Menstrual cycle-dependent variations of breast cyst fluid proteins and sex steroid receptors in the normal human breast

Menstrual cycle dependent variations in cytosol levels of estrogen receptor (ER), progesterone receptor (PR), and two breast cyst fluid glycoproteins, gross cystic disease fluid protein (CDP) and nonreceptor progesterone binding protein (PBP), were demonstrated in epithelial-enriched “normal” breast tissues from 56 premenopausal women. Criteria for normalcy were: (1) normal menstrual history; (2) absence of drug use or debilitating disease; (3) normal adrenal, ovarian and pituitary function; and (4) no clinical, gross or histologic evidence of breast disease. Highest mean levels of CDP (8180 ± 2850 ng/mg protein) and PBP (17750 ± 6320 ng/mg protein) were noted during the follicular phase (days 8–14) of the menstrual cycle, while lowest levels of CDP (450 ± 260) and PBP (1810 ± 380) were observed during the luteal phase (days 15–20). Both CDP and PBP had peak values on days 10–12 with a smaller peak on days 20–23. The number of samples with ER > 3 fmole/mg protein (8/14; 57%) and mean ER level (7.5 ± 2.9 fmole/mg protein) were significantly higher during the proliferative phase (days 3–7) than during other menstrual phases. Maximum ER values occurred on days 5–8. The greatest number of samples with PR > 3 fmole/mg protein (5/15, 33%) and highest mean levels of PR (36 ± 27.8 fmole/mg protein) were noted during the follicular phase of the menstrual cycle. These data demonstrate that the normal human breast has menstrual cycle variations of CDP and PBP which may be useful as markers of sex steroid receptor integrity. These data also documented that appreciable ER levels were found during the proliferative phase with low levels at other times in the menstrual cycle.