This was a non-masked, randomized controlled trial that applied the consolidated standards of reporting trials (CONSORT) statement. The study was registered in the Iranian registry of clinical trials with the reference code IRCT20150608022609N7 (https://www.irct.ir/).

We recruited spouses of women with breast cancer undergoing chemotherapy at the chemotherapy ward of the Shahid Rajaee Referral-chemotherapy Center in Babolsar city, Mazandaran province, Iran from May 2020 to August 2020.

Participants were spouses of women with stage 1–3 breast cancer and a history of at least 1 session of chemotherapy. Other inclusion criteria were age 25–60 years, Iranian nationality, and education level higher than primary school. Exclusion criteria were studies in the medical or paramedical field, use of any counseling services on stress management 6 months prior to the start of the study, presence of psychiatric disorders, use of psychotropic drugs, drug and alcohol addiction, severe anxiety (score above 12), and severe depression (score above 13) based on the depression anxiety stress scale (DASS-21). Women with recurrent breast cancer also were excluded from the study.

Based on the study by Gabriel and Mayers [16], and considering α=0.05, β=0.20, P1=0.18, and P2=0.02, the sample size was calculated to be 33 per group. Forty participants in each group (a total of 80 participants) were selected, considering a 20% attrition rate.

Sampling was established by attending the outpatient chemotherapy ward of the Shahid Rajaee Hospital to recruit spouses of women diagnosed with breast cancer. These women usually attended the hospital clinics with their relatives, such as their husbands, to receive pre-planned chemotherapy sessions. Using the permuted block randomization method, spouses were allocated to intervention (n=40) and control (n=40) groups. The intervention group comprised 20 blocks of 3–5 participants, such that in each block, the number of intervention and control groups were equal. Further, to adhere to the allocation concealment, 80 envelopes were prepared, and the indicated groups were placed in groups I (intervention) and C (control). The first eligible participant received the first envelope, and if it was written on the envelope of group I, he or she would be in the intervention group; thus, the participants would be in the control and intervention groups.

Primary outcome was care burden, and secondary outcomes were spouses’ stress, satisfaction with intervention, and partners’ quality of life (QOL).

After evaluating the eligibility criteria and explaining the objectives of the study, written informed consent was obtained from participants who were willing to participate in the study. The sessions were held by a pre-trained researcher under the supervision of the research team, including a reproductive health professor, psychiatrist, and psychologist. The intervention was conducted twice a week for six sessions. The first three sessions were small group sessions (3–5 participants in each group), and the next three sessions were held by telephone with each individual. The small group sessions lasted 45–60 minutes, followed by telephone sessions lasting 15–20 minutes.

The intervention sessions included information about breast cancer and its complications, defining stress management strategies in different situations, teaching different levels of problem-solving skills, strengthening creativity, optimism, and management in planning, and defining the role of the caregiver, self-care, strengthening communication skills, relaxation techniques, and related home work (Table 1). Creativity, optimism, problem-solving, and expert information (COPE) models were adopted to develop an intervention protocol [26]. The content validity of the sessions was developed by the research team and evaluated by the opinion of two experts in the field of mental health (psychiatrist and clinical psychologist) and a professor in the field of reproductive health. The experts’ comments were applied in the final version of the intervention protocol. During each session, the participants were given the opportunity to ask questions and any concerns about caring for their partners were addressed. The demographic and clinical checklist, DASS-21, CBI, and WHOQOL-BREF (only for women with breast cancer) were completed at recruitment, immediately after the intervention, and at 6-week follow-up by both groups. The client satisfaction questionnaire was completed by the intervention group at the aforementioned times.

Both groups received usual care from the study setting, which focused on caregivers of women with breast cancer at a 45-minute counseling session on the side effects of chemotherapy before the first session. To comply with ethical issues, at the end of the study, a brief version of the intervention protocol was provided to the control group as a booklet, and their questions were answered in case of questions regarding care and stress management.

Mean and standard deviation were used to describe numerical data. Frequencies and percentages were used for categorical data. The Shapiro-Wilk normality test was used to evaluate the normality of the numerical variables. The chi-square test was used to evaluate categorical variables. Repeated measures analysis of variance evaluated the mean difference in outcomes between the intervention and control groups with the Bonferroni post-hoc test to control for increased risk of type I error due to multiple comparisons. If the data were not normal, appropriate non-parametric tests were performed. A P-value of <0.05 was considered statistically significant with a per-protocol approach. The data were analyzed using SPSS version 26 (IBM Corp., Armonk, NY, USA).

A total of 223 participants met the eligibility criteria. Finally, 80 people were recruited, four of whom withdrew from the study, and 38 completed the study in each group (Fig. 1).

The mean age of the participants was 44.24±9.01 years, and most of them had secondary education. The demographic and clinical information of the participants and their partners are shown in Table 2.

At baseline, there were no significant differences between the two groups in terms of care burden, stress, and partners’ QOL; however, after the intervention and at 6 weeks of follow-up, they were significant (Table 3).

As shown in Table 4, repeated measures analysis of variance showed a significant difference in the care burden (P<0.05; effect size, 0.70), stress (P<0.05; effect size, 0.64), and women’s QOL (P<0.05; effect size, 0.67) before and after the intervention. The Bonferroni post-hoc test results for care burden pairwise comparisons between the groups are presented in Fig. 2.

The mean score for the satisfaction intervention was also assessed. The lowest score was 18, highest score was 29, and mean score was 24.82±2.42, which indicates acceptable satisfaction among the intervention group.

The results of this study should be interpreted in light of some limitations. Since several factors, such as the size of the mass, individual perception of the disease, and social culture are critical in determining the extent of the burden of care, it was not possible to examine them in this study. The timing and completion of chemotherapy sessions during the intervention sessions, number of chemotherapy sessions completed, and family history of cancer (due to earlier preparation in individuals and their greater adjustment to the disease) may increase caregiver burden and stress after the intervention. As all questionnaires were completed by the participants as self-reports, their burden, stress, and QOL may differ from reality. However, it should be noted that the research team tried to control this limitation by assuring the participants that their information was confidential; however, myths about non-emotional men are still widespread, and this affects people’s experiences and behaviors. This issue is more prominent in conservative societies, such as Iran, where cultural restrictions prevent caregiver spouses from honestly revealing their real thoughts and feelings, and the results may be prone to information bias. However, the researcher provided the necessary explanations regarding confidentiality of the data. The results of this study could be generalized to spouses caring for their partners with recurrent breast cancer, while not undergoing chemotherapy cautiously, as chemotherapy is a complex stage in the management of women with breast cancer. Notably, 6 weeks follow-up is a fairly short follow-up time after the intervention, and by considering this limitation, it is impossible to evaluate women with breast cancer progression. To understand whether these effects are sustained over a longer term, a long-term follow-up should be considered in future research. The nature of the interventional support program and lack of blinding of the participants’ allocation to the intervention or control groups may have increased the performance bias. Since a researcher implemented and evaluated the intervention, there might have been some detection bias as well. However, the data were collected using self-administered questionnaires, and it seems that this type of bias was inconsiderable. Despite the fact that the patients were administered chemotherapy on different days, there was a possibility that patients in the intervention and control groups might have met and may have been prone to contamination bias. However, the probability of this was very low, owing to the presence of two separate rooms in the chemotherapy ward, number of different chemotherapy sessions, and referral of patients for chemotherapy on different days.

A support program reduces the care burden and stress levels of the spouses of women with breast cancer undergoing chemotherapy, as well as increases their partners’ QOL, suggesting that informing oncologists, surgeons, and patients about non-pharmacological methods, including support programs along with empowering healthcare providers, can help to promote the health of spouses of women with breast cancer. The results of this study can be used to develop interventions, targeting the care burden and stress experienced by spouses of women with breast cancer undergoing chemotherapy. Further investigation with a blind control group may have implications for the integration of support program interventions into the usual care of women with breast cancer and their relatives. Additionally, as there is a possibility that not only the spouse of breast cancer patients but also the patient’s mental health status affected the outcome, an evaluation of the patient’s stress level or mental health will be investigated in future studies.