To evaluate changes in serum lipid parameters (cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and lipoprotein(a) [Lp(a)]), in postmenopausal women receiving letrozole after tamoxifen therapy. MA.17L is a sub-study of MA.17, a double-blind, placebo-controlled trial of extended adjuvant letrozole. Eligible postmenopausal women were non-hyperlipidemic and not on lipid-lowering drugs. This analysis considers the 183 patients on the letrozole arm. Lipid parameters evaluated at baseline, 6 months, 12 months, and yearly thereafter until completion of 5 years of letrozole. The median duration of letrozole treatment was 5.0 years with a range from 0.03 to 6.05 years. After 5 year tamoxifen, patients on letrozole experienced significant increases from baseline in total cholesterol, LDL cholesterol, and Lp(a) at all study time points but no statistically significant changes in triglycerides. Specifically, a statistically significant increase was found at 60 months in total cholesterol [mean percentage change from baseline (PC) 5.27; p = 0.003], HDL cholesterol (mean PC 6.75; p = 0.003), LDL cholesterol (mean PC 10.02; p = 0.001), Lp(a) (mean PC 105.95; p < 0.0001). 103 (56 %) women in the study had clinically significantly elevated levels of Lp(a) (106 % above baseline) after 5 years of therapy. The results were similar after excluding the 21 % of patients who had ever received anti-lipid treatment. Significant increases in total cholesterol, HDL cholesterol, LDL cholesterol, and, most notably, Lp(a) in postmenopausal women were observed following 5 years of adjuvant letrozole treatment and after 5 years of tamoxifen therapy and such patients should have monitoring of their lipid levels in clinical practice.
Letrozole Serum lipids Primary breast cancer Tamoxifen Postmenopausal women 5-year follow-up
This is a preview of subscription content, log in to check access.
This study was supported with a grant co-sponsored from the National Cancer Institute of Canada and Novartis (MA.17L; lipid sub-study). The authors would like to thank all the women who participated in this study, the investigators of the NCCTG and NCIC CTG and Catherine Elliot and Curtis McMahon who managed the data collected for this trial. PEG is supported by the Avon Foundation, New York. This is original research which has not been published elsewhere.
Conflict of interest
PEG has received speaker’s honoraria from Novartis and KMW has received research funding from AMCOL International Inc. and iCo Therapeutics Inc.
Wasan KM, Ramaswamy M, Haley J et al (1997) 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 86:876–879PubMedCrossRefGoogle Scholar
Goss PE, Ingle JN, Martino S et al (2003) A randomized trial of letrozole in postmenopausal women after 5 years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 349:1793–1802PubMedCrossRefGoogle Scholar
Harper-Wynne C, Ross G, Sacks N et al (2002) Effects of the aromatase inhibitor letrozole on normal breast epithelial cell proliferation and metabolic indices in postmenopausal women: a pilot study for breast cancer prevention. Cancer Epidemiol Biomarkers Prev 11:614–621PubMedGoogle Scholar
Heshmati HM, Khosla S, Robins SP et al (2002) Role of low levels of endogenous estrogen in regulation of bone resorption in late postmenopausal women. J Bone Miner Res 17:172–178PubMedCrossRefGoogle Scholar
Elisaf MS, Bairaktari ET, Nicolaides C et al (2001) Effect of letrozole on the lipid profile in postmenopausal women with breast cancer. Eur J Cancer 37:1510–1513PubMedCrossRefGoogle Scholar
Medina RA, Aranda E, Verdugo C et al (2003) The action of ovarian hormones in cardiovascular disease. Biol Res 36:325–341PubMedCrossRefGoogle Scholar
Shlipak MG, Chaput LA, Vittinghoff E et al (2003) Lipid changes on hormone therapy and coronary heart disease events in the heart and estrogen/progestin replacement study (HERS). Am Heart J 146:870–875PubMedCrossRefGoogle Scholar
Godsland IF (2001) Effects of postmenopausal hormone replacement therapy on lipid, lipoprotein, and apolipoprotein (a) concentrations: analysis of studies published from 1974–2000. Fertil Steril 75:898–915PubMedCrossRefGoogle Scholar
Wasan KM, Goss PE, Pritchard PH et al (2005) The Influence of letrozole on serum lipid concentrations in postmenopausal women with primary breast cancer who have completed 5 years of adjuvant tamoxifen (NCIC CTG MA.17L). Ann Oncol 16(5):707–715PubMedCrossRefGoogle Scholar
Buzdar AU (2004) Data from the arimidex, tamoxifen, alone or in combination (ATAC) trial: implications for use of aromatase inhibitors in 2003. Clinical Cancer Res 10:355s–361sCrossRefGoogle Scholar
Atalay G, Dirix L, Biganzoli L et al (2004) The effect of exemestane on serum lipid profile in postmenopausal women with metastatic breast cancer: a companion study to EORTC Trial 10951, ‘randomized phase II study in first line hormonal treatment for metastatic breast cancer with exemestane or tamoxifen in postmenopausal patients. Ann Oncol 15:211–217PubMedCrossRefGoogle Scholar
Demacker PN, Hijmans AG, Brenninkmeijer BJ et al (1984) Five methods for determining low-density lipoprotein cholesterol compared. Clin Chem 30:1797–1800PubMedGoogle Scholar
Bonanni B, Johansson H, Gandini S et al (2002) Effect of tamoxifen at low doses on ultrasensitive C-reactive protein in healthy women. J Thromb Haemost 1:2149–2152CrossRefGoogle Scholar
Wiseman H, Quinn P, Halliwell B (1993) Tamoxifen and related compounds decrease membrane fluidity in liposomes. Mechanism for the antioxidant action of tamoxifen and relevance to its anticancer and cardioprotective actions? FEBS 330:53–56CrossRefGoogle Scholar
Guetta V, Lush RM, Figg WD et al (1995) Effects of the antiestrogen tamoxifen on low-density lipoprotein concentrations and oxidation in postmenopausal women. Am J Cardiol 76:1072–1073PubMedCrossRefGoogle Scholar
Krag LE, Geisler J, Lonning PE, Ottestad L, Risberg T, Hagen AI, Lien EA, Polli A, Paolini J, Massimini G (2004) Lipid and coagulation profile in postmenopausal women with early breast cancer at low risk treated with exemestane: a randomized, placebo-controlled study. Proc Ann Meet Am Soc Clin Oncol 23:39, A650Google Scholar
Braithwaite RS, Chlebowski RT, Lau J et al (2003) Meta-analysis of vascular and neoplastic events associated with tamoxifen. J Gen Intern Med 18:937–947PubMedCrossRefGoogle Scholar
Goss PE, Ingle JN, Martino S, Robert NJ, Muss HG, Piccart MJ, Castiglione MM, Tu D, Shepherd LE, Pater JL (2004) Updated analysis of the NCIC CTG MA.17 randomized placebo (P) controlled trial of letrozole (L) after 5 years of tamoxifen in postmenopausal women with early stage breast cancer. Proc Ann Meet Am Soc Clin Oncol 23:87, A847Google Scholar
Turgeon JL, McDonnell DP, Martin KA, Wise PM (2004) Hormone therapy: physiological complexity belies therapeutic simplicity. Science 304:1269–1273PubMedCrossRefGoogle Scholar
Rossouw JE, Anderson GL, Prentice RL et al (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women’s health initiative randomized controlled trial. J Am Med Assoc 288:321–333CrossRefGoogle Scholar
Fisher B, Costantino JP, Wickerham DL et al (1998) Tamoxifen for prevention of breast cancer: report of the national surgical adjuvant breast and bowel project P-1 study. J Natl Cancer Inst 90(18):1371–1388PubMedCrossRefGoogle Scholar
Nordestgaard BG, Chapman MJ, Ray K et al (2010) Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J 31:2844–2853PubMedCrossRefGoogle Scholar