Mental Health Care among Cancer Patients with BRCA Gene Mutations: The Potential of Mindfulness-based Intervention
Article ID: 2024-0019-RE
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Article ID: 2024-0019-RE
Hereditary breast and ovarian cancer syndrome (HBOC) is a hereditary tumor syndrome caused by mutations in BRCA genes. Advances in genetic testing technologies have enabled surveillance and risk-reducing surgeries for carriers of BRCA mutations, allowing for the early detection and prevention of cancer. However, the research and support infrastructure for addressing the psychological and social impacts of genetic diagnostics remain insufficient, and there is a need for mental and psychological support based on the needs of patients and their families. Here, we provide an overview of mindfulness, a psychotherapy that has been demonstrated to be effective in alleviating psychological distress in cancer patients, and we discuss the prospects for mindfulness therapy in HBOC patients.
Patients with cancer experience various events, from suspicion and diagnosis of illness to recurrence and discontinuation of anticancer treatments. These events fundamentally change the lives of patients. Consequently, patients with cancer often experience psychological distress, such as anxiety and depression. Psychological distress not only manifests as unsettling symptoms for patients, but also leads to a decrease in quality of life,1 impedes appropriate decision-making,2 prolongs hospital stays,3 and imposes economic cost.4 Furthermore, psychological distress can affect physical health5 and even long-term prognosis,6 necessitating specialized care. Moreover, when psychological distress persists beyond normal ranges, it can lead to adjustment disorders, depression, and other mental health issues, with prevalence rates of 4%–35% for adjustment disorders and 3%–12% for depression, which are higher than those in the general population.7,8
Patients and families with hereditary tumors face additional challenges related to genetics, which can exacerbate psychological burden. Common psychosocial issues encountered by patients with hereditary tumors include: (a) how to cope with cancer risk (decision-making and conflicts regarding risk-reducing surgeries or having children); (b) practical issues (such as life insurance and employment); (c) family and social issues (deciding whether to disclose genetic test results to family members, feelings of blaming family members); (d) issues related to children (how to communicate high risk to children, feelings of guilt towards children); (e) living with cancer (worries and fears of cancer onset or recurrence); and (f) emotional issues (stress, anger, depression).9 Therefore, it is important to recognize the psychological distress experienced by patients with hereditary tumors and provide long-term psychological support. Collaboration with mental health professionals is crucial in cases of severe psychological distress.
Hereditary breast and ovarian cancer syndrome (HBOC) is a predisposition syndrome characterized by mutations in the BRCA1/2 genes, leading to increased susceptibility to various cancers, including breast and ovarian cancers. It follows an autosomal dominant inheritance pattern, and the results of BRCA genetic testing can affect not only the clients but also their relatives. Although there are still limited reports on diagnosis and psychosocial issues related to HBOC, it has been observed that patients diagnosed with genetic mutations experience a loss of psychological well-being.10 Positive testing for hereditary syndromes is considered to have significant implications for both the clients and their families.11
For young patients diagnosed with HBOC, BRCA1/2 genetic testing entails examining the risk of developing related cancers and their impact on relatives, in addition to the cancer diagnosis itself, leading to a significant psychological burden.12 Furthermore, knowing the possibility of genetic inheritance has been noted to increase anxiety regarding future pregnancies.13 Studies investigating the psychological reactions following genetic testing for BRCA in unaffected women reported that although the disclosure of pathogenic variant carriers did not have a significant impact on psychological distress, anxiety and depression increased over a long-term follow-up period of up to 5 years, with long-term distress being associated with cancer-specific distress at the time of testing, having young children, and losing relatives to breast or ovarian cancer.14
BRCA1/2 genetic testing can also provide guidance for cancer treatment decisions, including the consideration of risk-reducing surgeries (such as mastectomy and salpingo-oophorectomy) and individual circumstances, including the current stage of cancer and treatment status. Therefore, it is important to provide psychological care while supporting individuals in making long-term decisions.
Few studies have demonstrated the efficacy of psychotherapy alone in patients with BRCA mutations. However, a number of randomized controlled trials have reported the efficacy of psychotherapy for depression and anxiety in patients with cancer, and recent meta-analyses and systematic reviews have shown its usefulness.15,16 Reports have also indicated the usefulness of psychotherapy for depression in patients with incurable advanced cancer.17 Supportive psychotherapy is the primary psychosocial intervention for cancer patients; however, other approaches such as cognitive-behavioral therapy,18,19 problem-solving therapy,20,21 and mindfulness interventions22,23 have also demonstrated effectiveness in cancer patients. There are also psychotherapies specialized for end-of-life patients such as dignity therapy,24 Life Review (short-term reminiscence therapy),25 Managing Cancer And Living Meaningfully (CALM),26 and Meaning-centered Psychotherapy.27 This article provides an overview of mindfulness, one of the most prominent psychotherapeutic approaches in recent years.
An operational working definition of mindfulness is: “the awareness that emerges through paying attention on purpose, in the present moment, and non-judgmentally to the unfolding of experience moment by moment.”28 Mindfulness-based intervention involves cultivating skills of observation and acceptance through practices such as meditation, yoga, and cognitive exercises, focusing attention on what is happening here and now, including breathing, bodily sensations, thoughts, and emotions, and observing them without judgment. This therapy aims to nurture observation and acceptance skills.
Kabat-Zinn29 developed an 8-week program called Mindfulness-Based Stress Reduction (MBSR) in the 1970s, which was primarily applied to patients with chronic pain. Through mindfulness practice, patients become aware of the relationship between the sensation of pain and the thoughts and emotions that exacerbate it and learn effective ways to cope with pain. Reduction in pain severity and alleviation of psychological symptoms have been reported. Subsequently, Teasdale et al.30 developed mindfulness-based cognitive therapy (MBCT) based on MBSR. The efficacy of MBCT in preventing depressive relapse was demonstrated through randomized controlled trials in 2000,30 leading to increased awareness of mindfulness in the medical field and intervention studies being conducted for various conditions, including depression.
Mindfulness-based interventions are typically conducted in group sessions, targeting approximately 10–20 patients per session, lasting 2–2.5 h once a week for a total of eight sessions. Although there may be some variation between sessions, each session generally consists of exercises such as meditation and yoga for approximately half of the time, with the remaining time devoted to sharing experiences and providing psychoeducation. In addition, homework assignments are given between sessions, including activities such as 30–60 min of meditation or yoga per day and recording journal entries of daily events and accompanying emotions, such as “pleasant events” and “upsetting events.” Meditation begins by focusing on breathing and bodily sensations, gradually expanding to include sounds, thoughts, and emotions, with the goal of perceiving external and internal experiences as they are and consciously choosing one’s actions based on this awareness.
The effectiveness of mindfulness as care for patients with cancer was first reported in 2000 in a Canadian intervention study using MBSR.31 Subsequently, the number of reports related to cancer and mindfulness has increased significantly. Piet et al.32 conducted a systematic review of mindfulness-based interventions, reporting significant reductions in anxiety and depression (Hedgeʼs g =0.6, 0.42) in 13 non-randomized controlled trials when comparing pre- and post-treatment. In addition, significant reductions in anxiety and depression (Hedgeʼs g =0.37, 0.44) were reported in nine randomized trials.32 Moreover, Cillessen et al.33 conducted a meta-analysis of 29 randomized trials, comparing pre- and post-intervention, reporting significant decreases in psychological distress, fear of cancer recurrence, fatigue, and rumination, as well as significant increases in mindfulness skills and self-compassion (Hedge’s g =0.23–0.42). Follow-up assessments also reported significant decreases in psychological distress, anxiety, depression, pain, and sleep disturbance (Hedgeʼs g =0.19–0.43).33
Physiological changes include an increase in interleukin-4 production by T cells, a decrease in interferon-γ, and an improvement in the Th1/Th2 balance, similar to the immunological changes observed during recovery from depression.34 In patients with cancer, a significant negative correlation has been reported between cortisol levels and survival time; however, a decrease in cortisol levels after a mindfulness intervention has also been reported.35 Therefore, mindfulness-based interventions have shown positive effects not only on subjective measures but also on inflammatory cytokines and stress markers involved in cancer progression. Notably, many of these studies focused on patients with breast cancer. Patients with breast cancer who often maintain relatively preserved activities of daily living are considered more amenable to mindfulness research.
Our group has developed a program tailored for cancer patients based on MBCT (Table 1).36 The MBCT program for cancer patients consisted of weekly sessions lasting 2 h each and spread over 8 weeks. Each session was structured around specific themes and included meditation, yoga, cognitive therapy, group discussions, and various exercises. Daily homework involved practicing meditation for 30–45 min using meditation CDs and completing the worksheets provided in the program materials.
| Session | Theme | Contents |
|---|---|---|
| 1 | Overview of mindfulness | Psychoeducation: Psychological reactions of patients with cancer / About mindfulness |
| Exercise: Mindfulness eating / Body scan | ||
| Homework: Mindfulness eating / Body scan | ||
| 2 | Facing difficulties | Psychoeducation: Association of mood and thoughts |
| Exercise: Body scan / Mindful breathing meditation | ||
| Homework: Body scan / Mindful breathing meditation / Pleasant activity and event record | ||
| 3 | Mindful breathing | Psychoeducation: Pleasant activities and events |
| Exercise: Mindfulness meditation / Basic yoga / Mindful walking | ||
| Homework: Mindfulness meditation / Basic yoga / Mindful walking | ||
| 4 | Staying present | Psychoeducation: Reactions to pleasant and unpleasant events |
| Exercise: Mindfulness meditation | ||
| Homework: Mindfulness meditation / Three-minute breathing space exercise | ||
| 5 | Allowing (letting it be) | Psychoeducation: Compassion (appreciation and gratitude in life) |
| Exercise: Mindfulness meditation / Compassion meditation (loving and kindness) | ||
| Homework: Building pleasant habits / Record of appreciation and gratitude / Mindfulness meditation | ||
| 6 | Thoughts are not facts | Psychoeducation: Cognitive biases |
| Exercise: Mindfulness meditation / Compassion meditation | ||
| Homework: Record of appreciation and gratitude / Mindfulness meditation | ||
| 7 | Taking care of yourself | Psychoeducation: Choosing functional behaviors / Behavioral activation / Trigger identification |
| Exercise: Mindfulness meditation / Compassion meditation | ||
| Homework: Responses to triggers / Record of appreciation and gratitude / Mindfulness meditation | ||
| 8 | Dealing with future struggles | Review of course: Personal reflections of course / Plans for future practice / Farewell |
| Exercise: Body scan / Mindfulness meditation |
When addressing cognitive aspects during sessions, we incorporated experiences commonly shared by cancer patients and avoided meditation, which may provoke resistance to the implementation of difficult tasks. Instead, compassion-based meditation was included to foster empathy. Drawing on insights from positive psychology, we also incorporated strategies aimed at replenishing the patients’ depleted psychological energy.
To investigate the effectiveness of the MBCT program for cancer patients in Japan, we first conducted a feasibility study.36 Twelve patients with stage I–III breast cancer participated, and changes before and after the intervention and at 3 months were recorded. The results showed a significant effect size for anxiety (Cohen’s d =0.88, P < 0.05), as well as reductions in post-traumatic stress symptoms (Impact of Event Scale-revised; d =0.64, P < 0.01), functional assessment of cancer therapy-breast (FACT-B; d =0.72, P < 0.01), and mindfulness tendencies (five-faceted mindfulness questionnaire; FFMQ). Depression showed a trend towards improvement (d =0.53, P = 0.054). Interestingly, patients continued to practice mindfulness even after the intervention, interpreting the habituation and integration of mindfulness into their daily lives as contributing to its effectiveness. Based on these results, a randomized controlled trial of mindfulness classes for patients with breast cancer was conducted.37 The study included outpatients with stage I–III breast cancer without prior experience of mindfulness (n =74). The intervention group (n =38) attended weekly 2-h mindfulness classes for eight sessions, whereas the control group (n =36) received usual care. Thirty-four participants completed the study. Significant improvements in anxiety and depression were observed in the intervention group relative to the control group, with these effects maintained at 12 weeks. Furthermore, significant improvements were observed in fatigue and fear of cancer recurrence, along with an increase in quality of life, spirituality, and mindfulness.
Few studies have demonstrated the effectiveness of mindfulness on psychological distress in patients with ovarian cancer. Arden-Close et al.38 conducted a study to assess the feasibility and acceptability of a mindfulness-based intervention for women with recurrent ovarian cancer. The intervention spanned 6 weeks and included group sessions with 28 participants who were evaluated before, after, and at a 3-month follow-up. Psychological and physiological effects were measured using various scales and questionnaires, including the Hospital Anxiety and Depression Scale, the Warwick-Edinburgh Mental Well-being Scale (WEMWBS), the Freiburg Mindfulness Inventory (FMI), and the EORTC-QLQ-OV28 (European Organization for Research and Treatment of Cancer 28-item Quality-of-life Questionnaire for Ovarian Cancer). The results showed improvements in mental well-being and mindfulness as indicated by increased scores on the WEMWBS and FMI and initial positive trends in the EORTC-QLQ-OV28 scores.
Cohen et al.39 conducted a single-arm, open-label pilot study to assess the feasibility of implementing mindfulness-based cognitive therapy to alleviate fear of cancer recurrence (FCR) in ovarian cancer survivors. This involved an 8-week MBCT program. The results showed a significant decrease in FCR after 8 weeks, but not at 6 months. Anxiety also decreased significantly at both 8 weeks and at 6 months, whereas depression showed no significant changes.
These studies show that mindfulness has the potential to alleviate anxiety, depression, and fear of recurrence in patients with ovarian cancer, contributing to their mental well-being. However, there are few such reports, and further high-quality research is required.
Although there are currently no reports on the effects of mindfulness on psychological distress in BRCA mutation carriers, one study has reported menopausal symptoms after risk-reducing surgery. A Netherlands research group conducted a randomized controlled trial to investigate the short- and long-term effects of MBSR on quality of life, sexual functioning, and sexual distress after risk-reducing salpingo-oophorectomy (RRSO).40 Sixty-six women carrying the BRCA1/2 mutation with moderate-to-severe menopausal symptoms were randomly assigned to either an 8-week MBSR program group or a care-as-usual group (CAU). Changes in the Menopause-Specific Quality of Life Questionnaire (MENQOL), Female Sexual Function Index, and Female Sexual Distress Scale scores were compared at baseline and 3, 6, and 12 months after the intervention.
At 3 and 12 months, there were statistically significant improvements in MENQOL in the MBSR group relative to the CAU group (both P = 0.04). At 3 months, the mean MENQOL scores were 3.5 (95% confidence interval, [95% CI] 3.0–3.9) and 3.8 (95% CI 3.3–4.2) for the MBSR and CAU groups, respectively; at 12 months, the corresponding values were 3.6 (95% CI 3.1–4.0) and 3.9 (95% CI 3.5–4.4). No significant differences were found between the MBSR and CAU groups for the other scores. This study indicated that the MBSR program did not improve sexual function or reduce Sexual Distress in in BRCA mutation carriers who developed menopausal symptoms after risk-reducing surgery. However, MBSR has been shown to be effective in improving the quality of life over the long term.
Mindfulness, which has been shown to be effective for various diseases and symptoms, is gradually revealing its mechanisms of action. Mindfulness programs such as MBSR and MBCT focus on attention to the present moment, including corporeal functions such as breathing, bodily sensations, thoughts, and emotions through practices such as meditation, yoga, and cognitive exercises. By repeatedly engaging in the practice of observing these sensations without judgment and accepting them as they are, individuals cultivate skills in observation and acceptance. It is believed that as this process progresses, “decentering” occurs. Decentering refers to a perspective in which negative thoughts or feelings are seen as passing events in the mind rather than being perceived as true or an integral part of oneself.41 Through decentering, individuals are less likely to be engulfed by negative thoughts when they are faced with negative events. Instead, they can observe thoughts from a distance, acknowledge them as they are, and choose more adaptive cognitive and behavioral responses, leading to improvements in mental symptoms and the prevention of relapse. In fact, it has been demonstrated that the higher the skill level in decentering, the lower the recurrence rate of depression.42 In recent years, the number of studies using brain magnetic resonance imaging (MRI) and functional MRI to demonstrate changes in the brain attributed to mindfulness practice has increased. Previous research has shown that individuals who engage in long-term mindfulness meditation are less likely to experience amygdala overactivity, which highlights the impact of mindfulness on brain function.43
The development of molecular genetics has brought about important changes in the clinical assessment of the risk of inherited diseases, providing information about the possibility of inherited diseases, even in those who have not yet developed them. Despite these technological advances, there is insufficient research and support for the psychological and social consequences of genetic diagnoses.
In this study, we reviewed interventions based on mindfulness for patients with cancer. Although there are few reports verifying the effectiveness of mindfulness specifically for HBOC patients, there are reports on its effectiveness in alleviating psychological distress in breast cancer patients and ovarian cancer patients and reducing menopausal symptoms post-risk-reduction surgery. Mindfulness can serve as an adjunctive treatment to improve the mental and physical well-being of patients with HBOC.
The authors have declared that no conflict of interest exists.
