Taste Alterations Do Not Affect Change in Food Habits and Body Weight in Breast Cancer Patients

Abstract

Background/Aim: Chemotherapy-induced taste alterations (TAs) affect approximately 53-84% of breast cancer patients with significant consequences on flavor perception, possibly leading to food aversion and changes in daily dietary habits. The aim of this study was to investigate the relationship between TAs and changes in food habits and body weight among early breast cancer (EBC) patients undergoing adjuvant chemotherapy.

Patients and Methods: TAs were prospectively evaluated in 182 EBC patients from April 2014 to June 2018. TAs, dietary habits, and body weight were collected by a trained dietician. TAs were classified into different subtypes according to the following basic taste perception: metallic, sweet, bitter, salty, sour, and umami taste.

Results: During adjuvant chemotherapy, a significant reduction in the consumption of bread, breadsticks, red meat, fat salami, snacks, added sugar, milk, and alcoholic beverages was observed, regardless of TAs onset. No correlation between these dietary changes and different TAs subtypes was found. Body weight remained stable in most EBC patients (71.4%) and was not influenced by TAs onset and by different TAs subtypes.

Conclusion: EBC patients change their dietary habits during adjuvant chemotherapy, mostly following the World Cancer Research Fund recommendations, irrespective of TAs onset and without affecting body weight.

Dysgeusia is variably defined as an abnormal or impaired sense of taste, an unpleasant alteration of taste sensation, or a distortion or perversion of the sense of taste (1). Taste sensation is primarily based on the following basic qualities, namely sweet, bitter salty, sour; recently savory or umami (the taste of glutamate) was added as a new basic taste quality (2). Dysgeusia affects approximately 53-84% of breast cancer patients treated with chemotherapy (3,4) and taxanes are the cytotoxic drugs more frequently associated with the onset of this symptom (5). It has been shown that the main mechanism for taxane-related taste alteration is a neurological damage (6) involving both cranial nerves (VII, IX, and X) and taste receptors (7-9). Chemotherapy-induced taste alterations (TAs) may have significant consequence on flavor perception leading to food aversion, which in turn may lead to changes in daily dietary intake of certain foods (10), and consequently in body weight variation. It has been suggested that TAs are linked to a change in food-related behaviors in order to self-manage this unpleasant side-effect and some examples are eating strongly flavored food, eating candy before meals, drinking sweetened drinks (3). The high caloric intake correlated to this eating-behavior could justify weight gain reported frequently in early breast cancer (EBC) patients during adjuvant chemotherapy (11-15).

The aim of the study was to investigate the relationship between TAs and changes in dietary habits and in body weight among a consecutive series of EBC patients undergoing adjuvant chemotherapy and followed up to 12 months after the end of the treatment.

Patients and Methods

Trial oversight. A prospective, single-center trial was conducted at the Medical Oncology and Breast Unit of the ASST Spedali Civili of Brescia, registered in “ClinicalTrials.gov database” (NCT identification number: NCT03210441) and approved by the local Ethic Committee of Brescia.

The primary aim of the study was to evaluate eating habit changes during adjuvant chemotherapy and up to 12 months after its completion (16). The secondary aims were to assess TAs and weight changes during adjuvant chemotherapy and follow-up after the completion of adjuvant treatment.

This trial enrolled 205 EBC patients from April 2014 to June 2018 and the eligibility criteria, reported in detail elsewhere (16), were in briefly the following: histologically confirmed EBC; eligibility for adjuvant or neoadjuvant chemotherapy regardless of tumor biology and menopausal status; willingness to adhere to the study protocol. In the present paper we would like to report the results of the secondary aims of the study, that were to investigate the correlation between TAs, changes in dietary habits and in body weight. TAs assessment was performed by a trained dietician through two different questionnaires: 1) the National Cancer Institute Common Terminology Criteria for Adverse Event v4.0 (NCI-CTCAE) (17); 2) the Italian version of Chemotherapy-induced Taste Alteration Scale (CiTAS) (18,19). According to these questionnaires’ TAs were classified into six different taste impairment defined as: metallic taste, dysgeusia for sweet, dysgeusia for bitter, dysgeusia for salty, dysgeusia for sour and dysgeusia for umami.

Data collection. The questionnaires were administered at the following time point: T0) at baseline (before starting chemotherapy); T1) during chemotherapy; T2) after the last cycle of chemotherapy. Subsequently, they were administered every 3 months during the follow-up visits (P1 at 3 months, P2 at 6 months, P3 at 9 months and P4 at 12 months). Dietary habits, body-mass index (BMI) calculation and information about employment, physical activity and alcohol consumption were collected according to the methodology reported elsewhere (16).

Questionnaires and visits were completed at baseline (T0), during chemotherapy (T1 and T2) or during subsequent follow-up (P1, P2, P3, P4) by 182 patients out of 205 (88%). Therefore, we considered 182 patients evaluable for the analysis of this secondary end point. The consort diagram is shown in Figure 1.

Figure 1. Consort diagram. pts: Patients; CT: chemotherapy; T0: baseline evaluation; T1: first follow-up visit during chemotherapy; T2: second follow-up one week after chemotherapy end; P1: follow-up 3 months after chemotherapy; P2: follow-up 6 months after chemotherapy; P3: follow-up 9 months after chemotherapy; P4: follow-up 12 months after chemotherapy.

Statistical analysis. Categorical variables were expressed as frequencies and percentages; continuous variables were expressed as median and 95% confidence interval (95% CI). TAs were graduated according to NCI-CTCAE criteria (v4.0) and classified on the basis of toxicity grading as severe (grade 3-4), mild-to-moderate (grade 1-2), and none: for the aim of this study, since no severe toxicities were reported, TAs were classified as “present or absent”. Correlations between TAs (present vs. absent) with change in dietary habits and in body weight were explored at T1 considering the wider proportion of TAs in our population during chemotherapy; to assess differences between the 2 groups the Mann-Whitney U-test was used. As reported in a previous paper (16), we assessed the dietary intake of the following foods and beverages: fruit, vegetables, pasta, bread, breadsticks, potatoes, white meat, red meat, fish, fat salami, lean salami, eggs, fresh cheese, aged cheese, legumes, milk, yogurt, ice creams, snacks, added sugar (to coffee, tea, or other hot or cold beverages), soft drinks, wine, beer, schnapps, butter, and oil. The differences between eating habits from baseline to second follow-up T2 in each group of patients with and without TAs were assessed by Wilcoxon signed-rank test.

As reported previously (16) a weight gain or loss ≥5% following adjuvant chemotherapy was considered to be clinically meaningful (20,21): patients were classified as “increased weight”, “decreased weight” or “stable weight” if weight gained from baseline of at least 5%, decreased from baseline of at least 5% or did not change from baseline over threshold value of ±5%, respectively. TAs were assessed in the three weight categories by chi square test.

Results

Patient characteristics. The characteristics of all patients enrolled in the prospective trial were previously reported (16). The main clinical features of the 182 patients included in the current analysis are listed in Table I. Median age was 64 years (range=25-80); most patients were postmenopausal (58.2%). The most common chemotherapeutic drugs administered in 118 patients (64.8%) were the combination of anthracyclines and taxanes. The rate of TAs in patients included in the study showed a consistent increase from baseline (11%) to the first time point T1 (69.8%), remained substantially stable at T2 (64.8%), and consistently improved in the time points following the discontinuation of chemotherapy to reach baseline values at P4 (7.7%) (Figure 2).

Table I. Characteristics of the patients.

pT: Pathological tumor stage; pN: pathological nodal stage; G1: well differentiated tumor; G2 moderately differentiated tumor; G3: undifferentiated tumor; HER2: human epidermal growth factor receptor 2.

Figure 2. Taste alterations (TAs) evaluation at baseline, during chemotherapy, and subsequent follow-up. T0: Baseline evaluation; T1: first followup visit during chemotherapy; T2: second follow-up one week after chemotherapy end; P1: follow-up 3 months after chemotherapy; P2: follow-up 6 months after chemotherapy; P3: follow-up 9 months after chemotherapy; P4: follow-up 12 months after chemotherapy.

Correlation between TAs and dietary intakes. As reported in Table II, the patients reported a significant reduction in their intake of bread, breadsticks, red meat, fat salami, snacks, milk, beer, and wine regardless of having TAs or not. Similar data were obtained analyzing TAs according to subtypes (Table III and Table IV), except for snacks, that were consumed in greater quantity at T0 among patients developing bitter TA. The intake of other food and drink such as fruit, vegetables, pasta, potatoes, white meat, fish, lean salami, eggs, fresh cheese, aged cheese, legumes, yogurt, ice creams, added sugar, soft drinks, schnapps, butter, and oil did not change significantly in our series of patients (data not shown).

Table II. Correlation between taste alterations (TAs) and eating habits.

T0: Baseline; T1: first follow-up during chemotherapy. Food and beverage consumptions are expressed as mean of grams per week or milliliters per week with corresponding 95% confidence interval in brackets (95% CI).

Table III. Correlation between type of taste alterations (TAs) (metallic taste, sweet TA, bitter TA) and food or beverage’s habits.

T0: Baseline; T1: first follow-up during chemotherapy. Food and beverage consumptions are expressed as mean of grams per week or milliliters per week with corresponding 95% confidence interval in brackets (95% CI).

Table IV. Correlation between type of taste alterations (TAs) (salty TA, sour TA, and umami TA) and food or beverage’s habits.

T0: Baseline; T1: first follow-up during chemotherapy. Food and beverage consumptions are expressed as mean of grams per week or milliliters per week with corresponding 95% confidence interval in brackets (95% CI).

Correlation between TAs and body weight. As described in Table V, median weight and BMI did not change significantly during adjuvant chemotherapy irrespective of TAs onset. As reported previously (16), most patients (71.4%) maintained stable weight during treatment, 29 patients increased weight (15.9%) and 52 patients (12.6%) decreased weight. We did not find any correlation between TAs and the weight change categories (Table VI).

Table V. Correlation between taste alterations (TAs) at first follow-up during chemotherapy (T1) with weight and body-mass index (BMI) at baseline (T0), during chemotherapy (T1), and at the end of chemotherapy (T2).

Data are expressed with corresponding 95% confidence interval in brackets (95% CI).

Table VI. Taste alterations (TAs) and weight categories change.

Discussion

Despite TAs onset being a highly prevalent side-effect of chemotherapy (4,5,22), it remains a neglected side-effect compared to other toxicities of chemotherapy and literature is limited as well as clinician awareness and management support. TAs have also been reported even before starting chemotherapy in some cases (23).

The rate of TAs in EBC patients included in the study showed a consistent increase from baseline (11%) to the first time point T1 (69.8%), remained substantially constant at T2 (64.8%), and consistently improved in the time points following the discontinuation of chemotherapy, to reach baseline values at 12 months (7.7%). It is well known that TAs may cause food aversion and it has been reported that reduce energy intake, leading to malnutrition, weight loss, and a poorer prognosis in patients with advanced cancer on active treatment (24). On the other hand, compensation of TAs with tasting but high caloric foods may lead to weight gain (20). To the best of our knowledge, no papers have addressed this topic in EBC patients on adjuvant chemotherapy.

The aim of this study was to assess if TAs onset as general disorder and in all its single subtypes, such as metallic taste and sweet, bitter, sour, salty, and umami dysgeusia was associated with change in eating habits and in body weight during adjuvant chemotherapy.

As reported in a previously published paper (16), EBC patients nowadays are highly motivated and inclined to change eating habits towards a healthier direction early during adjuvant treatment, in order to prevent weight increase and potentially improve treatment efficacy. Most commonly, patients modified their diet through a reduction in consumption of animal fat, read meat, processed meat, added sugar, milk and other dairy products, bread, cereals and through a rise in fruit consumption (16,25). Among our patients, who underwent a TAs and dietary assessment by a trained dietician, we observed a significantly reduction of the consumption of bread, breadsticks, red meat, fat salami, milk, and alcoholic beverages during adjuvant chemotherapy, regardless of TAs onset.

The reduction in bread, breadsticks and snacks intake is in line with recommendation number 3 of the second report of the World Cancer Research Fund (WCRF) (26), advising to limit high energy foods. Moreover, it is in line with the fourth recommendation of the WCRF third report (2018) (27), advising to limit consumption of snacks and bakery foods. The decreased intake in red meat and fat salami is in line with recommendation number 5 of both reports (WCRF 2007 and 2018) (26,27), advising to limit the consumption of red and processed meat. Our patients significantly decreased the intake of two alcoholic beverages (wine and beer), in line with recommendations number 6 and 7, in WCRF 2007 and 2018, respectively, that advice to limit alcohol intake. For these reasons, most of the change in dietary habits are in line with WCRF recommendations for the primary prevention of cancer and also directed to cancer survivors (26,27).

As previously reported (16), cancer treatment did not significantly affect body weight and BMI; in this paper among patients with TAs, as well as in those who perceived metallic taste and who reported an impairment of sweet, bitter, sour, salty and umami taste, weight and BMI did not change significantly, compared with patients without any TAs.

To the best of our knowledge, this is the first report exploring the correlation between TAs and change in eating habits or in body weight among a large series of EBC patients, who underwent adjuvant chemotherapy and were prospectively followed. The strengths of the study include its prospective design and the standardized assessment of TAs carried out by a trained dietitian through a validated questionnaire, the Italian version of CiTAS, which was given at several timepoints. The large amount of data collected about different foods and beverages represents a further added value. However, the main limitations are related to the high level of dropouts (12%) for the secondary endpoint evaluation and to the lack of objective tool for TAs evaluation, which could have been complementary to the questionnaires employed.

In conclusion, our prospective study failed to confirm a correlation between TAs onset and food habits as well as with weight change during adjuvant chemotherapy. EBC women during adjuvant treatment tend to adopt some dietary habit changes as reported in a previous paper (16), irrespective to TAs onset, in agreement with WCRF recommendations (26,27), and without significantly affecting body weight.

Conflicts of Interest

The Authors declare no conflicts of interest.

Authors’ Contributions

RP, AB and BZ contributed to study conceptualization and design. RP, PdM, SB, AT, AZ, LL, GS contributed to data acquisition. MZ, LV, and DC contributed to data analysis. RP, PdM, and SM drafted the manuscript. AB, SG, VA, and ELS critically revised the manuscript. All Authors gave final approval.

Acknowledgements

A heartfelt thanks to the association of patients ESA (Educazione alla Salute Attiva), FIRM Onlus (Fondazione Internazionale di Ricerca in Medicina Onlus) and Beretta Foundation for their constant support to the Medical Oncology and Breast Unit of the ASST Spedali Civili of Brescia.