Suppression of Plasma Estrogen Levels by Letrozole and Anastrozole Is Related to Body Mass Index in Patients With Breast Cancer
ABSTRACT To investigate whether suppression of plasma estradiol and estrone sulfate levels by the aromatase inhibitors (AIs) anastrozole and letrozole is related to body mass index (BMI) in postmenopausal women with early estrogen receptor (ER) -positive breast cancer. Recent studies have reported that the AI anastrozole has lower effectiveness than tamoxifen in women with high BMI. This effect with high BMI might hypothetically be a result of reduced inhibition of aromatase and suppression of plasma estrogen levels and might be overcome by the use of an increased dose of anastrozole or, alternatively, the use of a more potent AI such as letrozole.
Plasma estradiol and estrone sulfate levels from a highly sensitive radioimmunoassay were available for 44 postmenopausal patients who received anastrozole (1 mg per day) for 3 months followed by letrozole (2.5 mg per day) for 3 months or the opposite sequence. Correlations between the estrogen suppression by each AI and BMI were assessed.
Baseline values of estradiol and estrone sulfate were significantly correlated with BMI (r = 0.57; P < .001, and r = 0.38; P = .006, respectively). Levels of estrogen in patients receiving treatment were greater at higher levels of BMI with both AIs, but although this was significant with letrozole (r = 0.35; P = .013, and r = 0.30; P = .035 for estradiol and estrone sulfate, respectively), it was not with anastrozole. Suppression of both estrogen types was greater with letrozole across the full range of BMIs in this study.
The suppressed levels of plasma estradiol and estrone sulfate in postmenopausal women with early ER-positive breast cancer treated with the AIs anastrozole and letrozole are related to BMI.
- SourceAvailable from: Mauro Mansutti[Show abstract] [Hide abstract]
ABSTRACT: Background: Obesity is an independent adverse prognostic factor in early breast cancer patients, but it is still controversial whether obesity may affect adjuvant endocrine therapy efficacy. The aim of our study (ancillary to the two clinical trials Gruppo Italiano Mammella (GIM)4 and GIM5) was to investigate whether the circulating oestrogen levels during treatment with the aromatase inhibitor letrozole are related to body mass index (BMI) in postmenopausal women with breast cancer. Methods: Plasma concentration of oestrone sulphate (ES) was evaluated by radioimmunoassay in 370 patients. Plasma samples were obtained after at least 6 weeks of letrozole therapy (steady-state time). Patients were divided into four groups according to BMI. Differences among the geometric means (by ANOVA and ANCOVA) and correlation (by Spearman's rho) between the ES levels and BMI were assessed. Results: Picomolar geometric mean values (95% confidence interval, n=patients) of circulating ES during letrozole were 58.6 (51.0–67.2, n=150) when BMI was <25.0 kg m−2; 65.6 (57.8–74.6, n=154) when 25.0–29.9 kg m−2; 59.3 (47.1–74.6, n=50) when 30.0–34.9 kg m−2; and 43.3 (23.0–81.7, n=16) when ⩾35.0 kg m−2. No statistically significant difference in terms of ES levels among groups and no correlation with BMI were observed. Conclusions: Body mass index does not seem to affect circulating oestrogen levels in letrozole-treated patients.British Journal of Cancer 01/2014; 110(5). DOI:10.1038/bjc.2014.2 · 4.82 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Background:We investigated whether body mass index (BMI) can be used as a predictive parameter indicating patients who benefit from extended aromatase inhibitor (AI) treatment.Methods:The ABCSG-6a trial re-randomised event-free postmenopausal hormone receptor-positive patients from the ABCSG-6 trial to receive either 3 additional years of endocrine therapy using anastrozole vs nil. In this retrospective analysis, we investigated the prognostic and predictive impact of BMI on disease outcome and safety.Results:In all, 634 patients (177 normal weight, 307 overweight, and 150 obese) patients were included in this analysis. Normal weight patients with additional 3 years of anastrozole halved their risk of disease recurrence (disease-free survival (DFS) HR 0.48; P=0.02) and death (HR 0.45; P=0.06) and had only a fifth of the risk of distant metastases (HR 0.22; P=0.05) compared with normal weight patients without any further treatment. In contrast, overweight+obese patients derived no benefit from additional 3 years of anastrozole (DFS HR 0.93; P=0.68; distant recurrence-free survival HR 0.91; P=0.78; and OS HR 0.9; P=0.68). The possible predictive impact of BMI on extended endocrine treatment could be strengthened by a Cox regression interaction model between BMI and treatment (P=0.07).Conclusion:Body mass index may be used to predict outcome benefit of extended AI treatment in patients with receptor-positive breast cancer.British Journal of Cancer advance online publication, 18 July 2013; doi:10.1038/bjc.2013.367 www.bjcancer.com.British Journal of Cancer 07/2013; 109(3). DOI:10.1038/bjc.2013.367 · 4.82 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Following their successfull implementation for the treatment of metastatic breast cancer, the 'third-generation' aromatase inhibitors (anastrozole, letrozole and exemestane) now has become standard adjuvant endocrine treatment for postmenopausal estrogen receptor positive breast cancers. These drugs are all characterized by potent aromatase inhibition, causing >98% inhibition of estrogen synthesis in vivo. A recent meta-analysis found no difference in anti-tumour efficacy between these three compounds. As of today, aromatase inhibitor monotherapy or sequential treatment using tamoxifen followed by an aromatase inhibitor for a total of 5 years are considered equipotent treatment options. Yet currently trials are addressing the potential benefit of extending treatment duration beyond 5 years. Regarding side effects, aromatase inhibitors are not found associated with enhanced risk of cardiovascular disease, and enhanced bone loss is prevented by adding bisphosphonates in concert for those at danger of developing osteoporosis. However, arthralgia and carpal tunnel syndrome preclude drug administration among a few patients. While recent findings have questioned the use of aromatase inhibitors among overweigth and, in particular, obese patients, this problem seems to focus on premenopausal patients treated with an aromatase inhibitor and an LH-RH analogue in concert, questioning the efficacy of LH-RH analogues rather than aromatase inhibitors among overweigth patients. Finally, recent findings revealing a benefit from adding the mTOR inhibitor everolimus to treatment endocrine treatment indicates targeted therapy against defined growth factor pathways to be a way forward reversing acquired resistance to endocrine therapy.Endocrine Related Cancer 04/2013; 20(4). DOI:10.1530/ERC-13-0099 · 4.91 Impact Factor