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1.1
Hot flashes are a major problem for many women as they reach
menopause. In most women, they can be managed quite effectively
with estrogen replacement therapy. Breast cancer survivors
are probably more prone to hot flashes than are women in
general. The reasons for this are threefold: (1) Adjuvant
therapy can cause an abrupt, premature menopause that could
lead to severe hot flashes; (2) tamoxifen, the most commonly
used therapy agent for breast cancer, causes hot flashes
as one of its primary side effects; and (3) we generally
proscribe estrogen replacement therapy for breast cancer
survivors because of theoretical fears that this therapy
may potentiate breast cancer growth.
Previous
NCCTG trials have evaluated nonhormonal agents such as clonidine
and vitamin E, but neither of these is very efficacious
at relieving hot flashes in breast cancer survivors. The
NCCTG has also evaluated megestrol acetate. While this antedote
does decrease hot flashes by approximately 80%, concern
has been raised by some with regard to the use of a synthetic
progesterone in breast cancer survivors. Thus, there remains
a need for the identification of new agents for alleviating
hot flashes in breast cancer survivors.
1.2
Soy products contain proteins which are known as isoflavones
or phytoestrogens. These phytoestrogens are compounds which
appear to have weak estrogenic activity in humans. Data
suggest that they can act as either estrogen agonists or
estrogen antagonists (Molteni
et al., 1995). Plant phytoestrogens are present in appreciable
amounts in commercial soy-based products (Dwyer
et al., 1994), and are detectable in the serum of women
who ingest these commercial soy products (Morton
et al., 1994).
1.3
There is appreciable information to suggest that soy products
may be associated with a decreased cancer risk. Epidemiologic
studies suggest an inverse association between soy intake
and breast cancer risk (Morton
et al., 1994). In vitro data have demonstrated that
isoflavones significantly reduce cancers in a large variety
of animal tumor model systems, including breast cancer models
(Barnes,
1995). In vitro data demonstrate that the isoflavone,
kievitone, appeared to inhibit the growth of estrogen receptor
positive and estrogen receptor negative breast cancer cell
lines (Hoffman,
1995). Genistein, a common phytoestrogen in soy products,
inhibits epidermal growth factor receptors (Hoffman,
1995). Genistein also antagonized Jurket T-leukemia
cell growth through cell cycle arrest and through induction
of apoptosis (Spinozzi
et al., 1994).
1.4
A recent review article from National Cancer Institute investigators
(Messina
et al., 1994), following an NCI workshop, concluded
that: 1) soy beans are a source of the weakly estrogenic
compound genistein; 2) genistein inhibits protein tyrosine
kinases; 3) 65 percent of animal carcinogenesis studies
reported protective effects from genistein, while no studies
suggested significant detrimental effects; 4) epidemiologic
data suggested a possible protective effect for both hormone-related
and nonhormone-related human cancers; and 5) that the available
data strongly suggested that soy products be further investigated
as chemopreventive agents. Additionally, another group of
NCI investigators, these investigators being from the chemoprevention
branch of the Division of Cancer Prevention and Control,
recently cited genistein in a list of compounds which deserved
further study as chemoprevention agents (Kelloff
et al., 1994).
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