carcinoma in situ (LCIS).
Most of the side
effects associated with tamoxifen in the study were temporary. However,
long-term increased risks were found for several serious health problems:
endometrial
cancer (cancer of the lining of the uterus),
uterine
sarcoma (cancer of the muscular wall of the uterus), pulmonary
embolism
(blood
clot in the lung),
deep vein thrombosis
(blood clot in a large vein), and stroke.
These increased risks for serious health problems were generally greater
among postmenopausal women than among premenopausal women. The increased
risk for endometrial cancer was found only among postmenopausal women.
In November 2005, updated results of the BCPT were published (2). The updated
results confirmed tamoxifen’s ability to reduce the risk of breast
cancer in women at increased risk of developing the disease. Through 7 years
of follow-up
(that is, at least 2 years past the maximum time that women assigned to
take tamoxifen received the drug), there were 43 percent fewer cases of
invasive breast cancer diagnosed among the women assigned to tamoxifen than
among the women assigned to the placebo. The reduction in risk of developing
noninvasive breast tumors also persisted at 7 years, with 27 percent fewer
diagnoses of noninvasive breast tumors among the women who took tamoxifen
than among the women who took the placebo. In addition, the previously observed
increased risks of stroke, pulmonary embolism, and deep vein thrombosis
were somewhat reduced at 7 years of follow-up.
In October 1998, based on the initial results of the BCPT, the U.S. Food
and Drug Administration (FDA) approved the use of tamoxifen for the prevention
of breast cancer in women at high risk of developing the disease.
More information about the BCPT is available on NCI’s Web site at
http://www.cancer.gov/clinicaltrials/digestpage/BCPT
on the Internet.
- What is the Study of Tamoxifen and Raloxifene
(STAR)?
The Study of Tamoxifen and Raloxifene, known as STAR, was a follow-up study
to the BCPT. In STAR, another SERM called raloxifene (Evista®) was compared
with tamoxifen in preventing breast cancer in postmenopausal women at increased
risk of developing the disease. The study, which was funded by NCI and conducted
by the NSABP, involved more than 19,000 postmenopausal women who were at
least 35 years of age and were at increased risk of developing breast cancer.
The women were randomly assigned to receive tamoxifen or raloxifene orally
each day for 5 years. STAR began recruiting participants in July 1999 and
completed enrollment in November 2004. More than 200 centers across the
United States, Canada, and Puerto Rico participated in the study.
Initial results from STAR were published in June 2006 (3). The results
showed that raloxifene and tamoxifen are equally effective in reducing breast
cancer risk in postmenopausal women who are at increased risk of the disease.
Both drugs reduced the risk of developing invasive breast cancer by about
50 percent. However, raloxifene, unlike tamoxifen, did not reduce the risk
of noninvasive breast tumors, such as DCIS and LCIS.
Information collected from STAR participants about their physical and mental
health revealed no significant
differences between the women who took raloxifene and those who took tamoxifen;
however, women in the tamoxifen group reported better sexual functioning.
Although symptom
severity in the study was generally low, women in the tamoxifen group also
reported more vasomotor
problems (e.g., hot
flashes, cold sweats), gynecologic
problems (e.g., bleeding or spotting, vaginal
discharge), bladder
problems (e.g., difficulty with bladder control when laughing or crying),
and leg cramps; women in the raloxifene group reported more musculoskeletal
problems (e.g., joint pain, muscle stiffness), pain during sexual intercourse,
and weight gain (4).
With regard to risks for serious health problems, there were fewer cases
of endometrial cancer, pulmonary embolism, and deep vein thrombosis among
the women who took raloxifene. There was no difference in the incidence
of stroke between the raloxifene group and the tamoxifen group.
More information about STAR is available on NCI’s Web site at http://www.cancer.gov/clinicaltrials/digestpage/STAR
on the Internet.
In September 2007, the FDA approved raloxifene to reduce the risk of invasive
breast cancer in postmenopausal women with osteoporosis
and in postmenopausal women at high risk for invasive breast cancer. Raloxifene
was approved by the FDA as a treatment for osteoporosis in 1999.
- What other breast cancer prevention studies
are being funded by NCI?
NCI is supporting additional clinical
studies to determine whether other drugs or natural products are able
to help prevent breast cancer in women who are at increased risk of developing
the disease. Drugs called aromatase
inhibitors (AIs) are being tested by NCI in a few small studies.
AIs block the activity of an enzyme
called aromatase, which the body uses to make estrogen. Although the ovary
is the main site of aromatase and estrogen production in a woman’s
body, other tissues, including adipose (fat), bone, and brain tissue, make
these substances as well.
Using AIs to block estrogen production in premenopausal women is not very
effective, in part because the ovary is stimulated to make more aromatase
(and, therefore, estrogen) when the blood level of estrogen falls below
normal. This does not happen in postmenopausal women, whose ovaries have
stopped making aromatase and estrogen. Therefore, AIs are being studied
primarily in postmenopausal women.
AIs have already been approved by the FDA for the treatment of hormone-sensitive
breast cancer in postmenopausal women. All three FDA-approved AIs are being
tested in breast cancer prevention studies. These drugs are anastrozole
(Arimidex®), exemestane
(Aromasin®), and letrozole
(Femara®).
In addition, scientists are continuing to study the basic biology and genetics
of breast cancer. This research may lead to other, better ways to prevent
breast cancer.
For information about ongoing clinical studies of breast cancer prevention,
visit NCI’s Web site at http://www.cancer.gov
or contact NCI’s Cancer
Information Service (CIS) (see below).
- What additional options are available for women
at increased risk of breast cancer?
Doctors generally suggest that high-risk women be closely monitored and
have regular medical checkups, so that if breast cancer develops, it is
likely to be detected at an early stage,
when it is most treatable (5). These women may also consider participating
in breast cancer prevention studies, taking tamoxifen or raloxifene, or
undergoing preventive
surgery
to reduce breast cancer risk.
Preventive
mastectomy is surgery to remove one or both breasts in an effort to
prevent or reduce the risk of breast cancer (6). Existing data suggest that
preventive mastectomy may significantly reduce (by about 90 percent) the
chance of developing breast cancer in women at high risk of developing the
disease due to BRCA1 or BRCA2 gene mutations
(7). Other data suggest that preventive oophorectomy
(surgery to remove the ovaries) in women at high risk of ovarian
cancer because of BRCA1 or BRCA2 gene mutations may also reduce the
risk of breast cancer by about 50 percent (8).
More information about preventive mastectomy can be found in the NCI fact
sheet Preventive Mastectomy: Questions and Answers, which is available
at http://www.cancer.gov/cancertopics/factsheet/Therapy/preventive-mastectomy
on the Internet.
The decision to join a clinical
study, take medication, or undergo preventive surgery is an individual
one. With any medical procedure or intervention, both the benefits and the
risks of the treatment must be considered. The balance of these factors
will vary depending on a woman’s personal and family health history
and how she weighs the benefits and risks. Women who are considering surgery
or other steps to reduce the risk of breast cancer should discuss their
personal risk
factors with their doctor.
- Where can women learn more about estimating
their risk for breast cancer?
NCI’s Cancer Risk: Understanding the Puzzle Web site is
an interactive site with information to help women make informed decisions
about lowering their risk of cancer. It includes a section on breast cancer
where women can find out the basics about breast cancer risk, determine
which risk factors apply to them, and identify ways to reduce their risk.
It includes questions women can ask their doctors about their risk for breast
cancer. The site also includes links to NCI’s Breast Cancer Risk Assessment
Tool and tips on how to analyze stories in the news about cancer. This site
is available at http://understandingrisk.cancer.gov
on the Internet.
Additional information can be found in the PDQ®
Breast Cancer Prevention summary for patients. This summary of information
from PDQ, NCI’s comprehensive cancer information database, provides
information about breast cancer and how often it occurs, describes breast
cancer prevention methods, and gives current facts about which people or
groups of people would most likely be helped by following breast cancer
prevention methods. This resource is available at http://www.cancer.gov/cancertopics/pdq/prevention/breast/patient
on the Internet.
People who are concerned about their cancer risk are encouraged to talk
with their doctor.
Selected References
- Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of
breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project
P–1 study. Journal of the National Cancer Institute 1998;
90(18):1371–1388.
- Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for the prevention
of breast cancer: Current status of the National Surgical Adjuvant Breast
and Bowel Project P–1 study. Journal of the National Cancer Institute
2005; 97(22):1652–1662.
- Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs raloxifene
on the risk of developing invasive breast cancer and other disease outcomes:
The NSABP Study of Tamoxifen and Raloxifene (STAR) P–2 trial. Journal
of the American Medical Association 2006; 295(23):2727–2741.
- Land SR, Wickerham DL, Costantino JP, et al. Patient-reported symptoms and
quality of life during treatment with tamoxifen or raloxifene for breast cancer
prevention: The NSABP Study of Tamoxifen and Raloxifene (STAR) P–2 trial.
Journal of the American Medical Association 2006; 295(23):2742–2751.
- Thull DL, Vogel VG. Recognition and management of hereditary breast cancer
syndromes. The Oncologist 2004; 9(1):13–24.
- Stefanek M, Hartmann L, Nelson W. Risk-reduction mastectomy: Clinical issues
and research needs. Journal of the National Cancer Institute 2001;
93(17):1297–1306.
- Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral prophylactic mastectomy
reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: The PROSE
Study Group. Journal of Clinical Oncology 2004; 22(6):1055–1062.
- Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prophylactic oophorectomy in
carriers of BRCA1 or BRCA2 mutations. New England Journal of Medicine
2002; 346(21):1616–1622.
# # #
Related NCI materials and Web pages:
For more help, contact:
- NCI's Cancer Information Service
Telephone
(toll-free): 18004CANCER (18004226237) TTY (toll-free):
18003328615 LiveHelp® online chat: https://cissecure.nci.nih.gov/livehelp/welcome.asp
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