Gross Cystic Disease Fluid Protein in Nipple Aspirates of Breast Fluid of Asian and Non-Asian Women1

Gross cystic disease fluid protein 1 5 (GCDFP-1 5) is universally present in the apocrine metaplastic epithelium of cystic breast disease and breast cancer, but it is rarely found in normal breast epithelium. Therefore GCDFP-15 detected in nipple aspirates of breast fluid (NAF) could serve as a biochemical marker of the presence and possibly extent of apocrine metaplasia within the breast. GCDFP-l5 levels were measured in NAF from 37 Asian and 78 non-Asian women using radioimmunoassay. GCDFP-15 (range, 0-81,643 pg/mI) was found in the NAF of all but 1 woman and was highly correlated between right and left breasts. Mean concentrations of GCDFP-1 5 were significantly lower in NAF from Asian compared with non-Asian women. Markedly reduced levels of GCDFP-1 5 were found in the l 7 women who had been parous in the previous 2 years. In women not parous within the prior 2 years, no relationship was found between GCDFP-1 5 levels and age, weight, age at menarche, first-degree family history of breast cancer, parity, oral contraceptive use, or smoking history. High concentrations of GCDFP-1 5 were found in the NAF of women with a history of a benign breast biopsy. Because similarly high levels of GCDFP-1 5 were found in NAF in over 40% of women without a history of benign breast biopsy, and because GCDFP-1 5 in the breast is produced only by apocrine metaplastic epithelium, we infer that the breasts of these women likely contain a significant degree of apocrine metaplasia. Significantly higher concentrations of GCDFP-1 5 were found in the NAF of Asian women with wet compared with dry cerumen. This preliminary study supports the hypothesis that GCDFP-1 5 in NAF may be a useful biomarker indicative of the presence of apocrine metaplasia in the breast. Introduction In 1 979, Haagensen et a!. (1 , 2) identified three major glycoproteins of 1 5,000, 24,000, and 44,000 kD molecular weight in the fluid from gross cystic breast disease. Based on their molecular weights they were named GCDFP-15,3 GCDFP-24 and GCDFP-44, respectively. The concentrations of the GCDFP, measured by nadioimmunoassay, are found in high concentration in fluid aspirated from breast cysts and in the plasma of many patients with breast cancer. GCDFP-1 5 is found by immunopenoxidase staining only in metaplastic breast epithelium, in epithelial cells of axillary, anogenital, and meimobian apocnine glands, and in the submaxillary gland (3). Although always present in metaplastic apocnine epithelium of cystic breast disease and breast cancer, GCDFP-1 5 is rarely found in normal breast epithelium (4). GCDFP-24 and GCDFP-44, while present in apocnine glands, are less specific, since they are also found in the epithelia of a variety of other organs (5). The present study was motivated by the foregoing neports of high concentrations of GCDFP-1 5 in cyst fluid in association with cystic apocnine metaplasia, by studies indicating that distinct ethnic and racial variations exist in the prevalence ofapocnine metaplasia (6-9), and bythe absence of information on GCDFP-1 5 concentrations in breast fluid obtained by nipple aspiration. We hypothesized that the concentration of GCDFP-1 5 in NAF might serve as a biochemical marker ofthe presence and, possibly, ofthe extent or severity of apocnine metaplasia within breasts. Because no population data exist on GCDFP-1 5 in nipple aspirate fluid, a preliminary evaluation of this hypothesis was undertaken by measuring the concentration of GCDFP-1 5 in NAF from Asian and non-Asian women and the relationship of GCDFP-1 5 concentration to breast cancer risk factors and to benign breast disease. We also determined whether the concentration of GCDFP-1 5 was related to the intake of calories, protein, fat, vitamins A and C, and caffeine. Lastly, because the alleles determining cerumen phenotype have been found to be associated with secretion by the breast and other apocrine glands (1 0-1 3), we compared the concentrations of GCDFP-15 in NAF from women with wet versus dry cenumen. Materials and Methods Subjects. The 1 1 3 volunteers were 68 white, 8 AfricanAmerican, 33 Chinese, and 4 Japanese women employed at the University of California, San Francisco, or were attendees at health fairs sponsored by the Northeast Health Center Received 3/1 0/93; revised 6/7/93; accepted 7/1 2/93. I Supported in part by USPHS Grant ROl CA 47288-02 from the National dancer Institute, Bethesda, Maryland. 2 To whom requests for reprints should be addressed. n The abbreviations used are: GCDFP, gross cystic disease fluid protein; NAF, nipple aspirate fluid; OR, odds ralio; dl, confidence interval; ZnGP, zinc a-2 glycoprotemn. on August 27, 2017. © 1993 American Association for Cancer Research. cebp.aacrjournals.org Downloaded from