INTRODUCTION
Breast cancer is the second most frequent cancer worldwide and the most prevalent among women. There is an estimated 59,700 new cases of breast cancer in Brazil; 1,670 in the state of Goiás and 560 in the city of Goiânia for each year of the biennium 2018-20191. In addition, the disease is the leading cause of cancer death, presenting high incidence and mortality, poor quality of life and high direct and indirect costs, becoming a public health problem2.
Breast cancer etiology is multifactorial and includes non-modifiable factors, such as age and family history of breast cancer and modifiable factors: nulliparity, absence of breastfeeding, the use of postmenopausal hormone therapy, physical inactivity, weight gain, alcohol consumption, and nutrition3,4. The American Cancer Society addresses factors related to the diet to reduce breast cancer risk, emphasizing plant-based foods. A diet pattern that is rich in fruits and vegetables promotes the adequate consumption of micronutrients4.
Nutritional and dietary factors are identified as possible protective factors to cancer development, since they may influence the expression of key genes in mammary carcinogenesis. They can silence, activate or modify, thus modulating hormonal axes and influencing the growth and proliferation among specific cellular populations5,6. Among the dietary components which may act blocking breast carcinogenesis, fiber, vitamins, minerals, phytochemicals and polyunsaturated fatty acids, omega-3 fatty acid and conjugated linoleic acid, present in some fruits, vegetables, eggs and milk, can be highlighted7.
Vitamin A and its derivatives are classified as antioxidants and perform an important role in biologic processes such as the control of cell differentiation, proliferation and apoptosis therefore it may act to inhibit malignant neoplasms8. Also, vitamin A may play a role in breast cancer development since studies have shown a correlation between the plasma concentration of carotenoids and the risk decrease of breast cancer development and mortality9,10. Thus, supporting the recommendation to consume plant-based foods since the source of carotenoids in diet are fruits and vegetables4,10. However, studies remain inconclusive3,4,5,6,7.
We evaluated associations between nutritional profile, micronutrient and macronutrient intake among women with and without breast cancer who attended a federal public referral center.
MATERIALS AND METHODS
We conducted a case-control study that used a convenience sample from the cohort project entitled “Impact of chemotherapy treatment on body composition, lipid and glycemic profiles among women with breast cancer”. The study was approved by the Research Ethics Committee of the Federal University of Goiás (CEP/UFG) under the report number 751.387 on August 2014. All the patients who agreed to participate in the study signed the Free and Informed Consent Form.
The study sample was divided into 80 women newly diagnosed with breast cancer (cases) who attended the Breast Diagnostic Reference Center at the Hospital das Clínicas at the Federal University of Goiás (CORA/HC-UFG), and 80 women without malignancy changes in the breast (controls). The volunteers were over 30 years of age, matched by age (quinquennium). We excluded women diagnosed with breast cancer recurrence and/or in treatment with palliative chemotherapy; with amputations or orthopedic problems that could compromise nutritional status, with psychiatric or neurological problems and presence of another neoplasia.
Data was collected through a pre-tested and standardized questionnaire. Sociodemographic variables investigated were age (in years), skin color (white/yellow and black/brown), marital status (with and without partner), city (Goiânia and outside the capital) and years of study.
The 24-hour dietary recalls were conducted on three non-consecutive days of the week; one of which had to a weekend11. This was done for the characterization of energy, macro and micro-nutrient food intake. The first questionnaire was completed in person and the last two were done through a telephone interview. The participants were asked about what kinds of food they ate and the amount that they consumed per meal. From the questionnaires we calculated macro and micronutrients using AVANUTRI software.
The results obtained for macronutrients were compared to the minimum and maximum intake amounts stipulated by the World Health Organization (WHO) and the United Nations Fund for Food and Agriculture (FAO)12. The cut-off point for energy consumption used was 1750 Kcal/day, which was based on the average intake among women diagnosed with breast cancer from a study conducted in Brazil13. As stipulated by the WHO, carbohydrates should make up 55-75%, proteins 10-15% and lipids 15-30%; these values were adopted as the standard for the study12.
The intake of micronutrients such as selenium (45μg/day), vitamin A (500mg/day), vitamin C (60mg/day), vitamin E (12mg/day), folate (320pg/dia) and fiber (20-35 mg/dia) were analyzed according to the Dietary Reference Intake recommendations10. Saturated fatty acids: <7%, polyunsaturated: <10%, monounsaturated: <20% are suggested by the Food and Nutrition Board of the Institute of Medicine, using the Estimated Average Requirements14. Dietary intake of cases and controls was verified.
Volunteers were also asked if they followed any sort of dietary recommendation, the type of fat that was most frequently used (subcategorized by vegetable and animal fat), the consumption of chicken/fish skin and/or excessive meat fat, the use of sweetener and the additional salt added to meals.
The database was prepared in Excel 2010 and statistical analysis was performed using SPSS Statistics software version 22.0 and Epinfo 7.0. Evaluation of data collected from dietary recalls was conducted on the Avanutri® software (Três Rios, Brazil).
Once the energy intake could influence the results of the analysis, all the evaluated nutrients were submitted to the energetic variation correction according to the WILLETT, HOWE, KUSHI residual method15.
Descriptive results were presented with mean and standard deviation or median (interquartile range), according to the presence or absence of a normal distribution, respectively, according to the Kolmogorov-Smirnov test.
Subsequently, a One-Way ANOVA test was performed to correct the micronutrient intake values, in order to determine the intra and interindividual variabilities and the total variance of the distribution. Other tests such as Student's t-test and Mann-Whitney/Wilcoxon Two-Sample were used to evaluate differences between groups, considering the level of significance of α <5.0% (p<0.05).
Odds Ratios were calculated in order to evaluate the odds of certain variables related to food consumption, energy intake, macro and micronutrients among participants with breast cancer (case) versus healthy controls, with a 95% confidence interval (CI). For all association analyses, the level of significance considered was α <5.0 (p <0.05).
RESULTS
From the 160 patients evaluated, we observed that the mean age of cases (52.89 ± 11.65 years) and controls (52.26 ± 11.88 years) was similar (p= 0.71), ranging from 31 to 86 years (cases) and from 30 to 87 years (controls), according the previous sample homogenization. The mean years of study was 7.9 ± 4.3 years (cases) and 11.9 ± 4.6 years (controls), ranging from 0 to 17 years (cases) and from 1 to 25 years (controls), with significant difference between groups (p= 0.01). The information on race, marital status and residence is presented in table 1.
Table 1 Sociodemographic variables investigated from women with and without breast cancer participating in the study. Goiânia-GO, 2014 - 2017 (n= 160).
Variables | Case (n= 80) | Control (n= 80) | Total (n= 160) | p* | ||||
---|---|---|---|---|---|---|---|---|
N | % | N | % | N | % | |||
Race | ||||||||
White | 28 | 35,0 | 35 | 43,7 | 43 | 26,9 | 0,33 | |
Black/Brown | 52 | 65,0 | 45 | 56,3 | 30 | 60,6 | ||
Marital Status | ||||||||
With partner | 46 | 57,5 | 48 | 60,0 | 94 | 58,7 | 0,87 | |
Without partner | 34 | 42,5 | 32 | 40,0 | 66 | 41,2 | ||
Residence | ||||||||
Goiânia | 42 | 52,5 | 73 | 91,3 | 115 | 71,9 | 0,01 | |
Others | 38 | 47,5 | 07 | 8,7 | 45 | 28,1 |
*Chi-square.
The results concerning dietary habits (Table 2) show that 77.5% (n= 124) of the volunteers did not followed any sort of dietary recommendation, in which the majority were breast cancer patients (p= 0.004). By analyzing macro and micronutrient intake, we observed that the consumption of energy, vitamin A, vitamin C, vitamin E, fiber, selenium and folic acid were below the recommended level for both groups (Table 3).
Table 2 Dietary habits of women, with and without breast cancer participating in the study. Goiânia GO, 2014 - 2017 (n= 160).
Variables | Case (n= 80) | Control (n= 80) | Total (n= 160) | p* | ||||
---|---|---|---|---|---|---|---|---|
N | % | N | % | N | % | |||
Follow dietary recommendation | ||||||||
No | 70 | 87,5 | 54 | 67,5 | 1 24 | 77,5 | 0,004 | |
Yes | 10 | 12,5 | 26 | 32,5 | 36 | 22,5 | ||
Type of fat | ||||||||
Fat from animal source | 7 | 8,8 | 6 | 7,5 | 13 | 8,1 | 0,75 | |
Fat from vegetable source | 73 | 91,2 | 74 | 92,5 | 147 | 91,9 | ||
Consumption of Chicken/Fish skin | ||||||||
Yes | 33 | 41,2 | 30 | 37,5 | 63 | 39,4 | 0,75 | |
No | 47 | 58,8 | 50 | 62,5 | 97 | 60,6 | ||
Consumption of meat fat | ||||||||
Yes | 25 | 31,6 | 28 | 35,0 | 53 | 33,3 | 0,74 | |
No | 54 | 68,4 | 52 | 65,0 | 106 | 66,7 | ||
Daily use of sweetener | ||||||||
Yes | 13 | 16,2 | 17 | 21,2 | 30 | 18,7 | 0,54 | |
No | 67 | 83,8 | 63 | 78,8 | 130 | 81,3 | ||
Addition of salt | ||||||||
Yes | 39 | 48,8 | 41 | 51,2 | 80 | 50,0 | 1,00 | |
No | 39 | 48,8 | 41 | 51,2 | 80 | 50,0 |
*Chi-square.
Table 3 Comparison of macro and micronutrient mean intake of women with and without breast cancer participating in the study. Goiânia-GO, 2014-2017 (n= 480 food recalls).
Nutrient1,2 | Case (n= 80) | Control (n= 80) | p |
---|---|---|---|
Energy (kcal) | 1453 ± 423,5 | 1513 ± 378,4 | 0,3513 |
Carbohydrates (g) | 211 (192 - 225) | 206 (189 - 221) | 0,2794 |
Proteins (g) | 58,6 (49,8 - 70,1) | 65,9 (58,7 - 74,8) | 0,0064 |
Lipids (g) | 38,9 (33,4 - 46,8) | 45,9 ± 8,97 | 0,00014 |
Saturated fatty acids (g) | 7,9 (5,2 - 11,4) | 10,2 (8,25 - 13,2) | 0,00024 |
Polyunsaturated fatty acids (g) | 5,00 (3,48 - 6,59) | 4,85 (3,56 - 7,51) | 0,7564 |
Monounsaturated fatty acids (g) | 10,0 (5,98 - 13,5) | 8,63 (6,65 - 11,9) | 0,626 |
Fibers (g) | 15,3 (11,1 - 19,1) | 13,7 (10,9 - 13,7) | 0,2864 |
Vitamin A (μgER) | 180 (102 - 395) | 319 (192 - 627) | 0,00034 |
Vitamin C (mg) | 46,4 (19,5 - 117,6) | 48,5 (27,5 - 105) | 0,7184 |
Vitamin E (mg) | 6,86 (4,61 - 10,9) | 6,96 (4,73 - 10,4) | 0,8894 |
Selenium (μg) | 35,8 (26,5 - 50,6) | 44,8 (35,4 - 68,5) | 0,1044 |
Folic acid (μg) | 71,0 (49,6 - 105,9) | 85,2 (63,7 - 116,8) | 0,1324 |
1Data presented as mean ± standard deviation or median (interquartile range).
2The nutrients were adjusted by energy according to the residual method (Willett, Howe and Kushi, 1997).
3Student's t test for dependent samples.
4Wilcoxon test.
Regarding the fat/oils used for cooking, fat from vegetable sources (soybean oil) was the most consumed (73.7%) in both groups. We observed that 39.4% (n= 63) reported consumption of fish skin. The consumption of fat visible on meat was 33.3% (n= 53). Daily use of sweetener was reported by 18.7% (n= 30) while the habit of adding additional salt to meals was reported by 50% (n= 80) of the respondents (Table 2).
We observed that the mean of total and saturated lipids consumption was significantly higher in the control group, but it did not exceed the recommended maximum values10 and the OR did not meet statistical significance (Table 4). Both groups presented vitamin A intake below the recommended level, however the case group presented even lower consumption, differing significantly from the control group.
Table 4 Odds ratio (OR) for food consumption variables among breast cancer cases versus controls. Goiania-GO, 2014-2017 (n= 480 food recalls).
Variables | Case (n= 80) | Control (n= 80) | OR | 95% CI | p* | ||
---|---|---|---|---|---|---|---|
N | % | N | % | ||||
Follow dietary recommendation (no) | 70 | 87,5 | 54 | 67,5 | 3,37 | 1,50-7,58 | 0,004 |
Consumption of fat/oils from animal source (yes) | 7 | 8,8 | 6 | 7,5 | 1,18 | 0,38 - 3,69 | 0,39 |
Consumption of chicken/fish skin (yes) | 33 | 41,3 | 47 | 58,8 | 1,17 | 0,62 - 2,21 | 0,63 |
Consumption of meat apparent fat (yes) | 25 | 31,7 | 28 | 35,0 | 0,86 | 0,44 - 1,66 | 0,65 |
Daily use of sweetener (yes) | 13 | 15,3 | 17 | 21,3 | 0,72 | 0,32 - 1,60 | 0,42 |
Addition of salt (yes) | 39 | 48,8 | 39 | 48,8 | 1,00 | 0,54 - 1,86 | 1,00 |
*Chi-square.
The results showed that the majority of women with breast cancer did not follow any sort of dietary recommendations. The odds of not following dietary recommendations were 3.37 times greater among those with breast cancer compared to those without breast cancer. The odds of consumption of chicken skin or fish skin and meat fat, as well as the use of sweetener and additional salt were not significantly higher among breast cancer patients compared to controls (Table 4).
Regarding to the consumption of total lipids, although the value of p was less than 0.05, the confidence interval included the value 1.0 (OR= 0.508, 95% CI = 0.24-1.06, p<0.05). On the other hand, breast cancer participants had greater odds of having insufficient vitamin A intake compared to controls (OR= 2.46, 95% CI= 1.19-5.05, p<0.01) (Table 5).
Table 5 Odds ratio (OR) for average energy, macro and micronutrients intake among breast cancer cases and controls. Goiania-GO, 2014-2017 (n= 480 food recalls).
Variables | Case (n= 80) | Control (n= 80) | OR | 95% CI | p* | ||
---|---|---|---|---|---|---|---|
N | % | N | % | ||||
Energy intake (IE) (>1750Kcal) | 19 | 23,8 | 61 | 76,3 | 1,350 | 0,63 - 2,89 | 0,220 |
Carbohydrate (g) (>75%) | 4 | 5,00 | 0 | 0,0 | – | – | 0,060 |
Proteins (g) (>15%) | 53 | 66,3 | 62 | 77,5 | 0,570 | 0,28 - 1,15 | 0,059 |
Lipids (g) (>30%) | 15 | 18,8 | 25 | 31,3 | 0,508 | 0,24 - 1,06 | 0,036 |
Saturated fatty acids (g) (>7% da IE) | 21 | 26,3 | 29 | 36,3 | 0,626 | 0,32 - 1,23 | 0,089 |
Polyunsaturated fatty acids (g) | 0 | 0 | 1 | 1,2 | 0,000 | – | 0,500 |
Monounsaturated fatty acids (g) | 80 | 100 | 80 | 100 | – | – | 1,00 |
Fibers (<20 g) | 62 | 77,5 | 70 | 87,5 | 0,492 | 0,21 - 1,15 | 0,051 |
Vitamin A (<500 mg/dia) | 65 | 81,3 | 51 | 63,8 | 2,464 | 1,19 - 5,05 | 0,007 |
Vitamin C (<60 mg) | 46 | 57,5 | 47 | 58,8 | 0,950 | 0.,51-1,78 | 0,437 |
Vitamin E (<12 mg) | 63 | 78,8 | 65 | 81,3 | 0,855 | 0,39 - 1,86 | 0,349 |
Selenium (<45 μg) | 52 | 65,0 | 49 | 61,3 | 1,175 | 0,62 - 2,24 | 0,314 |
Folic acid (<320 μg) | 80 | 100 | 80 | 100,0 | – | – | 1,00 |
*Chi-square.
DISCUSSION
The key findings of the study revealed that women with breast cancer were 3.37 and 2.46 times more likely to not follow dietary recommendations and consume less than 500 mg per day of vitamin A compared to women without breast cancer whom attended a federal public referral center in the Central-West region of Brazil.
As it is a multifactorial disease, breast cancer is associated not only with biological factors, but also with environmental and social aspects3. In the present study, when performing the sociodemographic characterization, the groups were similar in relation to race and marital status. However, they differed significantly in respect to residence. This result may be justified by the fact that CORA-HC-UFG is a reference center for the diagnosis and treatment of breast cancer in the central-western state and region, making it possible to access patients from surrounding municipalities.
We observed that more than three-quarters of the women interviewed did not follow food recommendations (such as decreasing salt, sugar, fat and/or pasta intake), which was also observed in every Brazilian region according to the last Family Budget Survey carried out in the country16.
Additionally, there was a greater likelihood of these patterns among women with breast cancer, possibly due to high consumption of pro-inflammatory foods, which are highly processed, rich in sugar, sodium and unhealthy fats and with a reduced consumption of anti-inflammatory foods and antioxidants such as fruits, vegetables and nuts17.
The process of industrialization and urbanization has possibly influenced food changes in the Brazilian population, contributing to increases of nearly 6.0% in ultra-processed food consumption in the country15,17. This is a contributing factor for some types of cancer, including breast cancer, because they create a favorable environment for breast tumor progression due to metabolic and hormonal dysregulation19. Therefore, adequate consumption of lipids concomitant with energy adequacy and increased consumption of fruits, vegetables and legumes may be crucial for reducing the risk for breast cancer as well as other chronic non-communicable diseases, which is in line with our results.
A review study suggests that the consumption of monounsaturated fatty acids (from olive oil and other sources) may modestly reduce the risk of breast neoplasia13. Another article, that considered prospective studies about the US population, showed an association between increased omega-3/omega-6 consumption and a reduced risk of developing breast cancer, suggesting their role in disease prevention20.
Dietary fiber may play a protective role against breast cancer because of its ability to reduce estrogen concentrations circulating in the bloodstream. In this way, they promote the inhibition of intestinal reabsorption of estrogen excreted in bile, in addition to favoring the increase of their fecal excretion21. Therefore, the adequate consumption of dietary fiber has been investigated as a possible protective factor against breast cancer21. In the present study, however, low fiber intake among breast cancer participants versus controls was borderline not significant. It should be noted that the majority of women (75.0%) with and without cancer had low consumption of dietary fiber, representing a concern.
Data from the Family Budget survey (2008-2009) shows that Brazilians have a low consumption of fiber18 reiterating the importance of promoting a diet rich in sources of fiber, such as fruits and vegetables.
A cohort study, using a convenience sample of 11,576 participants with breast cancer, found an inverse association of total dietary fiber intake and the disease incidence. Results were obtained using the Risk Ratio measured from the fifth to the first quintile of fiber consumption (RR= 0.95, 95% CI= 0.89-1.01, p= 0.03), concluding that diets rich in fibers, is associated with a modest risk reduction22.
Regarding micronutrients, we found that only insufficient consumption of vitamin A was higher in the group with breast cancer compared to controls. Vitamin A plays an important role in the protection of cell membranes against the action of free radicals and reactive species, in the control of cell differentiation, proliferation and apoptosis, and may act to inhibit malignant neoplasms8.
Vitamin A and its derivatives are part of a group of liposoluble compounds that play an important role in several biological processes due to their ability to promote adequate embryonic development and participate in metabolic processes and cell growth and differentiation until adulthood23. This micronutrient has been shown to play a protective role in the development of breast cancer24.
A critical literature review of the recently published literature has evaluated studies published over the past 15 years and has suggested that vitamin A consumption (retinol, B-carotene, and its analogues) may play a role in inhibiting carcinogenesis, concluding that deficiency of this micronutrient may have the inverse effect in patients with breast cancer25.
A meta-analysis aimed to investigate the association between the development of breast cancer and total vitamin A intake compared the highest and lowest intake of the vitamin, 10000 IU/day and 3000 IU/day, respectively. When grouping 51 studies, they observed a significant reduction of 17% (HR (grouped) = 0.83, 95% CI= 0.78-0.88, p<0.01). In addition, they compared total retinol intake, considering the highest value approximately 6000 mg/day and the lowest intake around 1000 mg/day. They analyzed 24 studies and found a 6% reduction in the risk of developing breast cancer (HR grouped)= 0.94, 95% CI= 0.89-0.99, p= 0.01)26.
Similar results to the present study were reported in a case-control study, conducted among Asian women with and without breast cancer. The authors found that the low plasma concentration, therefore low vitamin A intake, was twice as likely among the cases compared to controls (OR= 2.05, 95% CI= 0.19-4.10, p<0.05)27.
It is important to highlight the relevance of this research due to the lack of studies explore dietary intake of macro and micronutrients among breast cancer patients compared to controls, especially in the Brazilian population. In addition, the results obtained can be used to carry out actions to prevent illness and promote health, and contribute to the reduction of risks to breast cancer regarding to the diet. These actions are foreseen and can be strengthened by the Strategic Action Plan to Tackle Noncommunicable Diseases (NCD) in Brazil, 2011-2022, of the Ministry of Health18.
However, the study presents limitations, such as the convenience sample. In addition, the use of 24 h dietary recall is based on the self-reported description and depends on the interviewee's memory and may not represent the food consumed reliably. Specifically, the consumption of foods popularly known as less healthy may be underestimated, while those considered healthy can be overestimated28.