Clinical Review

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

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  • advanced age
  • history of fracture
  • glucocorticoid therapy
  • parental history of hip fracture
  • low body weight
  • current smoking status
  • excess alcohol consumption
  • rheumatoid arthritis
  • known risk factors for secondary osteoporosis.19

In breast cancer survivors initiating or continuing AI therapy, it is also appropriate to check a serum vitamin D level and ensure that intake of this nutrient is adequate.

Bisphosphonates may offer oncologic benefits, as well; preliminary evidence suggests that the drugs may prevent recurrence of the cancer and prolong survival.20

OBG Management: What can an ObGyn offer to a woman who complains of significant AI-related arthralgia?

Dr. Kaunitz: Bone and joint symptoms, including aches, pain, and stiffness that is bilateral and not associated with other evidence of rheumatologic disorders, are among the most common side effects of AI therapy. On the plus side of the equation, these symptoms are more likely to be mild to moderate than severe. On the negative side, no specific treatment has been found to be effective in relieving these symptoms, which usually resolve within 2 months or so after discontinuing AI therapy.10

OBG Management: Do AIs have a negative impact on cardiovascular health?

Dr. Kaunitz: Unlike tamoxifen, AIs do not increase the risk of thromboembolic disease. Although the use of an AI may modestly increase the risk of ischemic cardiovascular disease (and lipid changes), compared with tamoxifen, AIs do not appear to increase cardiovascular risk compared with placebo.21,22

OBG Management: Do the antiestrogenic effects of AIs have a significant impact on vaginal health and sexual desire?

Dr. Kaunitz: A review of published reports did not find that the use of AIs has a predictable impact on vaginal dryness or sexual desire.10 However, symptomatic genital atrophy is common in postmenopausal breast cancer survivors, whether or not they use adjuvant therapy.

Although the FDA considers the use of any estrogen (systemic or vaginal) following a diagnosis of breast cancer to be contraindicated, some breast cancer survivors who have symptomatic genital atrophy express an interest in the use of vaginal estrogen. Use of 25-μg estradiol tablets (Vagifem) is associated with a short-term increase in serum estradiol levels.23 This finding has reinforced caution among medical oncologists about the safety of vaginal estrogen in breast cancer survivors. (The 25-μg tablets are no longer marketed.) The lowest dosage of vaginal estrogen available for the treatment of genital atrophy is found in 10-μg estradiol tablets (Vagifem) and the estradiol (2-mg) 3-month vaginal ring (Estring). Nonetheless, in the absence of data, oncologists will likely continue to be concerned that even the lowest dosage of vaginal estrogen could attenuate the favorable impact of AIs on breast cancer. Accordingly, use of vaginal lubricants and moisturizers are the mainstay strategy for symptomatic genital atrophy.

OBG Management: What about the ubiquitous hot flush? Vasomotor symptoms may be more common in women who take tamoxifen, but women on AIs are also bothered by flushes. What are the alternatives to estrogen therapy?

Dr. Kaunitz: Both nonprescription and prescription alternatives are available. Nonprescription options include soy extract and red clover isoflavones, black cohosh, and Chinese herbs. However, none of these over-the-counter approaches has been found to be more effective than placebo in the treatment of menopausal hot flushes.24-26

As for prescription nonhormonal options, ObGyns should recognize that all such treatments are off-label and that none attain the efficacy of hormone therapy in the treatment of vasomotor symptoms. The best-studied and most effective medications include gabapentin, SSRIs (especially paroxetine), and serotonin-norepinephrine reuptake inhibitors (venlafaxine and desvenlafaxine).24,27

OBG Management: Is there any evidence that AIs impair cognitive function in postmenopausal women?

Dr. Kaunitz: Because estrogen is important for cognition, one might anticipate that the profound reduction in background estrogen associated with AI use would impair cognition. Fortunately, the evidence to date is reassuring. Substudies of the BIG trial and the Tamoxifen and Exemestane Adjuvant Multinational Trial indicate that, compared with tamoxifen (which is associated with declines in cognitive function in postmenopausal women), letrozole and exemestane do not diminish cognitive function.28,29

OBG Management: Overall, what is the typical impact of an AI on a woman’s quality of life?

Dr. Kaunitz: Most women do very well on an AI, finding it easier to tolerate than tamoxifen, as we have discussed. However, a significant minority of women is seriously bothered by the adverse effects, with arthralgias usually leading the pack of complaints.30,31

OBG Management: Do some women discontinue adjuvant endocrine therapy because of adverse effects?

Dr. Kaunitz: Regrettably, the answer is “Yes.” A recent study from Kaiser Permanente of northern California found that roughly 50% of women who are prescribed adjuvant endocrine therapy with tamoxifen or an AI discontinue the drug early.32


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