NEWS: Aromatase inhibitors linked to joint pain in breast-cancer patients

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Aromatase inhibitors linked to joint pain in breast-cancer patients



Sep 20, 2005



Janis

Boston, MA, and San Francisco, CA - The aromatase inhibitors have

revolutionized breast-cancer treatment by providing a more effective

alternative to tamoxifen. However, Drs T Felson (Boston

University, MA) and R Cummings (University of California, San

Francisco) point out in a review article in the September 2005 issue

of Arthritis & Rheumatism that (like other forms of estrogen

deprivation) these drugs are associated with significant levels of

arthralgias [1].

Felson tells rheumawire that in the breast-cancer clinical trials he

reviewed, " Women randomized to aromatase inhibitors consistently

showed higher rates of arthralgias than those randomized to placebo

or to tamoxifen. "

Estrogen deprivation affects inflammation, neural processing

Felson had been studying estrogen treatment and its relation to

arthritis before collaborating with Cummings on this review. The two

researchers reviewed evidence linking aromatase inhibitors and

estrogen deprivation with arthralgias.



Women randomized to aromatase inhibitors consistently showed higher

rates of arthralgias than those randomized to placebo or to tamoxifen.



Felson points out that pain can arise from a variety of articular

structures innervated with nociceptive fibers and that when the joint

is inflamed, a nociceptive neuron's receptor fields enlarge, so that

otherwise nonpainful stimuli cause pain.

Felson and Cummings say that estrogen influences inflammation and

neural processing of nociceptive input. " The effects of estrogen on

inflammation in the joint could account for enhanced nociception that

occurs with estrogen depletion, " they write. Estrogen also has direct

effects on opioid pain fibers in the central nervous system.

The aromatase inhibitors anastrozole (Arimidex, AstraZeneca),

exemestane (Aromasin, Pharmacia), and letrozole (Femara, Novartis

Pharmaceuticals) are commonly used in cancer treatment to cause

estrogen deprivation. Their efficacy and relative lack of side

effects have led to a paradigm shift in breast-cancer treatment [2].

Randomized, controlled trials have shown that aromatase inhibitors

are more effective than tamoxifen in advanced breast cancer and more

effective than tamoxifen as neoadjuvant therapy in early breast

cancer. After two to three years of adjuvant tamoxifen, switching to

an aromatase inhibitor is superior to continuing tamoxifen for a full

five years.

Felson and Cummings write, " In trials of women with advanced breast

cancer, arthralgias [symptoms without objective joint findings] have

been more common in women treated with aromatase inhibitors than in

the comparator group, despite their lower rates of metastases, which

might also cause bone pain. " In one major study, the rates of

musculoskeletal disorders were 27.8% in anastrozole patients vs 21.3%

in those receiving tamoxifen (p<0.0001) [3].

Felson and Cummings note that a " small but significant proportion of

women receiving estrogen-depleting treatments " will develop

arthralgias. They point out that symptoms are usually transient and

resolve with estrogen therapy or when the aromatase inhibitor is

discontinued.

However, Felson also tells rheumawire that clinicians should not be

too quick to dismiss joint pain in such patients as a treatment side

effect. " Make sure they don't have an identifiable and treatable

rheumatic disease, " he says.

If a patient's joint pain appears due to aromatase-inhibitor

treatment, Felson advises treating with NSAIDs.

http://www.jointandbone.org/viewArticle.do?primaryKey=564581