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Objective and Design: Gross cystic disease (GCD) of the breast is reported to occur in 7% of women in the developed world and, although not premalignant, is thought to be associated with an increased risk of breast cancer. Hormone and growth factor concentration levels were measured in breast cyst fluid (BCF) to correlate them with their mitogenic activity in tumour (MCF-7) or nontransformed (MCF-10A) cells., Results: Oestradiol (E2), oestrone (E1), E2-sulfate (E2-S), E1-sulfate (E1-S) and epidermal growth factor (EGF) concentrations were, as expected, significantly higher in type I than in type II cysts, while transforming growth factor-beta 2 (TGF-beta2) showed higher levels in type II cysts. Fifty per cent of the BCF samples stimulated [3H]-thymidine incorporation into MCF-7 cells while 34.5% inhibited this parameter. In MCF-10A cells, most BCF samples were stimulatory (85%). E2, E1 and EGF concentrations in BCF samples correlated significantly and positively with cell proliferation in MCF-7 cells, whereas a significant negative correlation was found for TGF-beta2. In MCF-10A cells, only E2-S and E1-S exhibited significant positive correlation, whereas a significant negative correlation was found for TGF-beta2. Progesterone (Pg), E2 and EGF incubated under the same conditions had a stimulatory effect on [3H]-thymidine incorporation into MCF-7 cells, whereas TGF-beta2 inhibited this parameter. Pg, E2, E1 and EGF significantly stimulated this parameter in MCF-10A cells., Conclusions: The stimulatory action of BCF on cell proliferation in a model of human breast epithelial cells could partly explain the increased incidence of breast cancer in cyst-bearing women.

Gross cystic breast disease (GCBD) is common in women, especially in the age range between 35 and the menopausal years. The present study examined the possible role of progesterone (Pg) in the chorionic gonadotropin (hCG) concentration in GCBD. The breast cyst fluids (BCFs) were drawn by fine needle aspiration between the sixth and the eighth day of the menstrual cycle and twenty days later. On the day of the first aspiration the patient began to take 100 mg of natural micronized Pg orally until the second aspiration. At both times blood samples were also taken. Determinations were done of both BCFs and blood sample using two fully automated chemiluminiscent enzyme immunometric assays. Pg has been demonstrated to induce a significant increment in hCG + free ss-hCG (median, range): 0.27 ng/ml, 0.12-6.24 vs. 1.92 ng/ml, 0.12-423.5; free ss-hCG: 0.11 ng/ml, 0.02-2.40 vs. 0.91 ng/ml, 0.02-58.40 in the BCFs, with no change in the circulating concentrations of the hormone. None of the sera studied presented levels of hCG + free ss-hCG or free ss-hCG above 0.5 ng/ml or 0.1 ng/ml, respectively. The occurrence of hCG or a derivative polypeptide in BCFs, when they are present in high concentrations suggests that this glycoprotein could be synthesized in situ and possibly involved in the pathogenesis of GCBD by the degree of differentiation of breast epithelial cells induced by the hormone.

Plasma lipid profile and abdominal obesity have been associated with breast cancer risk, however published results have been inconsistent. To clarify these associations we studied lipid and lipoprotein alterations, obesity degree and body fat distribution, in 30 newly diagnosed breast cancer patients without treatment and 30 controls matched by age and menopausal status. Both pre and postmenopausal breast cancer patients presented higher body mass index, waist/hip ratio and insulin levels than their matched controls. An increase in triglycerides and a decrease in HDL-cholesterol, especially in the HDL2 subfraction, were observed in patients with breast cancer. Besides, HDL particle from these patients showed increased apo A1/HDL-cholesterol ratio. These alterations were correlated with waist/hip ratio. The association between lipoprotein alterations and abdominal obesity independent of menopausal status, in untreated newly diagnosed breast cancer patients is reported for the first time in this study.

Levels of circulating estrone (E1), estradiol (E2), androst-4-ene-3,17-dione (Adione), 3,5,3'-triiodothyronine (T3), thyroxine (T4), and sex hormone-binding globulin (SHBG) were measured in 10 obese postmenopausal patients with breast cancer and in 10 obese postmenopausal control subjects matched for age, body size, and menopausal status. T3, T4, and SHBG were also measured in 10 lean postmenopausal control subjects. In cancer patients after mastectomy, the cytosolic estrogen receptors (E2R) in tumor specimens were determined. No significant differences between the two groups of obese postmenopausal women were found for levels of all determinations carried out in serum. Comparing obese subjects (with or without breast cancer) with lean controls, circulating levels of T3 were found approximately 50% higher in the obese group. Conversely, SHBG was found around 50% of the value observed in lean controls. The changes presumably produced by obesity on serum SHBG levels appear to be reversible, tending toward normality with weight reduction. In cancer patients SHBG correlated negatively with cytosolic E2R concentrations (P less than 0.01). In conclusion, it is considered that obesity implies a double risk for breast cancer in susceptible postmenopausal women, by inducing a decrease of SHBG and a concomitant increase of the supply of "free" E2 to target tissues, in absence of cyclic endogenous progesterone.