Summary
Side-effects following long-term endocrine therapy might have clinical implications. The aim of this study was to study potential methods to detect effects on plasma induced by hormonal therapies. The composite methylene (chemical shift between 1.2-1.4 ppm) and methyl (0.8-0.9 ppm) aliphatic peaks of the1H magnetic resonance spectrum (500 MHz) were analyzed in consecutive plasma samples of 23 cancer patients drawn before and during treatment with hormonally acting drugs. The aliphatic peaks were analyzed for line width at half-height and then averaged. In addition,13C magnetic resonance spectroscopy (125 MHz) analyses were done in selected patients. The blood samples were analyzed for triglyceride, cholesterol, apolipoprotein A1 (apo A1), and apolipoprotein B (apo B) levels.
The methylene line width increased significantly after 9 weeks of tamoxifen (41.4 vs. 37.6 Hz). A trend of differences was observed in the saturated part of the13C magnetic resonance spectrum. A significant decrease in total cholesterol (mean decrease, 13%), increases in apo A1 (9%) and in the ratio of apo A1 to apo B (28%), but unchanged total triglycerides were found, indicating a decrease in LDL and increase in HDL lipoproteins in these patients following tamoxifen therapy. During dose escalation with the aromatase inhibitor exemestane, the methylene line width seemed to decrease (31.9 vs. 38.8 Hz, at 12 weeks and baseline, respectively). Significant decreases in total (13%) and HDL (32%) cholesterol, apo A1 (25%), and total triglyceride (16%) levels were found during the same interval. The apo A1/apo B ratio decreased by 25%. For patients on dexamethasone, the proton aliphatic line widths increased one day after the initiation of therapy. The changes in line shape observed during dexamethasone therapy indicated lower levels of triglyceride-rich relative to triglyceride-poor lipoproteins, consistent with results from the lipid analyses.
In conclusion, nuclear magnetic resonance spectroscopy might have potential to detect effects on plasma induced by endocrine therapy. The lipid analyses in these patients were in support of the changes in lipid profile as evaluated by nuclear magnetic resonance spectroscopy.
References
Powles TJ, Tillyer CR, Jones AL, Ashley SE, Treleaven J, Davey JB, McKinna JA: Prevention of breast cancer with tamoxifen — an update on the Royal Marsden Hospital Pilot Programme. Eur J Cancer 26:680–684, 1990
Love RR, Newcomb PA, Wiebe DA, Surawicz TS, Jordan VC, Carbone PP, DeMets DL: Effects of tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node-negative breast cancer. J Natl Cancer Inst 82:1327–1332, 1990
Rössner S, Wallgren A: Serum lipoproteins and proteins after breast cancer surgery and effects of tamoxifen. Atherosclerosis 52:339–346, 1984
Bertelli G, Pronzato P, Amoroso D, Cusimano MP, Conte PF, Montagna G, Bertolini S, Rosso R: Adjuvant tamoxifen in primary breast cancer: influence on plasma lipids and antithrombin III levels. Breast Cancer Res Treat 12:307–310, 1988
Bruning PF, Bonfrer JMG, Hart AAM, de Jong-Bakker M, Linders D, van Loon J, Nooyen WJ: Tamoxifen, serum lipoproteins, and cardiovascular risk. Br J Cancer 58:497–499, 1988
Engan T, Krane J, Kvinnsland S: Proton nuclear magnetic resonance spectroscopy measurements of methylene and methyl line widths of plasma: significant variations with extent of breast cancer, duration of pregnancy, and ageing. NMR Biomed 4:142–149, 1991
Engan T, Krane J, Klepp O, Kvinnsland S: Proton nuclear magnetic resonance spectroscopy of plasma from healthy subjects and patients with cancer. N Engl J Med 322:949–953, 1990
Holmes KT, Mackinnon WB, May GL, Wright LC, Dyne M, Tattersall MHN, Mountford CE, Sullivan D: Hyperlipidemia as a biochemical basis of magnetic resonance plasma test for cancer. NMR Biomed 1:44–49, 1988
Chmurny GN, Hilton BD, Halverson D, McGregor GN, Klose J, Issaq HJ, Muschik GM, Urba WJ, Mellini ML, Costello R, Papadopoulos NM, Caporaso N, Smith ICP, Szuba M, Kroft T, Monck M, Saunders JK, Préfontaine M: An NMR blood test for cancer: a critical assessment. NMR Biomed 1:136–150, 1988
Herring FG, Phillips PS, Pritchard PH: Proton magnetic resonance spectroscopy of plasma from patients with dyslipoproteinemia: identification of factors governing methyl and methylene proton linewidths. J Lipid Res 30:521–528, 1989
Otvos JD, Jeyarajah EJ, Hayes LW, Freedman DS, Janjan NA, Anderson T: Relationships between the proton nuclear magnetic resonance properties of plasma lipoproteins and cancer. Clin Chem 37:369–376, 1991
Engan T, Bjerve KS, Høe AL, Krane J: Proton NMR spectroscopy of fractionated plasma lipoproteins and reconstituted plasma from healthy subjects and patients with cancer. Scand J Clin Lab Invest 52:393–408, 1992
Engan T, Krane J, Søreide JA, Bjerve KS, Kvinnsland S: Early changes in the1H-NMR plasma spectrum in patients following breast surgery. Eur J Surg Oncol 19:115–122, 1993
Wilding P, Senior MB, Inubushi T, Ludwick ML: Assessment of proton nuclear magnetic resonance spectroscopy for detection of malignancy. Clin Chem 34:505–511, 1988
Bernstein L, Ross RK, Henderson BE: Prospects for the primary prevention of breast cancer. Am J Epidemiol 135:142–152, 1992
Newnham HH: Oestrogens and atherosclerotic vascular disease — lipid factors. Baillière's Clinical Endocrinology and Metabolism 7:61–93, 1993
Cuzick J, Wang DY, Bulbrook RD: The prevention of breast cancer. Lancet i:83–86, 1986
Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR: High density lipoprotein as a protective factor against coronary heart disease. Am J Med 62:707–714, 1977
Peeling J, Sutherland G, Marat K, Tomchuk E, Bock E: 1H and 13C nuclear magnetic resonance studies of plasma from patients with primary intracranial neoplasms. J Neurosurg 68:931–937, 1988
Fossel ET, Hall FM, McDonagh J: C-13 NMR spectroscopy of plasma reduces interference of hypertriglyceridemia in the H-1 NMR detection of malignancy. Application in patients with breast lesions. Breast Cancer Res Treat 18:99–110, 1991
Engan T, Bjerve KSB, Høe AL, Krane J: Characterization of plasma lipids in patients with malignant disease by13C nuclear magnetic resonance spectroscopy and gas liquid chromatography. Blood, in press
Lønning PE, Dowsett M, Powles TJ: Postmenopausal estrogen synthesis and metabolism: alterations caused by aromatase inhibitors used for the treatment of breast cancer. J Steroid Biochem 35:355–366, 1990
Zimmerman J, Fainaru M, Eisenberg S: The effects of prednisone therapy on plasma lipoproteins and apolipoproteins: a prospective study. Metabolism 33:521–526, 1984
Niendorf A, Stang A, Beisiegel U, Peters A, Nagele H, Gebhardt A, Kuse R: Elevated lipoprotein(a) levels in patients with acute myeloblastic leukaemia after successful chemotherapeutic treatment. Clin Invest 70:683–685, 1992
Alexopoulos CG, Pournaras S, Vaslamatzis M, Avgerinos A, Raptis S: Changes in serum lipids and lipoproteins in cancer patients during chemotherapy. Cancer Chemother Pharmacol 30:412–416, 1992
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Engan, T., Krane, J., Johannessen, D.C. et al. Plasma changes in breast cancer patients during endocrine therapy — lipid measurements and nuclear magnetic resonance (NMR) spectroscopy. Breast Cancer Res Tr 36, 287–297 (1995). https://doi.org/10.1007/BF00713400
Issue Date:
DOI: https://doi.org/10.1007/BF00713400