Comparison of Changes in the Lipid Profile of Postmenopausal Women With Early Stage Breast Cancer Treated With Exemestane or Letrozole

Bell, Lauren N.; Nguyen, Anne; Li, Lang; Desta, Zeruesenay; Henry, Norah Lynn; Hayes, Daniel F.; Wolff, Antonio C.; Stearns, Vered; Storniolo, Anna Maria; Flockhart, David A.

doi:10.1177/0091270011424153

Cited by 30 publications

(38 citation statements)

References 30 publications

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“…Our general analysis is similar to results our group has previously reported in the ELPh cohort despite minor differences in cohort derivation (15). Overall, effects of both letrozole and exemestane on lipid profiles are unfavorable.…”

Section: Discussionsupporting

confidence: 90%

“…Failure to find any associations in exemestane-treated women in the SNP analysis may have been due to a small sample size being underpowered to detect modest pharmacogenetic effects. Alternatively, non-steroidal versus steroidal AIs have been shown to have different pharmacodynamic effects, and our results may indeed suggest different biological effects (15, 23–25). …”

Section: Discussionmentioning

confidence: 68%

“…Because of the intricate biological relationship of estrogen with lipid profiles and metabolism, the mixed results from previous studies may be explained by heterogeneity in genes involved in estrogen signaling, and estrogen and AI metabolism (15, 16). For example, certain polymorphisms in the estrogen receptor alpha ( ESR1 ) gene have been shown to be associated with increased low density lipoprotein cholesterol (LDL-C) and triglyceride concentrations in women treated with AIs (17).…”

Section: Introductionmentioning

confidence: 97%

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Association of Variants in Candidate Genes with Lipid Profiles in Women with Early Breast Cancer on Adjuvant Aromatase Inhibitor Therapy

Santa-Maria

Blackford

Nguyen

et al. 2016

Clinical Cancer Research

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Purpose Aromatase inhibitors (AI) can exert unfavorable effects on lipid profiles; however, previous studies have reported inconsistent results. We describe the association of single-nucleotide polymorphisms (SNP) in candidate genes with lipid profiles in women treated with adjuvant AIs. Experimental Design We conducted a prospective observational study to test the associations between SNPs in candidate genes in estrogen signaling and AI metabolism pathways with fasting lipid profiles during the first three months of AI therapy in postmenopausal women with early breast cancer randomized to adjuvant letrozole or exemestane. We performed genetic association analysis and multivariable linear regressions using dominant, recessive, and additive models. Results A total of 303 women had complete genetic and lipid data and were evaluable for analysis. In letrozole-treated patients, SNPs in CYP19A1, including rs4646, rs10046, rs700518, rs749292, rs2289106, rs3759811, and rs4775936 were significantly associated with decreases in triglycerides (TG) by 20.2 mg/dL and 39.3mg/dL (p<0.00053), respectively, and with variable changes in high-density lipoprotein (HDL-C) from decreases by 4.2 mg/dL to increases by 9.8 mg/dL (p<0.00053). Conclusion Variants in CYP19A1 are associated with decreases in TG and variable changes in HDL-C in postmenopausal women on adjuvant AIs. Future studies are needed to validate these findings, and to identify breast cancer survivors who are at higher risk for cardiovascular disease with AI therapy.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 97%

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Association of Variants in Candidate Genes with Lipid Profiles in Women with Early Breast Cancer on Adjuvant Aromatase Inhibitor Therapy

Santa-Maria

Blackford

Nguyen

et al. 2016

Clinical Cancer Research

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“…Moreover, Hozumi et al evaluated the serum lipids in postmenopausal patients with hormone‐sensitive early‐stage breast cancer who were treated with exemestane, anastrozole, or tamoxifen and reported that HDL‐C was slightly decreased in the exemestane group and significantly lower than anastrozole group at 3 months and 1 year ( P = .0179 and .0013, separately) . More recently, a prospective lipid panel analysis in postmenopausal patients compared the lipids 3 months before and after using letrozole and exemestane and found that HDL‐C was reduced in patients who received exemestane but unchanged in the letrozole group . Taken together, these studies suggest that the HDL‐C level does not show an apparent change in the long run, except for a short drop within 1 year of using exemestane.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Changes in the Lipid Profiles of Eastern Chinese Postmenopausal Women With Early‐Stage Breast Cancer Treated With Different Aromatase Inhibitors: A Retrospective Study

Tian

Deng

2017

Clinical Pharm in Drug Dev

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Cardiovascular morbidity is closely associated with serum lipid level. We aimed to investigate the effects of different aromatase inhibitors, including letrozole, anastrozole, and exemestane, on the lipid profile of eastern Chinese breast cancer patients. We evaluated a retrospective cohort of eastern Chinese postmenopausal women with early-stage breast cancer who received aromatase inhibitors. A total of 116 postmenopausal women with early-stage breast cancer without prior cardiovascular disease were included. Lipid changes at 3, 6, 12, and 24 months were compared across the endocrine therapy categories. Our data demonstrated that exemestane treatment significantly decreased triglyceride level compared with letrozole after 24 months. However, the aromatase inhibitors had almost equivalent impacts on high-density liportein cholesterol, low-density lipoprotein cholesterol, and triglyceride after long-term aromatase inhibitor treatment. As a small-size retrospective study, our data do not support a judgment about whether one AI or another carries more or less risk in terms of lipid disorders in eastern Chinese breast cancer patients. The exact effects need further randomized, controlled trials to investigate.

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“…In studies that do not use tamoxifen as a comparator, the effect of the AI on lipid profiles appears more neutral [6, 18,19], although prior therapy with adjuvant tamoxifen followed by adjuvant AI appears to have a negative impact on lipid profiles [20]. Hence, the adverse effects seen in comparison with tamoxifen, or in sequence with tamoxifen, may be due to a beneficial effect of this drug rather than a negative impact by AI therapy.…”

Section: Discussionmentioning

confidence: 99%

Lipid profiles within the SABRE trial of anastrozole with and without risedronate

Poznak

Makris²,

Clack

et al. 2012

Breast Cancer Res Treat

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Introduction Lipid profiles in women with early breast cancer receiving anastrozole with or without risedronate were examined within an international Phase III/IV study to assess for possible treatment related changes. Methods Postmenopausal women with hormone receptor-positive breast cancer were assigned to 1 of 3 strata by risk of fragility fracture. Patients with the highest risk for fracture received anastrozole plus risedronate (A+R). Moderate-risk patients were randomized in a double-blind manner to anastrozole and risedronate (A+R) or anastrozole and placebo (A+P). Lower-risk patients received anastrozole (A) alone. Serial fasting blood samples were assessed for changes in lipid parameters relative to baseline after 12 months of treatment with anastrozole with or without risedronate. Samples were centrally analyzed for low density lipoprotein cholesterol (LDL-cholesterol), high density lipoprotein (HDL) cholesterol, total cholesterol (TC) and triglycerides (TG). Analysis was performed as primary analysis population for lipids (A plus A+P), lipid intention to treat population and secondary population (A+R). Results Of the 119 patients treated with A plus A+P, there were 66 patients eligible for inclusion in the primary analysis population. Of the 115 patients treated with secondary population (A+R) there were 65 patients eligible for lipid profiling. For LDL cholesterol, HDL cholesterol, TC and TG there were no significant changes between the baseline and 12 month assessments to suggest that any of these therapies have a negative impact on the lipid profile. Conclusions In this study of postmenopausal women with early breast cancer receiving adjuvant anastrozole with or without risedronate, there was no adverse effect on LDL cholesterol, HDL cholesterol, TC or TG values over the 12 month monitoring period.

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Comparison of Changes in the Lipid Profile of Postmenopausal Women With Early Stage Breast Cancer Treated With Exemestane or Letrozole

Cited by 30 publications

References 30 publications

Association of Variants in Candidate Genes with Lipid Profiles in Women with Early Breast Cancer on Adjuvant Aromatase Inhibitor Therapy

Association of Variants in Candidate Genes with Lipid Profiles in Women with Early Breast Cancer on Adjuvant Aromatase Inhibitor Therapy

Comparison of Changes in the Lipid Profiles of Eastern Chinese Postmenopausal Women With Early‐Stage Breast Cancer Treated With Different Aromatase Inhibitors: A Retrospective Study

Lipid profiles within the SABRE trial of anastrozole with and without risedronate

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