Sorry about the mess of my first version! I had color-coded it for a private response and then decided to send it to lactnet. I won't do THAT again! Here's a nice cleaned up version in plain text. ~Lisa Esther, In the discussion of the study, they do try to deal with the enigma of the protective factor of lactation against breast cancer: "Both animal and in vitro models support the hypothesis that prolactin is involved in mammary carcinogenesis. Several studies have reported that breast cancer cells/tissue express prolactin (9 , 26, 27, 28) and the prolactin receptor (8, 9, 10 , 28) . Although normal tissue also expresses the prolactin receptor, primarily along the luminal cell border, several studies have reported higher levels in tumor tissue (10 , 29) with expression primarily in the cytoplasm (8) . In mice, prolactin appears to induce tumor formation (30 , 31) , increase tumor growth rate (5) , and increase the number of cells in the S phase (31) . In vitro studies also suggest that prolactin is associated with higher cell proliferation rates (3, 4, 5) , increases in cyclin D1 (3 , 4) , and it may induce motility of breast cancer cell lines (6) . Preliminary data also suggest that prolactin can enhance the responsiveness of breast cancer cells to estradiol (3) . In humans, prolactin concentrations were positively associated with mammographic density, a consistent strong breast cancer risk factor (32) , among 189 postmenopausal women after adjustment for age and waist circumference (33) . -->Paradoxically, prolactin is temporarily increased during breastfeeding, which is a protective factor for breast cancer. One possible explanation for this discrepancy is that pregnancy is associated with a lifetime decrease in prolactin levels (2), and this may outweigh the transient prolactin increase during breastfeeding. Secondly, the effect of prolactin during breastfeeding may differ from its effect at other times in the reproductive life of a woman; for example, it may lead to terminal cell differentiation during lactation but not at other times."<-- ***Quote from cited article 2 referenced in the text: "In addition, the relationship between plasma and tissue PRL levels is not well understood—further delineation of this relationship will require work from both epidemiologists and laboratory scientists. Parous women have been consistently observed to have lower PRL levels than nulliparous women." "In vivo, of course, mammary function is regulated by complex interactions among hormones, including PRL, estrogens, and progestins, as well as local growth factors, such as EGF family members, IGFs, and TGF, and the different cell types present in the mammary tumor environment. These factors can amplify or inhibit one another’s signals to the epithelial cells by several mechanisms, including altering expression of receptors, influencing the level or activities of signaling pathways, and activating paracrine modulators via action on different cell types (118, 322, 323). These complex opportunities for cross-talk are only beginning to be examined in these in vitro systems. Recent findings emphasize the importance of understanding PRL actions in cells of varying phenotype and environmental context." "Relatively little work has been done in nontumor human cell lines. The murine mammary epithelial cell line, HC11, a clonal derivative of COMMA-D cells, has been extensively studied. These cells proliferate in response to growth factors. However, PRL, in combination with glucocorticoids, causes these cells to grow more slowly, and differentiate, as characterized by milk protein synthesis (197, 324, 325, 326). This is an especially important area for study, which will increase our understanding of this hormone and its interactions with other factors in normal and pathogenic processes." ***I found the parity comment interesting, along with the statement that when gluocorticoids are combined with prolactin, cells grow more slowly. Glucocorticoids are involved in milk synthesis, so this pretty much explains why lactation would not be a risky state. From the primary article again: "This study has several limitations. First, several forms of prolactin circulate in human plasma, which appear to have different biological activities (45 , 46) . The immunoassay used in this study, which identify most prolactin isoforms (47) , cannot distinguish between them. Therefore, we cannot isolate which isoform or isoforms are most important in breast cancer development." ***All in all, this was interesting and I gleaned some info. They note that pregnancy (parity, from citation 2) is related to lower prolactin concentrations later in life. But then they also acknowledge that the immunoassay for prolactin receptor could not distinguish between types of receptors, which could also play a huge role in how things can go wrong and prolactin start feeding a cancer. Prolactin has a cross-over influence with estrogen, which often does mediate cancer growth. The bottom line is that there is more to the picture than just the finding of higher prolactin levels among cancer patients. Lactation, generally speaking, does not pose the risk; something going wrong with the normal phyisiology is the issue. But you are right; someone reading this uncritically could jump to conclusions. Lisa Marasco MA IBCLc *********************************************** Archives: http://community.lsoft.com/archives/LACTNET.html Mail all commands to [log in to unmask] To temporarily stop your subscription: set lactnet nomail To start it again: set lactnet mail (or [log in to unmask]) To unsubscribe: unsubscribe lactnet or ([log in to unmask]) To reach list owners: [log in to unmask]