My main role is to go around all of the hospitals in our area and check on our oncology and hematology patients for our institute. However, I have been also filling in for nurse practitioners at various oncology offices in our city when they are out of town, on vacation, sick, etc. I have really enjoyed the variety and movement within my institute and the chance to meet the team -- physicians and patients.
Recently, I have frequently found myself with two physicians who specialize in breast cancer. It has been a great experience. I have been involved in the continuum of care from pre-diagnosis to maintenance.
One complaint I have been hearing from many of the breast cancer patients who are hormone receptor positive is the increase in joint pain once they are started on an aromatase inhibitor (AI). As we know, AIs are indicated in postmenopausal women only. A woman who is premenopausal would use tamoxifen instead unless she has had a total hysterectomy; then tamoxifen could be used at any age if the patient could not tolerate AIs.
One of the physicians told me one day that the joint pain increase seems to vary depending on the AI used. In our busy day, I did not have a chance to ask her why this was the case, so I decided to research it on my own. I believe I found some reasons, and I wanted to share them with my peers in TheONC.
The doctor shared with me this list of AIs, ranked from highest to lowest incidence of joint pain:
- Femara (Letrozole)
- Arimidex (Anastrozole)
- Aromasin (Exemestane)
- Tamoxifen (which is not an AI but has an estrogen agonist and antagonist activities)
I remember lists like this one better with acronyms, so I use FAAT to remember the medications most likely and least likely to cause joint pain. I remember that Aromasin is toward the low end and almost last in the row (as in the "ro" in Aromasin). Can you tell I have taken one too many exams and certification tests in my life?
I also learned that Femara has the highest concentration of all the AIs. Therefore its effect will likely be felt more than the other AIs. I also learned that Femara and Arimidex are nonsteriodal competitive inhibitors, whereas Aromasin is an irreversible, steroidal aromatase inactivator. I am guessing this is also going to make a difference in the level of joint pain experienced by some.
This was nicely summarized in a chart I found on UpToDate for AIs.
| Generation |
Steroidal (type 1) |
Nonsteroidal (type 2) |
| First (nonselective) |
---- |
Aminoglutethimide |
| Second (selective) |
Formestane |
Fadrozole |
| Third (superselective) |
Exemestane (Aromasin) |
Anastrozole (Arimidex) |
| ---- |
---- |
Letrozole (Femara) |
AIs are well known to be associated with musculoskeletal side effects, especially when compared to tamoxifen. This side effect alone is responsible for more than 10-20 percent of all patients discontinuing the use of AIs. Again, the exact mechanism is unknown, but research suggests that decreased estrogen levels may play a role. Also, if a patient were obese or had prior chemotherapy or a preexisting musculoskeletal history or disorder, the joint symptoms would tend to occur more frequently than they would in patients who were not obese, had no prior history of musculoskeletal issues, and were chemotherapy-naïve.
Other possible long-term complications include an increased risk for osteoporosis and fractures. The use of Zometa and other medications to combat this bone loss effect can also add to the joint pain experienced with the use of both.
I compared the reported incidence of joint pain and/or arthralgias side effects for each medication. Here is what I found.
- Femara (Letrozole): 5-25 percent
- Arimidex (Anastrozole): 2-15 percent
- Aromasin (Exemestane): 9-29 percent
- Tamoxifen: 6-11 percent
With hormone receptor positive-type breast cancer making up more than 75 percent of all breast cancers, this is an important piece of information for those using any of these medications in their treatment regimen.
Have any of your patients shared the difference in joint pain experienced among the different medications? If so, which medication produced the least amount of joint pain? What remedies have they tried to lessen the side effects?
Reference:
- Pritchard, K.I., Hayes, D.F. & Dizon, D.S. (2012). Adjuvant endocrine therapy for hormone receptor-positive breast cancer. Available at http://www.uptodate.com/contents/adjuvant-endocrine-therapy-for-hormone-receptor-positive-breast-cancer.
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