The Effect of Uncertainty-Tolerance-based Intervention in Couples on the Mental Adaptation to Disease in Women With Breast Cancer: a Randomized Clinical Trial


 Purpose: The aim of this study was to evaluate the effect of a couple-coping intervention aiming to improve uncertainty tolerance in women diagnosed with breast cancer and their spouses on the patients’ mental adaption to their disease. Methods: The present study was conducted on 90 women with breast cancer referred to educational, medical and research centers in Urmia, IRAN, which 45 patients were randomly assigned to each treatment and control groups. Outcome measures were assessed at baseline and 6 weeks using short form mental adjustment to cancer (Mini-MAC) questionnaire. The intervention was performed in 6 group-based sessions consisting of patients and their spouses. Results: comparing the change from before to after intervention revealed that the effect of the intervention was significant in reducing hopeless-helpless (-5.42 ± 2.42 in intervention group VS -0.13 ± 0.46 in control group, P<0.001) and anxious preoccupation (-6.80 ± 2.87 VS -0.16 ± 0.82, P<0.001). It has also been significant in increasing fatalism (4.89 ± 2.09 VS 0.22 ± 1.24) and fighting spirit (3.58 ± 2.05 VS 0.11 ± 1.61). The effect of intervention on changing avoidance scale was not significant (P = 0.83).Conclusion: Couple-centered intervention program based on increasing uncertainty tolerance can be used to improve the situation in order to increase the patients' adjustment and it has an effective support for breast cancer patients in helping to cope with cancer. Trial registration number: IRCT20150125020778N21.Date of registration: 2020-12-13.


Introduction
Breast cancer is one of the most important health problems worldwide which is the most common cancer in women, accounting for 22% of cancer deaths in 2017 (1). The incidence of breast cancer in the United States has increased signi cantly over the past 50 years (2). It has been estimated that the number of new cases of breast cancer would increase from 1 million to 15 million annually by 2020 (3). Similar to other developing countries, the incidence of breast cancer in Iran is high, making it is the most common cancer among Iranian women which accounts for 76% of the common cancers in Iranian women (4,5).
Moreover, studies reported that the incidence and prevalence of breast cancer have been dramatically increased in the past decades (6-8) and it is estimated that the incidence rate of breast cancer will be doubled by 2030 (5,9,10).
Breast cancer leads to signi cant challenges in women and their families. Physical changes throughout the course of the disease, especially due to the side effects caused by treatment can affect the patients' self-awareness, self-con dence and sense of worth and acceptance. Following changes in patients' physical and mental condition, their social relationships and intimate interactions with others will be changed and the patients may feel disrupted in their family and social life (11,12). Cancer can have a signi cant impact on couples' emotional life (13).
Patients with breast cancer cope with their condition with various strategies (14); however, coping with cancer may face numerous obstacles. Intolerance of uncertainty in individuals with cancer is shown to affect patients' mental wellbeing and their coping strategies (15). Additionally, uncertainty can adversely affect the quality of life in patients with cancer and their spouses (16,17). To the best of our knowledge, few studies have aimed to evaluate the effect of intervention targeting uncertainty on patients' coping status. Moreover, only one study was found to target couples in this matter, concerning the important role of spouses in supporting the patients to mentally adapt to the disease (14,18). The aim of this study was to evaluate the effect of a couple-coping intervention aiming to improve uncertainty tolerance in women diagnosed with breast cancer and their spouses on the patients' mental adaption to their disease.

Participants
The present study is an experimental clinical trial that was conducted on women with breast cancer referred to educational, medical and research centers in Urmia, west Azerbaijan, Iran in 2020-2021 (clinical trial code: IRCT20150125020778N21). The study population included women with breast cancer The inclusion criteria of patients were as follows: patients aged 30 to 60 years, having breast cancer stage 1, 2 and 3 based on the pathology results, having information about breast cancer, more than 48 hours after chemotherapy, was married and has lived with his wife for more than 12 months, not attending another training session, having mental health (the patient and his wife) on the basis that they do not have a history of hospitalization in psychiatric wards and a history of taking anti-drugs. The occurrence of any stressful event for the patient or rst class members of the patient's family during the study, the absence of more than two sessions related to the intervention, other cancers or any lifethreatening illness caused the patient to exude from the study. Taking into inclusion criteria of present study, it was decided that 200 couples to enter the study by convenience sampling method and using an envelope containing even or odd numbers, 100 patients were randomly assigned to each group but due to the prevalence of Covid-19 from March 2020, which itself became a stressful event and could be affect the results of the study, the ethics committee decided to stop sampling and eventually 90 patients were considered as nal cases which 45 patients were randomly assigned to each treatment and control groups ( Figure 1).

Measurement tools
A brief questionnaire was completed to obtain basic characteristics and disease related information including age, number of child, patient and her spouse education level, economic status, stage of breast cancer, duration of awareness about cancer diagnosis, and surgery status. Mental adjustment was measured using a shortened form of the Mental Adjustment to Cancer (Mini-MAC) questionnaire that its factor structure and psychometric properties evaluated in a sample of Iranian adults who suffer from cancer (19). This questionnaire has 5 subscales and the higher the score on each subscale, the stronger the use of that coping strategy and this means that the subject uses that subscale as a style or strategy for adapting to more cancer. Items are scored on a 4-point Likert scale from 1 = "De nitely does not apply" to 4 = "De nitely applies to me". HH: Helpless-Hopeless, AP: Anxious Preoccupation, CA: Cognitive Avoidance, FA: Fatalism, and FS: Fighting Spirit are the Mini-Mac subscales. In the present study, Based on pre-treatment information of 25 primary patients the reliability of the Mini-MAC questionnaire was assessed through internal consistency, with a Cronbach's alpha coe cient of 0.79 for the HH subscale, 0.87 for AP, 0.71 for CA, 0.83 for FA, and 0.72 for the CA subscale were achieved.

Intervention
Design interventions included helping to develop the ability to tolerate ambiguous situations, reinforcing positive beliefs about worry, cognitive avoidance, and negative orientation toward the problem. The intervention was performed in 6 group-based sessions consisting of patients and their spouses in groups of 6 to 10 people. The duration of each session was about 1.5-2 hours per week for 6 weeks. The topics and strategies used in the meetings are detailed in Table 1. To evaluate the participants in both groups, a notebook was provided to record their daily behavior. The control group did not receive any intervention program before the post-test and only received routine care in cancer patients that all cancer patients receive. At the end of the sixth session, the questionnaires were completed again and the results were entered, cleaned and analyzed by software. Table 1 The topics and strategies used in the groups-based meetings in the intervention group.

Results
Baseline characteristics and disease related features of 90 patients, randomly assigned to the intervention and control groups, are shown in Table 2. The mean (median) and distribution (frequency, percent) of measured variables were compared between groups. Study participants did not signi cantly differed considering age, number of child, economic status, education level and their husband's education level, economic status, and home ownership (P>0.05). In terms of disease related factors including disease onset, disease stage and surgery status, patients were homogeneous in the two groups and there was no signi cant difference (P>0.05). Data represented as frequency (percent), mean ± SD or median (Q1 -Q3).
The percentage for categorical variables is calculated in columns and the total column percentage is equal to 100.
* How long has the participant been informed of the disease? (Month).
The mean of MAC dimensions compared between intervention and control groups at the before and after intervention (Table 3). Considering study time, at the before intervention, all dimensions did not signi cantly differed between intervention and control groups (P>0.05) whereas, after intervention, except for avoidance scale (P=0.51) other dimensions of Mac were signi cantly differed between the two groups (P<0.001); For hopeless-helpless and anxious preoccupation, a signi cant decrease was observed in the intervention group compared to the control group and fatalism along with ghting spirit increased signi cantly in the intervention group. Also, the mean of MAC dimensions compared along study times (before and after) in the intervention and control groups separately ( Table 2). In the control group, all dimensions did not signi cantly differ between before and after intervention (P>0.05) whereas, in the intervention group a signi cant decrease was observed for hopeless-helpless and anxious preoccupation while fatalism and ghting spirit were signi cantly increased after intervention. The avoidance scale did not signi cant differences between before and after intervention (P=0.59).
Finally, the change from before to after intervention, which is known as the intervention effect, was calculated for MAC dimensions in "difference" column ( Table 4) and mean of this value was compared between intervention and control group. Comparisons shows that the effect of the intervention was signi cant in reducing hopeless-helpless (-5.42 ± 2.42 in intervention group VS -0.13 ± 0.46 in control group, P<0.001) and anxious preoccupation (-6.80 ± 2.87 VS -0.16 ± 0.82, P<0.001). It has also been signi cant in increasing fatalism (4.89 ± 2.09 VS 0.22 ± 1.24) and ghting spirit (3.58 ± 2.05 VS 0.11 ± 1.61). The effect of intervention on changing avoidance scale was not signi cant (P = 0.83). The percentage of score change in MAC dimensions revealed that the maximum change (increasing) observed for ghting spirit (53 % for intervention versus 6.7 % for control group) and fatalism (40.5 % for intervention versus 1.7 % for control group) is in the next rank. The percentage reduction of the score of Hopeless-Helpless and Fighting Spirit subscales shows that the percentage of reduction was higher in the intervention group compared to the control group ( Figure 2).

Discussion
As being diagnosed with breast cancer causes a great distress in patients struggling to be cured, psychosocial factors should be considered as an important part of breast cancer treatment (20). For patients with breast cancer, intolerance of uncertainty is a huge problem. Intolerance of uncertainty is associated with high levels of worry and its maintenance in breast cancer patients (21). Additionally, it is suggested that intolerance of uncertainty is associated with worsened depressive symptoms and concerns about cancer after being treated (22). It is suggested that early detection of emotional needs in the process of breast cancer treatment not only reduces the cost of cancer treatment, but also improves the quality of life of the patients (23). Thus, this study aimed to evaluate the effect of an intervention aiming to improve uncertainty tolerance in women diagnosed with breast cancer and their spouses on patients' mental adaptation to their disease. The results of the current study indicated that the intervention was effective to improve hopelessness and helplessness, anxious preoccupation, fatalism and ghting spirit in patients with breast cancer.
The results of the current study have shown that the hopelessness-helplessness was signi cantly decreased in intervention group patients in comparison with control group. Hope plays a crucial role in breast cancer treatment, since the diagnosis of the disease could be assumed as a threat or a death sentence (24). A study which conducted to assess the interventions which aim to increase hope in patients with breast cancer has a critical role to increase their quality of life and help them to cope with their disease (25). Kazemi et al conducted a study in 2010 to evaluate the effect of logotherapy training on reducing hopelessness in women with breast cancer and reported that people who have higher hopes during their treatment are more resistant to long-term painful treatments, side effects of chemotherapy and radiation therapy (26). In a study aimed to investigate the association between psychosocial adaptation and hopelessness in women with breast cancer, it was reported that psychosocial adaptation is poor in 63.3% of women with breast cancer. it has also demonstrated that as hopelessness increase, psychosocial adaptation in patients with breast cancer decrease (27). It could be estimated that interventions which aim to increase the patients hope might also help them to psychosocially adapt themselves to their new conditions.
The current study showed that increasing uncertainty tolerance decreases anxious preoccupation in patients with breast cancer. Anxiety and depressive disorders are psychiatric disorders which are common in breast cancer patients. Anxiety disorder could be found in 1 to 49% of breast cancer patients (28). In addition, depressive disorder is found in 1.5 to 46% of these patients (28, 29), varied in time and population. Morris et al suggested that the prevalence of depression in women went under mastectomy for breast cancer was 22% (30). Moreover, Meyer and Aspergren reported that 30% of women with veyear treatment of breast cancer had anxiety or depressive symptoms (31). Decreasing anxiety level in patients may help them to cope with their disease easier. Anxiety and depression are common mental disorders in most patients with cancer, leading to lack of energy, inappetence in continuing treatment and reducing the quality of life of them (32,33).
The current study was effective in increasing ghting spirit in patients with breast cancer. Adopting a ghting spirit improves the chances of survival in cancer patients (34). In this regard, the results of the study of Mohammad et al. (2018) showed that psychotherapy intervention in breast cancer patients helps them to better adapt to the disease and have a better ghting spirit (23). The results of Dastan et al.'s study also showed that psychotherapy intervention sessions increase the ghting spirit in patients with breast cancer. Based on the results of their study, psychological interventions and training cause help cancer patients to cope with their disease (35). The current study was also effective to decrease fatalism in patients with breast cancer. The results of Dastan et al.'s study reported that there was a signi cant decrease in the mean scores of fatalism, which indicates the effectiveness of the intervention for mental adjustment to breast cancer (35).

Conclusion
This study showed that a couple-centered intervention program based on increasing uncertainty tolerance can be an effective support for breast cancer patients in helping to cope with cancer. Educating patients' spouses and gaining their support can help them be relieved of stress in various areas such as emotional, psychological and psychological. Also, by reminding the spouses of the di culties of adjustment in these patients, such as depression, feelings of hopelessness, fatigue, and anxiety, their help can be used to improve the situation in order to increase the patients' adjustment.
Declarations Acknowledgment: We would like to thank the patients, their families, and caregivers who participated and cooperated in this study.

Funding:
This work was supported by Urmia University of medical sciences. The funder provided nancial support and study samples but did not involve in experimental design, data collection, and data analysis.

Con ict of interest:
Authors have no con ict of interest to declare. The authors have full control of all primary data and agreed to allow the journal to review their data if requested.

Availability of data and material:
The data that support the ndings of this study are available from the corresponding author, [FMT], upon reasonable request.  Bar chart of percentage changes in Mac dimension score. percentage change de ned as: (after scorebefore score)/ before score)*100).