(Remember, what follows is the result of my search for answers as just another HysterSister, not a medical professional. This is the first part. The second part will go into assessing risk and steps to take to minimize risk.)
As Dr. Susan Love, a breast cancer surgeon and researcher, says, "The problem with breast cancer is that we don't fully understand it." However, it's fairly clear that HRT increases the risk of getting breast cancer, but it's a relatively small increase in risk. As the Mayo Clinic Health Oasis says, "an average woman with no other risks for breast cancer has approximately a 12% chance, or absolute risk, of getting breast cancer in her lifetime. If she takes combination HRT, her absolute risk would increase to a little over 15%." But that small difference might be significant if you 've got a lot of other risks for breast cancer. Other factors, some of them controllable (for instance, exercise, overweight, and alcohol consumption) raise the risk by much more than even combined HRT does (see Part II of this article, coming soon).
What's not clear at all is how the risks of taking or not taking HRT compare for a woman in surgical menopause.
Breast Cancers
The word "cancer" has to be plural here because there are at least three kinds of hormone-dependent breast cancers and two kinds of hormone-independent cancer. So, there are many causes and different risks.
But, when worrying about HRT, it's the hormone-dependent cancers that bother us. Weirdly enough, even these aren't as straightforward as they seem because pregnancy, with its flood of hormones, does not increase breast cancer.
The trouble actually seems to start in a woman's teens and twenties. The mammary gland, unlike other organs, isn't developed at birth. What the breast cells have are estrogen and progesterone receptors. So when estrogen and progesterone show up at puberty, the breast cells know to divide and change, but the receptors stay in the breast cells and the signal to divide and change can go wrong.
The lesion that will become breast cancer can form quite early. That's why some of the known risk factors involve adolescence--starting menstruation before the age of 11, rapid growth during adolescence (becoming tall), being lean at age 10, not having a baby until after 30 or even at all. They also suspect that smoking and drinking alcohol and not getting enough fruit and vegetables in adolescence may contribute to forming the tiny lesions that will eventually turn into cancer. That's why age alone is such a risk factor. The longer you live, the longer the time that the lesion has to become cancer. When they talk about lifetime risk, they're talking about the risk by age 90.
HRT and Risk
So, apparently, HRT brings the cancer to light sooner, but it doesn't actually "cause" it. Obviously, hormones affect hormone-dependent breast cancer, but it's the length of time that makes a difference.
For women who take HRT after natural menopause, there is no increase in risk for the first five (or so) years of taking HRT. But after 10 years of HRT, there starts to be a difference between users and non-users. Around age 60, after natural menopause with no HRT, 77 women out of 1,000 will get breast cancer. At the same age after 10 years of taking HRT, 83 women out of 1,000 will get breast cancer. After 15 years of HRT the gap gets even wider. Around age 75, without HRT, 77 women per 1,000 will get it. At 75, with 15 years of HRT, 89 out of 1,000 will get breast cancer.
But, as Dr. Ronald Barentsen points out when talking about natural menopause, these statistics don't take into account when menopause occurs. To calculate risk, one would have to take into account both the estrogen you make yourself (endogenous) and the estrogen that you get from HRT (exogenous). So, as Dr. Barentsen says, a woman who hits natural menopause at 50 probably has 15 years before the risk starts to climb and a woman who hits natural menopause at 55 has 10 years before the risk climbs. He was just speculating from available information (nothing was proven scientifically), but I'm glad to have someone express the theory that some of us have had about surgical menopause. It's the total exposure to endogenous and exogenous estrogen that needs to be taken into account--and since we have very little endogenous estrogen, the number of years of HRT use before the risk increases needs to be recalculated for us.
It's also reassuring that, if you decide to stop HRT, the risk of breast cancer drops to normal five years after stopping HRT.
Prognosis for HRT Users
Though there is a slowly increasing risk of getting breast cancer while taking HRT, women who get it while taking HRT seem to be more easily cured. Their cancer is more localized, is caught earlier, and is more responsive to the drugs they have now to fight cancer with. The researchers aren't sure why. It could just be that women who take HRT do their monthly breast self-exams regularly, get mammograms more regularly, and generally take better care of themselves, but it could be the kind of cancer affected by HRT. While one large recent study in the British Medical Journal found that HRT made no difference in prognosis, a 1999 JAMA article concluded that, except for one particular kind of cancer, the types of breast cancer that women get while taking HRT are less aggressive and so more treatable. The researchers will know more about all this in 2006 when the results of a big study called the Women's Health Initiative start to be published.
If your risk of breast cancer is very high, as after genetic testing, then having an oopherectomy and taking no HRT does drop your risk down.
Which Hormones Do What?
So which hormones actually affect hormone-dependent cancers?
There was one study that applied a wide range of hormones to three kinds of cells in test tubes--benign breast cells, atypical nonmalignant breast cells, and one kind of malignant breast cancer cells. In the test tube, the estrogens tested (17 beta-estradiol, estriol), prolactin, and growth hormone all stimulated the growth of normal cells more frequently than the growth of malignant cells. Testosterone and hydrocortisone stimulated malignant cells more frequently than normal cells. And progesterone stimulated the growth of cells from malignant specimens but not the growth of cells from normal and nonmalignant atypical samples.
In women (as opposed to test tubes) with breast cancer, it's noticeable that, in some kinds of cancer, huge quantities of estrone sulfate (the kind of estrogen manufactured in body fat) and estradiol sulfate, as well as a significant increase in progesterone receptors, are found in their breast tissues. Other studies have shown that women with breast cancer have the highest levels of DHEA. And testosterone also is a likely culprit.
Estriol
Estriol has been proposed as a form of estrogen that's better because it is rapidly eliminated from the body and because it can't convert to estradiol. In animal (ok, rat) studies, estriol shows very little carcinogenic activity until it's given in large doses. It also doesn't break down into carcinogenic types of estrogen as often as estradiol does (though a few of estriol's conjugates are perfect fits in breast cancer cell receptors). In one small study of Japanese women taking estriol for a year, there was no change in their breast ultrasounds, but there was also no apparent effect on their bone mass or plasma lipids either. A review of 47 studies of estriol concluded that it is milder (and less likely to create high blood pressure) but still stimulates breast tissue. So, while estriol is an option, it shouldn't be relied on as something that eliminates risk.
Progesterone
Progesterone also has been touted as a preventative hormone, but that too is a murky picture. As an article in the International Journal of Fertility and Women's Health in 1998 said, "both proliferation and inhibition have been observed with various progestational agents." In other words, it makes some breast cancers worse and some cancers better.
In January 2000, an article appeared in JAMA that grabbed headlines saying that taking progestin with estrogen increased the risk of breast cancer. Women (in natural menopause) in the study who took estrogen alone had a 1% per year increase in the risk of getting breast cancer. Women taking estrogen and Provera together had an 8% per year increase. However, the increase in risk was for women who were lean. And even for them there was virtually no risk for four years. It's also been argued that some of the numbers in the study might not really add up (the statistical tests are marginal)..
The reason that they say "progestational agents" and "progestins" is that, for most studies, they are not using bio-identical progesterone but rather something like Provera. The one large study that has really compared Provera and bio-identical progesterone, the PEPI study, unfortunately wasn't studying breast cancer. But they did compare changes in breast density, which is a risk factor for breast cancer. For all kinds of HRT, breast density increased. And, as in the notorious JAMA article, combined estrogen/progestegen treatment increased it even more. However, bio-identical progesterone increased the density less than the Provera did.
Conclusion
So, here's the big picture that I end up with. All of the studies have been done on natural menopause, not surgical menopause. And what they've found is that there is no significant increase in risk for the first 5 years, then there is a small steady increase in risk every year. Since the risk is tied to total lifetime exposure to hormones, for women in surgical menopause, it takes longer for risk to increase, especially if the HRT is a low dose. A woman in natural menopause with no HRT has a 12% lifetime risk of getting breast cancer and a woman in natural menopause who takes estrogen/progesterone for more than 10 years has a 15% lifetime risk, a relatively small increase in risk.
So it really depends on what your other risk factors are. If you have a high risk of osteoporosis, then HRT is probably a good choice. For the average woman, your risk of dying from a broken hip is higher than your risk of dying from cancer. For heart disease, the picture is less clear. If you have no pre-existing heart conditions, there seems to be a lot of long-term protection (and some short-term risk) from HRT. If you have a high family risk of breast cancer, don't exercise, are very overweight, drink a lot of alcohol, got your period before age 11, and had no children or first child after 30, then your risk profile for breast cancer is higher. So, all told, HRT alone makes a slowly increasing difference in risk, but sometimes that is all the difference that matters.
Good News
So, I thought I'd end with the most hopeful news I've encountered in the current research. It seems that scientists are close to developing a test for breast cancer that can catch it as early as a Pap test can catch cervical cancer, when the tiny lurking lesions are just a few cells starting to become abnormal. Most breast cancers begin in the milk ducts, and what they're developing is a minor painless (ok, they call it painless) procedure to collect cells from the ducts. This procedure would catch breast cancer 10 years before a mammogram could find it. And the treatment options would be very different than they are today. And catching breast cancer that early would make all the difference in the world.
This content was written by staff of HysterSisters.com by non-medical professionals based on discussions, resources and input from other patients for the purpose of patient-to-patient support.
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