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Non-metastatic breast cancer patients often experience psychological distress which may influence disease progression and survival. Cognitive-behavioral stress management (CBSM) improves psychological adaptation and lowers distress during breast cancer treatment and long-term follow-ups. We examined whether breast cancer patients randomized to CBSM had improved survival and recurrence 8–15 years post-enrollment. From 1998 to 2005, women ( N  = 240) 2–10 weeks post-surgery for non-metastatic Stage 0–IIIb breast cancer were randomized to a 10-week, group-based CBSM intervention ( n  = 120) or a 1-day psychoeducational seminar control ( n  = 120). In 2013, 8–15 years post-study enrollment (11-year median), recurrence and survival data were collected. Cox Proportional Hazards Models and Weibull Accelerated Failure Time tests were used to assess group differences in all-cause mortality, breast cancer-specific mortality, and disease-free interval, controlling for biomedical confounders. Relative to the control, the CBSM group was found to have a reduced risk of all-cause mortality (HR = 0.21; 95 % CI [0.05, 0.93]; p  = .040). Restricting analyses to women with invasive disease revealed significant effects of CBSM on breast cancer-related mortality ( p = .006) and disease-free interval ( p  = .011). CBSM intervention delivered post-surgery may provide long-term clinical benefit for non-metastatic breast cancer patients in addition to previously established psychological benefits. Results should be interpreted with caution; however, the findings contribute to the limited evidence regarding physical benefits of psychosocial intervention post-surgery for non-metastatic breast cancer. Additional research is necessary to confirm these results and investigate potential explanatory mechanisms, including physiological pathways, health behaviors, and treatment adherence changes.

The relationship between psychosocial factors and cancer has intrigued people for centuries. In the last several decades there has been an expansion of mechanistic research that has revealed insights regarding how stress activates neuroendocrine stress-response systems to impact cancer progression. Here, we review emerging mechanistic findings on key pathways implicated in the effect of stress on cancer progression, including the cellular immune response, inflammation, angiogenesis, and metastasis, with a primary focus on the mediating role of the sympathetic nervous system. We discuss converging findings from preclinical and clinical cancer research that describe these pathways and research that reveals how these stress pathways may be targeted via pharmacological and mind-body based interventions. While further research is required, the body of work reviewed here highlights the need for and feasibility of an integrated approach to target stress pathways in cancer patients to achieve comprehensive cancer treatment.

The digital stress-management intervention StressProffen has been shown to be associated with improved well-being and quality of life for cancer survivors. In the Coping After Breast Cancer (CABC) trial, effects of 6 months’ access to modified versions of StressProffen, delivered through a digital download-only model, were examined. Women with breast cancer were invited to participate in the trial 6–9 months following diagnosis. Eligible participants were randomized to either: (1) digital cognitive behavioral therapy stress-management intervention (CBI), n  = 140, (2) digital mindfulness-based stress-management intervention (MBI), n  = 143, or (3) usual-care (control group), n  = 147. Primary outcome was change in perceived stress level (PSS-10), while secondary outcomes included changes in health-related quality of life (HRQoL), anxiety and depression, fatigue, mindfulness, sleep and coping. Perceived stress level at baseline was low for all groups. No statistically significant mean differences (MD) were detected between either of the intervention groups and the control group from baseline to 6-month follow-up for perceived stress level (MBI: MD -0.28 [95%CI: -1.75, 1.19], CBI: MD -0.42 [95%CI: -1.89, 1.06]), nor for the majority of the secondary outcomes. After 6 months of access, the CBI and MBI stress-management interventions did not yield significantly improved outcomes for women with breast cancer compared with usual-care controls. Further explorations of which interventions and delivery models may optimize use and effect, best timing for delivery, and individual preferences are needed. ClinicalTrials.gov identifier NCT04480203.

Young adult (YA) cancer survivors frequently report unmet health information and peer support needs, as well as poor health-related quality of life (HRQOL). YAs also have expressed a desire that behavioral interventions be convenient. In response to this, our team has developed a 10-week, group-based, supportive care intervention titled TOGETHER to improve YA cancer survivors' HRQOL. TOGETHER is delivered via videoconference and has shown initial feasibility, acceptability, and promise for improving HRQOL among YA survivors. In an effort to increase convenience, the goal of this 2-part study was to design and test a website to host the TOGETHER intervention for YA cancer survivors aged 18-39 years at the time of participation and aged 15-39 years at the time of initial cancer diagnosis. In part 1, we leveraged an existing web-based platform and adapted it to meet the needs of TOGETHER. We conducted 3 iterative waves of usability testing with 3 YAs per wave to refine the website. In part 2, we conducted a single-group feasibility trial of TOGETHER using the website. Primary outcomes were feasibility (ie, recruitment, retention, and attendance) and acceptability (ie, satisfaction). Usability testing participants (n=9) indicated that the TOGETHER website was easy to use (mean 5.9, SD 1.3) and easy to learn (mean 6.5, SD 0.9; possible ranges 1-7). Qualitative feedback identified needed revisions to the aesthetics (eg, images), content (eg, session titles), function (eg, clarity of functionality), and structure (eg, expandable sections), which were implemented. In the feasibility trial, participants (n=7) were an average of 25 (SD 4.7) years old and mostly non-Hispanic White (n=4, 57%). Recruitment (58%) and retention (71%) rates and average session attendance (mean 7.1 , SD 4.2) supported feasibility. Participant agreement with positive statements about TOGETHER and average satisfaction ratings (mean 5.06, SD 1.64; possible range: 1-7) demonstrated acceptability. Results supported the usability, feasibility, and acceptability of the TOGETHER program and website. By providing the content digitally, the program effectively addresses YAs' expressed preference for convenience. Future studies are needed to increase TOGETHER's efficiency and explore its efficacy for improving targeted outcomes.

Background Cyclin‐dependent kinase 4 and 6 (CDK4/6) inhibitor targeted therapies dramatically improve survival outcomes for metastatic breast cancer (MBC), but they are associated with significant symptom burden that can impact patients’ health‐related quality of life (HRQOL) and treatment outcomes. This study is the first to describe CDK4/6 inhibitor symptoms from the lived perspectives of MBC patients taking CDK4/6 inhibitors and healthcare providers involved in MBC care. This study also explored patients’ symptom management and HRQOL concerns, and gathered feedback about developing supportive interventions for MBC. Methods MBC patients taking CDK4/6 inhibitors (N = 20) and MBC healthcare providers (N = 12) participated in semi‐structured interviews that were analyzed for qualitative themes. MBC patients completed surveys about HRQOL, symptoms, and unmet needs. Results Patient and provider perceptions of CDK4/6 inhibitor symptoms did not align with patients perceiving symptoms as more burdensome. Patients reported that supportive resources (e.g., support groups, blogs) that are not specific to MBC do not adequately meet their needs. Patients and providers were enthusiastic about developing supportive interventions specifically for MBC and offered considerations for designing such interventions. Conclusions Findings highlight differences in perceptions of CDK4/6 inhibitor symptom burden between MBC patients and providers. Results will inform the development of supportive interventions to assist MBC patients in managing CDK4/6 inhibitor symptom burden and maintaining HRQOL. Such interventions could also improve treatment outcomes. Metastatic breast cancer (MBC) patient and provider perceptions of symptoms associated with CDK4/6 inhibitor did not align, with patients perceiving symptoms as more burdensome. Patients reported that supportive resources (e.g., support groups, blogs) that are not specific to MBC do not adequately meet their needs, however patients and providers were enthusiastic about developing supportive interventions specifically for MBC and offered considerations for designing such interventions. Results will inform the development of supportive interventions to assist MBC patients in managing CDK4/6 inhibitor symptom burden and maintaining health‐related quality of life.

One-third or more of breast cancer survivors report stress and other psychological and physical complaints that can negatively impact their quality of life. Psychosocial stress management interventions, shown to mitigate the negative impact of these complaints, can now be delivered as accessible and convenient (for the patient and provider) eHealth interventions. In this randomized controlled trial (RCT), Coping After Breast Cancer (CABC), 2 modified versions of the stress management eHealth intervention program StressProffen were created: one with predominantly cognitive behavioral stress management content (StressProffen-cognitive behavioral therapy intervention [StressProffen-CBI]) and another with predominantly mindfulness-based stress management content (StressProffen-mindfulness-based intervention [StressProffen-MBI]). This study aims to investigate the effects in breast cancer survivors of using StressProffen-CBI and StressProffen-MBI compared with a control group (treatment as usual). Women diagnosed with breast cancer (stage I-III, unequivocally human epidermal growth factor receptor 2-positive or estrogen receptor-negative tumors) or ductal carcinoma in situ (DCIS) aged 21-69 years who completed the Cancer Registry of Norway-initiated health survey on quality of life are invited to the CABC trial about 7 months after diagnosis. Women who give consent to participate are randomized (1:1:1) to either the StressProffen-CBI, StressProffen-MBI, or control group. Both StressProffen interventions consist of 10 modules of stress management content delivered through text, sound, video, and images. The primary outcome is between-group changes in perceived stress at 6 months, assessed with Cohen 10-item Perceived Stress Scale. The secondary outcomes comprise changes in quality of life, anxiety, depression, fatigue, sleep, neuropathy, coping, mindfulness, and work-related outcomes approximately 1, 2, and 3 years after diagnosis. Long-term effects of the interventions on work participation, comorbidities, relapse or new cancers, and mortality will be assessed using data from national health registries. Recruitment is scheduled from January 2021 to May 2023. The goal is to recruit 430 participants (100 in each group). As of April 14 2023, 428 participants have been enrolled. The CABC trial is possibly the largest ongoing psychosocial eHealth RCT in patients with breast cancer. If 1 or both interventions prove to be effective in reducing stress and improving psychosocial and physical complains, the StressProffen eHealth interventions could be beneficial, inexpensive, and easily implementable tools for breast cancer survivors when coping with late effects after cancer and cancer treatments. Clinicaltrials.gov NCT04480203; https://clinicaltrials.gov/ct2/show/NCT04480203. DERR1-10.2196/47195.

PurposeShorter breast cancer (BC) survival outcomes persist by neighborhood disadvantage independent of patient, tumor, and treatment characteristics. This suggests unaccounted mechanisms by which neighborhood disadvantage “gets under the skin” to impact BC survival outcomes. Here, we evaluate the relationship between neighborhood disadvantage and clinical and neuroendocrine markers of stress in BC patients.MethodsWomen with stage 0–III BC were enrolled 2–10 weeks post-surgery and before initiating adjuvant treatment in a study examining stress and stress management processes. Women provided an afternoon-evening (PM) serum cortisol sample and were administered the Hamilton Anxiety Rating Scale (HAM-A). Home addresses were used to determine the Area Deprivation Index (ADI), a validated measure of neighborhood disadvantage. Multiple regression assessed the relationship between ADI and PM serum cortisol and the presence of elevated HAM-A symptoms.ResultsOur sample (n = 225) was predominately middle-aged (M = 50.4 years; range 23–70 years), non-Hispanic White (64.3%), with stage I (38.1%), or II (38.6%) disease. The majority (n = 175) lived in advantaged neighborhoods (ADI 1–3). After controlling for age, stage, and surgery type, women from high ADI (4–10) (vs low ADI) neighborhoods had higher PM cortisol levels (β = 0.19, 95% CI [0.24, 5.00], p = 0.031) and were nearly two times as likely to report the presence of elevated anxiety symptoms (OR = 1.96, 95% CI [1.00, 3.86], p = 0.050).ConclusionNeighborhood disadvantage is significantly associated with higher levels of PM cortisol and elevated anxiety symptoms suggesting stress pathways could potentially contribute to relationships between neighborhood disadvantage and BC survival.

Minority and older adult patients remain underrepresented in cancer clinical trials (CCTs). The current study sought to examine sociodemographic inequities in CCT interest, eligibility, enrollment, decline motivation, and attrition across two psychosocial CCTs for gynecologic, gastrointestinal, and thoracic cancers. Patients were approached for recruitment to one of two interventions: (1) a randomized control trial (RCT) examining effects of a cognitive-behavioral intervention targeting sleep, pain, mood, cytokines, and cortisol following surgery, or (2) a yoga intervention to determine its feasibility, acceptability, and effects on mitigating distress. Prospective RCT participants were queried about interest and screened for eligibility. All eligible patients across trials were offered enrollment. Patients who declined yoga intervention enrollment provided reasons for decline. Sociodemographic predictors of enrollment decisions and attrition were explored. No sociodemographic differences in RCT interest were observed, and older patients were more likely to be ineligible. Eligible Hispanic patients across trials were significantly more likely to enroll than non-Hispanic patients. Sociodemographic factors predicted differences in decline motivation. In one trial, individuals originating from more urban areas were more likely to prematurely discontinue participation. These results corroborate evidence of no significant differences in CCT interest across minority groups, with older adults less likely to fulfill eligibility criteria. While absolute Hispanic enrollment was modest, Hispanic patients were more likely to enroll relative to non-Hispanic patients. Additional sociodemographic trends were noted in decline motivation and geographical prediction of attrition. Further investigation is necessary to better understand inequities, barriers, and best recruitment practices for representative CCTs.

Despite emerging evidence that distress and adversity can contribute to negative health outcomes in cancer, little is known about the brain networks, regions, or circuits that can contribute to individual differences in affect/distress states and health outcomes in treated cancer patients. To understand the state-of-the-science in this regard, we reviewed neuroimaging studies with cancer patients that examined the associations between negative affect (distress) and changes in the metabolism or structure of brain regions. Cancer patients showed changes in function and/or structure of key brain regions such as the prefrontal cortex, thalamus, amygdala, hippocampus, cingulate cortex (mainly subgenual area), hypothalamus, basal ganglia (striatum and caudate), and insula, which are associated with greater anxiety, depression, posttraumatic stress disorder (PTSD) symptoms, and distress. These results provide insights for understanding the effects of these psychological and emotional factors on peripheral stress-related biobehavioral pathways known to contribute to cancer progression and long-term health outcomes. This line of work provides leads for understanding the brain-mediated mechanisms that may explain the health effects of psychosocial interventions in cancer patients and survivors. A multilevel and integrated model for distress management intervention effects on psychological adaptation, biobehavioral processes, cancer pathogenesis, and clinical outcomes is proposed for future research.

During the 40 years since the Yale conference on Behavioral Medicine and the founding of the Journal of Behavioral Medicine considerable progress has been made in understanding the role of psychosocial risk and management of physical diseases. We here describe the development of these fundamental concepts from early research on stress through studies of the Type A behavior pattern to more contemporary approaches to the relationship between psychosocial risks and benefits in relation to disease processes. This includes the relationship of psychosocial risk to cancers, cardiovascular diseases (CVD), cardiometabolic disorders, Human Immunodeficiency Virus (HIV)/Acquired Human Immune Deficiency Syndrome. During the past 40 years the effects of prolonged distress responses in the pathogenesis of some cancers and CVD have been well-established and modifiable behavioral, cognitive and social factors have been shown to produce favorable outcome components in the management of such diseases as breast cancer, coronary heart disease and HIV.