Is there a link between a high-fat diet during puberty and breast cancer risk?

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ISSN 1745-5057
Women's Health (2011) 7(1), 1–3
10.2217/WHE.10.83 © 2011 Future Medicine Ltd
(i.e., puberty or adulthood) on mammary can-
cer susceptibility. Many studies in rodents, in
a variety of breast cancer models, consistently
demonstrate increased mammary tumorigenesis
in animals fed a HFD without the confound-
ing effects of obesity. For example, a HFD can
increase the numbers of mammary tumors in
transgenic MMTV-HER2/Neu mice with little
weight gain [7] and fatless transgenic A-Zip/F-1
mice show increased mammary tumorigenesis,
while being diabetic with expression of many
inflammatory products that promote tumor
progression [8]. It was also found that HFD can
enhance mammary tumorigenesis in transgenic
MMTV-TGF-a mice without obesity [9]. Thus,
the expansion of adipose mass associated with
obesity need not be the source of inflammatory
factors promoting tumorigenesis in the meta-
bolic syndrome. Even more compelling is that
human epidemiological studies have demon-
strated that a HFD in itself is a risk factor for
breast cancer [10].
In the USA and western Europe, increased
BMI and obesity are largely attributable to the
consumption of a ‘western diet’ high in satu-
rated fat. The literature supporting the notion
that a HFD can enhance tumorigenesis with-
out obesity has implications for the broader
population that consumes a HFD without
becoming obese. Among the mechanisms pro-
posed for obesity-associated breast cancer risk,
are altered glucose metabolism, altered steroid
hormone levels and inflammatory processes
[11]. It is entirely possible that a HFD during
puberty may alter breast development, inde-
pendently of increasing BMI, through one or
more of these mechanisms, thereby modifying
the risk for breast cancer.
A chronic HFD can induce insulin resist-
ance [11]. The resulting chronic hyperinsulin-
emia and increased availability of IGF-1 may
stimulate tumor growth. However, epidemio-
logical studies on the association of heightened
levels of IGF-1 with breast cancer incidence have
come down on both sides of this issue.
Recent data demonstrated that 19% of US chil-
dren aged 6–11 years of age are overweight, as
defined by being over the 95th percentile for
their age in BMI [1]. The typical western diet,
high in saturated fat, is largely credited for
the obesity epidemic in the USA. However, it
should be noted that there are more people who
eat a high-fat western diet and potentially suffer
its consequences, than are actually obese. Ample
literature is available showing that the dietary
habits that lead to overweight and obesity corre-
late with the onset of diabetes and heart disease
later in life [2].
“...studies are needed to assess
dietary influences on hormonal
levels, particularly during puberty
given the association of early puberty
with increased breast cancer risk.”
Obesity and being overweight are also impli-
cated in the etiology of breast cancer. Prepubertal
overweight and obesity are at the forefront of
suspected contributors to early puberty [3] and
early puberty is clearly a risk factor for breast
cancer [4]. Studies have established that girls with
higher BMIs are likely to experience puberty at
an earlier age [5], but the mechanisms by which
this occurs are not well understood. An impor-
tant gap in our understanding is how diet specif-
ically influences pubertal breast development. At
the same time, the effects of diet versus those of
increased BMI are difficult to distinguish, since
a high-fat diet (HFD) often results in increased
BMI. While very little is known about how diet
versus childhood obesity affects an individual’s
future risk for breast cancer, it is acknowledged
that the relationship of diet, weight status and
weight gain in childhood deserves further atten-
tion [6]. In this regard, animal studies offer a
number of advantages for elucidating the under-
lying mechanisms of the effects of a HFD and
distinguishing between the effects of a HFD
and obesity at a given age/developmental stage
EDITORIAL
Is there a link between a high-fat diet
during puberty and breast cancer risk?
“...increased prepubertal BMI is highly associated with early pubertal
maturation and the onset of menses – known risk factors for breast cancer.”
Keywords
• breast cancer • high fat diet
• puberty
Sandra Z
Haslam
Department of Physiology, Breast
Cancer & The Environment Research
Center, 2201 Biomedical & Physical
Sciences Building, Michigan State
University, East Lansing,
MI 48824, USA
Richard C
Schwartz
Author for correspondence:
Department of Microbiology &
Molecular Genetics, Breast Cancer &
The Environment Research Center,
2209 Biomedical & Physical Sciences
Building Michigan State University,
East Lansing, MI 48824, USA
Tel.: +1 517 884 5317
Fax: +1 517 353 8957
Schwart9@msu.edu
part of
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EDITORIAL – Haslam & Schwartz
The exact mechanisms through which
hormonal factors increase breast cancer risk
remain unknown. However, the ovarian
hormones, estrogen and progesterone are
believed to play an important role in the etiol-
ogy of breast cancer. Progesterone in combi-
nation with estrogen is a potent mitogen in
the human breast [12] and in animal models
[13,14]. Recent studies have shown that exog-
enous progestins, used in combination with
estrogens in menopausal HRT, increase breast
cancer risk, whereas estrogen-alone HRT is
not associated with an increase [15]. In this
regard, it is notable that the recent decrease
in breast cancer incidence has been attributed
to the decreased use of combined estrogen
plus progestin HRT [16]. Adipose tissue is an
endogenous source of estrogen through the
activity of aromatases and this is the major
source of estrogen in postmenopausal women
[11]. Hyperinsulinemia associated with obesity
inhibits secreted levels of sex hormone-binding
globulin, further contributing to elevated lev-
els of estrogen [11]. Notwithstanding the low
risk of estrogen-alone HRT, elevated estrogen
levels are associated with the elevated breast
cancer risk observed in postmenopausal obese
women [11]. We recently demonstrated that
progestins can induce inflammatory processes
in the mammary gland, recruiting leukocytes
to sites adjacent to the mammary epithelium
[17]. Several studies have shown that inflamma-
tion contributes to tumor growth and meta-
stasis [18]. This may be one factor that explains
the breast cancer risk associated with proges-
tin-containing HRT. Given the implications
for estrogen and progesterone in breast cancer
development, studies are needed to assess die-
tary influences on hormonal levels, particularly
during puberty given the association of early
puberty with increased breast cancer risk.
Much focus has been placed on adult obes-
ity as a low-grade inflammatory condition
and diets abundant in saturated fat have been
reported to directly induce inflammation
through the activation of Toll-like receptor sig-
naling in murine adipocytes and macrophages
[19], leading to NF-kB and JNK activation with
subsequent cytokine production. Palmitate, a
major component of animal fat in the western
HFD has been implicated particularly in these
effects [20]. A HFD can also acutely induce low-
grade inflammation after feeding [21]. This
may occur through increased permeability of
the gut, allowing increased levels of bacterial
endotoxins to enter the circulation [22]. There
is significant evidence at the molecular level
that many cancers, including breast cancer,
are linked to a dysregulated inflammatory
response. Epidemiological studies also indicate
that anti-inflammatory drugs reduce the risk of
both receptor-positive and -negative breast can-
cer [23]. Animal models of breast cancer have
demonstrated that inflammatory processes
contribute to tumor proliferation and meta-
stasis [18]. Consistent with this, anti-inflamma-
tory drugs have been used in animal models
for chemoprevention of mammary cancer [24].
The association of a HFD with inflammation
has clear implications for its possible impact on
breast cancer risk.
Finally, the effects of HFD may be refracted
through the genetic backgrounds of the
affected individuals. Divergent effects of
HFD are observed between the BALB/c and
C57BL/6 strains of mice [25]. While HFD
induces the proliferation and development
of mammary glands in BALB/c mice in the
absence of obesity, a HFD causes obesity and
actually stunts mammary gland development in
C57BL/6 mice. While the underlying basis of
these strain-specific differences is not known,
the genetic variability of human populations
suggest that the effects of a HFD may vary
between individuals.
As stated previously, increased prepubertal
BMI is highly associated with early pubertal
maturation and the onset of menses – known
risk factors for breast cancer. While the under-
lying mechanisms are not completely under-
stood, the western diet, high in saturated fat
and largely credited for the obesity epidemic
in the USA, is suspected to be causal. Given
the associations of a HFD with both increased
breast cancer risk and inflammation, and the
association of inflammation with cancer, fur-
ther research is clearly needed to define these
processes in children because of their potential
significance for the predisposition to chronic
diseases and breast cancer, in particular.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involve-
ment with any organization or entity with a financial interest
in or financial conflict with the subject matter or materials
discussed in the manuscript. This includes employment, con-
sultancies, honoraria, stock ownership or options, expert
testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of
this manuscript.

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future science group
Women's Health (2011) 7(1)
High-fat diet during puberty & breast cancer risk – EDITORIAL
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