الفهرس 
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Abstract
The mammary gland is the only organ that undergoes
most of its development postnatally. The anatomical and
histological structure of the mammary gland undergoes
substantial changes during the period from early adolescence
to menopause. It is composed of lobes which contain a
network of glandular tissue consisting of branching ducts and
terminal secretory lobules in a connective tissue stroma.
Hormone therapy (HT) is one of the alternative
treatments for the relief of symptoms in postmenopausal
women. However, there are reports of adverse effects with
long-term estro-progestative therapy, in particular about the
increased risk of breast cancer. Phytoestrogens are a group of
non-steroidal compounds of plant origin that present structural
and functional similarities with estradiol. Isoflavones are their
most widely known category. There are different mechanisms
of action of isoflavones accepted, although they may be
considered as selective modulators of estrogen receptors.
Tamoxifen is currently used for the treatment of both
early and advanced ER+ (Estrogen Receptor positive) breast
cancer in pre- and post-menopausal women.
Summary
190
The goal of this work was to examine the effect of
Estrogen (as a representative of HRT) on mammary gland and
overlying skin compared to effect of Isoflavone (as a
representative of natural replacement therapy), with
highlighting the effect of Tamoxifen combination with both
treatments.
Eighty adult resting non-lactating female rats were
chosen for this experiment, and divided into six groups.
Group 1 was further subdivided into three groups (unoperated,
sham operated and sesame oil-injected) all served as
control. Group 2 in which rats were subjected to bilateral
oophorectomy. Group 3 received subcutaneous injection of 30
microL. of 17-β estradiol (Folone ampoule) dissolved in 7.5 ml
of 10 % alcohol, and this solution was dissolved in 7.5 ml of
sesame oil. Then 0.5 cm was given from the prepared solution
as single daily subcutaneous dose for 8 weeks (=25μg ∕kg/day)
after one month of bilateral oophorectomy. Group 4 was
orally treated by soy-derived isoflavones (Iprivone 300 mg
tablets dissolved in their drinking water) in a daily dose of 100
mg/Kg body weight for 8 weeks after one month of bilateral
oophorectomy. Group 5 was orally treated by Tamoxifen
(Tamoxifen 20 mg tablets dissolved in their drinking water) in
a daily dose of 10 mg/Kg and subcutaneous injection of 17-β
Summary
191
estradiol in the same dose as Group 3, both for 8 weeks after
one month of bilateral oophorectomy. Group 6 were orally
treated with combined isoflavone and Tamoxifen
administration. Tamoxifen was administered in the same dose
as Group 5 and Isoflavone in the same dose as Group 4. Both
were dissolved in their drinking water and taken for 8 weeks
after one month of bilateral oophorectomy. Mammary gland
specimens and the overlying skin were excised and prepared
for microscopic examination.
In each group: Mammary gland sections were
represented by subgroup A. Skin sections were represented by
subgroup B.
Microscopic examination of the mammary gland
specimens revealed marked atrophy of the glandular
components in those who received either Isoflavone alone or
Tamoxifen combination with either Estrogen or Isoflavone,
compared to those who received Estrogen alone, which
showed marked ductal and acinar proliferation. There was
marked increase in the peri-ductal connective tissue strands in
the oophorectomized group. The stromal component was
preserved in all groups except those who received Tamoxifen
combinations, where the fatty connective tissue stroma was
Summary
192
replaced by fibro-fatty tissue with degeneration of the fat cells
and decrease in their sizes. There was also positive Estrogen
Receptor immune-reactivity in those who were subjected to
bilateral oophorectomy and those who received Estrogen alone
compared to negative reaction in other groups. Moreover, there
was positive Caspase-3 immune-reactivity in those who
experienced bilateral oophorectomy, those who received
isoflavone alone or Tamoxifen combination with either
Estrogen or Isoflavone in addition to the control group
compared to negative reaction in Estrogen group.
Regarding the skin specimens, there was increase in
epidermal and dermal thickness in groups that received
Estrogen and isoflavone, compared to marked epidermal
atrophy and increased thickness and density of dermal collagen
fibers in Tamoxifen groups.
Additionally, there was atrophy of the dermal papillary
layer of the skin with its replacement by the thick fibers of the
reticular layer in the oophorectomized group, together with the
Tamoxifen combinations. While, on the other hand, it reappeared
on Estrogen and isoflavone supplementation.
Moreover, Tamoxifen groups showed apparent increase in
dermal fibroblasts, compared to other groups.
Summary
193
It is concluded that isoflavone has an anti-proliferative
protective role on mammary glandular tissue compared to
estrogen hormone, associated with its proliferative role on skin
epidermis and dermis. Isoflavone possessed atrophic effect on
the epithelial (glandular) component of the mammary gland,
however, it preserved the stromal element with its fatty
architecture. Tamoxifen combinations produced atrophy of the
stromal element as well as the glandular one, with
degeneration of the mammary gland fat and replacement by
fibro-fatty connective tissue. This combination also revealed
atrophy of the overlying skin (epidermis and papillary dermis).