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6
Opportunities for Action
to Reduce Environmental
Risks for Breast Cancer
T
he committee was asked to consider the potential for evidence-based
actions to reduce the risk of breast cancer. Individual women, health
care providers, advocacy organizations, and many other stakeholders
are all eager to know what concrete steps can be taken to reduce the risk of
breast cancer for an individual or the population, and when during the life
course those actions might be most effective. This chapter outlines several
evidence-based actions that women can take. However, the scientific com-
munity still has only limited understanding of which exposures might best
be avoided and when, and which actions might have a long-term positive
benefit in reducing risk for breast cancer.
Even when research strongly supports classifying an exposure as a risk
factor for breast cancer, that research does not necessarily provide the infor-
mation needed to determine the appropriate response to reduce risk. Should
exposure be avoided completely? Will reducing or eliminating exposure in
adulthood reduce a risk that has accrued from exposure at younger ages?
Will the presence or absence of other risk factors for breast cancer influ-
ence the likely benefit or harm from a change in exposure to a given risk
factor? Will changing one type of exposure lead to another that carries new
and possibly as yet unrecognized risks for breast cancer, other diseases, or
perhaps some other adverse economic or environmental outcome?
Finding ways to reduce risk and avert cases of breast cancer is a high
priority for everyone concerned about this disease. Although some definite
actions can be taken to reduce risk, the committee found overall that evi-
dence-based options are limited because few studies have been done to test
the effectiveness of actions that may be hypothesized to reduce risk. In this
283
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284 BREAST CANCER AND THE ENVIRONMENT
chapter, the committee discusses some specific areas where action appears
warranted, but it first summarizes the significance of the uncertainty around
preventive action.
RECOGNIZING UNCERTAINTY OF BENEFITS AND RISKS
Potential for Introducing New Hazards or Risks
A key concept to remember when evaluating a particular risk associated
with a particular factor is that an action that is aimed at eliminating the
specific risk of concern may result in a substitution of one risk for another,
or perhaps shifting risk from one group to another. Any risk of the alterna-
tive action thus needs to be considered and weighed against the risk that
the change is intended to reduce or eliminate.
The complexity of trade-offs from substitutions can be illustrated with
the case of contamination of potable ground water sources with pesticides
or industrial chemicals shown to be carcinogenic in experimental animals
or humans. Reducing exposures to potentially carcinogenic substances in
drinking water from groundwater sources seems to be a logical, health-
protective action, even if the actual or perceived risk from the contaminants
is small. A typical action to reduce the potential cancer risk from using the
contaminated ground water is to switch the consumer to an alternative
source of potable water, such as a public water supply system. However,
such systems require disinfection, usually by chlorination, and chlorination
of surface water introduces trace levels of disinfection by-products (DBPs).
Several DBPs have been found to be carcinogenic in animal bioassays (e.g.,
NTP, 2007a,b), and some epidemiologic studies have suggested that long-
term exposure to DBPs is associated with an increase in bladder cancer
(reviewed in Richardson et al., 2007), especially in a subset of the popula-
tion with specific genetic polymorphisms (Cantor et al., 2010).
In this scenario, one would have to consider many factors, including (1)
the relative carcinogenic potency of the groundwater contaminant(s) versus
that of the DBPs, (2) the concentrations of the groundwater contaminants
or the DBPs in the drinking water and indoor air following use, and (3)
the duration and frequency of likely exposure to a given drinking water
source over a lifetime. Depending on these values, it is possible that a com-
parative risk assessment would show that switching from the contaminated
groundwater supply to the uncontaminated but disinfected surface water
supply actually increased, rather than decreased, potential cancer risks to
the exposed population.
This example, however, also illustrates the challenges in assessing trade-
offs in population- and individual-level risks and benefits. There are cer-
tainly no clear benefits, at least to the individual consumer, of drinking
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OPPORTUNITIES FOR ACTION TO REDUCE ENVIRONMENTAL RISKS
groundwater contaminated with low levels of pesticides. But the potential
cancer risk associated with the presence of DBPs in a public water system
must be assessed against the very real risks of widespread acute illness from
microbial contamination that could result in the absence of disinfection
(Gibbons and Laha, 1999; Schoeny, 2010).
This pattern of trading one hazardous substance for another is not
uncommon. Although federal agencies evaluate the toxicity and carcinoge-
nicity of new pesticides and prescription drugs before they are approved for
sale, the United States does not have a comprehensive program to evaluate
the safety of chemicals before their widespread use in consumer products.
In the face of consumer concern about bisphenol A (BPA), for example,
BPA-free plastics are now available, but new research appears to show
that BPA-free plastics may leach other chemicals with estrogenic activity
comparable to that of BPA (Yang et al., 2011). As noted in Chapter 2, the
European Union has adopted a program (Registration, Evaluation, Authori-
sation and Restriction of Chemical Substances, or REACH) for broader
safety testing by manufacturers of their products before they are approved
for use. In the United States, the Government Accountability Office (GAO,
2009a,b) has recommended changes to improve the effectiveness of federal
regulation of chemicals.
Risk trade-offs may also be hard to judge because a given factor can
have both positive and negative health effects. For example, there is fairly
compelling evidence that moderate alcohol consumption is associated with
a small but consistently observed increase in the risk of breast cancer.1
However, there is also compelling evidence that consumption of the same
moderate amounts of alcohol is associated with a reduction in mortality
from cardiovascular disease (Maskarinec et al., 1998; Gunzerath et al.,
2004; Klatsky, 2009; Ronksley et al., 2011). The risks associated with
any specific environmental exposure occur against the background of a
woman’s genetic susceptibility, reproductive history, and lifestyle.
Challenges in Public Health Policy Aimed at Risk Reduction
A significant challenge—relevant to the discussion of environmental
risk factors for breast cancer and frequently faced by regulators of envi-
ronmental pollutants and public health officials—is a lack of information
about the nature of the effects of many exposures on risks for breast cancer.
Chapter 4 reviewed the diverse challenges in trying to generate and interpret
relevant information. Noted here are a few specific areas where substantial
uncertainty faces policy makers.
Assessing the net effect of environmental exposures is one challenge.
1 The trade-offs associated with alcohol use are discussed further later in this chapter.
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286 BREAST CANCER AND THE ENVIRONMENT
Individuals and populations are never exposed to only one risk or protec-
tive factor at a time, but complex combinations of exposures are rarely the
subject of laboratory or epidemiologic studies. The U.S. Environmental
Protection Agency (EPA) and other environmental regulatory agency scien-
tists often assume that cancer risks in a population are simply the sum of
risks estimated for each individual chemical in the absence of data on risks
of co-exposures. In practice, this means that one might be confident that a
lifetime of exposure to a single chemical that causes a theoretical increase in
cancer risk of 1 additional case per 1 million exposed people is essentially
lost in the background and that the risk from that exposure may be consid-
ered minimal. But what if a population is exposed to 1,000 of these types
of “1 in 1 million” lifetime risks? Are the risks simply additive (e.g., the
increase in lifetime risk becomes 1,000 per 1 million, or 1 in 1,000), or is
it possible that the chemicals can interact to alter risk in some nonadditive
manner, either by reducing each other’s effects (e.g., competition for recep-
tor binding) or by mutually enhancing each other’s effects? For example,
smoking and asbestos exposure are each well-recognized risk factors for
lung cancer, but exposure to both multiplies the risk of lung cancer, making
the risk far greater than the addition of the individual effects of these two
exposures. A study of asbestos workers found that the lung cancer mortality
rate was 122.6 per 100,000 among men with a history of smoking and no
asbestos exposure; 58.4 per 100,000 among those with asbestos exposure
but no history of smoking; and 601.6 per 100,000 with exposure to both
smoking and asbestos (Hammond et al., 1979). As a qualitative example,
cigarette smoke is a mixture of relatively low levels of numerous carcino-
gens, and both direct and passive exposure to cigarette smoke are associ-
ated with a variety of cancers, including breast cancer. On the other hand,
some exposures may increase risks for breast cancer, but reduce them for
other cancers. In the vast majority of instances, the scientific information is
typically not sufficiently developed to calculate the joint effects of multiple
exposures with confidence.
Another area of uncertainty is whether risks occur at very low levels
of exposures and whether those risks can be estimated from information
on hazards and risks that are determined for high-dose exposures. The
EPA and other regulatory agencies have made specific assumptions about
the shape of the dose–response curve in relation to certain mechanisms of
action. For example, a linear extrapolation of cancer risk from high doses
to low doses is used for carcinogenic agents determined to be mutagenic.
Although linear extrapolation may not apply in some circumstances, it is
considered a protective approach in the absence of evidence to guide the
selection of an alternative model (EPA, 2005). Directly detecting small
differences in risk in human or animal studies may be difficult, if not
impossible, because of challenges that include the need for very large study
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OPPORTUNITIES FOR ACTION TO REDUCE ENVIRONMENTAL RISKS
populations, the potential for errors in measuring exposure, and the pos-
sibility of unrecognized confounding.
Finally, as highlighted in earlier chapters, the risk from a given expo-
sure may depend on the age at which it occurs, although current knowledge
about susceptible windows pertains to few exposures. Perhaps most salient
is the difficulty in assessing whether reduction or elimination of an exposure
will alter long-term risk of breast cancer, and if so, by how much.
EVIDENCE-BASED OPPORTUNITIES FOR
ACTION TO REDUCE RISK
Identifying evidence-based opportunities for action to reduce risk
of breast cancer depends, ideally, on a convergence of several elements,
including
• sufficient evidence to demonstrate that a specific factor is associated
with increasing or decreasing breast cancer risk;
• a means by which to modify exposure to the risk factor;
• an understanding of whether effective changes can be made by
an individual or would require instead, or in addition, changes at
governmental, social, or cultural levels;
• evidence that a specific action to modify exposure will result in the
desired impact on breast cancer risk, the characteristics of women
who could be expected to benefit, and when the intervention needs
to occur; and
• awareness of the trade-offs (potentially as yet unrecognized) that
may occur in terms of other health outcomes, personal preferences,
or economic consequences.
As illustrated in the reviews in Chapter 3, the evidence on many of the
environmental factors that have been investigated as potential risk factors
for breast cancer remains inconclusive. But for a modest set, the evidence
is relatively strong and points to likely opportunities for prevention when
these factors are modifiable. What, then, is the distinction between “modi-
fiable” and “nonmodifiable” risk factors? For example, the age at which
women have a first full-term pregnancy is known to influence the risk of
breast cancer, with later age at first birth generally associated with higher
risk. At the individual level, women can make decisions as to when they will
have their first pregnancy, but changes at the population level are influenced
by a range of social, economic, educational, cultural, and personal forces,
and any effort to influence personal choices could have unexpected conse-
quences. Furthermore, opportunities for modification of some factors may
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288 BREAST CANCER AND THE ENVIRONMENT
be limited to certain ages—a woman’s age at a first full-term pregnancy may
be modifiable before menopause, but obviously it is not after menopause.
Another question is whether particular actions to change a modifiable
risk factor will actually translate into lowered risk. For example, although
the evidence is relatively strong that greater body fatness is associated with
increased risk of breast cancer for postmenopausal women (WCRF/AICR,
2007), it is less clear whether these women can reduce their risk if they lose
weight during the postmenopausal period. It is possible that the adverse
effects of being overweight are hard to reverse at older ages and can best
be prevented by avoiding overweight and obesity throughout life.
Overweight and weight reduction also illustrate the complexity of fram-
ing guidance on action when the consequences of an exposure differ among
groups in a population. Whereas evidence indicates that greater weight is
associated with an increased risk for breast cancer for postmenopausal
women, it also indicates that greater weight is associated with a lower risk
of breast cancer for premenopausal women (WCRF/AICR, 2007). There-
fore, avoiding overweight is not a reasonable strategy for reducing the low,
but still present, risk of premenopausal breast cancer, although avoiding
overweight has many other important health benefits for women of all ages.
The association between shift work and increased risk of breast cancer
concerns the committee, but it does not see a sound basis, at this time, for
proposing action. More research is needed to understand the mechanisms
underlying the association between shift work and breast cancer and to
develop a clearer, more consistent characterization of the kind of work or
work schedule that is associated with increased risk. This deeper under-
standing is needed to guide any effort to frame and test interventions in
a realm with significant socioeconomic ramifications. A specific call for
research on shift work is included in the recommendations in Chapter 7.
In some cases, the available evidence from animal or mechanistic stud-
ies suggests that a chemical or other factor may be a hazard, but evidence
to directly assess the breast cancer risk for women is lacking (or perhaps
not possible to obtain). In such circumstances, policy makers may use
formal risk assessments to gauge the magnitude of possible risk and the
appropriateness of actions to mitigate it. The identification of hazards—
factors that have the ability to cause adverse effects—is an essential element
in risk assessment and is often based on laboratory studies of biological
mechanisms and effects of exposures on laboratory animals. Estimates of
risk represent the probability that a particular adverse outcome—breast
cancer in this case—will occur in an individual person or a population as
a result of defined exposures to a hazard. A risk assessment considers not
only the hazard of the substance, but also its potency (roughly speaking,
how strong its effect is for a given dose) and the magnitude, nature, and
timing of expected human exposure. A highly potent carcinogen may pose
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OPPORTUNITIES FOR ACTION TO REDUCE ENVIRONMENTAL RISKS
substantial risk to an exposed individual, but if exposure to the general
public is very low or extremely uncommon, the population risk will tend
to be low. Alternatively, a low-potency carcinogen may pose risks that are
low, but if exposures are common, it may be associated with a measureable
effect in the population as a whole.
The committee did not undertake formal risk assessments for the envi-
ronmental chemicals it found to be biologically plausible or possible con-
tributors to breast cancer. Critical pieces of information were lacking,
particularly robust data for estimating the magnitude of human breast
cancer risk for a given dose (potency) at different life stages, and the preva-
lence and magnitude of the exposures across the population at different
life stages. These data gaps were an obstacle to proposing evidence-based
action that women could take to reduce risks from exposure to any par-
ticular chemical.
LIKELY OPPORTUNITIES TO ACT TO
REDUCE RISK OF BREAST CANCER
With these limitations to the evidence in mind, the committee high-
lights here the areas where it sees the clearest indications of opportuni-
ties for actions to reduce breast cancer risk. These actions are reviewed
in this section and summarized in Table 6-1. It is important to recognize
that the evidence is generally more extensive and therefore stronger for
postmenopausal women than for premenopausal women, and for white,
non-Hispanic women than for women of other races and ethnicities. In
addition, some of the prevention opportunities that the committee points to
appear more likely to apply to the prevention of the more common estro-
gen receptor–positive (ER+) tumors than estrogen receptor–negative (ER–)
tumors. Younger women, however, tend to have ER– forms of breast cancer,
as do women who have strong inherited susceptibility to breast cancer, such
as carrying a mutation in BRCA1. All women should know their personal
risk factors for breast cancer and seek clinical guidance from their health
care providers regarding their breast cancer risk and how to modify it.
Medical Radiation
Among the strongest evidence reviewed by the committee regarding
environmental exposures that have been causally linked to breast cancer
was the evidence on ionizing radiation. Based on standard models developed
from the radiation exposures of the Japanese atomic bomb survivors, it is
commonly assumed that the breasts are most sensitive to carcinogenic effects
of radiation at early ages (e.g., below ages 20–30). Nevertheless, models
also predict elevated risks after exposure, even in middle age (Berrington
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290 BREAST CANCER AND THE ENVIRONMENT
TABLE 6-1 Summary of Committee Assessment of Opportunities for
Actions by Women That May Reduce Risk of Breast Cancer
Modification of
Exposure
Strength of Evidence That Personal Requires
Opportunity for Exposure Is Associated Action Action
with Breast Cancer Riska
Action Possible by Others
Avoid +++ Yes Yes
inappropriate
medical radiation
exposured
Avoid combination +++ Yes Confer with physician
menopausal
hormone therapy,
unless medically
appropriatee
Avoid or end active + Yes Others can facilitate
smoking
Avoid passive (no committee consensus) Varies Yes
smoking
Limit or ++ Yes Others can facilitate
eliminate alcohol
consumption
– –f
Maintain or Yes Others can facilitate
increase physical
activity
Maintain healthy +++ Yes Others can facilitate
weight or reduce
overweight or
obesity to reduce
postmenopausal
risk
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OPPORTUNITIES FOR ACTION TO REDUCE ENVIRONMENTAL RISKS
Action
Other Prominent
Effective Form Known Risks or
Target Population and Timing Affects Risk for Benefits from Taking
Establishedb Actionc
Defined Specific Subtype
All ages Yes, especially at ? May result in loss
younger ages of clinically useful
information in some
instances
Likely to decrease risk
for other cancers
Postmenopausal Yes ER+ May experience
women moderate to
severe menopausal
symptoms, continued
menopausal associated
bone loss
All ages, especially Yes (form) ? Likely to reduce risk
before first pregnancy No (timing) for other cancers,
heart disease, stroke
All ages Yes ? Likely to reduce risk
for other cancers,
heart disease
All women Yes (form) ER? May increase risk for
No (timing) cardiovascular disease
No known benefit
of high alcohol
consumption
All ages No ? Likely to reduce risk
for cardiovascular
disease, diabetes
May increase risk for
injury
Unclear No ER+? Likely to reduce risk
for cardiovascular
disease, diabetes, other
cancers
continued
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292 BREAST CANCER AND THE ENVIRONMENT
TABLE 6-1 Continued
Modification of
Exposure
Strength of Evidence That Personal Requires
Opportunity for Exposure Is Associated Action Action
with Breast Cancer Riska
Action Possible by Others
Limit or eliminate Varies by chemical Varies Yes
workplace,
consumer, and
environmental
exposure to
chemicals that
are plausible
contributors to
breast cancer risk
while considering
risks of substitutesg
– – –h
If at high risk Yes Confer with physician
for breast cancer,
consider use of
chemoprevention
aThe assessments of the evidence of an association between an exposure and risk of breast
cancer are qualitative representations of the committee’s conclusions from its review of avail-
able evidence: strong conclusion of increased risk, +++; moderately strong conclusion of
increased risk, ++; conclusion of increased risk, +; unclear, ?; conclusion of reduced risk, –;
moderately strong conclusion of reduced risk, – –; strong conclusion of reduced risk, – – –.
bActions to address risk factors can take various forms, some of which may be more effec-
tive than others. For example, increasing physical activity might be based on amount of time
spent in any one exercise opportunity, on increasing specific types of exercise, or increasing
the frequency of exercise, or perhaps some combination of any of these. Studies have not been
done that provide evidence that a specific form of physical activity is optimal for reducing
breast cancer risk.
cThe committee’s comments on other benefits or risks highlight major considerations, but
are not intended to be exhaustive.
de Gonzalez et al., 2009; Shuryak et al., 2010). Recent models suggest the
possibility that exposures to ionizing radiation across the age range of 10 to
50 years may result in excess relative risks of tumors in breast tissue that are
more similar than previously estimated (Preston et al., 2007).
For the U.S. population, about half of the exposure to ionizing radia-
tion comes from medical radiation, primarily in the diagnostic setting and
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OPPORTUNITIES FOR ACTION TO REDUCE ENVIRONMENTAL RISKS
Action
Other Prominent
Effective Form Known Risks or
Target Population and Timing Affects Risk for Benefits from Taking
Establishedb Actionc
Defined Specific Subtype
Varies No ? May reduce risk for
other forms of cancer
May result in
replacement with
products that have
health or other risks
not yet identified
High-risk women Yes ER+ Depending on the
agent, increased risk
of endometrial cancer,
stroke, deep-vein
thrombosis among
others
dWhile recognizing the risks of ionizing radiation exposure, particularly for certain higher
dose methods (e.g., CT scans), it was not the committee’s intent to dissuade women from
routine mammography screening, which aids in detecting early-stage tumors.
eCombination hormone therapy with estrogen and progestin increases the risk of breast
cancer and the associated risk is reduced upon stopping therapy. Oral contraceptives are
also associated with an increased risk of breast cancer while they are being used. This risk is
superimposed on a low background risk for younger women, who are most likely to use oral
contraceptives. These contraceptives are associated with long-term risk reduction for ovarian
and endometrial cancer.
fReflects reduced risk of breast cancer associated with greater physical activity.
gPlausibility may be indicated by epidemiologic evidence, animal bioassays, or mechanistic
studies.
hReflects reduced risk of breast cancer associated with use of chemopreventive agents.
especially from computed tomography (CT) scans and myocardial perfu-
sion imaging (Fazel et al., 2009). As outlined in a paper commissioned by
the committee (see Appendix F), the average annual dose of radiation from
medical diagnostic sources in the U.S. population approximately doubled
from 1985 to 2006 (Smith-Bindman, 2011). As further elaborated in that
paper, there is evidence that exposure doses for the same imaging tests vary
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314 BREAST CANCER AND THE ENVIRONMENT
of overweight and obesity to breast cancer cases in the population as a
whole. An uncommon exposure will usually have a small PAR because the
percentage of all cases that is attributable to the exposure will be small.
However, for a woman who has that exposure, reducing or eliminating it
could substantially lower her risk and be very important to her individually.
That is, a rare, high-risk exposure may have little impact on population
rates of cancer, but it may be a quite important determinant of an exposed
woman’s personal risk.
Recent efforts have tried to further clarify risks for both individual
women and populations by developing models that estimate the absolute
risk of breast cancer from relative risks and estimates of attributable risk. In
a study by Petracci et al. (2011), the authors used data on Italian women to
develop a model to predict breast cancer risk, making use of both nonmodi-
fiable risk factors and the modifiable risk factors of BMI, alcohol consump-
tion, and physical activity. Data from a cohort study were used to assess
the potential impact on absolute breast cancer risk of reducing exposures
to the modifiable risk factors. The projected 20-year absolute risk of breast
cancer for 65-year-old women, for example, ranged from 6.5 to 18.6 per-
cent, depending on their risk profiles. If these women optimized their BMI,
alcohol consumption, and physical activity, the estimated 20-year absolute
risks would be reduced to 4.9 and 14.1 percent, respectively (Petracci et al.,
2011). Presentation of the absolute risk reductions along with estimates of
relative risk and the PAR reduction that could maximally be achieved may
be a useful approach to both individual counseling and public health deci-
sion making (Schwartz et al., 2006; Akl et al., 2011; Helzlsouer, 2011). It
illustrates the well-known concept that small changes at the individual level
can have a large impact at the population level (Rose, 1992).
SUMMARY
Many of the established risk factors for breast cancer—age, sex, age
at menarche and menopause, age at first full-term pregnancy—offer little
or no opportunity to intervene. For a limited set of other risk factors, evi-
dence suggests that action can be taken in ways that that have the potential
to reduce risk for breast cancer for many women: eliminating unneces-
sary medical radiation throughout life, avoiding use of postmenopausal
hormone therapy, avoiding active and passive smoking, reducing alcohol
consumption, increasing physical activity, and minimizing weight gain.
Chemoprevention may be an appropriate choice for some women.
For the many chemicals that are manufactured or generated as by-
products of other processes, the committee found little basis in the human
evidence it examined to point to avoiding or eliminating exposure as a
specific strategy for reducing breast cancer risk. Exceptions were benzene,
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OPPORTUNITIES FOR ACTION TO REDUCE ENVIRONMENTAL RISKS
1,3-butadiene, ethylene oxide, for which certain measures to control occu-
pational exposures are already be in place. However, these chemicals can
also be encountered by the general public (although likely at much lower
exposure levels) through exposure to facilities emissions, tobacco smoke,
and gasoline vapors and vehicular exhaust (benzene and 1,3-butadiene).
While for other compounds that were reviewed, such as BPA, animal and
mechanistic evidence may indicate breast cancer hazard is biologically
plausible, given sufficient dosing, information to assess the magnitude of
risk in humans is lacking or inadequate in human studies, posing a sub-
stantial challenge for gauging the extent to which an individual’s actions
may reduce risk.
Even when action appears possible, most approaches to risk reduction
come with potentially complex trade-offs. These trade-offs may be social
or economic (e.g., the potential influence of earlier age at first birth on a
woman’s education or employment), or they may be health related (e.g.,
moderate alcohol consumption increases breast cancer risk, but it may
reduce risk of heart disease; tamoxifen reduces risk for breast cancer but
increases risk for stroke and endometrial cancer). It is also important to
keep in mind that what the committee has outlined in this chapter are areas
where the evidence indicates that action is likely to reduce risk in an average
population. The actual change in risk for any individual woman who takes
such actions might range from very small to moderate.
Chapter 7 outlines the committee’s recommendations for further
research to strengthen the knowledge base on breast cancer and, hopefully,
to point to more and better opportunities to reduce risk for this disease.
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