CORRESPONDENCE

RESPONSE: Re: Urinary 2-Hydroxyestrone/16{alpha}-Hydroxyestrone Ratio and Risk of Breast Cancer in Postmenopausal Women

Giske Ursin, Stephanie London

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{alpha}-hydroxyestrone (2-OHE1/16{alpha}-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{alpha}-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{alpha}-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{alpha}-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{alpha}-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{alpha}-hydroxyestrone ratio and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 1999;91:1067-72.[Abstract/Free Full Text]



             
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