Research on outcomes of psychological interventions for breast cancer patients has built upon a body of research substantiating the use of cognitive-behavioral approaches in health psychology. Current outcomes research studies are reviewed below with the aim to summarize and to clarify the impact of psychological interventions on breast cancer patients. Importantly, outcomes are reliant upon the interplay between therapeutic variables and patient variables (Fig. 1). This review is a sampling of recent outcomes research and includes studies that focus on therapeutic variables and patient variables.

Fig. 1

Patient and Treatment Variables Affecting Psychological Outcomes in Breast Cancer Patients

Therapeutic Variables

A wide body of prior research has provided evidence that psychological interventions improve both the outcomes of cancer treatment (e.g. decreased recurrence rate, improved survival rate) and the quality of life of the individual receiving psychosocial interventions during cancer treatment. Within breast cancer treatment, most of these studies have been with metastatic breast cancer patients. Examples of the outcomes of psychological intervention in this group are higher survival rates at ten-year follow-up, decreased depressive symptoms, and improved quality of life in individuals with metastatic breast cancer [19,20,21]. Recently, support has been garnered for the positive impact of psychological treatment on non-metastatic breast cancer patients. In a 2021 study, Diaz and colleagues found that exposure to a brief CBT-based stress management or a brief relaxation training intervention both yielded beneficial effects on perceived stress-management skills and serum inflammatory markers (NF-kB expression) compared to the control group [22•].

Cognitive-Behavioral Strategies

The beneficial impact of Cognitive Behavioral Therapy (CBT) interventions in health psychology have been widely demonstrated. CBT treatments utilized in health psychology are designed to modify patients’ thoughts, feelings, and behaviors. Many are offered in a manualized treatment approach that conforms well to research design and offers measurable patient outcomes.

One such example of CBT intervention-based research is a randomized clinical trial (RCT) by Anderson’s group [13]. A group of 227 breast cancer patients were provided either a year-long psychological CBT treatment condition or an assessment-only control condition. All were followed for a median period of eleven years post-breast cancer diagnosis. Psychological treatment condition patients were provided CBT interventions targeting relaxation training, problem-solving, assertiveness skill-development, and behavioral interventions to target increased daily activities, improved diet and coping with side effects. Statistically significant differences were found in recurrence and mortality between treatment participants and assessment-only participants. These effects were observed above and beyond the contribution of known predictors of disease progression in breast cancer, such as lymph node status, receptor status, histology, and others. This suggests that psychological intervention provided during active cancer treatment may influence the long-term health outcomes for patients with breast cancer.

The authors identified several possible explanations of how psychological treatment improved recurrence and mortality rates. They suggested the outcomes could be directly related to the treatment provided; e.g., the treatment itself was essential to the outcomes seen in the research. Other hypotheses explored the relationship that treatment may have had on biological processes, particularly as they related to biologically based stress-reduction. Reduction in the presence of stress-hormones found to be associated with tumor growth could be responsible for recurrence and mortality outcomes. Relatedly, the authors suggest that the psychological intervention could interrupt the inflammatory process and mediate the intervention effect to reduce risk of progression. In this scenario, the treatment condition could decrease inflammatory response by decreasing stress-hormones, thus improving the cancer treatment impact. Further research is needed to clarify the precise biopsychosocial mechanisms responsible for these positive outcomes. These research findings suggest the importance of psychological treatment during the initial treatment phase for breast cancer patients on long-term health outcomes.

Much research has utilized general CBT principles in the treatment condition. Formalized CBT manualized treatment protocols allow for clearly circumscribed treatment conditions and measurable, replicable outcomes. An example of a CBT manualized treatment approach shown to be related to positive outcomes in breast cancer patients is Cognitive Behavioral Stress Management (CBSM). CBSM is a standardized protocol developed by Michael Antoni Ph.D. integrating CBT principles and practices such as cognitive restructuring (identifying and disputing irrational or maladaptive thoughts), behavioral activation (engagement in pleasant experiences, social activity or experiences of mastery), and relaxation strategies (diaphragmatic breathing, progressive muscle relaxation and meditation/imagery). Research has shown, for example, that CBSM has strong evidence of improving quality of life in women with breast cancer, as well as biological impacts on breast cancer patients like favorable changes in leukocyte pro-inflammatory gene-expression [23].

Stagl and Antoni’s group found that participation in a CBSM group during cancer treatment was associated with lower incidence of breast cancer mortality and greater disease-free interval than patients provided only a brief, educational session during cancer treatment [12]. Their psychological intervention group was provided a manualized CBSM treatment that included cognitive-behavioral interventions (i.e. cognitive reframing, stress re-appraisal, effective coping skills training, assertiveness training, anger management, optimizing use of social support) and relaxation training (e.g., progressive muscle relaxation, guided visual imagery, diaphragmatic breathing).

Their analysis found that women with Stage 0–IIIb breast cancer who were randomly assigned to a 10-week CBSM intervention, 2–10 weeks post-surgery, had longer survival, up to 11-years post-enrollment, compared to those in the control group, while accounting for disease relevant characteristics. The authors suggest that the mechanisms of outcome may be multimodal, including improved ability to modify those cognitive appraisals that thereby bolster stress-reduction, as well as adaptive coping techniques and re-appraisals of harm and loss that contribute to depressive symptoms. The relationship between stress biology and pro-metastatic molecular processes has been substantiated in prior animal studies. Results like these may support the hypothesis that psychological interventions affect disease recurrence by their direct impact on the biological stress process.

The same research group, using a cohort of 51 patients for whom survival and gene expression data were available, attempted to understand why CBSM participation was associated with improved disease-free survival in breast cancer patients. Theories had emerged suggesting a link between stress and a number of prometastatic molecular processes (i.e. inflammation, monocyte/macrophage lineage cell recruitment, evasion of immune system surveillance, etc.). Antoni et al. were interested in the relationship between CBSM participation during cancer treatment and patients’ inflammatory and immunologic functioning [24]. Specifically, the study posited that CBSM may mitigate or reverse the conserved transcriptional response to adversity (CTRA) gene response in participants. The CTRA gene response, when activated by stress, increases the likelihood of these prometastatic processes. Thus, CBSM would mediate the relationship between stress and disease recurrence.

The authors found that patients randomized to the CBSM condition showed both improved psychological symptoms (i.e. cancer-associated intrusive thoughts, interviewed rated anxiety symptoms and negative affect) and attenuated 6–12 month change in CTRA gene expression, whereas the control group showed increased CTRA gene expression. Greater 6–12-month CTRA increases predicted shorter 11-year DFS. This finding provides support for the protective impact on disease progression of CBSM intervention provided during cancer treatment that may last for up to fifteen years post-treatment.

Expanding further with the same data set, the Diaz et al. study sought to understand the molecular mechanisms involved in the relationship between psychological interventions and positive health and longevity outcomes seen their prior research [22•]. The group specifically examined the effects of the CBSM-based interventions on the transcription factor NF-κB DNA binding activity in leukocytes in parallel with circulating inflammatory markers, stress management skill efficacy and multiple distress indicators.

The authors found a significant effect on NF-κB expression over time in the treatment groups, whereas treatment participants did not evidence an increase in NF-κB. The health-education only group showed a steady increase in NF-κB over the twelve months of the study. They also found change in serum cytokines (IL-1β, IL-6 and TNF-α); and s100A8/A9, a circulating inflammatory marker important in breast cancer progression in the same pattern as that found in NF-κB expression. Attendance data demonstrated that patients attending 5 out of 10 weekly sessions showed equivalent improvement as those who attended 8–10 sessions. Those who had higher perceived stress management skills following the interventions had less increase in NF-κB binding over time.

The authors conclude that brief stress management interventions provided to breast cancer patients with high levels of distress can mitigate increases in pro-inflammatory leukocyte NF-κB binding. Thus, increased stress management skills appear to provide a direct beneficial impact on underlying molecular mechanisms involved in cancer progression.

Mindfulness-Based Interventions

A promising addition to cognitive-behavioral strategies include Mindfulness-Based Interventions (MBIs), which incorporate focus on the present moment, awareness and self-compassion. Park et al. found in a group of nonmetastatic, Japanese participants that those who were provided an 8-week course of Mindfulness-Based Cognitive Therapy (MBCT) had significantly better outcomes in psychological distress, fatigue, spiritual well-being, and quality of life than the study’s wait-list control group [25]. Similarly, Zhu et al. found that breast cancer patients in early chemotherapy treatment who were provided an 8-week Mindfulness-Based Stress Reduction (MBSR) group experienced significantly better outcomes in quality of life, psychological distress, and emotion-regulation than the control group [26•]. In a 2020 study, Mirmahmoodi et al. found that Iranian breast cancer patients provided an 8-week MBSR group demonstrated significantly less anxiety than the control group [27]. Mindfulness-based interventions appear to be promising across cultures; however, additional research is needed to understand their effectiveness with diverse samples.

Patient Variables

While much is left to be studied regarding the role and impact of patient-specific variables (e.g. mental health symptoms, situational circumstances, adherence to treatment, cultural variables, etc.) as a contributor to cancer outcomes, recent research has yielded several valuable findings. Meta-analytic evidence suggests that cancer patients with higher levels of anxiety and distress benefit the most from psychosocial intervention [28]. Younger breast cancer survivors showed reduction in depressive symptoms at 6-month follow-up after participating in mindful awareness practices [29]. Personality factors appear to contribute to the impact of MBSR on psychological wellbeing, including variation in traits such as conscientiousness and neuroticism [30]. Cross-cultural groups in the United States and Singapore both showed significant improvement in anxiety, depression, and fatigue scores after exposure to a 4-session, mindfulness-based treatment in a 2020 pilot RCT [31].

Suppli et al. examined a large group of 45,325 women from Denmark diagnosed with breast cancer compared by groups; those without pre-existing treatment for depression, those with pharmacologic treatment for depression prior to breast cancer diagnosis and a third group, those with hospital treatment (inpatient or outpatient) of depression prior to breast cancer diagnosis [32]. The researchers found that patients treated with antidepressant medication prior to the diagnosis of early-stage breast cancer were more likely to receive nonguideline medical treatment and had significantly worse overall survival rates and breast cancer-specific survival rates than those who had never taken antidepressant medication. The authors posit that the poorer outcomes were due to the quality of care depressed women received through breast cancer treatment. They found that those who had taken antidepressant medication were more likely to receive only biopsy (not surgery) and, as a result, to have unknown tumor size, number of tumor-positive lymph nodes, and estrogen receptor status. They were also less likely to receive guideline systemic adjuvant therapy. The group had a significantly higher breast cancer-specific mortality rate and worse overall survival rates.

In the group of depressed women who received guideline adjuvant systemic therapy, the survival rates mirrored the non-depressed group also receiving this therapy. Thus, the deleterious impact of depression on outcome seemed to be mitigated by involvement in and adherence to guideline cancer treatment. The authors assert that the 2% of participants in their study with depression prior to breast cancer diagnosis is consistent with prior research findings and compel treatment centers to increase engagement and completion of guideline adjuvant treatment in women with the co-occurring diagnoses of depression and breast cancer.

Limitations of the Suppli et al. study include the use of antidepressant medication as an identifier for depression when these medications can be used for other purposes (e.g. controlling menopausal symptoms, anxiety-reduction, pain, etc.) and the exclusion of women who may have received psychotherapy only in a non-hospital setting for the treatment of their depression. Many of the statistically significant results seen in the antidepressant group were not replicated in the hospital treatment group. Clarification is needed to understand the differences between these two groups of women with depression before applying results to the clinical setting. The clear practical application that may be drawn from their research, however, is the importance of outreach and engagement for individuals with pre-existing depression to increase their adherence to breast-cancer treatment.