Invasive breast carcinoma - IARC

similar effects within different populations.
Although lifetime physical activity
is desirable, beginning re c re a t i o n a l
physical activity after the menopause
can probably be beneficial for both
weight control and breast cancer risk
reduction {1292}.
Fig. 1.07 Age distribution of benign and maligmant breast lesions in patients presenting with a discrete
breast lump. From Dixon and Sainsbury {707}.
Endogenous hormones
There is overwhelming evidence from
epidemiological studies that sex steroids
( a n d rogens, estrogens, pro g e s t o g e n s )
have an important role in the development
of breast tumours. Breast cancer
incidence rates rise more steeply with
age before menopause than after, when
ovarian synthesis of estrogens and progesterone
ceases and ovarian androgen
production gradually diminishes {1447}.
The estrogen excess hypothesis is central,
stipulating that breast cancer risk
depends directly on breast tissue expos
u re to estrogens. In vitro studies show
i n c reased breast cell proliferation and
inhibition of apoptosis. Animal studies
show increased rates of tumour development
when estrogens are administere d .
The risk is higher among postmenopausal
women who have elevated plasma levels
of testosterone and andro s t e n e d i o n e ,
reduced levels of sex horm o n e - b i n d i n g
globulin (SHBG), and increased levels of
o e s t rone, oestradiol, and bioavailable
oestradiol not bound to SHBG.
A second major theory, the estro g e n
plus progestogen hypothesis {255,
1446}, postulates that, compared to
e x p o s u re to estrogens alone (as in postmenopausal
women not using exogenous
hormones), risk of breast cancer is
f u rther increased in women who have
elevated plasma and tissue levels of
e s t rogens in combination with pro g e s t o-
gens. This theory is supported by observations
that proliferation of mammary
epithelial cells is increased during the
luteal phase of the menstrual cycle,
c o m p a red to the follicular phase.
Among premenopausal women, several
studies have not shown any clear association
between breast cancer risk and
c i rculating levels of androgens, estrogens,
or pro g e s t e rone {255,1183,2448,
2 6 1 3 , 2 9 0 9 } .
A metabolic consequence of excess
body weight and lack of physical activity
is development of insulin re s i s t a n c e .
Elevated insulin levels, may lead to
increased ovarian and/or adrenal synthesis
of sex steroids, particularly of androgens,
and decrease the hepatic synthesis
and circulating levels of SHBG
{1376}. Especially in postmenopausal
women, elevated plasma andro g e n s
lead to increased estrogen formation in
adipose tissue, and hence to increased
levels of oestrone and oestradiol. The
hypothesis that chronic hyperinsulinemia
might explain the observed associations
of breast cancer risk with low plasma
SHBG and elevated androgens and
e s t rogens, among postmenopausal
women {1376} has, however, received
only limited support {661,1377}. Insulingrowth
factor-I (IGF-I) and IGF-binding
proteins (IGFBP) appear to be significant
risk predictors {1127,1377}.
F u t u re adult cancer risk is in part set by
conditions of exposure in utero. The preventive
effect of gravidic toxaemia is re c-
ognized {1288} and since the 1950s studies
have incriminated high birth weight as
a risk factor for cancer, in particular of the
b reast {1857}. Similarly, among twins, the
risk of breast cancer may be affected by
the type of twinning (dizygotic versus
monozygotic) and sex of the dizygotic
twin {429}. A study of maternal pre g n a n-
cy hormone levels in China and the
United States of America (USA) did not
find, however, the expected higher levels
in the USA but rather the reverse {1676}.
Another important period is adolescence,
w h e re diet may play a role either dire c t l y
or possibly indirectly through a modification
of growth velocity {242}.
Some specific exposures
Only limited data is available on specific
exposures in relation to breast cancer.
Long-term follow-up of women exposed
to the Hiroshima or Nagasaki nuclear
explosions indicates an increased risk of
breast cancer, in particular for women
exposed around puberty {2938}.
Similarly, exposure as a result of treatment
and surveillance of tuberculosis is
associated with risk {304}. Yet there is little
evidence for a different pattern of risk
as a function of fractionated versus one
time only irradiation {1678}. Systematic
reviews on occupation and breast cancer
are few, indicating an increased risk
for selected occupations and specific
chemical and physical exposures. This
data contrasts with the long-held view
that risk of breast cancer is related to
social class, with higher risk for execu-
Table 1.01
Frequency of symptoms of women presenting in a
breast clinic {288,698}.
Lump 60-70%
Pain 14-18%
Nipple problems 7-9%
Deformity 1%
Inflammation 1%
Family history 3-14%
16 Tumours of the breast