May 2013 Ask the Expert: Understanding Hormonal Therapy

May 1, 2013

During the month of May, Living Beyond Breast Cancer expert Vijayakrishna K. Gadi, MD, PhD, answered your questions about what hormonal therapyinfo-icon is, how it works to treat breast cancer and reduce your risk of recurrenceinfo-icon, and how possible side effects may impact your day-to-day life.

Question: I have been on tamoxifen since November 2012. After being on it for about 3 weeks, I experienced joint pain and fatigue. I am taking fish oil capsules as suggested by my oncologist, but it doesn't help. I'm 59 and now feel like Iʼm 80 years old. Is this a common side effect? Do you have any suggestions for me? I am survivor of DCIS (stage 0), high grade, and am post-mastectomy.

Dr. Gadi: Because tamoxifeninfo-icon blocks the estrogen receptorinfo-icon in a number of tissues, including the joints, arthralgiainfo-icon, or pain in the joints, and accompanying fatigueinfo-icon are common symptoms experienced by many women.

In 2011, results of a study by Paul E. Goss, FRCP, MB BCH, PhD, of Harvard University, and his colleagues at several other major cancer centers were published in the New England Journal of Medicineinfo-icon. In the study, women at high risk of breast cancer (including women with a history of DCISinfo-icon who underwent a mastectomyinfo-icon but still retained the unaffected breast) were randomly assigned to receive a placeboinfo-icon (an inactive substance) or the medicine exemestaneinfo-icon (Aromasininfo-icon).

Exemestane is one of three aromatase inhibitors commercially available in the United States. These new medicines work by blocking the enzyme responsible for helping “pre-estrogens” become the active estrogeninfo-icon used by tissues. By lessening estrogen in the body, abnormalinfo-icon cells that lead to DCIS or even invasive cancerinfo-icon are essentially stopped in their tracks.

Not surprisingly, Dr. Gossʼs study showed that women who received exemestane instead of the placebo had substantially fewer breast cancer events. Moreover, side effects such as joint paininfo-icon were only slightly more common than observed with the placebo pill. You may want to inquire with your physicianinfo-icon if exemestane or similar medicines are an option for you.

Question: Does the joint pain associated with aromatase inhibitors (AIs) cause actual damage to the joints? For instance, does it CAUSE arthritis, or merely mimic arthritis pain?

Dr. Gadi: To the best of our knowledge, AIʼs do not cause arthritis, or actual joint destruction, but only cause joint paininfo-icon. However, it is not unreasonable to ask for an arthritis work-up by your physicianinfo-icon.

Diseases such as rheumatoid arthritis or osteoarthritis are extremely common and may co-occur with breast cancer. If you have honest-to-goodness arthritis, your doctor can provide more effective therapyinfo-icon to specifically address it.

Question: Is there any new evidence about which aromatase inhibitors are better than others, such as which lead to lower recurrence of breast cancer and fewer side effects?

Dr. Gadi: All three of the aromatase inhibitors appear to work equally effectively at preventing recurrenceinfo-icon as reported in numerous high-quality, large trials in people with breast cancer. Although in theory all three of the available agents work by blocking estrogeninfo-icon production, some women experience slightly different side effects depending on which agent their doctors give them.

Two medicines, anastrozoleinfo-icon (Arimidex) and letrozoleinfo-icon (Femarainfo-icon), share a similar chemical structure while the other, exemestaneinfo-icon (Aromasininfo-icon), has a distinct structure. If you have been prescribed one class of aromatase inhibitorinfo-icon (anastrazole, for example) and are having unacceptable side effects, consideration should be given to switching to exemestane to see if those side effects decrease.

Question: My time for hormonal therapy (Arimidex) is coming to an end. I don't know if this is good news or bad. Is there an advantage to have taken it for 5 years? Or am I now back to square one and as vulnerable to estrogen as I was when I started?

Dr. Gadi: You have substantially reduced the risk of recurrenceinfo-icon and the risk of forming a new breast cancer because you have taken 5 years of Arimidex. The current standard of careinfo-icon in medical oncologyinfo-icon in the United States is to provide 5 years of aromatase inhibitors (such as Arimidex) to prevent recurrence of invasive breast cancerinfo-icon. Even in women who complete 5 years of therapyinfo-icon, there are a small number who will have a recurrence later.

At the present time, it is not clear whether taking Arimidex for longer will prevent any of those recurrences from happening. I donʼt think you are back to square one for this reason. I will acknowledge the field is confusing, because studies exist that support taking 5 additional years of an aromatase inhibitorinfo-icon (if you have taken 5 years of tamoxifeninfo-icon already), or taking 10 years of tamoxifen instead of 5 years of tamoxifen alone.

Question: I have heard that side effects of Arimidex can include mood changes. Is this true? Could it cause sadness/depression? Might I feel better when I quit taking it – in other words, at the end of 5 years?

Dr. Gadi: Many women report mood alterations while on medicines such as Arimidex. However, it is controversial whether this reported side effectinfo-icon is truly caused by them.

Clinicalinfo-icon depressioninfo-icon and anxietyinfo-icon are extremely common following a breast cancer diagnosisinfo-icon and may last for several years. Please make sure that clinical depression is not the diagnosis at hand. That said, typically side effects that are caused by aromatase inhibitors generally improve soon after stopping the medicines.

Question: I have a local recurrence (returned after 15 years). I am estrogen receptor-positive. Will the medications work the same way as they would if it were a first breast cancer?

Dr. Gadi: Breast cancer reappearing in the same breast 15 years later may either be a recurrenceinfo-icon of the old cancer or a new breast cancer. In either event, it is possible that the same sorts of anti-estrogeninfo-icon therapies would work again. However, compared to 15 years ago, the present standard of careinfo-icon for the management of a woman with post-menopausal, hormoneinfo-icon-positive breast cancer is to offer an aromatase inhibitorinfo-icon (for example, Arimidex, Femarainfo-icon or Aromasininfo-icon) instead of tamoxifeninfo-icon, the prior standard. These newer medicines work fundamentally differently and may therefore work even if the cancer recurs 15 years after treatment with tamoxifen.

Question: The latest research results encourage women to take tamoxifen for 10 years, not 5 years. When will similar study results be available for anastrozole?

Dr. Gadi: I should first clarify that two separate trials recently presented at major breast cancer meetings suggest that women who take tamoxifeninfo-icon for 10 years as opposed to 5 years have a lower risk of breast cancer returning. Collectively, both studies suggest that for approximately every 30 women treated for 10 years as opposed to 5, one additional woman may have her recurrenceinfo-icon prevented. Another way to state this same information is that 29 women received treatment who would not benefit. Although the findings were considered statistically significantinfo-icon for survival, there were also certain harms that became more frequent with longer exposure to the drug (clots, endometrial cancer, etc.).

Although there is still interest in understanding whether 10 years’ use of drugs such as aromatase inhibitors will be better than just 5, these trials are large and still in active follow-up of participants. I doubt results will be available for many years to come. Moreover, in my personal opinion, they are unlikely to demonstrate much improvement over the studies that have been reported on the 10 years of tamoxifen use.

Question: With an estrogen-positive cancer diagnosis, if the tumor markers still rise after 2 years of hormone therapy treatment, would chemo and/or radiation be considered in case the breast cancer has turned into another cancer, such as bone cancer?

Dr. Gadi: Rising tumorinfo-icon markers in the setting of hormone therapyinfo-icon might suggest that the breast cancer will recur. However, as a rule we don’t try to treat patients with chemotherapyinfo-icon unless we can actually see disease on scans in other places such as bone or the visceral organs like the liver, lungs, brain, etc.

There is no guarantee that treating patients will improve their survival or outcomes, but there is a guarantee they will suffer the side effects. Perhaps the more prudent consideration is to switch around the anti-estrogeninfo-icon strategy. Such endocrine therapyinfo-icon has fewer serious side effects than chemotherapy and may result in decreasing tumor markers.

One final note for the sake of completeness is to be aware that tumor markers are not very specific for any one type of cancer. In other words, working up the abnormalinfo-icon lab findings should include seeing if there are other emergent cancers in places such as the ovaries or colon, for example, because these tumors may also produce tumor markers that are also made by breast cancer.

Question: Are there any updated hormone therapy treatments on the market that in combination lower tumor markers, other than Femara with Faslodex injections?

Dr. Gadi: Yes, one recent option is using aromatase inhibitors such as Aromasininfo-icon (exemestaneinfo-icon) with a new drug called Afinitor (everolimusinfo-icon). Afinitor is not quite chemotherapyinfo-icon and works in a precise manner to block pathways that make cancer cells resistant to hormonal therapyinfo-icon when used alone. A large clinical trialinfo-icon showed the effectiveness of this regimeninfo-icon compared with Aromasin alone in women with metastaticinfo-icon breast cancer and led to its FDAinfo-icon approval in 2012.

Question: Is there any trial that my sister can try for her cancer? She had breast cancer 15 years ago, and now it has metastasized to the lungs and ribs. She is currently on hormone treatment, but she is willing to participate in any study.

Dr. Gadi: There are numerous clinicalinfo-icon trials for breast cancer in this country and others. The single best way to find out about trials is to visit the National Cancer Instituteinfo-icon’s website at Within the clinical trials section, there is a searchable database for all open trials around the world based on specific tumorinfo-icon type and locations of the various trials. Very detailed information about your sister’s case can be entered in the query field, and several results will be returned.

I, other investigators and patients cannot thank your sister enough for considering participating in research. It’s the only way we will ever get to a point where women don’t die of this disease anymore.