Cermin Dunia Kedokteran

Body Adiposity, Body Fat Distribution,

Sex Hormones and

Risk of Breast Cancer

Junaidah Ba - Barnett, Ph.

* Assistant Professor, Nutrition it, Department of Community Health, Tufts University School of Medicine,

and Tufts University School of Nutrition, U.S.A.

** Faculty, Department of Co ' nity Nutrition and Family Resources (GMSK), Bogor Agricultural Institute, Indonesia,

Research Associate, Tufts University School of Nutrition, U.S.A.

Obesity has been well documented to increase the risk of

several diseases such as cardiovascular disease, diabetes,

hypertension and gall bladder disease

(1-3)

. Obesity is defined as

a state of adiposity in which body fatness is above the ideal. A

body mass index (BMI) of 27 or greater generally indicates

obesity and increasing risk of developing health

problems

(4)

.The most frequently used measure of body fat

distribution is the waist to hip ratio (WHR). The WHR is also

called the abdominal/gluteal ratio which differentiates between

android, characterized by the "apple shape" typical of mean,

and gynoid, characterized by the "pear shape" common to

women, obesity. The waist or abdominal circumference is

defined as the smallest circumference between the rib cage and

the umbilicus, and the hip circumference as the largest

circumference between the waist and the knees

(5)

. Abdominal

or android obesity is indicated by a WHR of 1.0 or greater in

men and 0.8 or greater in women

(6)

. Other measures such as the

subcutaneous fat distribution, i.e., skinfold measures at various

body sites such as the chest, subscapular, suprailiac, biceps,

triceps, abdominal, and thigh areas have also been used to

measure regional fat distribution.

Growing evidence suggests that obesity may be a risk factor

for the development of endometrial, and ovarian cancers

(7,8)

Several studies have also demonstrated an association between

degree of adiposity and breast cancer

(9-12)

. Obese women are

more likely to have menstrual disturbances, and have been shown

to have elevated levels of non-protein bound and total estro-

gens

(13-15)

. Compared to controls, women with breast cancer have

higher levels of non-protein bound estradiol and albumin-bound

estradiol

(16-20)

, lower levels of sex-hormone-binding globulin

(SHBG)

(21,22)

, and a decrease in SHB capacity

(17,18,22)

. The sex

steroids are bound to SHBG with high affinity and to albumin

with much lower affinity

(23,24)

. It is the fraction of sex steroids

that is not bound to SHBG and the very loosely albumin bound

sex steroids, and not the total concentration of sex steroids, that

are available for biological activity on the breast

(16-19,25)

. In

addition, the level of SHBG determines the amount of available

estrogen that.can interact with the breast

(26)

Although several investigators found either decreased

(27)

no difference

(21,28)

in the levels of estrone and/or estradiol-17-

beta in obese women comparedto normal weight subjects,

others have reported that in both pre- and postmenopausal

women, the greater the level of obesity, the greater the

proportion of bioavailable estradiol, i.e., the nonprotein bound

and albumin bound components, and the lower the total levels

of SHBG, and the SHBG capacity to bind

(15,26.29.30)

. The

findings that increased weight was associated with an early age

at menarche and with a late age at menopause, both well-

recognized risk factors for breast cancer

(31,32)

indirectly support

the relationship between obesity and hormones and breast

cancer. The increased biological availability and activity of

estrogen due to general adiposity may be via alterations in

estrogen protein binding

(33)

, postmenopausal estrogen

production

(34)

, increased conversion of estrone and estradiol

from their precursors by aromatase enzymes in the lipocytes

(15)

and 2-versus 16-hydroxylation of estradiol

(35)

Growing evidence also suggests that body fat distribution is

an important risk factor in the development

(36)

and prognosis

(26)

breast cancer. A higher incidence of breast cancer has been

suggested to be directly related to abdominal adiposity(8,36). A

recent study suggests that "increased central to peripheral body

fat distribution predicts breast cancer risk independently of the

degree of adiposity and may be a more specific marker of a

premalignant hormonal pattern than degree of adiposity

"(8)

These

findings are supported by another recent study which showed an

increased risk of breast cancer among postmenopausal women

with increased waist to hip ratio

(37)

. Hence, women on the typical

high-fat, low-fiber Western diet which is mainly reflected by

Cermin Dunia Kedokteran No. 95, 1994 57

abdominal fat accumulation

(33)

, are possibly at higher risk of

developing breast cancer.

Decreased binding of estrogen to sex hormone binding

globulin (SHBG) has been associated with both abdominal

obesity and increased abdominal fat cell size

(33)

. An

increased

localization of fat in the upper body in healthy premenopausal

women was shown by Evans et al

(38)

to be associated with a

continuous decline of plasma SHBG levels. Women with

abdominal (i.e. central) obesity have been found by Kirschner et

(39)

to have increased concentrations of free estradiol While

women with femoral (i.e. peripheral) obesity had higher

amounts of estrone due to increased peripheral aromatization of

androstenedione. Despite findings of increases in various forms

of estrogen in women with femoral and abdominal obesity, the

latter have been suggested by various studies

(33,40-42)

to have

greater increases in biologically significant estrogens.

As body adiposity and body fat distribution are risk factors

that are potentially modifiable, studies determining the relation-

ship between these factors and breast cancer risk are considerably

important. Further studies are needed to determine whether or

not, and if so, how changes in degree of adiposity and in body fat

distribution over time affect the risk of breast cancer. Physical

activity has been found to influence body composition and body

fat distribution

(43-48)

, and to be associated with endogenous

estrogen metabolism and levels of sex-hormone binding globulin

(SHBG)

(43,49)

. More definitive studies are needed to establish

the relationships of all three factors (body adiposity, body fat

distribution, and physical activity) and levels of endogenous sex-

hormones as well as the nature of their interactions. Long-term

epidemiologic studies using large prospective cohorts of both

pre and postmenopausal women whose diets, endogenous sex-

hormones, body adiposity, body fat distribution, and level of

physical activity are monitored with breat cancer as one of the

outcome variables, for example, would add considerably to

existing knowledge on these relationships and their interactions,

as well as to knowledge on the etiology and progression of

hormone-dependent breast cancer.

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