The effect of endocrine therapy for breast cancer on blood lipids in postmenopausal women
Keywords:hormone-sensitive breast cancer, dyslipidemia, serum lipid profile, adjuvant endocrine therapy for breast cancer, selective estrogen receptor modulators, aromatase inhibitors
AbstractBackground. Breast cancer ranks first in the world among all malignant neoplasms in women. The proportion of hormone-sensitive breast cancer in the morbidity structure is more than 60 %. Adjuvant endocrine therapy is an integral part of postoperative treatment of patients with hormone-sensitive breast cancer. Recent publications suggest that breast cancer endocrine therapy has some effect on serum lipid levels. However, the number of studies focusing exclusively on this problem is insignificant, and the question about the nature of the effect of various drugs for breast cancer endocrine therapy on the lipid profile remains controversial. A significant proportion of patients with hormone-sensitive breast cancer are women with natural or artificial postmenopause. In the group of patients aged 60 years and older, diseases of the cardiovascular system rank first in the structure of mortality. Thanks to modern approaches to the treatment of breast cancer, the overall survival has increased significantly, and a comprehensive approach to the treatment of patients with age-related comorbidities, no less important in terms of duration and quality of life, has become relevant. This article discusses the effect of the most common endocrine therapies on the lipid profile, which is extremely relevant for the prevention of morbidity and mortality from cardiovascular events in postmenopausal women. Materials and methods. This article is based on the results of 13 clinical studies obtained in the search resource PubMed on the keywords: “hormone-sensitive breast cancer”, “dyslipidemia”, “serum lipid profile”, “adjuvant endocrine therapy for breast cancer”, “selective estrogen receptor modulators”, “aromatase inhibitors”; NCCN clinical guidelines; clinical guidelines of the European Society of Cardiology and the European Atherosclerosis Society for the treatment of dyslipidemia. Results. Selective estrogen receptor modulators have a positive effect on the lipid profile with some differences between toremifene and tamoxifen (does not cause an increase in triglycerides). Aromatase inhibitors, according to the studies, have a rather neutral effect; among common aromatase inhibitors, letrozole has the most pronounced negative effect on the lipid profile of postmenopausal women with hormone-sensitive breast cancer. Conclusions. Selective estrogen receptor modulators may be the drugs of choice for patients at high risk of dyslipidemia, other than women with isolated hypertriglyceridemia. The use of aromatase inhibitors should be accompanied by a closer monitoring of lipid metabolism and may require additional prescription of lipid-lowering drugs (statins, fibrates, bile acid sequestrants, etc.). The problem needs further study, taking into account the attention paid to the correction of dyslipidemia as a mean for preventing the development of diseases of the cardiovascular system, which are the leading cause of death in the studied age group.
Bray F., Ferlay J., Soerjomataram I. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018. 68. Р. 394-424.
Bulletin of national cancer registry of Ukraine № 21, Kyiv, 2020.
Chapman J.A., Meng D., Shepherd L. et al. Competing causes of death from a randomized trial of extended adjuvant endocrine therapy for breast cancer. J. Natl Cancer Inst. 2008. 100(4). Р. 252-260.
Fietz T., Tesch H., Rauh J. et al. Palliative systemic therapy and overall survival of 1,395 patients with advanced breast cancer — results from the prospective German TMK cohort study. Breast. 2017. 34. Р. 122-130.
NCCN guidelines for breast cancer version 4.2020 — May 8, 2020.
Baigent C., Mach F., Catapano A.L. et al. ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur. Heart J. Aug. 31, 2019. doi: 10.1093/eurheartj/ehz455.
Cholesterol Treatment Trialists Collaboration. Baigent C., Blackwell L., Emberson J. et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a metaanalysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010. 376. 16701681.
Cholesterol Treatment Trialists Collaboration. Fulcher J., O’Connell R., Voysey M. et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet. 2015. 385. 13971405.
Cholesterol Treatment Trialists Collaboration. Mihaylova B., Emberson J., Blackwell L. et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012. 380. 581590.
Emerging Risk Factors Collaboration. Di Angelantonio E., Gao P., Pennells L. et al. Lipid-related markers and cardiovascular disease prediction. JAMA. 2012. 307. 24992506.
Prospective Studies Collaboration. Lewington S., Whitlock G., Clarke R. et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet. 2007. 370. 18291839.
Holmes M.V., Asselbergs F.W., Palmer T.M. et al. Mendelian randomization of blood lipids for coronary heart disease. Eur. Heart J. 2015. 36. 539550.
Frikke-Schmidt R., Nordestgaard B.G., Stene M.C. et al. Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease. JAMA. 2008. 299. 25242532.
Schwartz G.G., Olsson A.G., Abt M. et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N. Engl. J. Med. 2012. 367. 20892099.
Nelson E.R., Wardell S.E., Jasper J.S. et al. 27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Science. 2013. 342(6162). Р. 1094-1098. doi: 10.1126/science.1241908.
Simigdala N., Gao Q., Pancholi S. et al. Cholesterol biosynthesis pathway as a novel mechanism of resistance to estrogen deprivation in estrogen receptor-positive breast cancer. Breast Cancer Res. 2016. 18(1). 58. Published 2016, Jun 1. doi: 10.1186/s13058-016-0713-5.
Baek A.E., Yu Y.A., He S. et al. The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells. Nat. Commun. 2017. 8(1). 864. Published 2017, Oct 11. doi: 10.1038/s41467-017-00910-z.
Cyster J., Dang E., Reboldi A. et al. 25-Hydroxycholesterols in innate and adaptive immunity. Nat. Rev. Immunol. 2014. 14. Р. 731-743. https://doi.org/10.1038/nri3755.
Raza, Uzma et al. Hyperlipidemia and hyper glycaemia in Breast Cancer Patients is related to disease stage. Pakistan Journal of Medical Sciences. 2018. Vol. 34. 1. Р. 209-214. doi:10.12669/pjms.341.14841
Bahl M. et al. Serum lipids and outcome of early-stage breast cancer: results of a prospective cohort study. Breast Cancer Res. Treat. 2005. 94. Р. 135-144. doi: 10.1007/s10549-005-6654-9.
Borgquist S., Giobbie-Hurder A., Ahern T.P. et al. Cholesterol, Cholesterol-Lowering Medication Use, and Breast Cancer Outcome in the BIG 1-98 Study. J. Clin. Oncol. 2017. 35(11). Р. 1179-1188. doi: 10.1200/JCO.2016.70.3116.
Wake R., Yoshiyama M. Gender differences in ischemic heart disease. Recent Pat. Cardiovasc. Drug Discov. 2009 Nov. 4(3). Р. 234-240.
Iorga A., Cunningham C.M., Moazeni S., Ruffenach G., Umar S., Eghbali M. The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy. Biol. Sex Differ. 2017. 8(1). Р. 33. Published 2017, Oct 24. doi: 10.1186/s13293-017-0152-8.
Gylling H., Pyrhönen S., Mäntylä E., Mäenpää H., Kangas L., Miettinen T.A. Tamoxifen and toremifene lower serum cholesterol by inhibition of delta 8-cholesterol conversion to lathosterol in women with breast cancer. J. Clin. Oncol. 1995. 13(12). Р. 2900-2905. doi: 10.1200/JCO.19220.127.116.1100.
Wasan K.M., Ramaswamy M., Haley J., Dunn B.P. Administration of long-term tamoxifen therapy modifies the plasma lipoprotein-lipid concentration and lipid transfer protein I activity in postmenopausal women with breast cancer. J. Pharm. Sci. 1997. 86(7). Р. 876-879. doi: 10.1021/js970097w.
Berglund A., Wigertz A., Adolfsson J. et al. Impact of comorbidity on management and mortality in women diagnosed with breast cancer. Breast Cancer Res. Treat. 2012. 135. Р. 281-289.
Ariazi E.A., Leitão A., Oprea T.I. et al. Exemestane’s 17-hydroxylated metabolite exerts biological effects as an androgen. Mol. Cancer Ther. 2007. 6(11). Р. 2817-2827. doi: 10.1158/1535-7163.MCT-07-0312.
Hozumi Y., Suemasu K., Takei et al. The effect of exemestane, anastrozole, and tamoxifen on lipid profiles in Japanese postmenopausal early breast cancer patients: final results of National Surgical Adjuvant Study BC 04, the TEAM Japan sub-study. Annals of Oncology. 2011. 22(8). Р. 1777-1782. doi: 10.1093/annonc/mdq707.
Markopoulos C., Polychronis A., Zobolas V. et al. The Effect of Exemestane on the Lipidemic Profile of Postmenopausal Early Breast Cancer Patients: Preliminary Results of the TEAM Greek Sub-study. Breast Cancer Res. Treat. 2005. 93. Р. 61-66. https://doi.org/10.1007/s10549-005-3783-0.
Bell L.N., Nguyen A.T., Li L. et al. Comparison of changes in the lipid profile of postmenopausal women with early stage breast cancer treated with exemestane or letrozole. J. Clin. Pharmacol. 2012. 52(12). Р. 1852-1860. doi: 10.1177/0091270011424153.
Tian W., Wu M., Deng Y. 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. Clin. Pharmacol. Drug. Dev. 2018. 7(8). Р. 837-843. doi: 10.1002/cpdd.420.
Wasan K.M., Goss P.E., Pritchard P.H. et al. Lipid concentrations in postmenopausal women on letrozole after 5 years of tamoxifen: an NCIC CTG MA.17 sub-study. Breast Cancer Res. Treat. 2012. 136. Р. 769-776. https://doi.org/10.1007/s10549-012-2294-z.
Elisaf M.S., Bairaktari E.T., Nicolaides C. et al. Effect of letrozole on the lipid profile in postmenopausal women with breast cancer. Eur. J. Cancer. 2001. https://doi.org/10.1016/s0959-8049(01)00155-1.
Shien T., Doihara H., Sato N. et al. Serum lipid and bone metabolism effects of Toremifene vs. Letrozole as adjuvant therapy for postmenopausal early breast cancer patients: results of a multicenter open randomized study. Cancer Chemother. Pharmacol. 2018. 81. Р. 269-275. https://doi.org/10.1007/s00280-017-3491-6.
Anan K., Mitsuyama S., Yanagita Y. et al. Effects of toremifene and anastrozole on serum lipids and bone metabolism in postmenopausal females with estrogen receptor–positive breast cancer: the results of a 2-year multicenter open randomized study. Breast Cancer Res. Treat. 2011. 128. Р. 775-781. https://doi.org/10.1007/s10549-011-1608-x.
Shojiro Sawada, Kazuhiko Sato, Masatoshi Kusuhara et al. Effect of anastrozole and tamoxifen on lipid metabolism in Japanese postmenopausal women with early breast cancer. Acta Oncologica. 2005. 44. 2. Р. 134-141. doi: 10.1080/02841860510007585.
Kusama M., Miyauchi K., Aoyama H. et al. Effects of toremifene (TOR) and tamoxifen (TAM) on serum lipids. Breast Cancer Res. Treat. 2004. 88. Р. 1-8. https://doi.org/10.1007/s10549-004-4384-z.
Takeshi Tominaga, Izo Kimijima, Morihiko Kimura et al. Effects of Toremifene and Tamoxifen on Lipid Profiles in Post-menopausal Patients with Early Breast Cancer: Interim Results from a Japanese Phase III Trial. Japanese Journal of Clinical Oncology. July 2010. Vol. 40. Is. 7. P. 627-633. https://doi.org/10.1093/jjco/hyq021.
Kusama M., Kaise H., Nakayama S. et al. Crossover trial for lipid abnormality in postmenopausal breast cancer patients during selective estrogen receptor modulators (SERMs) administrations. Breast Cancer Res. Treat. 2004. 88. Р. 9-16. https://doi.org/10.1007/s10549-004-5449-8.
Iwao N., Iwao S., Muller D.C. et al. Differences in the relationship between lipid CHD risk factors and body composition in Caucasians and Japanese. Int. J. Obes. 2005. 29. Р. 228-235.
Zotov О.S., Hryvkova L.V., Zaiveleva Y.І. et al. Endocrine therapy for breast cancer: doctor’s manual. Ed. by O.S. Zotov. 2 ed. Кiev: Publiher A.Y. Zaslavskyi, 2018.
Copyright (c) 2020 Practical oncology
This work is licensed under a Creative Commons Attribution 4.0 International License.
Our edition uses the copyright terms of Creative Commons for open access journals.
Authors, who are published in this journal, agree with the following terms:
- The authors retain rights for authorship of their article and grant to the edition the right of first publication of the article on a Creative Commons Attribution 4.0 International License, which allows others to freely distribute the published article, with the obligatory reference to the authors of original works and original publication in this journal.
- Directing the article for the publication to the editorial board (publisher), the author agrees with transmitting of rights for the protection and using the article, including parts of the article, which are protected by the copyrights, such as the author’s photo, pictures, charts, tables, etc., including the reproduction in the media and the Internet; for distributing; for the translation of the manuscript in all languages; for export and import of the publications copies of the writers’ article to spread, bringing to the general information.
- The rights mentioned above authors transfer to the edition (publisher) for the unlimited period of validity and on the territory of all countries of the world.
- The authors guarantee that they have exclusive rights for using of the article, which they have sent to the edition (publisher). The edition (the publisher) is not responsible for the violation of given guarantees by the authors to the third parties.
- The authors have the right to conclude separate supplement agreements that relate to non-exclusive distribution of their article in the form in which it had been published in the journal (for example, to upload the work to the online storage of the journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this journal is included.
- The policy of the journal permits and encourages the publication of the article in the Internet (in institutional repository or on a personal website) by the authors, because it contributes to productive scientific discussion and a positive effect on efficiency and dynamics of the citation of the article.
- The rights to the article are deemed transferred by the authors to the edition (the publisher) since the moment of the publication of the article in the printed or electronic version of journal.