The study below is included  for three reasons:

Title:  Effects of sex steroids on proliferation in normal mammary tissue. 
Author:   Söderqvist G 
Address:  Department of Woman and Child Health, Karolinska Hospital,  Stockholm, Sweden. [email protected] 
Source:   Ann Med, 1998 Dec, 30:6, 511-24 
Abstract:   Numerous women are treated with a combination of oestrogen and progestogen for contraception and hormone replacement therapy worldwide. A possible increased risk of cancer in target organs has been discussed vividly for many years. While oestrogens are clearly mitogenic for breast epithelial cells, there has been considerable uncertainty about the effects of progestogens. This article reviews current knowledge on this field, including our own data. Oestrogen receptors are down-regulated during the luteal phase, while progesterone receptors remain at a high level throughout the menstrual cycle. According to most studies, in vivo proliferation of normal breast epithelial cells is higher during the luteal phase in the vast majority of women. Normal breast tissue can convert oestrone sulphate to oestradiol. A negative correlation between the levels of circulating oestradiol and the enzyme converting oestrone into oestradiol suggests a local regulatory mechanism of tissue oestradiol formation. Serum progesterone levels correlate positively with sulphatase activity while 19-norsteroid progestogens may be inhibitory. We found that long-term continuous combined hormonal treatment with conjugated equine oestrogens and medroxyprogesterone acetate induced a proliferative response in the breasts of surgically postmenopausal macaques. The effect of combined treatment was more pronounced than that of oestrogen treatment alone. Both endogenous progesterone and exogenous progestogens increase proliferation of breast epithelial cells. Exogenous progestogens down-regulate both oestrogen and progesterone receptors. Oestrogen and progestogens may have both direct and indirect stimulating effects on proliferation. The finding of a positive correlation between insulin-like growth factor I messenger RNA and proliferation found in hormonally treated women with low receptor levels suggests the possibility of nonreceptor-mediated effects of sex steroids on proliferation, which needs to be investigated further. 
Language of Publication:  English 
Unique Identifier:  99117080 

I am a research paper illiterate.  Does this article say that combined hormone replacement on surgically menopausal women causes malignant breast cell growth?     Please summarize, if possible.

With only the abstract that's a daunting task, but I'll give it a shot. There are a lot of caveats here that you need to pay careful attention to.

First - the study is done in macaques ( kind of primate)  who were made menopausal through (presumably) castration. Women aren't macaques and intact women are the only ones (normally) who are prescribed combined continuous hormone "therapy."  So women who are candidates for these drugs have some estrogen of their own and testosterone which are produced by the ovaries after menopause. So we may be talking about a different hormonal milieu in addition to the difference in species.

Second -  there's no information about dosage so I don't know whether these effects were produced by the same kind of serum levels used in women or whether they were using huge doses. That's also important to remember. The macaque study used a combined continuous hormone regimen. That means both drugs given every day.  This abstract says little about cyclic regimens where premarin is used for 21 days and provera for 10 or 12. 

Third  - I don't know how long "long term" is as the word is used in the abstract,  or what it would translate into in human terms.

Fourth -  The abstract doesn't supply numbers which is crucial. If there were only 5 macaques then the results are not particularly meaningful. The abstract does refer to 'other work in this area' so that might increase its significance.

Okay

The researchers discuss the various types of hormone receptors in the breast and write that the uncertainty in the equation is what progesterone or synthetic progestins  do to the proliferation of tissue in the breast. It's generally accepted that increased cell growth is a risk factor for cancer since the possibility of malignant changes in cells is most likely during times when they are reproducing quickly. Therefore anything that encourages proliferation of breast tissue is suspected of causing breast cancer or of encouraging its spread.  Estrogen is known to encourage proliferation, and has also been implicated in actually changing DNA and causing cancer that way. The effect of progesterone or synthetic progestins is less certain. The researchers stipulate that they are studying both endogenous (produced within the body) progesterone and synthetic progestins. The endogenous progesterone part of the article must refer to something other than the macaque study since they've been castrated and have no or very little endogenous progesterone. 

These researchers found that combined continuous administration of the drugs found in prempro or premphase  - specifically premarin and provera - causeed increased growth of breast tissue cells over the long term in these surgically altered animals. This may have implications for the use of these drugs over the long term in post menopausal women - i.e. using these drugs in this manner might cause increased cell division and eventually breast cancer in women over time. They attribute this effect to both direct and non-direct stimulation of proliferation. They may do this through changes in RNA (direct) and through changes in the number of hormone receptors in the breast.(indirect).

Comment here (by Terri)
 I *think* that dangers found in animal studies are more significant than benefits found in those studies.  I think these dangers are especially significant when they are found in drugs intended for preventative use rather than to cure an existing disease. That's *opinion* not fact. It's a prejudice of mine that I think should be stated up front.  It may or may not be valid: there are certainly many who believe differently.

I don't know if this is of any benefit or not, but it's my best shot.

Terri