Clinical Review

An ObGyn’s guide to aromatase inhibitors as adjuvant therapy for breast CA

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References

After 4 years of follow-up in the ATAC trial, women taking anastrozole continued to have more favorable disease-free survival (86.9% vs 84.5% for anastrozole and tamoxifen, respectively; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.76–0.99; P =.03).13 They also had a more favorable time to recurrence than did women taking tamoxifen (HR, 0.83; 95% CI, 0.71–0.96; P =.015). And women taking anastrozole had a lower incidence of contralateral breast cancer, as well, although this different did not achieve statistical significance (HR, 0.62; 95% CI, 0.38–1.02; P =.062).13

In the BIG study, women taking letrozole had a 5-year disease-free survival estimate of 84.0%, compared with 81.4% for women taking tamoxifen.14 In addition, women taking letrozole were significantly less likely than those taking tamoxifen to experience an event that ended a period of disease-free survival (HR, 0.81; 95% CI, 0.70–0.93; P =.003), especially the event of distant recurrence (HR, 0.73; 95% CI, 0.60–0.88; P =.001).14

And a phase-3 study of exemestane versus tamoxifen in women who had metastatic breast cancer found that the AI produced a superior response rate (46% vs 31% for exemestane and tamoxifen, respectively; odds ratio [OR], 1.85; 95% CI, 1.21–2.82; P =.005). In addition, median progression-free survival was greater with exemestane (9.9 months; 95% CI, 8.7–11.8 months) than with tamoxifen (5.8 months; 95% CI, 5.3–8.1 months). However, there was no difference between arms in progression-free survival or overall survival.

ASCO guidelines emphasize the importance of aromatase inhibitors

Postmenopausal women who have hormone-receptor–positive breast cancer should consider taking an aromatase inhibitor (AI) to lengthen disease-free survival and lower the risk of recurrence. That’s one of the recommendations in updated guidelines issued earlier this year by the American Society of Clinical Oncology (ASCO). The guidelines suggest a duration of AI therapy of 5 years. In the event that a woman discontinues AI therapy before 5 years are up, she should consider using tamoxifen to bring the total duration of treatment to 5 years.

Other recommendations in the guidelines include:

  • Women who have taken tamoxifen for 5 years stand to benefit from switching to an AI for as long as 5 additional years.
  • When advising a woman about adjuvant therapy with an AI, clinicians should consider the potential adverse effects, which include osteoporosis, fracture, and arthralgias.
  • The third-generation AIs on the market today have not been found to have clinically important differences between them. A woman who cannot tolerate a particular AI should consider switching to a different AI.
  • Switching from an AI to tamoxifen (or vice versa) may be an appropriate option for patients who cannot tolerate a drug’s adverse effects. In the event of a switch to tamoxifen, the clinician should counsel the patient about its adverse effects, which include venous thromboembolism and endometrial polyps, hyperplasia, and cancer.

The full guidelines can be accessed at http://jco.ascopubs.org/content/early/2010/07/12/JCO.2009.26.3756.full.pdf.

Andrew M. Kaunitz, MD

How well tolerated are AIs?

OBG Management: What adverse effects are associated with AIs?

Dr. Kaunitz: Although AIs, overall, are safe medications, their use is associated with a number of adverse events. The most prominent side effects include arthralgias and hot flushes, while the most serious health impact appears to be a decrease in bone mineral density (BMD).

However, the drugs are generally perceived as being easier to tolerate than tamoxifen. That’s because endometrial cancer, vaginal bleeding and discharge, cerebrovascular events, venous thromboembolic events, and hot flushes all are less common among women taking an AI than among those taking tamoxifen.8,13

For overweight women, who face an elevated baseline risk of thromboembolism, the availability of AIs represents a major advantage over tamoxifen. Similarly, AIs offer advantages over tamoxifen for women who have an intact uterus. In addition, postmenopausal women who are taking a selective serotonin reuptake inhibitor (SSRI) such as paroxetine should take an AI rather than tamoxifen, because the concomitant use of SSRIs attenuates the efficacy of tamoxifen.15

What can be done about the most prominent risks?

OBG Management: Let’s focus on what’s probably the best-known adverse effect of AIs—the heightened risk of osteoporosis and fracture. How significant is this effect?

Dr. Kaunitz: Because use of an AI is associated with a profound reduction in endogenous estrogen levels, it also decreases BMD and can lead to osteoporotic fractures. All major phase-3 trials of adjuvant use of AIs in women who have early breast cancer found an increased risk of fracture, with no significant differences between AIs.16

Fortunately, bisphosphonate therapy (oral or intravenous) has been found to reduce bone loss associated with AI therapy.17,18

Assessing baseline BMD is important as women initiate AI therapy. Although no consensus exists regarding follow-up BMD assessment in the setting of AI use, an interval of 2 years is prudent, with the follow-up study preferably performed at the same imaging center and by the same technician as the first. If baseline osteoporosis is observed at the lumbar spine or hip, bisphosphonate therapy is appropriate. If a woman taking an AI has low bone mass (osteopenia) but not osteoporosis, bisphosphonate therapy should be considered if any of the following risk factors are present:

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