Genetic polymorphism at Val80 (rs700518) of the CYP19A1 gene is associated with body composition changes in women on aromatase inhibitors for ER (+) breast cancer

Abstract

Purpose Polymorphisms in the CYP19A1 (aromatase) gene influence disease-free survival and bone loss in patients taking aromatase inhibitors (AIs) for estrogen receptor positive (ER+) breast cancers. Because AI use results in profound estrogen deficiency which may lead to changes in body composition, the objective of this study was to determine the effect of the rs700518 polymorphism in the CYP19A1 gene, on the changes in body composition among postmenopausal women who were treated with AIs for ER+ breast cancer. Methods This is a 1-year prospective study of changes in body composition in postmenopausal women who were initiated on third-generation AIs for ER+ breast cancer. Body composition was measured by dual energy absorptiometry at 6 and 12 months, serum estradiol by radioimmunoassay and genotyping by Taqman SNP allelic discrimination assay. Results Eighty-two women were able to provide at least one follow-up body composition measurement. Women with the GG genotype for the rs700518 (G/A at Val80) developed a significant increase in Truncal fat mass index (p=0.03) and a significant decrease in fat-free mass index (p=0.01) at 12 months relative to patients carrying the A allele (GA/AA). There was no significant difference in the changes in estradiol levels among the genotypes. Conclusion Patients with the GG genotype for the rs700518 polymorphism in the CYP19A1 gene are at risk for significant loss of fat-free mass and increase in truncal fat with AI therapy. Whether there are associated metabolic abnormalities and whether changes would persist with long-term AI therapy, need to be confirmed in a larger study with a longer duration of follow-up.

Effects of resistance plus aerobic training on body composition and metabolic markers in older breast cancer survivors undergoing aromatase inhibitor therapy

“…In postmenopausal women, 80% of breast cancer cases are hormone receptor positive (Bardia et al, 2012) and aromatase inhibitor therapy (AI) is typically prescribed as standard treatment, which increases survival rates upwards of 40% compared to tamoxifen (Riemsma et al, 2010). However, treatment of breast cancer with aromatase inhibitor therapy can produce alterations in body composition, such as increases in body fat mass as well as decreases in lean body mass and bone mineral density (Napoli et al, 2015;Battisti et al, 2014;Van Londen et al, 2011) and, these alterations can increase the risk of fractures, osteoporosis, and chronic diseases (Akyol et al, 2016;Saarto et al, 2008). In addition, the side effects of AI also include loss of bone mineral density of 2.6% per year and symptoms of arthralgia and myalgia (Limburg, 2007;Peppone et al, 2010).…”

The effect of exercise on body composition and bone mineral density in breast cancer survivors taking aromatase inhibitors

“…Furthermore, 80% of breast cancers in postmenopausal women are hormone receptor positive , and the current standard of care is taking an aromatase inhibitor (AI) for 5 years, which increases disease free survival by 10% to 40% compared with tamoxifen . While AIs are associated with clinically meaningful recurrence and mortality risk reductions , a side effect is loss of BMD .…”

“…Postmenopausal breast cancer survivors taking AIs lose about 2.6% of their BMD annually, which is double the amount of BMD loss in healthy postmenopausal women . Research examining the effects of AIs on other components of body composition have been mixed, with some studies showing loss of LBM and increases in body fat or maintenance of total body fat and other studies showing no changes in body weight or LBM . Side effects from AIs, such as arthralgia or bone loss, lead some women to stop taking AIs, thereby greatly increasing their chance of recurrence .…”

The implications of genetic variation for the pharmacokinetics and pharmacodynamics of aromatase inhibitors

“…Patients with rs700518 genetic variant experienced negative effects on body composition with a significantly higher truncal fat mass index (4.63% vs. -2.21%) and a significant lower fat-free mass index (-2.12% vs. 0.39%) at 12 months compared with patients who carried the A allele [77]. These finding suggests the necessity of functional studies of rs700518 to explain the underlying mechanisms.…”