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Studies of cytologic and biochemical constituents of nipple aspirates of breast fluid have contributed to understanding the natural history of benign and malignant breast disease. We conducted multivariate analyses using 1428 women from a recent case-control study of breast disease to determine which factors were independently associated with the ability to obtain breast fluid from nonlactating women. We then compared results from these analyses to the results from five previous studies that also used the aspiration technique of Sartorius. Four factors were consistently associated across studies with increased ability to obtain breast fluid: 1) age up to 35 to 50 years; 2) earlier age at menarche; 3) non-Asian compared to Asian ethnicity; and 4) history of lactation. Exogenous estrogen use, endogenous estrogen concentrations, phase of menstrual cycle, family history of breast cancer, type of menopause, and less than full-term pregnancy consistently did not influence ability to obtain fluid. New findings from this study shed light on some apparently contradictory findings from the previous studies. In particular, this study showed that the effects of age on ability to obtain fluid appeared to be independent of the effects of menopause. Furthermore, discrepancies in previous findings on the effects of parity on ability to obtain fluid may be explained by our finding that the increased ability to obtain fluid from parous compared to nulliparous women applied only to parous women who had breastfed.

A selected ion monitoring gas chromatography/mass spectrometric method for the quantitative determination of 3,4,4'-trichlorocarbanilide (TCC) and its major metabolites (the 2'-hydroxy sulfate and the N- and N'-glucuronides) in human plasma and urine was developed using the deuterium-labelled compounds as internal standards. Limits of detection of 3 ng/mL in urine for the N-glucuronides and of 1.5 ng/mL in plasma for the 2'-hydroxy sulfate were attained. Use of the method was illustrated in a study in human subjects employing TCC-containing bar soaps.

In nipple aspirates of breast fluid from nonpregnant healthy women, cholesterol and cholesterol epoxide levels were determined with gas-liquid chromatography and mass spectrophotometric techniques. Cholesterol levels were found to be elevated above plasma levels averaging 2200 +/- 1995 (S.D.) mg/dl and showing progressive increases in mean breast fluid cholesterol levels with advancing age, averaging 187, 1957, and 3554 mg/dl in women of age groups 20 to 29, 30 to 39, an 40 to 49 years, respectively. Cholesterol epoxide was detected in a significant number of women who yielded high levels of breast fluid cholesterol. Cholesterol epoxide has been reported by other workers to have transforming activity for embryo hamster cells and to be carcinogenic in animals. The findings lend support to our hypothesis and observation that the human breast secretes mutagenic and cancer-promoting substances which may have relevance in studies of the etiology of benign breast disease and cancer.

A method for the quantitative determination of chlorpromazine and five of its major metabolites in a single sample of biological fluid in the ng/ml range has been developed utilizing gas chromatography/mass spectrometry with selected ion recording. The assay is highly specific and quantification is accomplished by an inverse stable isotope dilution technique, using deuterium-labeled variants of the compounds as internal standards. In this way the concentrations of chlorpromazine and five of its major metabolites (the sulfoxide, the N-oxide, the monodemethylated, the didemethylated, and the 7-hydroxylated compounds) can be determined in biological fluids. Levels in humans have been measured both in plasma and in red blood cells and are compared to those found in related in vitro studies.

A method has been developed for the quantitative determination of cholesterol and three of its major oxidative metabolites (the 5 alpha,6 alpha-epoxide, the 3 beta,5 alpha,6 beta-triol, and the 5 beta,6 beta-epoxide) in a single sample of human breast fluid (2-50 microliters), using gas chromatography/mass spectrometry with selected ion monitoring. High specificity and reliable quantification is achieved by the use of the inverse stable isotope dilution method, employing deuterium-labeled variants of the compounds as internal standards.