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In vivo experiments on strains of mice that differ in the risk of developing mammary cancer have demonstrated a correlation between the extent of 16 alpha-hydroxylation of estradiol and incidence of mammary cancer. The ability of human mammary terminal duct lobular unit (TDLU), the site of neoplastic transformation, to metabolize estradiol or to accumulate estradiol metabolites has not been unequivocally established. Using a newly developed human mammary TDLU explant culture system and a radiometric assay for estradiol metabolism, we compared the site-specific metabolism of estradiol by the 17-oxidation, 2-hydroxylation, and 16 alpha-hydroxylation pathways in noninvolved human mammary tissue. The relative extent of estradiol 16 alpha-hydroxylation was found to be increased in TDLU from patients in the luteal phase of the menstrual cycle in relation to either those from patients in the follicular phase or from postmenopausal subjects. This study demonstrates that TDLU can metabolize estradiol extrahepatically and that 16 alpha-hydroxylation in the target tissue is dependent on the phase of the menstrual cycle. Furthermore, the specific, risk-related increase in 16 alpha-hydroxylation suggests that intrinsic metabolic ability of the target tissue leading to the formation of 16 alpha-hydroxyestrone from estradiol may be a determinant in, or a marker for, the relative risk of developing mammary cancer.

The metabolism of E2 via the 16 alpha-hydroxylation pathway is reported to be elevated in breast cancer patients as well as in subjects at high risk for developing breast cancer. The biological relevance of the metabolic pathway during the initiational events that lead to the tumorigenic transformation of mammary epithelium is not fully understood. The results obtained from the in vitro experiments discussed in this report permit the following conclusions: 1. Human mammary TDLU, the presumptive target site for breast cancer, possesses metabolic competence to biotransform E2. 2. The biotransformation of E2 in TDLU via the 16 alpha-hydroxylation pathway is responsive to endogenous hormonal changes and to the presence of cancer, and is susceptible to carcinogenic insult. 3. The relative extent of E2 16 alpha-hydroxylation may constitute a sensitive metabolic marker for evaluating the susceptibility of noninvolved mammary epithelium to carcinogen-induced transformation.

A case of sigmoid carcinoma in a 16-year-old boy is presented and the topic of colonic carcinoma in the young is reviewed. Although colon carcinoma in the younger patient is uncommon, its prognosis is distinctly worse than in the adult population, because the preponderance of mucinous adenocarcinoma in children and young adults represents a more virulent type of colonic malignancy and because the delay in diagnosis contributes to a more advanced stage of the disease at the time of presentation. When dealing with symptoms potentially referrable to this disease, a thorough diagnostic work-up should ensue.

Analysis of estrogen and progesterone receptor proteins was carried out in 75 premenopausal and 79 postmenopausal patients with primary operable breast carcinoma who were treated from January 1983 to December 1984. The frequency of estrogen receptor protein positive/progesterone receptor protein positive (+/+); estrogen receptor protein negative/progesterone receptor protein negative (-/-); estrogen receptor protein negative/progesterone receptor protein positive (-/+); and estrogen receptor protein positive/progesterone receptor protein negative (+/-) was 40.5%, 30.5%, 23%, and 6% in premenopausal patients, respectively, and 52%, 24%, 2.5%, and 21.5% in postmenopausal patients, respectively (p less than 0.001). The mean positive estrogen receptor protein concentration (expressed as femtomoles per milligram of protein +/- SEM) was significantly higher in postmenopausal patients (54 +/- 6) than in premenopausal patients (19 +/- 2) (p less than 0.005). The progesterone receptor protein values did not differ significantly between these two groups. The phase of the menstrual cycle was recorded at the time of surgery in the 75 premenopausal women. Maximum receptor positivity occurred in the secretory phase, however, this difference is not statistically significant, and our data suggest that there are no distributional differences between the phase of menses and positivity of estrogen and progesterone receptor proteins. Future studies which included analyses of circulating sex steroid levels and receptor proteins will provide a better understanding of complex hormonal regulatory mechanisms which exist in patients with breast cancer.