Affiliation of authors: G. Ursin, Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles; S. London, National Institute of Environmental Health Sciences, Research Triangle Park, NC.
Correspondence to: Giske Ursin, M.D., Ph.D., Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Ave., MS #44, Suite 4407, Los Angeles, CA 90089.
We thank Drs. Castagnetta and Carruba for their comments. In our
study of the association between the urinary ratio of
2-hydroxyestrone to 16-hydroxyestrone
(2-OHE1/16
-OHE1) and breast cancer
(1), we only included women with cancer detected at an early
stage to avoid a potential bias from differential survival by level of
the ratio. Thus, we did not address the question of whether women with
a more advanced stage at diagnosis have a lower urinary
2-OHE1/16
-OHE1 ratio than control subjects. If
the results of Dr. Castagnetta and co-workers hold true, then tissue
levels of 2-OHE1 may represent a prognostic factor in breast
cancer patients. However, this possibility does not mean that the ratio
is associated with risk of developing advanced breast cancer; this
question would still need to be addressed.
We agree that the samples in our study should ideally have been obtained prediagnostically.
However, any disappearance of tumor-associated changes in estrogen metabolism patterns
because of the time lag since diagnosis would not actually be a problem. The question we asked is
whether this ratio represents a biomarker for breast cancer risk detectable before detection of the
tumor, not whether it is present after the tumor has occurred and can be diagnosed. Also note
that, if general anesthesia causes an increase in 16-hydroxylation, then this increase may
have biased the results in studies that have examined this association in recently diagnosed case
subjects.
We agree that a ratio of only two metabolites is at best a crude measure of estrogen
metabolism along the 2- and 16-hydroxylation pathways. However, the methoxy derivatives
are not, as far as we know, as easily measurable in urine. The tritium-release method is not
feasible in a large epidemiologic study. We certainly agree that the urine level may not adequately
reflect tissue levels. However, we are unaware of any noninvasive methods of estimating tissue
levels of these compounds that could be used in epidemiologic studies.
We were simply evaluating whether the urinary ratio of 2-OHE1 to 16-OHE1 is associated with breast cancer risk. The results from our study do not support that
hypothesis.
REFERENCES
1
Ursin G, London S, Stanczyk FZ, Gentzschein E, Paganini-Hill A,
Ross RK, et al. Urinary 2-hydroxyestrone/16-hydroxyestrone ratio and risk of breast cancer
in postmenopausal women. J Natl Cancer Inst 1999;91:1067-72.
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