Associations between HIV infection status, psychosocial factors, and adjuvant endocrine therapy adherence among South African women with early-stage breast cancer.

Purpose: We aimed to evaluate for associations between HIV status, psychosocial factors, and adjuvant endocrine therapy (AET) adherence in South African (SA) women with estrogen receptor positive (ER+) breast cancer (BC). Methods: We enrolled South African women with early-stage ER + BC in remission and prescribed tamoxifen or an aromatase inhibitor to the prospective observational study. We performed AET pill counts at enrollment, 12 weeks, and 24 weeks, and calculated adherence ratios of pills consumed between visits to days between visits. Women completed questionnaires on social support, attitude towards medication, health literacy, self-efficacy, mental health, and AET toxicity. We collected household wealth data. We used hierarchical linear (HLM) and structural equation modelling (SEM) to compare adherence ratios between women with and without HIV while adjusting for psychosocial factors. Results: We collected adherence data from 239 women, 63 (26.4%) with co-morbid HIV. Comparing women with and without HIV, median AET adherence ratio was 0.88 vs 0.89, respectively (HLM p = 0.31). In our SEM model for the full cohort, mental health, healthcare savvy, and side effect burden latent variables were not significantly associated with adherence. In the subgroup of women living with HIV, lower SES quintile (ß 0.04, SE 0.02, p = 0.08) and poorer mental health (ß -0.02, SE 0.01, p = 0.10) showed trends toward association with adherence. Conclusions: HIV status is not predictive of AET adherence among SA women with ER + BC, though decreasing SES status and increasing mental health symptoms are marginally associated with adherence in women with BC and HIV.

Effects of neighborhood disadvantage on cortisol and interviewer-rated anxiety symptoms in breast cancer patients initiating treatment.

PURPOSE: Shorter 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. METHODS: Women 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. RESULTS: Our 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 (ß = 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). CONCLUSION: Neighborhood 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.

Predictors of initial engagement with an asynchronous cognitive behavioral stress management website among older women with nonmetastatic breast cancer.

PURPOSE: Digital interventions, like websites, offer greater access to psychosocial treatments; however, engagement is often suboptimal. Initial use may be a target to "hook" participants. Few studies examine engagement with cognitive behavioral stress management (CBSM). We tested predictors of engagement in the first week of using a CBSM website among women with breast cancer (BC). METHODS: Older women (≥ 50 years) with nonmetastatic BC enrolled in an on-going trial (8/2016-4/2022, #NCT03955991) and were randomized to receive 10 synchronous, virtual CBSM group sessions immediately (n = 41) or after a 6-month waitlist (n = 34). All received simultaneous access to an asynchronous website, where supplemental videos and resources were released weekly. Engagement was tracked via breadth (features used) and depth (clicks within content). Multilevel modeling tested predictors of engagement (i.e., time, condition, age, daily stress, depression, race, ethnicity, disease stage). RESULTS: Breadth decreased over the first week of CBSM (b = -0.93, p < .01), and women with more advanced stage disease engaged with more breadth (b = 0.52, p < .01) and depth (b = 14.06, p < .01) than women with earlier stage disease. Non-Hispanic (b = -0.59, p = .03) and White (b = -0.97, p < .01) women engaged with more features. Cancer stage and intervention timing interacted. Women with more advanced cancer stage who received CBSM later engaged with the most depth (b = -11.73, p = .04). All other characteristics did not predict engagement. CONCLUSIONS: Disease stage, race, ethnicity, and intervention timing predicted engagement with a CBSM website in older BC patients. IMPLICATIONS FOR CANCER SURVIVORS: Delivering CBSM later in cancer treatment may mitigate competing demands. Fostering greater engagement in racial/ethnic minorities is needed.

Cognitive behavioral stress management affects different dimensions of benefit finding in breast cancer survivors: a multilevel mediation model.

Objective. This study aimed to confirm the multidimensionality of benefit finding (BF), or silver linings within the cancer experience, assess the effects of Cognitive Behavioral Stress Management (CBSM) on those dimensions, and test the mediating role of perceived stress management skills targeted by CBSM.Methods. This secondary analysis used data from 240 women with stage 0-III breast cancer who completed measures of BF (Benefit Finding Scale) and perceived stress management skills (PSMS) at baseline, 6-months, and 12-months post-randomization into CBSM or a psycho-education condition. We tested a six-factor BF model using Confirmatory Factor Analysis and assessed CBSM-related changes in BF and PSMS using Hierarchical Linear Models. We included significantly affected BF dimensions in mediation models.Results. A six-factor model of BF had good fit [χ2(212) = 391.5, p < .001; CFI = 0.94; RMSEA = 0.06; SRMR = 0.04]. CBSM positively affected changes in personal growth (ß = 0.06, p = .01), social relations (ß = 0.05, p = .05), and worldview (ß = 0.05, p = .02) BF. Perceived relaxation skill increases significantly mediated changes in personal growth (ß = 0.03, p = .04) and social relations (ß = 0.03, p = .04).Conclusion. Some aspects of perceived stress management skills appear to account for specific BF dimensions and should be considered in future efforts to develop interventions to modulate BF.

Brief Post-Surgical Stress Management Reduces Pro-Inflammatory Cytokines in Overweight and Obese Breast Cancer Patients Undergoing Primary Treatment.

BACKGROUND: Overweight and obese (OW/OB) body mass index (BMI) is associated with greater inflammation and poorer outcomes in breast cancer (BC). Stress management interventions using cognitive behavioral therapy (CBT) and relaxation training (RT) have reduced inflammation in BC patients but have not been tested specifically in OW/OB patients undergoing primary treatment. We developed brief CBT and RT-based group interventions and tested their effects (vs time-matched Health Education [HE] control) on serum inflammatory cytokines (IL-6, IL-1ß and TNF-α) in OW/OB vs normal weight (NW) BC patients during primary treatment. We hypothesized OW/OB women would show higher levels of inflammatory cytokines, and that stress management would decrease these cytokines more in OW/OB women than in NW women. METHODS: Stage 0 - III BC patients were enrolled post-surgery and before initiating adjuvant therapy, were randomized to either 5 weeks of CBT, RT, or HE, and provided questionnaires and blood samples at baseline and 6-months. Serum cytokine levels were measured by ELISA. Repeated measures analysis of variance tested the interaction of condition by BMI by time in predicting cytokine levels over 6 months, controlling for age, stage, ethnicity, and income. RESULTS: The sample (N = 153) majority was OW/OB (55.6%). We found differences in baseline IL-6 and IL-1ß across BMI categories, with greater IL-6 (p < 0.005) and IL-1ß (p < 0.04) in OW and OB vs NW women, but no difference between OW and OB women. There were no differences in baseline TNF-α among BMI groups. BMI category moderated the effect of brief stress management interventions on IL-6 changes over 6-months (p = 0.028): CBT/RT vs HE decreased IL-6 in OW/OB (p = 0.045) but not in NW patients (p = 0.664). There were no effects on IL-1ß or TNF-α. Results could not be explained by differences in receipt of adjuvant therapy, prescription medications, or changes in physical activity. CONCLUSIONS: OW/OB women with newly diagnosed BC had significantly greater serum IL-6 and IL-1ß than NW women post-surgery. Brief stress management delivered with primary treatment among OW/OB patients may reduce the increases in inflammatory markers known to accompany adjuvant treatments and could thus promote better outcomes. CLINICAL TRIAL REGISTRATION: NCT02103387.

A latent profile analysis to assess physical, cognitive and emotional symptom clusters in women with breast cancer.

OBJECTIVE: Current research on the physical and psychological functioning of breast cancer survivors often takes an approach where symptoms are studied independently even though they often occur in clusters This paper aims to identify physical and psychological symptom clusters among breast cancer survivors while assessing clinical, psychosocial and demographic characteristics that predict subgroup membership. DESIGN: Using post-surgical data collected from 240 women with stage 0-III breast cancer, symptom clusters were identified using latent profile analysis of patient-reported symptoms. MAIN OUTCOME MEASURES: Baseline measures included the Pittsburg Sleep Quality Index, the Fatigue Symptom Inventory, the Hamilton Rating Scales for depression and anxiety and the Impact of Event Scale. RESULTS: Three distinct classes were identified: (1) mild physical, cognitive and emotional symptoms, (2) moderate across all domains and (3) high levels of all symptoms. Lower socio-economic status, minority ethnicity, younger age, advanced disease stage along with lower self-efficacy and less internal locus of control were significantly associated with a higher likelihood of class 3 membership. CONCLUSION: By identifying those most at risk for severe physical and psychological symptoms in the post-surgical period, our results can guide the development of tailored interventions to optimise quality of life during breast cancer treatment.

Brief relaxation training is associated with long-term endocrine therapy adherence among women with breast cancer: post hoc analysis of a randomized controlled trial.

PURPOSE: Despite life-saving potential, many women struggle to adhere to adjuvant endocrine therapy (AET) for their breast cancer (BCa). Prior research has demonstrated that emotional distress is a barrier to AET adherence. We followed women from a trial to test the long-term effects of two 5-week post-surgical group-based stress management interventions, cognitive behavioral therapy (CBT), and relaxation training versus an attention-matched health education control, on AET adherence. METHODS: We conducted a long-term follow-up (median = 8 years) of women randomized to CBT, relaxation training, or health education after surgery for stage 0-3 BCa. We measured adherence with the Endocrine Therapy Medication Usage Questionnaire (ETMUQ). First, we established factors on the ETMUQ via confirmatory factor analysis. We then used Bayesian structural equation modeling to regress these factors on study arm, controlling for age and treatments received. RESULTS: Of those who completed long-term follow-up (n = 59, 44.7%), over half (n = 33; 55.9%) reported problems with adherence generally. Women receiving relaxation training (n = 15) had better adherence than those receiving health education (n = 24) on the Forgetfulness/Inconsistency [B(SE) = 0.25(0.14), p = 0.049] and Intentional Nonadherence [B(SE) = 0.31(0.14), p = 0.018] factors of the ETMUQ. Similar results were observed for those receiving relaxation training compared to CBT (n = 20): Forgetfulness/Inconsistency [B(SE) = - 0.47(0.25), p = 0.031]; Intentional Nonadherence [B(SE) = - 0.31(0.15), p = 0.027]. CONCLUSION: Women receiving relaxation training were less likely to (1) forget to take their AET and (2) intentionally miss doses of AET in the long term compared to women receiving health education or CBT. This is evidence for the need of randomized trials that aim to improve adherence by incorporating theoretically based behavioral change techniques. TRIAL REGISTRATION AND DATES: Trial 2R01-CA-064710 was registered March 26, 2006.

Elucidating mechanisms of quality-of-life disparities in Hispanic women with breast cancer: An examination of disease stage, coping, and affect.

OBJECTIVES: Compared to non-Hispanic white (NHW) women, Hispanic women with breast cancer (BCa) are more likely to be diagnosed at later stages of disease and experience reduced quality of life (QOL) following diagnosis. We hypothesized that the demands of later-stage disease results in a perceived inability to cope and greater distress for Hispanic women, resulting in decreased QOL. METHODS: Hispanic (51%) and NHW (49%) women (N = 198) with newly diagnosed stage 0-3 BCa in Miami were enrolled in two trials between 2006 and 2019. In this cross-sectional analysis, a multiple-group structural equation modeling approach was applied to baseline measures of coping confidence (Measure of Current Status Scale), negative and positive affect (Affect Balance Scale), QOL (Functional Assessment of Cancer Therapy - Breast), and disease stage. RESULTS: In our model, later-stage disease was not associated with worse QOL for Hispanic or NHW women. However, there were differences between Hispanic and NHW women on the path from disease stage to (1) coping confidence, (2) positive affect, and (3) negative affect, such that later disease stage was associated with lower coping confidence (b[SE] = -1.75[0.59], p = 0.002), less positive affect (b[SE] = -0.21[0.10], p = 0.026), and greater negative affect (b[SE] = 0.15[0.08], p = 0.052) among Hispanic, but not NHW, women. In addition, an indirect effect was found from greater stage to poorer QOL via less positive affect among Hispanic women only (b[SE] = -0.49[0.24], p = 0.041). CONCLUSIONS: This data supports our theory that Hispanic women experience worse emotional distress at later-stage disease than do NHW women, in turn impacting QOL.

Randomized Trial of a Smartphone Mobile App to Improve Symptoms and Adherence to Oral Therapy for Cancer.

BACKGROUND: Patients with cancer are increasingly prescribed oral therapies, bearing greater responsibility for self-management of treatment adherence and adverse events. We conducted a randomized trial to test the use of a smartphone mobile app to improve symptoms and adherence to oral cancer therapy. MATERIALS AND METHODS: From February 18, 2015, through December 31, 2016, 181 patients with diverse cancers who were prescribed oral therapy were randomized to receive either the smartphone mobile app or standard care. The mobile app included a medication plan with reminders, a symptom-reporting module, and patient education. Primary outcomes were adherence (per electronic pill caps), symptom burden (per MD Anderson Symptom Inventory), and quality of life (per the Functional Assessment of Cancer Therapy-General). Participants also completed self-report measures of medication adherence, anxiety and depression symptoms, social support, quality of care, and healthcare utilization. Linear regression was used to assess intervention effects on adherence and change in self-report outcomes from baseline to week 12, controlling for baseline scores and social support. RESULTS: Study groups did not differ across any outcome measure, with an overall mean adherence of 78.81% (SD, 26.66%) per electronic pill caps. However, moderation analyses showed that intervention effects on the primary adherence measure varied by baseline self-reported adherence and anxiety symptoms. Specifically, adherence rates per electronic pill caps were higher in patients randomized to the mobile app versus standard care within the subsamples of patients who reported baseline adherence problems (mean difference, -22.30%; 95% CI, -42.82 to -1.78; P=.034) and elevated anxiety (mean difference, -16.08%; 95% CI, -31.74 to -0.41; P=.044). CONCLUSIONS: Although the mobile app may not improve outcomes for all patients prescribed oral cancer therapy, the intervention may be beneficial for those with certain risk factors, such as difficulties with adherence or anxiety.

Patient Experiences With Oral Chemotherapy: Adherence, Symptoms, and Quality of Life.

BACKGROUND: Oral therapies are increasingly common in oncology care. However, data are lacking regarding the physical and psychologic symptoms patients experience, or how these factors relate to medication adherence and quality of life (QoL). MATERIALS AND METHODS: From December 2014 through August 2016, a total of 181 adult patients who were prescribed oral targeted therapy or chemotherapy enrolled in a randomized study of adherence and symptom management at Massachusetts General Hospital Cancer Center. Patients completed baseline assessments of adherence with electronic pill cap, QoL, symptom severity, mood, social support, fatigue, and satisfaction with clinicians and treatment. Relationships among these factors were examined using Pearson product-moment correlations and multivariable linear regression. RESULTS: At baseline, the mean electronic pill cap adherence rate showed that patients took 85.57% of their oral therapy. The most commonly reported cancer-related symptoms were fatigue (88.60%), drowsiness (76.50%), disturbed sleep (68.20%), memory problems (63.10%), and emotional distress (60.80%). Patients who reported greater cancer-related symptom severity had lower adherence (r= -0.20). In a multivariable regression, greater depressive and anxiety symptoms, worse fatigue, less social support, lower satisfaction with clinicians and treatment, and higher symptom burden were associated with worse QoL (F[10, 146]=50.53; adjusted R2=0.77). Anxiety symptoms were most strongly associated with clinically meaningful decrements in QoL (ß= -7.10; SE=0.22). CONCLUSIONS: Patients prescribed oral therapies struggle with adherence, and cancer-related symptom burden is high and related to worse adherence and QoL. Given perceptions that oral therapies are less impairing, these data underscore the strong need to address adherence issues, symptom burden, and QoL for these patients.