We briefly review some biochemical aspects of benign
breast disease (BBD), mainly focusing on free and conjugate
estrogen content of
breast cyst fluid (BCF), also in relation to
cyst type. Evidence is reported that high K(+)-type I-
cysts clearly associate with low Cl- levels and accumulate significantly higher quantities of
dehydroepiandrosterone sulfate (
DHAS) and
estrone-3-sulfate (E1S). In spite of the limited number of cases, both increasing
DHAS and E1S levels correlate with the increment of K+ to Na+ ratio. A positive correlation was also found between
DHAS and E1S. Using electrochemical detection (ECD) on-line to high performance liquid chromatography (HPLC) in the reverse phase mode, we also studied the free
estrogen profile. We observed that in type I BCF there are significantly increased amounts of free
estrone (E1). The E1S to E1 ratio was significantly different in the two
cyst subpopulations; again, a positive correlation was found between free and sulfated E1 (r = 0.820, p less than 10(-6). This last, together with other experimental observations, allows us to hypothesize that in BCF a main pathway of
steroids should be E1S----E1. Besides, high specific activity of
sulfatase, as well as
beta-glucuronidase enzymes, has been demonstrated for BBD. Preliminary information is also reported concerning the BCF pattern of free
estrogens, including the highly polar ones, i.e.,
catecholestrogens (CCE) and the parent methoxy (MeO) conjugates, which represent, in BCF, a predominant portion of all free
estrogens. Both CCE levels and ratios appear unevenly distributed in the two different
cyst types. In addition, some BCFs show very high concentrations of 16 alpha-
OH-E1. Further studies are needed to answer the main question: whether
estrogen patterns could represent additive parameters to further categorize
breast cystic disease (BCD) or whether they are of minor interest to determine patients' risk of developing
breast cancer.