May 2013 Ask the Expert: Understanding Hormonal Therapy
Dr. Gadi: Because tamoxifen blocks the estrogen receptor in a number of tissues, including the joints, arthralgia, or pain in the joints, and accompanying fatigue 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 Medicine. In the study, women at high risk of breast cancer (including women with a history of DCIS who underwent a mastectomy but still retained the unaffected breast) were randomly assigned to receive a placebo (an inactive substance) or the medicine exemestane (Aromasin).
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 estrogen used by tissues. By lessening estrogen in the body, abnormal cells that lead to DCIS or even invasive cancer 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 pain were only slightly more common than observed with the placebo pill. You may want to inquire with your physician if exemestane or similar medicines are an option for you.
Dr. Gadi: To the best of our knowledge, AIʼs do not cause arthritis, or actual joint destruction, but only cause joint pain. However, it is not unreasonable to ask for an arthritis work-up by your physician.
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 therapy to specifically address it.
Dr. Gadi: All three of the aromatase inhibitors appear to work equally effectively at preventing recurrence 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 estrogen production, some women experience slightly different side effects depending on which agent their doctors give them.
Two medicines, anastrozole (Arimidex) and letrozole (Femara), share a similar chemical structure while the other, exemestane (Aromasin), has a distinct structure. If you have been prescribed one class of aromatase inhibitor (anastrazole, for example) and are having unacceptable side effects, consideration should be given to switching to exemestane to see if those side effects decrease.
Dr. Gadi: You have substantially reduced the risk of recurrence and the risk of forming a new breast cancer because you have taken 5 years of Arimidex. The current standard of care in medical oncology in the United States is to provide 5 years of aromatase inhibitors (such as Arimidex) to prevent recurrence of invasive breast cancer. Even in women who complete 5 years of therapy, 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 inhibitor (if you have taken 5 years of tamoxifen already), or taking 10 years of tamoxifen instead of 5 years of tamoxifen alone.
Dr. Gadi: Many women report mood alterations while on medicines such as Arimidex. However, it is controversial whether this reported side effect is truly caused by them.
Clinical depression and anxiety are extremely common following a breast cancer diagnosis 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.
Dr. Gadi: Breast cancer reappearing in the same breast 15 years later may either be a recurrence of the old cancer or a new breast cancer. In either event, it is possible that the same sorts of anti-estrogen therapies would work again. However, compared to 15 years ago, the present standard of care for the management of a woman with post-menopausal, hormone-positive breast cancer is to offer an aromatase inhibitor (for example, Arimidex, Femara or Aromasin) instead of tamoxifen, the prior standard. These newer medicines work fundamentally differently and may therefore work even if the cancer recurs 15 years after treatment with tamoxifen.
Dr. Gadi: I should first clarify that two separate trials recently presented at major breast cancer meetings suggest that women who take tamoxifen 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 recurrence prevented. Another way to state this same information is that 29 women received treatment who would not benefit. Although the findings were considered statistically significant 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.
Dr. Gadi: Rising tumor markers in the setting of hormone therapy might suggest that the breast cancer will recur. However, as a rule we don’t try to treat patients with chemotherapy 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-estrogen strategy. Such endocrine therapy 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 abnormal 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.
Dr. Gadi: Yes, one recent option is using aromatase inhibitors such as Aromasin (exemestane) with a new drug called Afinitor (everolimus). Afinitor is not quite chemotherapy and works in a precise manner to block pathways that make cancer cells resistant to hormonal therapy when used alone. A large clinical trial showed the effectiveness of this regimen compared with Aromasin alone in women with metastatic breast cancer and led to its FDA approval in 2012.
Dr. Gadi: There are numerous clinical trials for breast cancer in this country and others. The single best way to find out about trials is to visit the National Cancer Institute’s website at cancer.gov. Within the clinical trials section, there is a searchable database for all open trials around the world based on specific tumor 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.