Hormone replacement after breast cancer

Hormone replacement therapy (HRT) is a major area of concern among women with a history of breast cancer. If you are in the crisis of a recent breast cancer diagnosis, the issue of HRT may seem relatively unimportant. However, as you get farther along and finish your treatment and proceed with your life, questions regarding HRT will certainly arise. I include this chapter here for you to review when you are ready.

Much has been written on the issue of HRT in general. Less is known specifically about HRT for breast cancer survivors because doctors have been concerned about prescribing anything for their patients that may increase the risk of recurrent disease. However, new research suggest this traditional tendency not to prescribe HRT for breast cancer survivors needs to be reevaluated. But, along with this, I must say blanket statements regarding HRT are not appropriate. Each individual woman must consider the risks and benefits of HRT based on her personal situation. Each woman experiences menopause differently, with varying degrees of symptoms. Some women ease into menopause with little problem and without increased risk of osteoporosis or heart disease. The menopause experience for others is traumatic and can introduce increased chances of illness into their lives.

The medical profession has endorsed allowing women to replace ovarian hormones with HRT once the ovaries begin to fail. Evidence and clinical experience indicate that the benefits clearly outweigh the risks and expense of such therapy. However, we do not have evidence of the risks to women surviving breast cancer. Our concerns are based on speculation and anecdotal experience alone.

For most women, the question is the relationship between HRT and an increased risk of breast cancer. Does hormone replacement contribute to breast cancer? At least 24 different studies and two meta-analyses (combining similar small studies to give greater statistical power) fail to show a causal relationship between the two. Researchers found no difference in breast cancer incidence for those women taking HRT and those women who did not in studies that controlled mammographic screening. Before starting HRT, physicians often requires their patients to get a baseline screening mammogram, and because women receiving HRT are under a physician’s surveillance, they are more likely to continue to get annual screenings. These women detect early cancer years before women not on HRT, who are less likely to get mammograms. If a researcher looks at breast cancer incidence over a short span of time, he/she may incorrectly conclude that HRT is responsible for an increased number of breast cancer incidence over a short span of time, he/she may incorrectly conclude that HRT is responsible for an increased number of breast cancers when it is actually a case of early detection due to regular mammographic screening. Although there is no difference between women not taking HRT and those taking HRT for less than ten years, once the duration exceeds the ten-year mark, there is a slight increase in breast cancer incidence, but the numbers are small. There also appears to be anecdotal data that women with lobular neoplasia, either lobular cancer in situ (LCIS) or atypical lobular hyperplasia, may have an increased risk for recurrence with HRT. As we discussed previously, however, these women are at an increased risk regardless of hormone replacement usage.

Research has led us to conclude that low-dose HRT for less than ten years does not significantly contribute to the development of breast cancer in the general population. Does this apply to the population of women cured of breast cancer? Unfortunately, there are no studies to tell us this, and we do not know the answer. My own opinion is that for women with a high probability of cure, the benefits of HRT outweigh the risks.

How do you know you are cured, however? Unfortunately, there is no absolute way to know. We can give a statistical probability based on your cancer’s characteristics. If you are destined to relapse, it will usually happen in the first five years after diagnosis. Unfortunately, late recurrence do rarely occur. I advice my patients that once treatment is complete, they should consider themselves cured and move on. Granted, they are never the same there is that “gray cloud on the horizon,” but they become smaller as time passes.

Women often ask me, “But what if I’m not cured? Can HRT cause increased harm?” I don’t know the answer to this, either. Theoretically, HRT could stimulate cells that have escaped systematically and stimulate them to grow and appear more rapidly. On the other hand, if this were to happen, tamoxifen or one of the newer hormonal therapies should then make the cancer regress.

We have only roundabout evidence regarding HRT in breast cancer survivors. For example, we know that younger women who have had breast cancer and then go on to become pregnant, with the associated high levels of estrogen and progesterone, do not have a worse prognosis or earlier relapse of breast cancer than women who do not experience a pregnancy. If estrogen can theoretically stimulate breast cancer growth, why do we see breast cancer appear in older post menopausal women who are not on HRT? This is a fairly frequent occurrence, and most of these cancers are hormone receptor positive, yet they are growing in an estrogen-poor environment. This seems to counter what we know about the environment that is conducive to breast cancer, but this is just another reminder of how much we do not understand about this disease.

In most cases, if a young premenopausal women with hormones receptor positive breast cancer is given tamoxifen, the cancer will get smaller and regress. At the same time, the tamoxifen will cause the woman’s blood estrogen levels to increase. The cancer must have a higher affinity to tamoxifen than to estrogen in order for the drug to be effective. In spite of high estrogen levels, the tamoxifen works to kill the cancer. It is then possible to give both HRT and tamoxifen together and get the benefits of each?

Doctors have prescribed this dual treatment in the United Kingdom without reported ill effects, but American oncologists have been very hesitant to do this routinely without longer experience to assess risk of HRT plus tamoxifen versus tamoxifen alone versus no hormonal treatment. Such a trial, unfortunately, would take a large numbers of women, “arm,” or protocol. That has yet to be done. Researchers are also diligently working on new SERMs that are less stimulatory to the uterus and may potentially relieve menopausal symptoms while maintaining the ability to kill cancer cells. If such a new drug is found, there will be no need to administer both HRT and tamoxifen.

Let’s put the theoretical data to work for us and look at what to do with the information at hands. Are the benefits of HRT for the breast cancer survivors adequate to outweigh the theoretical risks? This is obviously not an easy question, and each individual woman’s situation is quite different in regard to it. Some factors for you to consider are your

•  risk of recurrence

•  type of breast cancer (presence of lobular neoplasis and hormone receptors)

•  risk of heart disease

• cholesterol and lipoprotein levels

•  risk of osteoporosis

•  bone mineral density

•  risk of uterine cancer

• quality-of-like issues (libido, vaginal atrophy, hot flashes, depression, memory loss)

• risk of Alzheimer’s disease (Some recent intriguing reports indicate)

That HRT may prevent Alzheimer’s. Although very preliminary, this new information perhaps should also be factored into the equation).

I suggest you meet  with your oncologist and discuss the risks and benefits of HRT in your individual situation based on the above factors. If you and your doctor make the joint decision that you take HRT, the question then becomes whether there is one preparation that is better than another.

Here again, we face the problem of lack of evidence and controlled studies as we make these decisions. The literature indicates that different estrogen preparations stimulates the ductal glandular tissue to varying degrees. Estradiol is much more stimulatory than estriol. The most commonly used preparation, Premarin, is primarily estriol and appears to benefit bones and lower cholesterol. The unanswered question is, what is the benefit of adding tamoxifen to HRT? For women who have a uterus, the addition of low-dose progesterone appears to protect against uterine cancer.

A new SERM, raloxifene hydrochloride (Evista), has been approved in the United States for the treatment of osteoporosis, Raloxifene does not appear to stimulate the uterine lining, nor does it appear to stimulate breast glandular tissue to activate.

Presently, it is being tested against tamoxifen as a breast cancer prevention therapy. Breast cancer survivors who have completed therapy and are concerned about osteoporosis and heart disease might consider raloxifene hydrochloride as an alternative to HRT. Unfortunately raloxifene hydrochloride does not usually alleviate menopausal symptoms such as hot flashes and vaginal dryness. This is something you should discuss with your oncologist. As I mentioned earlier, the pharmaceutical industry is striving to produce the “perfect” SERM. Until then, one must weigh the risks and benefits of what is available.