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breast cancer cases are characterized by a low 2-hy-
droxyestrone/16␣-hydroxyestrone metabolite ratio in the
urine of patients [14], a report that has been confirmed and
extended to the serum [15]. Parenthetically, this ratio is
subject to modulation by dietary and drug intervention [16,
17]. Enhanced 4-hydroxylation relative to 2-hydroxylation
of estradiol has been shown in microsomes derived from
human mammary adenocarcinoma and uterine myoma [18,
19]. In our studies we could not find estriol or estriol sulfate
(E3S). Our efforts were constrained by the limited sampling
of cyst fluid needed for identification of E3S by GC/MS. In
conclusion, our demonstration of the synthesis in situ of a
variety of biologically active steroids, complement obser-
vations on the capability of the constituents of BCF to
impact on sulfokinase, sulfatase, and 17-dehydrogenase
activities in breast cancer cells in vitro [20].
The consensus of epidemiologic studies on cystic disease
of the breast supports a positive association with breast
cancer risk. This finding has stimulated the search for con-
stituents in BCF that may identify a subset of patients with
palpable cysts who are at higher risk for breast cancer. One
focus has been on the cationic contents of BCF. A majority
of cysts, designated Type I, resemble an intracellular milieu
in that the Kϩ/Naϩ ratio is greater than 3, whereas low ratio
Type II cysts mimic extracellular fluids more closely. In-
terestingly, BCF from Type I cysts show much higher con-
centrations of sex steroids than Type II. However a recent
study examining the connection between cyst Type and
breast cancer risk did not identify Type I cysts as a risk [4],
as had previously been reported [21]. We studied too few
cysts to have any influence on the controversy concerning
the relationship between BCF Type, steroid composition
and cancer risk. This issue would only be resolved by an
epidemiologic study involving quantification of the putative
carcinogens identified in our study.
[14] Kabat GC, Chang CJ, Sparano JA, Sepkovic DW, Hu XP, Khalil A,
Rosenblatt R, Bradlow HL. Urinary estrogen metabolites and breast
cancer: a case-control study. Cancer Epidemiol Biomarkers Prev
1997;6:505–9.
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D, Cantor A, Cox C. The prognostic value of altered estrogen me-
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Estrogen metabolism and laryngeal papillomatosis: a piolot study on
dietary prevention. Anticancer Res 1998;18:4569–73.
Acknowledgments
[17] Yuan F, Chen DZ, Liu K, Sepkovic DW, Bradlow HL, Auborn K.
Anti-estrogenic activities of indole-3-carbinol in cervical cells: im-
plication for prevention of cervical cancer. Anticancer Res 1999;19:
1673–80.
This investigation was supported by grants from The
Isabella and Murray Rayburn Foundation and The Irving
Weinstein Foundation.
[18] Liehr JG, Ricci MJ. 4-Hydroxylation of estrogens as marker of
human mammary tumors. Proc Natl Acad Sci USA 1996;93:3294–
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