Chemoprevention of Breast Cancer: Recommendations and Rationale
[07/02/2002; Annals of Internal Medicine]
This statement summarizes the current recommendations of the U.S.
Preventive Services Task Force (USPSTF) for chemoprevention of
The complete USPSTF recommendation and rationale
statement on this topic, including a summary of the supporting
evidence, is available through the USPSTF Web site
the National Guideline Clearinghouse
and in print through the Agency for Healthcare Research and Quality
Publications Clearinghouse; telephone, 800-358-9295; e-mail,
The complete information on which this statement
is based, including evidence tables and references, is available
in the accompanying article in this issue and in the summary
of the evidence and systematic evidence review on the Web sites
Summary of the Recommendations The U.S. Preventive Services Task
Force (USPSTF) recommends against the routine use of tamoxifen
or raloxifene for the primary prevention of breast cancer in
women at low or average risk for breast cancer (see Clinical
Considerations). This is a grade D recommendation (see Appendix
Table 1 for a description of the USPSTF classification of recommendations).
USPSTF found fair evidence that tamoxifen and raloxifene may
prevent some cases of breast cancer in women at low or average
risk for breast cancer, based on extrapolation from studies of
women at higher risk. (See Appendix Table 2 for a description
of the USPSTF classification of levels of evidence.)
concluded, however, that the potential harms of chemoprevention
may outweigh the potential benefits in women who are not at high
risk for breast cancer.
The USPSTF recommends that clinicians
discuss chemoprevention with women at high risk for breast cancer
and at low risk for adverse effects of chemoprevention (see Clinical
Clinicians should inform patients of the potential
benefits and harms of chemoprevention. This is a grade B recommendation.The
USPSTF found fair evidence that treatment with tamoxifen can
significantly reduce the risk for invasive estrogen receptor-positive
breast cancer in women at high risk for breast cancer and that
the likelihood of benefit increases as the risk for breast cancer
The USPSTF found consistent but less abundant evidence
for the benefit of raloxifene. The USPSTF found good evidence
that tamoxifen and raloxifene increase the risk for thromboembolic
events (for example, stroke, pulmonary embolism, and deep venous
thrombosis) and symptomatic side effects (for example, hot flashes)
and that tamoxifen, but not raloxifene, increases the risk for
The USPSTF concluded that the balance of
benefits and harms may be favorable for some high-risk women
but will depend on breast cancer risk, risk for potential harms,
and individual patient preferences.
should consider both the risk for breast cancer and the risk
for adverse effects when identifying women who may be candidates
Risk for Breast Cancer Older age; a family
history of breast cancer in a mother, sister, or daughter; and
a history of atypical hyperplasia on a breast biopsy are the
strongest risk factors for breast cancer.
The Table indicates
how the estimated benefits of tamoxifen vary depending on age
and family history.
Other factors that contribute to risk include
race or ethnicity, early age at menarche, pregnancy history (nulliparity
or older age at first birth), and number of breast biopsies.
Risk factor information can be used to estimate the risk for
breast cancer within the next 5 years by completing the U.S.
National Cancer Institute Breast Cancer Risk Tool (the Gail model
, available at http://cancer.gov/bcrisktool/ or 800-4-CANCER).
Clinicians can use this information to help individual patients
considering tamoxifen therapy estimate the potential benefit.
However, the validity, feasibility, and impact of using the Gail
model to identify appropriate candidates for chemoprevention
have not been tested in a primary care setting.
The Gail model
does not incorporate estradiol levels or estrogen use, factors
that some studies suggest may influence the effectiveness of
Risk for Adverse Effects
Women are at lower risk for
adverse effects from chemoprevention if they are younger; have
no predisposition to thromboembolic events such as stroke, pulmonary
embolism, or deep venous thrombosis; or do not have a uterus.
Balance of Benefits and Harms
In general, the balance of benefits
and harms of chemoprevention is more favorable for 1) women in
their 40s who are at increased risk for breast cancer and have
no predisposition to thromboembolic events and 2) women in their
50s who are at increased risk for breast cancer, have no predisposition
to thromboembolic events, and do not have a uterus.
a woman who is 45 years of age and has a mother, sister, or daughter
with breast cancer would have approximately a 1.6% risk for breast
cancer over the next 5 years (Table 1).
On average, treating
such women with tamoxifen for 5 years would prevent approximately
three times as many cases of invasive cancer (8 per 1000 women)
as the number of serious thromboembolic complications caused
(1 stroke and 1 to 2 pulmonary emboli per 1000 women).
among women 55 years of age, benefits exceed harms only for those
who are not at risk for endometrial cancer, and the margin of
benefit is small unless risk for breast cancer is substantially
increased (for example, 4% over 5 years).
Women younger than 40
years of age have a lower risk for breast cancer and thus will
not experience as large an absolute benefit from breast cancer
chemoprevention as older women.
Women 60 years of age and older,
who have the highest risk for breast cancer, also have the highest
risk for complications from chemoprevention, with a less favorable
balance of benefits and harms.
The USPSTF found more evidence
for the benefits of tamoxifen than for the benefits of raloxifene.
Currently, only tamoxifen is approved by the U.S. Food and Drug
Administration (FDA) for the specific indication of breast cancer
Although there are biological reasons to suspect
that raloxifene should have similar benefits, trial data currently
are limited to one study in which the primary outcome was fracture
Additional trials to further evaluate raloxifene's
efficacy for breast cancer chemoprevention are under way, including
a trial comparing efficacy and safety of raloxifene and tamoxifen.
Raloxifene is approved by the FDA for preventing and treating
The brief review of the evidence that is normally
included in USPSTF recommendations is available in the complete
Recommendation and Rationale Statement on the USPSTF Web site
Recommendations of Others
The American College of
Obstetricians and Gynecologists emphasizes
the importance of clinician judgment and recommends that any
decision to use tamoxifen be made on an individual basis after
consideration of the patient's medical history, risk assessment,
It also stresses that ability to manage complications
of therapy should be considered (2).
The American Society of
Clinical Oncology suggests that tamoxifen should be offered to
women with a 5-year projected risk for breast cancer greater
than or equal to 1.66% in order to reduce their risk.
recommends that raloxifene use should be reserved for treatment
of osteoporosis in postmenopausal women (3).
The Canadian Task
Force on Preventive Health Care recommends that clinicians counsel
women at high risk for breast cancer (Gail index 1.66% for 5
years) about the potential benefits and harms of breast cancer
prevention with tamoxifen (4).
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