Abstract
Aims:
The major aim of this study is to examine the role of alterations in lipid profile in women developing breast cancer. This study was carried out between May 2009 and December 2010.
Background:
The relationship between lipids and breast cancer is undistinguished. Until now, conflicting results have been reported on the association between lipids and risk of breast cancer development in women.
Materials and Methods:
Plasma lipids (i.e., total cholesterol [TC], high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides [TG] were analyzed from 60 controls and 120 untreated breast cancer patients with clinical and histopathological evidence, under aseptic conditions. Venous blood was drawn from the cases and controls and estimations of lipid profile were done utilizing the standard procedures.
Statistical Analysis Used:
Independent sample t-test to compare the mean serum levels of lipid profile and TC/HDL ratio between patients and controls.
Results:
A significant rise in serum total cholesterol, low-density lipoprotein cholesterol, and ratio of total cholesterol: high density lipoprotein cholesterol values, whereas high density lipoprotein cholesterol and very low density lipoprotein cholesterol were not affected significantly by the breast cancer.
Conclusions:
The developing breast cancer might be considered as one of the factors in alterations in lipid profile levels.
Keywords: Breast cancer, high-density lipoprotein, lipid profile total cholesterol, low-density lipoprotein, triglycerides
INTRODUCTION
The lipid profile---also known as lipid panel---is a group of tests that are often ordered together to determine risk of coronary heart disease.[1] A physician may ask the patient to carry out a lipid profile as part of an annual medical check or if there is specific concern about cardiovascular disease (CVD), especially coronary artery disease. They are tests that have been shown to be good indicators of whether someone is likely to have a heart attack or stroke caused by blockage of blood vessels or hardening of the arteries (atherosclerosis).[2] The lipid profile typically includes: [3
Total cholesterol
High density lipoprotein cholesterol (HDL-C)-often referred to as good cholesterol
Low density lipoprotein cholesterol (LDL-C)-often referred to as bad cholesterol
Very low density lipoprotein cholesterol (VLDL-C)
The lipid profile report may include the ratio of cholesterol to HDL.[3] This ratio is sometimes used in place of total blood cholesterol. The goal is to keep the ratio optimally at 3.5:1.[4]
A lipid profile should be done after a nine- to twelve-hour fasting. If fasting is difficult to achieve, the values for total cholesterol and HDL-C may still be useful.[5]
If total cholesterol is 200 mg/dl or higher or HDL-C is less than 40 mg/dl, the individual will require to have a follow-up lipoprotein profile to determine LDL-C and triglyceride levels.[6] VLDL is a calculated number and not a typical measurement. It is estimated that VLDL equals 20% of total triglyceride levels, which is why triglycerides are divided by 5 to provide an estimated VLDL level. [ 7 ]
Several studies have demonstrated changes in serum lipids in cancer patients. Studies in patients with many types of cancers have demonstrated an increase in serum triglyceride concentrations with disease progression, which may also be accompanied by a decrease in serum HDL cholesterol.[8]
Breast cancer remains the most common type of cancer in females in the developed countries.[9] It has been postulated that changes in the concentrations of serum lipids in breast cancer could result from increased production of tumor necrosis factor (TNFa) by activated macrophages in response to the tumor.[10]
Breast cancer occurs when cells in the breast tissue divide and grow without control. Physicians divide cancer into four main stages. Most physicians use the American Joint Committee on Cancer staging system.[11]
Stage I breast cancer
The tumor is no more than 2 centimeters (cm), there are no cancer cells in the lymph nodes in the armpit, and the cancer has not spread anywhere else.
Stage II breast cancer
The lymph nodes under the arm contain cancer and the cancer has not spread and the lymph nodes under the arm contain cancer but the cancer has not spread.
In the stage 2A the tumor is less than 2 cm while in the stage 2B the tumor is between 2 and 5 cm.
Stage III breast cancer
Although no tumor is seen in the breast, the lymph nodes under the arm contain cancer cells and are stuck together or to other structures, but there is no sign of cancer spread. In the stage 3A, the tumor is more than 5 cm, in stage 3 B the tumor is fixed to the skin or chest wall, the lymph nodes may or may not contain cancer cells, but there is no further spread while in stage 3C, the tumor can be any size and has spread to lymph nodes in the armpit and under the breast bone, or to nodes above or below the collarbone, but there is no further spread.
Stage IV breast cancer
The tumor can be measured any size, the lymph nodes may or may not contain cancer cells, and the cancer has spread (metastasised) to other parts of the body such as the lungs, liver or bones.
The relationship between lipids and breast cancer is undistinguished. Until now, conflicting results have been reported on the association between lipids and risk of breast cancer in women. Some studies found that the dietary fat increases breast cancer risk. These studies have been strongly supported by international data collected among developed countries during the past few decades. Population aggregates with elevated lipid intake have tended to report elevated breast cancer incidence and mortality.[12]
The major aim of this study is to examine the role of developing breast cancer in alterations in lipid profile in women.
MATERIALS AND METHODS
Serum was obtained from 60 normal healthy persons (control) and 120 patients with different stages of untreated breast cancer patients with clinical and histopathological evidence, from the out patients and hospital admissions admitted to the Radiation and Isotopes Center Khartoum (RICK) in period between January, 2008 and December, 2009. The patients and control groups were all females and were age matched. The sample size was calculated by using the formula:
N = z2pq/d2
Were N ≡ sample size
z ≡ the standard normal deviation (1.96) which corresponded to the level of 95% confidence level
p ≡ proportion in target population
q ≡ 1-p
d ≡ degree of the accuracy desired
Many factors have been previously mentioned by many authors to influencing lipid profile in patients other than these with breast cancer were excluded from this study. These factors include diabetes mellitus, thyroid disorder, pregnancy, cardiac disease, obesity, alcohol abuse, renal diseases and other factors. [ 7 ] . Fasting 10 ml venous blood was drawn and serum was separated and analyzed within 6 hours at maximum. The lipid profile tests (T-C, HDL-C, LDL-C, VLDL, and T-C: HDL ratio) were analyzed in each sample.
The estimations were done using ready made enzymatic kits for cholesterol, triglyceride, and high density lipoprotein.[13] Very low density lipoprotein and low density lipoprotein results are obtained by Friedewald's equation[14] in which:
VLDL = TG/5
LDL = T. Cholesterol - HDL - VLDL
Obtained data were analyzed by using independent sample t-test by Statistical Packages for Social Science Software (SPSS). Statistical analysis where the value of P < 0.05 is considered as significant and P < 0.01 as highly significant.
Ethical clearance
This study was approved by the ethical committee of Radiation and Isotopes Center Khartoum (RICK) as a cross-sectional study. Informed consent was obtained from each participant.
RESULTS
The results showed that the values of T-C, LDL-C, and T-C/ HDL-C ratio were significantly increased in all the four stages of breast cancer comparing to the control group. The values of HDL-C and VLDL were not affected. Lipid profile and T-C: HDL-C ratio showed insignificant variations when comparison was carried between stages results [Table 1].
Table 1.
Serum lipoproteins values during different stages of breast (mean ± SD)

The values of lipid profile and T-C: HDL-C ratios in relation to parity in breast cancer patients were insignificantly changed when compare the results between primiparity (one birth) and multiparity (2-5 birth) [Table 2].
Table 2.
Effect of parity in breast cancer patients on serum lipoproteins values (mean ± SD)

The patients with breast cancer, in this study, were classified into three age groups. The values of lipid profile and T-C: HDL-C ratios were insignificantly changed when compare the results between these 3 groups [Table 3].
Table 3.
Effect of age in breast cancer patients on serum lipoproteins values (mean ± SD)

The patients with breast cancer (all cancer stages) were divided as premenopaused ladies and postmenopaused ladies. The values of lipid profile and T-C: HDL-C ratios were insignificantly changed when compare the results between the two groups [Table 4].
Table 4.
Serum lipoproteins values of breast cancer patients during pre and postmenopausal status (mean ± SD)

DISCUSSION
Getting breast cancer will undoubtedly change the patient life. Most women share a common fear: developing breast cancer. This is not an unfounded fear when considering that, except for lung cancer, breast cancer is the most common cancer found in women, accounting for one of every three diagnoses.[15] Cancerous tumors in the breast usually grow slowly. It is thought that by the time a tumor is large enough to be felt as a lump, it may have been growing for as long as 10 years. Early diagnosis is the best way to reduce the risk of dying from breast cancer.[16]
In this study, as in Table 1, values of T-C, LDL-C, and T-C/ HDL-C ratio were significantly increased in all the four stages of breast cancer (P value <0.05), while the values of HDL-C and VLDL were not significantly changed. These findings are in agreement with Florenza et al.[17] and Michael et al.,[18] but disagreed with Patricia et al.[19] who found that HDL-C levels were significantly decreased, and also disagrees with Kiran et al.[20] who found that TG results (and VLDL-C levels) were significantly increased especially in stage IV patients with breast cancer.
The increased T-C and LDL-C values and decreased HDL-C value increases the risk of coronary heart disease.[21]
From the results and as demonstrated in Tables 2–4, all parameters (parity, age, and menopausal status respectively) showed insignificant effect on lipid profile. These findings were agreeing with those of Tornberg et al.[22]
CONCLUSION
Lipid profile and T-C: HDL-C ratios were increased significantly in breast cancer in all stages.
ACKNOWLEDGMENTS
Authors are grateful to the V R Center for providing automated analyzer and its reagents.
It is to be mentioned that the project was self-sponsored financially.
Footnotes
Source of Support: Nil
Conflict of Interest: None declared.
REFERENCES
- 1.Washington, DC: NIH Publication No. 01-3670, National Institutes of Health; 2001. Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), Executive Summary. [Google Scholar]
 - 2.Birtcher KK, Bowden C, Ballantyne CM, Huyen M. Strategies for implementing lipid-lowering therapy: Pharmacy-based approach. Am J Cardiol. 2000;85:30–5. doi: 10.1016/s0002-9149(99)00936-4. [DOI] [PubMed] [Google Scholar]
 - 3.Drexel H. Reducing risk by raising HDL-cholesterol: The evidence. Eur Heart J Suppl. 2006;8:F23. [Google Scholar]
 - 4.Rader Daniel J. Raising HDL in clinical practice.2004. [Retrieved October 8, 2009]. http://www.medscape.org/viewarticle/479499_5 .
 - 5.University of Michigan Health System. [Retrieved October 8, 2009]. http://www.med.umich.edu/mdrtc/cores/ChemCore/lipids.htm .
 - 6.Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, et al. HDL Cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357:1301–10. doi: 10.1056/NEJMoa064278. [DOI] [PubMed] [Google Scholar]
 - 7.Nelson DL, Cox MM. 3rd ed. New York: Worth Publishing; 2000. Lehninger, Principles of Biochemistry. [Google Scholar]
 - 8.Nydegger UE, Butler RE. Serum lipoprotein levels in patients with cancer. Cancer Res. 1972;32:1756–60. [PubMed] [Google Scholar]
 - 9.Tehrani AM, Farajzadegan Z, Rajabi FM, Zamani AR. Belonging to a peer support group enhance the quality of life and adherence rate in patients affected by breast cancer: A non-randomized controlled clinical trial. J Res Med Sci. 2011;16:658–65. [PMC free article] [PubMed] [Google Scholar]
 - 10.Barclay M, Skipski VP. Lipoproteinins relation to cancer. Prog Biochem Pharmacol. 1975;10:76–111. [PubMed] [Google Scholar]
 - 11.Lacroix M. Significance, detection and markers of disseminated breast cancer cells. Endocr Relat Cancer. 2006;13:1033–67. doi: 10.1677/ERC-06-0001. [DOI] [PubMed] [Google Scholar]
 - 12.Park SY, Kolonel LN, Henderson BE, Wilkens LR. Dietary fat and breast cancer in postmenopausal women according to ethnicity and hormone receptor status: The Multiethnic Cohort Study. Cancer Prev Res (Phila) 2012;5:216–28. doi: 10.1158/1940-6207.CAPR-11-0260. Epub 2011 Dec 13. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - 13.Rifai N, Warnick GR, McNamara JR, Belcher JD. Measurement of low density lipoprotein cholesterol in serum: A status report. Clin Chem. 1992;38:150–60. [PubMed] [Google Scholar]
 - 14.Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low density lipoprotein cholesterol in plasma, without the use of preparative centrifuge. Clin Chem. 1972;18:499–502. [PubMed] [Google Scholar]
 - 15.Rodriguez-Pinilla SM, Sarrio D, Honrado E, Hardisson D, Calero F, Benitez J, et al. Prognostic significance of basallike phenotype and fascin expression in node-negative invasive breast carcinomas. Clin Cancer Res. 2006;12:1533–9. doi: 10.1158/1078-0432.CCR-05-2281. [DOI] [PubMed] [Google Scholar]
 - 16.Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO. Prognostic markers in triple-negative breast cancer. Cancer. 2007;109:25–32. doi: 10.1002/cncr.22381. [DOI] [PubMed] [Google Scholar]
 - 17.Florenza AM, Branchi A, Sommaviva D. Serum lipoprotein profile in patients with cancer.A comparison with non-cancer subjects. Int J Clin Lab Res. 2000;30:141–5. doi: 10.1007/s005990070013. [DOI] [PubMed] [Google Scholar]
 - 18.Paillasse MR, de Medina P, Amouroux G, Mhamdi L, Poirot M, Silvente-Poirot S. Signaling through cholesterol esterification: A new pathway for the cholecystokinin 2 receptor involved in cell growth and invasion. J Lipid Res. 2009;50:2203–11. doi: 10.1194/jlr.M800668-JLR200. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - 19.Yancey PG, Jerome GW, Yu H, Griffin EE, Cox BE, Babaev VR, et al. Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI. J Lipid Res. 2007;48:1140–9. doi: 10.1194/jlr.M600539-JLR200. [DOI] [PubMed] [Google Scholar]
 - 20.Hasija K, Bagga HK. Alterations of serum cholesterol and serum lipoprotein in breast cancer of women. Indian J Clin Biochem. 2005;20:61–6. doi: 10.1007/BF02893044. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - 21.Boekholdt MS, Thompson JF. Natural genetic variation as a tool in understanding the role of CETP in lipid levels and disease. J Lipid Res. 2003;44:1080–93. doi: 10.1194/jlr.R200018-JLR200. [DOI] [PubMed] [Google Scholar]
 - 22.Tornberg SA, Holm LE, Carstensen JM. Breast cancer risk in relation to serum cholesterol, serum beta lipoprotein, height, weight and blood pressure. Acta Oncol. 1988;27:31–7. doi: 10.3109/02841868809090315. [DOI] [PubMed] [Google Scholar]
 
