FAQs about Antihormonal Therapy

This content has been reviewed and approved by

William J. Gradishar, MD FACP
Director, Breast Medical Oncology, Professor of Medicine
Robert H. Lurie Comprehensive Cancer Center
Northwestern University Feinberg School of Medicine

Duration

 
What is the optimal duration for antihormonal therapy?

That depends on your situation. If you have advanced breast cancer and this therapy is being used to keep the disease under control and palliate symptoms, then you will be on it for an indefinite length of time until your oncologist believes that it is no longer working. Beyond that, you may be switched to another antihormonal therapy.

If this is already your second, third, or fourth line therapy, or if your tumor is believed to be growing rapidly, you may be switched to chemotherapy. However, if antihormonal therapy is being given in the curative setting for early stage breast cancer, then the choice of therapy depends on whether you are under 50 and still menstruating or you have already had your menopause (generally older than 50.) For younger, premenopausal women still able to menstruate, tamoxifen is the most common choice for antihormonal therapy in the United States, alternatively shutting off the ovarian function can be considered.

In postmenopausal women, however, there are three options: (1) To start with tamoxifen and switch in the after 2 to 3 years of treatment to an aromatase inhibitor; (2) give tamoxifen for 5 years and then switch to an aromatase inhibitor for another 5 years; or (3) start an aromatase inhibitor immediately and give that for 5 years.

Currently, research is looking at the worth of continuing an aromatase inhibitor beyond the tenth year of therapy. There is some evidence that starting an aromatase inhibitor, even if you have finished 5 years of tamoxifen within the last 2 to 3 years, is also of some benefit. It is also being examined whether switching from tamoxifen to an aromatase inhibitor in the third year of use is as good as the opposite sequence, that is, switch from an aromatase inhibitor to tamoxifen.

Although all of these questions are being studied, a general consensus is emerging that 5 years of antihormonal therapy may not be optimal, and longer duration of treatment may render additional benefit. Only the completion of clinical trials addressing these issues will answer these questions. You should discuss this with your oncologist as every treatment has its side effects, cost, and convenience issues that need to be taken into account for an individual patient.

Both of these approaches have been looked at in the postoperative setting in hormone receptor-positive women who have already undergone menopause. Both of these approaches are superior to just taking tamoxifen for 5 years. You may have options based on your personal preference, status of your bone health, or your concern about it, and the cost of therapy. 

The sequence of switching from tamoxifen to an aromatase inhibitor, such as letrozole, Arimidex^® (anastrozole), or Aromasin^® (exemestane), versus the opposite sequential approach is currently the subject of clinical trials. We do not know the answer to this question. What seems likely is that 5 years of antihormonal therapy in postmenopausal women may not be optimal and longer duration might be better, but there is no conclusive evidence to date. You should discuss this with your oncologist. 

Options

Which antihormonal therapy is the best for me?

Only your oncologist can decide what treatment is best for you by taking your whole situation into account. For example, the recommendation will vary by whether you are receiving treatment for cancer that is being treated early in the curative setting or late when it has already spread to some other part of the body (such as bone), and is being treated to palliate symptoms and prolong survival.

It will also depend on whether you are young and still able to have your periods or are older and have already undergone menopause. It will also depend on how good your bone health is and what other medical conditions you might have. You ask an extremely important question and one that needs to be discussed in great depth with your oncologist to make an informed decision.

First let me clarify that they may not always be taken "instead of tamoxifen"; you may have the option to use them "in addition to tamoxifen" (in sequence, but not together). The pills you have heard about are a different class of drugs called aromatase inhibitors. Aromatase is an enzyme in the fatty tissue of the body that is the primary source for production of estrogen in women who have already undergone menopause (unlike younger women who make the female hormone estrogen from their ovaries.)

Older women convert hormone from their adrenal glands to estrogen in their fatty tissue with the help of this enzyme aromatase. These pills Aromasin^® (exemestane), Arimidex^® (anastrozole), and Femara^® (letrozole) block the activity of this enzyme and create a very low estrogen environment in your body thus starving your breast cancer cells of estrogen resulting in their demise. All three drugs have been shown to be superior to tamoxifen in various settings. It has, however, also been shown that switching to these drugs after 2 to 3 years or 5 years of use of tamoxifen is superior to 5 years of tamoxifen alone. It remains unclear that one aromatase inhibitor is superior to another.

It really depends on the reason for this advice. If this is being advised as antihormonal therapy for breast cancer, there is evidence in the literature that it might help. However, your other treatment choice might be to take tamoxifen.

If this in the context of decreasing your risk of developing ovarian cancer because you are positive for one of the breast cancer susceptibility genes (such as BRCA1 or BRCA2), then that has whole different connotations. You should discuss this in more detail with your physician and talk to a genetic counselor as well. There are blood tests available to look for BRCA1 and BRCA2 gene, and you should ask if you have been tested or if you are a appropriate candidate to undergo this testing.

Your doctor is perhaps making this recommendation in light of recent data reported in December of 2005 from the original study evaluating letrozole following 5 years of tamoxifen therapy. This additional data showed that women who switched to letrozole from the placebo arm of the study—as the positive results became available 2½ years after their randomization to placebo or letrozole after 5 years of tamoxifen—seemed to be doing better in terms of their disease-free survival, contralateral breast cancer rates, and overall survival when compared with those who chose not to take letrozole.

Oncotype DX

My doctor is not sure if I should receive chemotherapy because I have an axillary node-negative, 2-centimeter tumor that is antihormonal receptor-positive. He wants to do a test on the tumor to help make the decision. Have you heard of such a test?

There is now a test called Oncotype DX by Genomic Health that can separate patients with hormone receptor-positive, node-negative breast cancer who will receive adjuvant tamoxifen into low-, intermediate-, and high-risk categories for the likelihood of cancer recurring at distant (metastatic) sites 10 years in the future.

A low-risk patient has only about a 6 percent risk of cancer recurrence and a high-risk patient may have greater than 30 percent risk of the same. Such information can be helpful to you and your physician to make the decision about chemotherapy. However, if you have other worrisome features in your tumor that can guide you towards the decision or you are already strongly in favor of, or strongly against receiving chemotherapy, then the result of this test may not turn out to be very helpful. You should ask your physician whether this test will really make a difference in decision making and proceed accordingly.

Osteoporosis

I have been told about the increased risk of fractures if I take any of the aromatase inhibitors. Is there anything I can do to decrease that risk?

That is a very important question because aromatase inhibitors, such as Femara^® (letrozole), Arimidex^® (anastrozole), and Aromasin^® (exemestane) increase your risk of osteoporosis (thinning of bones.) First and foremost, you should have a DEXA scan at baseline before starting these medications and then every year to assess your bone density.

You should be taking calcium and vitamin D. If you have significant osteoporosis, your doctor may recommend that you take intravenous bisphosphonate therapy with drugs such as Fosamax^® (alendronate) or Boniva^® (ibandronate) every month. Studies are being conducted to determine if intravenous bisphosphonate therapy every 3 to 6 months may maintain bone density. You should also maintain an active healthy lifestyle, which helps your bone health not to mention your overall health.

You should discuss that with your doctor, who will assess the degree of your osteoporosis and what measures you have already taken or not taken to help it. You still may be a candidate for aromatase inhibitor therapy based on those factors.