£These authors share first authorship.
The authors declare no conflict of interest.
Breast cancer (BC) is a heterogeneous disease characterized by the presence of a lump or mass in the breast tissue. BC has been associated with an abnormal lipid profile; however, this relationship is controversial. This study investigated the relationship of circulating lipid profiles with BC among Saudi women attending King Fahad Specialist Hospital, Dammam (KFSH-D), KSA.
Three hundred and ninety-nine (399) women between the years 2018 and 2021 were selected for this case control study based on the presence (for cases) or absence (for controls) of BC at the KFSH-D. The lipid levels of women with BC were compared to the lipid levels of healthy women. Data on total cholesterol (TC), triglyceride (TG), high-density lipoproteins (HDL), and low-density lipoproteins (LDL) were collected from 200 BC diagnosed patients and 199 healthy individuals. Statistical analysis was performed using the t-test and regression analysis.
This study showed significant differences between BC patients and healthy controls in terms of total cholesterol, HDL, and TG levels. No significant difference was observed in LDL levels.
This study revealed a significant relationship between the circulating lipid profile and breast cancer in a cohort of Saudi women.
Breast cancer (BC) is a heterogeneous disease characterized by the presence of a lump or mass in the breast tissue. It ranges from non-invasive to aggressive and invasive, depending on the degree of cancer spread and the type of lymph nodes affected.
Several studies have shown that women with BC are associated with obesity and dyslipidemia.
There are several diagnostic techniques for breast examination, such as mammography, breast ultrasound, computed tomography (CT), breast biopsy and breast magnetic resonance imaging (MRI).
Due to the high number of undiagnosed cases, significant efforts are needed to diagnose, monitor, and manage these patients as their condition progresses. Therefore, early diagnosis is an essential protocol for women at risk for breast cancer.
The relationship between BC and increased levels of serum lipids is controversial, with conflicting reports on the serum lipid profiles of patients with breast cancer compared with healthy controls.
This study investigated the relationship of the circulating lipid profile with BC among Saudi women. We hypothesized that, compared with healthy individuals, high levels of circulating lipid profile would be associated with a worse prognosis of breast cancer.
In this case control study, 399 female participants were selected on the basis of the presence (cases) or absence (controls) of BC at KFSH-D, KSA, in the period between 2018 to 2021. This study was approved by the human research ethics committees at KFSH-D (LAB0318).
The data on TC, HDL, LDL, and TGs levels were collected from the records of 200 diagnosed patients with BC and 199 healthy individuals attending KFSH-D, KSA. Dyslipidemia was defined according to the National Cholesterol Education Program–Adult Treatment Panel III (NCEP– ATP III) guidelines as TC > 5.2 mmol/L, LDL > 3.40 mmol/L, HDL< 1.3 mmol/L, or TG> 1.7 mmol/L.
The Alinity ci (chemistry immunoassay) system was used to analyze the lipid profiles (total cholesterol, TG, LDL, and HDL) from the blood specimens of the participants after an overnight fast (10–12 hours). The Alinity ci system is a fully automated chemistry analyzer designed to generate up to 1350 tests per hour and allows for random and continuous access as well as priority and automated retest processing. In addition, this system uses photometric detection technology to measure the sample absorbance for the quantification of the analyte concentration. A calculated absorbance is generated based on the reaction mode of the assay (rate or endpoint), and this absorbance is measured using a calibration curve to generate a result.
The raw data were collected and organized using Microsoft Excel (Microsoft Corp) and then analyzed using SPSS, version 26 (IBM Corp). Descriptive statistics, such as frequencies and percentages, were used to describe the characteristics of the study sample. Comparisons of the total cholesterol, TG, LDL, and HDL levels in the patients with BC and in the healthy control participants were performed using the independent samples t test. Associations of lipid profiles of patients with BC and healthy controls were assessed using binary logistic regression, and odds ratios (ORs) with 95% confidence interval (CI), were calculated. A P value ≤ 0.05 was considered statistically significant.
Table 1 shows the demographic and clinical characteristics of the 399 participants. They were 199 healthy adults, who ranged in age between 26 and 87 years, and 200 BC patients, ranging in age between 25 and 60, with a mean age of 41 and 59, respectively. The age of the majority of participants (49.6%), ranged between 45 and 64 years, and the fewest number of participants (14%) were ≥65. The average levels of total cholesterol, HDL, LDL, and TG for the patients were 4.88 mmol/L, 1.36 mmol/L, 3.00 mmol/L, and 1.54 mmol/L, respectively. The mean levels of total cholesterol, HDL, LDL, and TG for the healthy controls were 2.50 mmol/L, 1.20 mmol/L, 2.98 mmol/L, and 0.95 mmol/L, respectively.
| Group | Parameter | n | Minimum | Maximum | Mean (SD) |
|---|---|---|---|---|---|
| Patients | Total cholesterol, mmol/L | 200 | 2.60 | 8.38 | 4.88 (1.12) |
| HDL, mmol/L | 200 | 0.32 | 2.46 | 1.36 (0.37) | |
| LDL, mmol/L | 200 | 0.64 | 5.99 | 3.00 (0.97) | |
| Triglycerides, mmol/L | 200 | 0.33 | 8.26 | 1.54 (1.00) | |
| Age, year | 200 | 26.00 | 87.00 | 59.22 (9.54) | |
| Valid number (listwise) | 200 | ||||
| Controls | Total cholesterol, mmol/L | 199 | 0.34 | 6.70 | 2.50 (1.39) |
| HDL, mmol/L | 199 | 0.54 | 4.90 | 1.20 (0.45) | |
| LDL, mmol/L | 199 | 2.15 | 3.99 | 2.98 (0.27) | |
| Triglycerides, mmol/L | 198 | 0.34 | 5.10 | 0.95 (0.42) | |
| Age, year | 199 | 25.00 | 60.00 | 40.97 (8.09) | |
| Valid number (listwise) | 198 |
HDL, high-density lipoprotein; LDL, low-density lipoprotein.
Table 2 shows the results of the statistical analysis of the total cholesterol, TG, LDL, and HDL levels in patients with BC and the healthy controls. The analysis using independent samples t tests indicated significant differences (P < 0.001) between the total cholesterol, TG, and HDL levels of the patients with BC and the healthy controls. However, there was no significant difference (P = 0.74) between the LDL cholesterol levels of the 2 groups.
| Parameter | Healthy (n = 199), mean (SD) | Cancer (n = 200), mean (SD) | Independent t test | ||
|---|---|---|---|---|---|
| t | df | P value | |||
| Total cholesterol, mmol/L | 2.48 (1.39) | 4.88 (1.12) | −18.84 | 378.67 | <0.001 |
| Triglycerides, mmol/L | 0.95 (0.41) | 1.53 (1.00) | −7.52 | 266.37 | <0.001 |
| LDL, mmol/L | 2.98 (0.27) | 3.00 (0.96) | −0.33 | 230.88 | 0.74 |
| HDL, mmol/L | 1.20 (0.45) | 1.35 (0.37) | −3.64 | 381.14 | <0.001 |
HDL, high-density lipoprotein; LDL, low-density lipoprotein.
Table 3 below shows regression analysis of the lipid profile parameters and age, which indicates a significant association with BC, and the P values were as follows: TC (P < 0.001); HDL (P < 0.001); TGs (P < 0.001); and age (P < 0.001). Table 3 also shows that TC, TG, HDL, and age increases the risk for breast cancer by 5.10 fold (95% CI = 3.60–7.23), 6.88 fold (95% CI = 3.95–12.00), 3.26 fold (95% CI = 1.66–6.44), and 1.27 fold (95% CI = 1.22–1.34), respectively. After adjusting for other types of lipids and age the odds of developing breast cancer for TC and HDL were found to be 4.6 fold (95% CI = 3.60–7.23) and 3.2 fold (95% CI = 1.11–4.82), respectively, which remains stable and strongly increases breast cancer risk, independent of TG and age. TG showed a strong crude effect but a weaker after adjustment with odds of 2.3 fold (95% CI = 1.29–8.33). Older age increases breast cancer risk by 1.3 times (95% CI = 1.23–1.44) independently of TC, HDL and TG.
| Parameter | Crude OR (95% CI) | P value | Adjusted OR (95% CI) | P value |
|---|---|---|---|---|
| Total cholesterol (TC) | 5.10 (3.59-7.23) | < 0.001* | 4.62 (2.79-7.65) | < 0.001* |
| High-density lipoproteins (HDL) | 3.26 (1.65-6.43) | < 0.001* | 3.27 (1.29-8.33) | < 0.013* |
| Triglyceride (TG) | 6.88 (3.94-11.99) | < 0.001* | 2.30 (1.10-4.82) | < 0.027* |
| Age | 1.27 (1.21-1.34) | < 0.001* | 1.32 (1.22-1.43) | < 0.001* |
BC continues to be the most commonly diagnosed cancer in women and is the second leading cause of cancer death worldwide. It is the most common cause of cancer among women in both high-resource and low-resource settings.
Several studies have found that elevated serum total cholesterol levels play a significant role in the development of cancer, while others have found no significant effect. The results of this study indicated that total cholesterol was significantly higher in the patients with BC than in the healthy controls. These findings are in line with several previous studies.
In contrast to our study, some research has found that hypercholesterolemia is either negatively associated with BC or has no effect.
Our study also showed a significant difference between the TG levels of BC cases and healthy controls. Similar results were reported by previous studies.
The results for HDL also showed a significant difference between the HDL levels of BC cases and healthy individuals. Similar results were also obtained in several studies, which reported a significant association between HDL and the risk of breast cancer.
The way in which higher HDL levels are associated with BC is unknown; however, it could be due to the fact that higher HDL levels may reflect higher levels of endogenous estrogens or a stronger response to them, both of which are linked to an increased risk of BC.
In this study, we found no significant differences in the LDL levels between the patients with BC and the healthy controls, which is supported by several studies but refuted by others.
The higher odds ratios obtained by regression analysis indicate that there is a significant association between serum lipid profiles and age and the chance of developing breast cancer. It is important to note that, compared to healthy individuals, people with breast cancer have a greater likelihood of developing hypercholesterolemia, hypertriglyceridemia, and high HDL levels. The results of this research suggest that abnormal lipid metabolism and age are related to the development of breast cancer. This result is consistent with the available data in the literature, which views lipids
The findings of this study may encourage further research into the processes through which lipid metabolism may influence the occurrence and progression of breast cancer. These findings may also have implications for risk assessment, the development of early detection methods, and the formulation of treatment strategies that focus on lipid pathways with a view to lowering the risk of breast cancer.
It is of utmost significance to recognize the limitations of the research, which include its retrospective design, possible confounding variables that were not accounted for in the analysis, menopausal status, and the absence of causal inference owing to the observational character of the study. Further investigations using larger sample sizes and more extensive data gathering have the potential to provide a more thorough understanding of the complicated association between lipid profiles and breast cancer.
In summary, our findings confirm that dyslipidemia is linked to the development of BC and that total cholesterol, HDL cholesterol, and TGs are major risk factors for the development of BC. This study highlights the need to reduce the incidence and mortality of breast cancer by altering lifestyle choices, monitoring serum lipid levels, and preventing and treating dyslipidemia. Further clinical studies that focus on lipid metabolism in cancer are necessary because the most prevalent method of lowering serum lipid levels to support cancer treatments is the use of medications that block lipid production.
The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board at King Fahad Specialist Hospital–Dammam (protocol LAB0318; approved June 9, 2021). Patient consent was waived due to the retrospective nature of the study and the fact that the participants remained anonymous.
The data that support the findings of this study are not publicly available due to privacy and ethical restrictions.
This research received no external funding.
The authors would like to thank King Fahad Specialist Hospital–Dammam, Kingdom of Saudi Arabia, for providing the data used in this research.