Consumption of foods with a higher degree of processing is associated with overweight and abdominal obesity in women with breast cancer undergoing chemotherapy

Abstract This study evaluated food consumption according to its degree of processing and its relationship with body adiposity in 218 women with breast cancer. Food consumption was categorised according to the NOVA classification. Two groups were formed, the first composed by consumption of in natura, minimally processed foods and culinary ingredients (less processed foods) and the second one of processed and ultra-processed foods (more processed foods). The increase of 5% in the caloric contribution of more processed foods was associated with a 4% increase in the prevalence of overweight (p = 0.028) and 3% in prevalence of abdominal obesity (p = 0.018). This reinforces the importance of evaluating food consumption with a focus on the degree of processing, as it can contribute to the prevention of excess body fat in this group, as this excess is associated with a worse prognosis and survival.


Introduction
Cancer is one of the biggest public health problems today, causing around 10 million victims worldwide in 2020 (INCA 2019;WHO 2022).
Cancer risk factors can be divided into modifiable and non-modifiable.Among the modifiable factors, being overweight, inadequate eating habits, a sedentary lifestyle, smoking and excessive alcohol intake stand out and are associated with approximately 80%-90% of cancers (INCA 2015).
Inadequate nutrition is considered the second leading preventable cause of cancer, accounting for up to 35% of deaths from the disease (Garófolo et al. 2004).There is evidence that a diet rich in fruits, vegetables, whole grains and legumes and poor in processed and ultra-processed foods can prevent 3-4 million new cancer cases each year worldwide.In addition, implementing a healthy diet is essential for a better prognosis among cancer patients and should be encouraged and targeted by public health policies (Garófolo et al. 2004;Ministério da Saúde 2013).
More processed foods (e.g., such as processed meats) have a significant content of additives such as nitrates and nitrites, used as preservatives and to enhance flavour.When ingested, they can produce nitrosamines and carcinogenic agents (Almeida et al. 2017;Fiolet et al. 2018).Nitrosamines and BHA (butyl hydroxyanisole antioxidants) can damage or cause mutations in the DNA, probably triggering neoplasia.Some artificial dyes, especially erythrosine, and tartrazine, also have carcinogenic potential in humans and animals.These substances alter the "turn-over" of cells during their expected growth or in the process of regenerative hyperplasia, contributing to cancer (Polônio and Peres 2009).
Another essential aspect to consider is that, in general, more processed foods are products rich in lipids and carbohydrates, contributing to increased weight gain and obesity, which are related to a higher risk of cancer (INCA 2017) in addition to worse prognosis and higher mortality in patients with the disease (Requejo and Rodríguez 2015;Almeida et al. 2017;Fiolet et al. 2018).
Knowing that chemotherapy produces adverse effects that negatively impact food acceptance, which may cause selectivity (Fernandes et al. 2020), it is necessary to investigate the degree of food processing consumed by these patients as more processed foods are more accessible in periods of greater weakness of the patient, once they come ready-to-eat or semi-ready, are more palatable and inviting (Macedo et al. 2020).This investigation may allow us to understand how this impact occurs in terms of the degree of processing of the food ingested.
It is important to highlight that few studies in the literature associate food consumption according to the degree of processing with indicators of body adiposity in cancer patients (Da Silva et al. 2022;Kliemann et al. 2023), especially in breast cancer (BC).Given the importance of food, it is essential to conduct a detailed assessment of cancer patients' food consumption to direct them to nutritional education actions and to take appropriate interventions.Thus, this study aimed to evaluate food consumption according to the degree of processing and its relationship with body adiposity in patients with BC undergoing chemotherapy.

Study design and ethical aspects
This is a cross-sectional study, which is part of a larger project called "Assessment of the association between nutritional status indicators, food consumption, inflammatory markers, and clinical outcomes of cancer patients treated at hospitals in the Viçosa region," developed by Pró-Onco Project, which seeks to provide nutritional care and guidance to cancer patients in the city of Viçosa, Minas Gerais and region.The study was approved by the Ethics Committee for Research with Human Beings of the Federal University of Viçosa (Opinion No. 4.893.180).Furthermore, it complies with the norms of the National Health Council (resolution 466/2012) (CNS 2012) that regulate research involving human beings.All participants included in the study signed an Informed Consent Form.
Data collection occurred from December 2021 to June 2022 at the Cancer Hospital of Muriaé -Cristiano Varella Foundation.The sample calculation was performed on the OpenEpi® website (http://www.openepi.com/Menu/OE_Menu.htm)based on an estimate of 398 patients with BC/year provided by the hospital itself.A precision of 5% and a frequency of overweight of 53% were considered (based on a verification of frequency in a subsample of 45 patients) (Miot 2011).An additional 10% was added to cover losses and control for possible confounding factors, resulting in a calculated sample of 216 patients.
The study included all female patients undergoing outpatient chemotherapy for BC during the data collection period and who were lucid, literate (or with a caregiver who could provide the necessary information), without risk of falling and without amputation or paralysis.

Anthropometric assessment
All anthropometric measurements were performed by the same person, trained to reduce measurement error.
Waist circumference (WC) was measured at the midpoint between the lower edge of the costal arch and the iliac crest at the midaxillary line (Callaway et al. 1988), and the classification for abdominal obesity was > 80 cm (WHO 1998).
The waist-hip ratio (WHR) was also calculated by dividing the WC (cm) by the hip circumference (cm).This measurement reflects the centralised distribution of body adipose tissue (Petribú et al. 2012), and the cut-off point for excess fat was > 0.85 (WHO 1998).
The waist-to-height ratio (WHtR) was calculated by dividing the WC (cm) by the height (cm), and the cut-off point was ≥ 0.5 as an indication of excess abdominal fat (Ashwell and Hsieh 2005).
The conicity index (CI) was also calculated, a model for evaluating the distribution of body fat that uses weight, height and WC as variables (Valdez 1991).The cut-off point for excess fat in the central region was > 1.18 (Pitanga and Lessa 2004).The anthropometric assessment was carried out before or after the chemotherapy session, depending on the patient's availability to participate in the study.

Assessment of food consumption
Food consumption was categorised according to the NOVA classification, and foods were classified as in natura or minimally processed, culinary ingredients, processed and ultra-processed (Monteiro et al. 2016).
The food survey was the 24-h dietary recall (R24h).In the R24h, the type of food consumed the day before, how it was prepared, and the amounts in household measurements were specified using the Automated Multiple-Pass Method (AMPM) as a reference (Moshfegh et al. 2008).To minimise errors in estimating portions, the household measurements were based on a food photo album in digital format (de Souza et al. 2021).The calculation of the calories of the food consumed was performed using the DietPro® Software, prioritising the Brazilian Food Composition Table (TACO) in its database (NEPA 2011).Oil and salt added during cooking in preparations not included in the TACO were not accounted for as the patients did not know how to report the amount used; on the other hand, the sugar added in these same preparations was accounted for when possible.
For the assessment regarding the degree of processing, in natura or minimally processed foods, and culinary ingredients were grouped together (less processed foods) as culinary ingredients are not consumed alone.The same combination happened with processed and ultra-processed foods (more processed foods).The assortment was done due to the similarity of effects the excessive consumption of these foods holds on health, originating the two groups (Ministério da Saúde 2014; Monteiro et al. 2016).Mixed preparations were classified according to the proportion of the main ingredients used.Thus, if the largest proportion of the main ingredients came from ultra-processed foods, the preparation was considered part of this group, and the same happened for the other food groups (Filha et al. 2012).The consumption of each group was evaluated as a percentage of the total calorie consumption.

Covariates
Data were collected through a semi-structured questionnaire already widely used by the Pró-Onco Project team, containing sociodemographic information, clinical history and lifestyle.In addition, tumour staging was collected from the patient's electronic medical record.
The covariates analysed were stage of life (adult or elderly), marital status, education, income, smoking, alcoholism, physical activity (based on patient self-report), complementary treatments to chemotherapy (surgery and radiotherapy), time since BC diagnosis, adverse effects on food intake produced by chemotherapy of impact: nausea and vomiting, mucositis, heartburn, gastric fullness, anorexia, odynophagia, dysphagia, and taste alteration (based on patient self-report of each adverse effect) and tumour staging.

Statistical analysis
The database was organised using Microsoft Excel®, and statistical analyses were performed using the Social Package Statistical Science -SPSS®, version 22 (Inc., Chicago, IL, USA) and STATA ® (College Station, TX, USA) software, version 14.
Quantitative variables were evaluated for normality using histogram, boxplot, asymmetry and kurtosis coefficients, quantile-quantile graphs and Shapiro-Wilk test, expressed as median and quartiles: percentile 25 (p25) and percentile 75 (p75) or mean and standard deviation (SD).Qualitative variables, in turn, were expressed in absolute values and relative frequencies.Finally, Mann-Whitney and Kruskal-Wallis tests (with Dunn's post hoc) were used to compare groups.
Poisson regression was used to analyse the association of food consumption according to the degree of processing with indicators of body adiposity, with robust variance.Prevalence ratios (PRs) were estimated, crude and adjusted for potential confounding factors defined according to the literature, with their respective 95% confidence intervals (95% CI).In all analyses, the significance level adopted was 5%.

Results
The study included 218 women aged between 27 and 84 (mean 54; SD = 11.9 years).The sample mainly consisted of married women or with a partner (52.8%), with incomplete primary education (50.5%), and with a family income between one and two minimum wages (58.3%).Regarding lifestyle, most never smoked (70.2%) or consumed alcohol (70.6%) and did not practice physical activity (64.7%).As for the treatment, the majority had the diagnosis for a maximum of one year (60.1%) and underwent surgery (67.4%) and radiotherapy (93.0%) as complementary treatments to chemotherapy.In addition, the largest proportion of participants had adverse effects on food intake resulting from chemotherapy (61.9%).Only 9.2% had stage I disease at diagnosis, 36.2% were in stage II, 21.1% were already in stage III and 11.9% were in stage IV.Mean BMI was 27.5 kg/m 2 (SD = 5.2), WC was 88.4 cm (SD = 12.1), WHR was 0.9 (SD = 0.4), WHtR was 0.6 (SD = 0.1) and the CI was 1.2 (SD = 0.1).According to the BMI classification, 59.2% of the participants were overweight.Regarding central body adiposity, 73.4% had abdominal obesity according to WC, 54.1% according to WHR, 97.7% according to WHtR and 65.1% according to CI (Table 1).
Concerning food consumption, the caloric contribution of more processed foods in the diet was 28.4%, representing almost 1/3 of total caloric consumption.It was also identified that patients with incomplete secondary education had significantly higher consumption of less processed foods and lower consumption of more processed foods than those with incomplete primary education (p = 0.044 for both comparisons).In addition, those with abdominal obesity, according to the WC, consumed fewer amounts of less processed foods (p = 0.017) and a greater amount of more processed foods (p = 0.013).No significant differences were observed in food consumption according to the degree of processing according to the other analysed variables (Table 1).
The caloric contribution of less processed foods in the diet was 71.6%, representing more than 2/3 of the total caloric intake.Among the less processed foods, the meat group contributed the most to the total caloric value of food (19.4%), followed by cereals and derivatives (18%) and then fruits (9%).On the other hand, sugar and similar products (7.4%), beans and pulses (5.8%) and milk and derivatives (5.4%) had a more significant contribution than legumes (4.6%) and vegetables (1.0%).Among the more processed foods, the groups with the highest contribution were bakery products (14.6%), sugary foods/sweets/ candies/supplements (3.6%) and processed meats (3.2%) (Table 2).
In crude and adjusted regression models for potential confounding factors, less processed foods consumption was inversely associated with overweight by BMI and abdominal obesity by WC.In contrast, more processed foods consumption was positively associated with these outcomes.The 5% increase in less processed foods caloric contribution was associated with a 3% reduction in prevalence of overweight (RP = 0.97, 95% CI = 0.93 − 1.00, p = 0.032) and abdominal obesity (RP = 0.97, 95% CI = 0.95 − 1.00, p = 0.021), while a 5% increase in the caloric contribution of more processed foods was associated with a 4% increase in prevalence of overweight (RP = 1.04, 95% CI = 1.00 − 1.07, p = 0.028) and 3% increase in prevalence of abdominal obesity (RP = 1.03, 95% CI = 1.00 − 1.05, p = 0.018) (Table 3).Additional analysis with more processed foods subgroups did not reveal associations with body adiposity variables, which can be attributed to the low individual caloric contribution of these subgroups (Supplementary Tables 1 and 2).

Discussion
As far as known, this is the first study that associates food consumption by the degree of processing with indicators that reflect body adiposity in cancer patients, especially in BC.
Previous studies carried out with the population have identified an association between food consumption according to the degree of processing and excess weight and abdominal obesity (Cordova et al. 2021;Pagliai et al. 2021).One cohort observed that the mean BMI and WC were higher as the intake of ultra-processed foods increased, even after adjusting for sociodemographic and socioeconomic characteristics, health-related behaviours and comorbidities.Individuals in the last quartile of ultra-processed foods consumption had a mean BMI of 0.80 kg/m 2 higher (95% CI: 0.53; 1.07) than individuals in the first quartile.Individuals in the last quartile of ultra-processed foods consumption had a mean WC 1.71 cm higher (95% CI: 1.02; 2.40) than individuals in the first quartile group (Silva et al. 2018).
The associations found in the study can be explained, in part, by the composition of the more processed foods, which have low levels of fibre and micronutrients, high content of total lipids, saturated and trans fatty acids, sugar, sodium and high caloric density, which have the potential to increase the caloric value of the diet and contribute to weight gain and abdominal obesity.Furthermore, these foods are practical, highly palatable, convenient, microbiologically safe and aggressively advertised and marketed (Monteiro et al. 2009;Silva et al. 2018;Blanco-Rojo et al. 2019).
In this work, the consumption of more processed foods was not predominant, which corroborates the study by Sales et al. (2020) in which only 27.1% of the calories ingested by patients with BC came from more processed foods.However, although the consumption of more processed foods was not predominant, these foods represented almost 1/3 of the total caloric intake, which is a worrying fact as these foods are associated with the occurrence of metabolic complications, in addition to worse prognosis and survival in BC (Pinheiro and Monteiro 2019).However, it is important to reflect on whether the weakness of patients due to the adverse effects of the treatment does not lead them to seek more processed foods because of the palatability, comfort and practicality.This leads to increased weight/body fat, and not weight loss, as the literature agrees.In this sense, there was a considerable prevalence of overweight in our sample.These data prove that the metabolic changes related to cancer, the location of the tumour and the oncological treatment impact the patient's relationship with food (INCA 2015).Patients undergoing chemotherapy may suffer different impacts on weight due to these conditions.However, the literature generally points out that weight gain may result from metabolic and hormonal changes and the impact on physical capacity caused by chemotherapy.In contrast, weight loss may result from adverse effects impairing food intake and losing lean body mass (Gadéa et al. 2012;Saxton et al. 2022).
Another major point is that even though consumption of less processed foods represents more than 2/3 of the total caloric intake, fruits, legumes and vegetables, essential foods for their micronutrients, fibres, antioxidants and bioactive compounds, were not the ones that most contributed to the total caloric intake, contrary to what is expected with the high consumption of foods in this group.Instead, meat consumption stood out the most, and cereals and derivatives (rich in carbohydrates) were consumed more than fruits, while sugar and similar products were consumed more than vegetables and legumes, with carbohydrates-rich foods, sugars and the like factors linked to overweight.However, analysing the consumption of fruits and vegetables together, in grams (399.5 g), the average per patient is close to the Brazilian recommendation, which is 400 g/day.
In a Brazilian study with BC patients, the main ultra-processed foods consumed were bakery products (12% of total kcal) and processed meats (2.5%) (Sales et al. 2020).In our work, bakery products were also highlighted, as well as processed meats.In the less processed foods group, the meat and eggs (13.6%) and fruit (9.3%) categories stood out (Sales et al. 2020), also similar to our findings.
Consuming unprocessed meat is beneficial for cancer patients, especially white meat since it is a source of protein, an essential element for preventing the loss of lean mass (Kałędkiewicz et al. 2020;Saxton et al. 2022).In addition, a higher intake of proteins may be associated with better BC survival (Gadéa et al. 2012;Holmes et al. 2017).
However, consuming non-whole grains and derivatives (carbohydrate sources) and sweetened or sugary foods should also be reduced.Excess refined carbohydrates in the diet can increase plasma triglyceride concentrations and reduce HDL concentrations (Carvalho and Alfenas 2008;Valença et al. 2021).Furthermore, the high consumption of refined carbohydrates directly affects overweight and the development of obesity, which are factors that worsen the prognosis of BC (Lee et al. 2019).It is also associated with dyslipidemia, glucose intolerance, diabetes mellitus and insulin resistance, risk factors for cardiovascular diseases (Carvalho and Alfenas 2008;Valença et al. 2021), which can also worsen the situation.As for sweetened or sugary foods, a cohort showed that women who consumed sugar-sweetened beverages had higher specific mortality from BC (Farvid et al. 2021).
The results of this study concerning body adiposity indicators were similar to those found in another Brazilian study carried out with women with BC undergoing chemotherapy, in which the BMI had a mean of 29.1 (SD = 6.7) kg/m 2 , the mean WC was 92.3 (SD = 20.2) cm and WHtR was 0.6 (SD = 0.1) (Ferreira et al. 2016).These data are worrying since obesity is linked to the genesis of cancer (Das and Webster 2022).Evidence suggests that excess adiposity is associated with worse disease-free survival and overall survival, despite appropriate local and systemic therapies.Excess body fat increases the risk of BC recurrence because it is directly related to the levels of many circulating hormones, such as insulin and oestrogen, in addition to producing inflammatory mediators.This picture induces metabolic and endocrine abnormalities that exert a proliferative and anti-apoptotic effect, facilitating the replication of tumour cells (WCRF 2018).
It should also be noted that overweight patients have high chemotherapy-related complications, and that systemic chemotherapy is less effective in this condition, even when adequately dosed based on actual weight (Lee et al. 2019).
We also verified, in this study, that the consumption of more processed foods was similar among different levels of education, differing only in those patients with incomplete secondary education, in agreement with Sales et al. (2020), income was also not a determining factor for consumption of more processed foods among the patients in our study.These findings demonstrate that the process of choosing, acquiring and consuming food is driven by a combination of biological, social and cultural factors, in addition to just knowledge and economic power (Simões et al. 2018).

Strengths and limitations
This study's strength is the use of a 24-h food recall to analyse the degree of food processing because, compared to the food consumption frequency questionnaire, it allows for greater detailing of the type of food and, consequently, a more appropriate classification.Furthermore, as far as we know, this is the first study that associates food consumption according to the degree of processing with indicators that reflect body adiposity in cancer patients, especially BC.However, as a limitation, we have the study's cross-sectional design, which does not guarantee the temporality of the associations observed between food consumption according to the degree of processing and body adiposity indicators.Moreover, another limitation is the analysis of data from only one R24h recall due to the impracticability of applying more than one because of the characteristics of the studied sample.Finally, the Table 3. association of food consumption according to the degree of processing (each 5% of caloric contribution) with body adiposity in women with Bc undergoing chemotherapy, Muriaé, Minas Gerais, Brazil, 2021-2022, (N = 218).collapsing of NOVA categories can also be considered a limitation, since less processed foods and more processed foods have a monotonic relationship.However, additional analysis with processed and ultra-processed foods assessed separately did not reveal statistically significant associations, which can be attributed to the lower individual caloric contribution of these subgroups in our study population.

Conclusion
In this cross-sectional study with BC patients undergoing chemotherapy, less processed foods consumption was inversely associated with overweight by BMI and abdominal obesity by WC.More processed foods consumption, in turn, was positively associated with excess weight and abdominal obesity.Although the consumption of foods from the more processed foods group was not predominant, it represented almost 1/3 of the total caloric value.
Our results reinforce the importance of assessing food consumption in BC patients undergoing chemotherapy, focusing on the degree of processing, as it can contribute to the prevention of excess body adiposity in this group, as this excess is associated with a worse prognosis of the disease and lower survival.

Table 1 .
consumption of in natura and minimally processed, processed and ultra-processed foods according to sociodemographic factors, aspects related to treatment and body adiposity in women with Bc undergoing chemotherapy,Muriaé, Minas Gerais, Brazil, 2021-2022, (N = 218).
In natura/minimally processed foods and culinary ingredients Processed foods and ultra-processed Values in bold p < 0.05.Poisson regression model with robust variance.Model adjusted for age, education, physical activity, time since diagnosis and presence of adverse effects impacting food intake.abbreviations: Bc: breast cancer; BMI: body mass index; cI: conicity index; cI 95%: 95% confidence interval; N: number of patients; Pr: prevalence ratio; WHr: waist-to-hip ratio; WHtr: waist-to-height ratio; Wc: waist circumference.