Women With Breast Cancer Undergoing Chemotherapy: Implications in Quality of Life

Study Overview
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Brief Summary
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Breast cancer is a major public health problem and is the main cancer disease in women worldwide and in Europe. In Portugal it is the most common cancer, the third cause of cancer death, following the European trend. Breast cancer (BC) triggers a myriad of physical and psychosocial stressors with repercussions on quality of life (QoL). This study is a pioneering Randomized Controlled Trial (RCT) in Portugal, which seeks to study the impact of a hedonic aroma during chemotherapy on women with breast cancer (3, 6 and 9 weeks, and 3 months after completion of chemotherapy). To this end, participants will be randomly assigned to one of the groups. The experimental group (EG) will be exposed to chemotherapy together with a hedonic aroma, while the control group (CG) will only be exposed to chemotherapy. Both groups will be assessed on psychological morbidity, illness perception, self-efficacy for coping, executive function, cortisol levels, side-effects, beliefs about chemotherapy and QoL. The aim of this study is to assess the impact of a hedonic aroma on the clinical, emotional and neurocognitive variables that contribute to reducing the side effects of chemotherapy and promoting QoL in women with BC.

Detailed Description
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The sample is non-probabilistic, consisting of 56 participants in the control group (CG) and 56 in the experimental group (EG). According to the calculations made for RCT studies (Noordzij et al., 2010), it will take approximately a total of 100 participants (50 participants per group) to detect a 10-point difference between the groups in the result variable QoL (e.g. EORCT QLQ-C30), with a population standard deviation of 15.43, according to previous study data (Lua et al., 2015), assuming a power of 90% and a significance level of 5%. This study contemplates four moments of evaluation: T1 (baseline: 2nd Cycle of CT but before intervention), T2 (6 weeks - 3rd Cycle), T3 (9 weeks - 4th Cycle) and T4 (3 months after the end of the CT). These moments were chosen taking into account the classes of drugs used in the CT. Each cycle has an interval of 21. This is a randomized controlled clinical trial (RCT) being single blind (the participant does not know which group he belongs to, only the investigator) and longitudinal. Intervention procedure: From the 2nd. Chemotherapy cycle (T1), the GC received the standard chemotherapy treatment; while the EG, in addition to the standard chemotherapy treatment, inhaled a hedonic aroma selected at the time of the chemotherapy (among three types of essential oils: bergamot, exotic verbena and geranium). The participant, as she received the CT, would inhale the aroma in a phased manner and under the supervision of the researcher, until the end of the treatment (about two hours). This intervention took place over three cycles of CT (2nd, 3rd and 4th Cycles). Inhalation was carried out using cotton rolls impregnated with the selected oil, since the more directly the odoriferous molecules are applied to the nose, the greater their impact into the organism (Schneider, 2016). However, since it was necessary that the researcher supervised the participants during the inhalation process, the number of times the researcher was in contact with participants from both groups (GC and EG) were the same: 4 times during the chemotherapy treatment to assure the participants from the EG would not have more contacts what could bias the results.

Official Title
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Clinical, Emotional, Cognitive and Neuropsychophysiological Impact of a Hedonic Aroma in Women With Breast Cancer Undergoing Chemotherapy: Implications in Quality of Life.

Conditions
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Breast Cancer Female

Intervention / Treatment
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* Biological: Inhalation of essential oils


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women with BC in stages 0-2; level 0-2 on the Zubrod scale, without cognitive impairment, adjuvant chemotherapy (AQ) treatment. Exclusion Criteria: Severe mental disturbance; olfactory impairment (≤6), evaluated before CT through the instrument smell diskettes and only in the EG participants

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: On each moment of data collection, the researcher will apply the evaluation protocol to the participant regardless of the group and before chemotherapy treatment. Regarding the psychophysiological variable, each participant's saliva will be collected using salivettes®, while cortisol concentrations will be analyzed through ELISA kits. At the time of the sample collection, before the CT, the participant who accepted to participate and fulfilled the inclusion criteria will be provided with three salivettes and an explanatory leaflet so that, on the day before the 2nd Cycle, they can collect their own saliva, around 23h, and on the day of CT, on waking up and thirty minutes after, fasting. This process will be replicated throughout the remaining evaluation moments. Subsequently, it is also our goal to evaluate the cortisol levels to CT by performing one collection of saliva before and another thirty minutes after CT.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>The Experimental Group participants will be submitted to the inhalation of the hedonic aroma during the chemotherapeutic treatment, this being the intervention of the study.The control group is not subject to intervention. | Biological: Inhalation of essential oils<br>* Intervention Inhalation of essential oils: From the T1 (2nd Cycle CT), Experimental Group Arms will undergo the inhalation of the hedonic aroma selected by them at the time of chemotherapy (among several types of aromas). It is intended that the participant, when receiving the CT, inhales the aroma phase-in and under the investigator's observation until the end of the treatment (about two hours). The inhalation of essential oils will occur using cotton rolls impregnated with the selected oil. The control group is not subject to intervention during chemotherapy treatment.<br>|
| No Intervention: Control Group<br>The control group is not subject to intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life - The experimental group presented, in comparison to the control group, lower level of QLQ | Assessment instruments: the European Organization for Research and Treatment of Cancer - Quality of Life (EORTC QLQ-C30) (Aaronson et al., 1993; Pais-Ribeiro, Pinto & Santos, 2008). Interpretation of the results, the higher the value obtained, the better the total quality of life - total quality of life result, through weighting formulas carried out by the European Organization for Research and Treatment of Cancer (EORTC) (http://groups.eortc.be/qol/manuals) | Changes from the 2nd cycle of CT(T1) (each cycle takes, on average, 2 hours with 3-week intervals) until 4th cycle of CT, assessed up to an average 1,5 months (T3) and again in the follow up (T4) (3 months after to the end CT, an average 6 months | 
| Anxiety and depression - The experimental group presented, in comparison to the control group, lower anxiety and depression | Assessment instruments: Hospital Anxiety and Depression Scale (HADS, Pais-Ribeiro et al., 2007) comprising both anxiety and depression scales. Scores range between 0 and 42 (anxiety between 0 and 21 and depression the same), with higher results indicating higher levels of distress. | Changes from the 2nd cycle of CT(T1) (each cycle takes, on average, 2 hours with 3-week intervals) until 4th cycle of CT, assessed up to an average 1,5 months (T3) and again in the follow up (T4) (3 months after to the end CT, an average 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distress | Assessment instruments: Emotions Thermometer (TE, Mitchell, Baker-Glenn, Granger, & Symonds, 2010; Teixeira et al., 2019) consisting of five analogue-visual scales, with four domains to identify emotional complications (distress, anxiety, depression, anger) and one outcome domain (need for help). In each thermometer de scores range between 0 and 10. A high result indicates emotional distress. | Changes from the 2nd cycle of CT(T1) (each cycle takes, on average, 2 hours with 3-week intervals) until 4th cycle of CT, assessed up to an average 1,5 months (T3) and again in the follow up (T4) (3 months after to the end CT, an average 6 months | 
| Saliva cortisol | The collection of saliva for the evaluation of cortisol concentrations was performed using salivettes® (Starsedt). The procedure to assess salivary cortisol concentrations was implemented according to the protocol stipulated by IBL International (Cortisol Saliva ELISA, IBL International GMBH). | Changes from the 2nd cycle of CT(T1) (each cycle takes, on average, 2 hours with 3-week intervals) until 4th cycle of CT, assessed up to an average 1,5 months (T3) and again in the follow up (T4) (3 months after to the end CT, an average 6 months | 
| Subscales of the Quality of Life in Breast Cancer | Assessment instruments: the European Organization for Research and Treatment of Cancer - Quality of Life, Module for Breast Cancer (EORTC QLQ-BR23, Sprangers et al., 2006. In this study, only the breast symptoms (scores range between 4-16), body image (scores range between 4-16), sexual functioning (scores range between 2-8) and side effects (scores range between 7-28) subscales were used. High scores indicate higher body image, sexual functioning and breast symptoms. | Changes from the 2nd cycle of CT(T1) (each cycle takes, on average, 2 hours with 3-week intervals) until 4th cycle of CT, assessed up to an average 1,5 months (T3) and again in the follow up (T4) (3 months after to the end CT, an average 6 months | 
| Illness Perceptions | Assessment instruments: Illness Perception Questionnaire (IPQ-Brief, Broadbent, Petrie, Main, & Weinman, 2006; Figueiras et al., 2010). This instrument comprises 9 items that assess patients' cognitive and emotional representations of the disease. There is one item that is open-ended and asks the perceived causes of the disease (not used in the study). Scores range between 0 and 80. Higher scores indicate a more threatening illness perception. | Changes from the 2nd cycle of CT(T1) (each cycle takes, on average, 2 hours with 3-week intervals) until 4th cycle of CT, assessed up to an average 1,5 months (T3) and again in the follow up (T4) (3 months after to the end CT, an average 6 months | 
| Self-efficacy for coping | Assessment instruments: Cancer Behavior Inventory-Brief Version (CBI-B, Heitzmann et al., 2011). This instrument evaluates self-efficacy for coping in cancer patients through 12-item. Scores range between 12 and 108 and higher scores indicate more effective coping strategies. | Changes from the 2nd cycle of CT(T1) (each cycle takes, on average, 2 hours with 3-week intervals) until 4th cycle of CT, assessed up to an average 1,5 months (T3) and again in the follow up (T4) (3 months after to the end CT, an average 6 months | 
| Working memory | Assessment instruments: WAIS III Subtest - Digit Span (Wechsler, 2008). It evaluates patients' working memory in clinical practice consisting of two parts: The Digit Span Forward (scores range between 0-16 maximum) and Digit Span Backward (DSB) (scores range between 0-14 maximum). High scores indicate high immediate auditory memory and working memory. | Changes from the 2nd cycle of CT(T1) (each cycle takes, on average, 2 hours with 3-week intervals) until 4th cycle of CT, assessed up to an average 1,5 months (T3) and again in the follow up (T4) (3 months after to the end CT, an average 6 months | 
| Cognitive Flexibility | Assessment instruments: Trail Making Test (TMT, Partington & Leiter, 1949; Cavaco et al., 2013). This instrument is composed of part A, which evaluates attention, visual tracking and speed of graphomotor coordination and information processing; and Part B evaluates Part A functions and the ability to switch between a set of stimuli. Lower raw indices and higher adjusted scores correspond to better cognitive performance. | Changes from the 2nd cycle of CT(T1) (each cycle takes, on average, 2 hours with 3-week intervals) until 4th cycle of CT, assessed up to an average 1,5 months (T3) and again in the follow up (T4) (3 months after to the end CT, an average 6 months | 
| Beliefs about chemotherapy | Assessment instruments: Beliefs about chemotherapy (BMQ, Horne, Weinman, & Hankins, 1997; Pereira, Pedras, & Machado, 2013). This instrument is composed of 18 items and comprises two sections: BMQ - Specific and BMQ-General. In this study, only the specific section was used regarding chemotherapy. The BMQ - Specific section incorporates two sub-scales of five items each: Specific Needs and Specific Concerns related to the dangers of dependence and toxicity and concerns regarding long-term side effects, respectively. The total on the Specific Needs Scale ranges from 5 to 25 and on the Specific Concerns Scale from 5 to 25. Higher scores in each subscale indicate stronger beliefs regarding the need of treatment and regarding concerns towards the treatment, respectively. | Changes from the 2nd cycle of chemotherapy (T1) (each cycle takes, on average, 2 hours with 3-week intervals between each cycle) until the date of 4th cycle of CT, assessed up to an average 1,5 months (T3) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Quality of Life, Breast Cancer, Essentials Oils, Adjuvant Chemotherapy, Salivary cortisol, Neuropsychophysiology