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

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