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Efficacy of letrozole, anastrozole linked to BMI
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BMI was observed to be associated with suppressed levels of plasma estradiol and estrone sulfate in postmenopausal women with early ER-positive breast cancer who were treated with the aromatase inhibitors anastrozole and letrozole.
High BMI has been known to be a risk factor for breast cancer in postmenopausal women, and recent studies have indicated that anastrozole (Arimidex, AstraZeneca) has lower effectiveness than tamoxifen (Nolvadex, AstraZeneca) in women with high BMI. This association with high BMI could be a result of reduced inhibition of aromatase and suppression of plasma estrogen levels that may be overcome by the use of an increased dose of anastrozole or letrozole (Femara, Novartis Pharmaceuticals).
To determine whether there was any evidence of incomplete suppression of plasma estrogens by anastrozole in heavier women and whether incomplete suppression can be overcome by the greater potency of letrozole in suppressing aromatase, researchers analyzed the estrogen data from the Anastrozole vs. Letrozole, an Investigation of Quality Of Life and Tolerability (ALIQUOT) study in relation to BMI.
Based on data from the ALIQUOT study, 54 postmenopausal women with hormone receptor–positive breast cancer who received adjuvant aromatase inhibition were randomly assigned to receive either 3 months of anastrozole (1 mg per day) followed by 3 months of letrozole (2.5 mg per day), or the opposite sequence.
None of the patients had received previous treatment with chemotherapy, and half of the patients had received 5 years of adjuvant tamoxifen before aromatase inhibitor therapy. There was no significant difference in estrogen levels either at baseline or during aromatase inhibitor treatment between the patients who had received tamoxifen previously and those who had not received tamoxifen.
According to study results, baseline values of estradiol (r=0.57; P<.001) and estrone sulfate (r=0.38; P=.006) were significantly associated with BMI. Levels of estrogen in patients receiving treatment were greater at higher levels of BMI with both aromatase inhibitors, but whereas this was significant with letrozole (r=0.35; P=.013 for estradiol, r=0.30; P=.035 for estrone sulfate), it was not with anastrozole. Suppression of both estrogen types was greater with letrozole across the full range of BMIs in this study.
“We found that women with higher BMIs had more oestrogen remaining in their blood after treatment than healthy-weight women, which is consistent with previous suggestions that aromatase inhibitors might be slightly less effective in these women,” Mitch Dowsett, PhD, team leader at the Breakthrough Breast Cancer Research Centre in London, said in a press release.
“Our findings are based on laboratory studies, so we would need to carry out clinical trials to tell us whether women with a higher BMI would benefit from changes to their treatment. Women with higher BMIs should certainly not be alarmed by this finding or stop taking their treatment. Our study takes us a step closer to understanding which of the treatment options available might be the most suitable for individual women.”
Disclosure: Dr. Dowsett reported a consulting position with AstraZeneca, as well as research funding contributions from Novartis and AstraZeneca.
Perspective
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Stephen Y. Chui, MD
It is not surprising that the efficacy of aromatase inhibitors to prevent the conversion of androgens into estrogens appears to be decreased in patients with an increased BMI. While this report does not describe an increased risk for breast cancer relapse in obese women taking aromatase inhibitors, we can easily surmise that this will be the case.
Obesity has been long recognized to be associated with increased aromatase activity, increased levels of circulating estrogens, an increased risk of developing breast cancer, and an increased risk for breast cancer relapse after an initial diagnosis of disease. While “association” does not necessarily equate “causation,” I am at a loss to identify significant health benefits from being obese. Similarly, there is a huge body of data showing that healthy eating choices and robust activity promotes not just breast cancer health, but nearly all aspects of health.
There is nothing less than an ongoing epidemic of obesity and the associated diseases of overindulgence in America, Europe and beyond. Physicians are excellent at administering drugs, performing surgeries and offering other medical interventions. However, we fail miserably at encouraging our patients to eat better and exercise, because we are not incentivized as physicians to promote healthy lifestyles, and because our society does not put a value upon healthy dietary and activity behaviors.
Eating well, exercise and an active lifestyle needs to become an expectation in our society, and not sidelined as mere recreation.
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