Older Breast Cancer Survivors Research Articles

Alzheimer's disease susceptibility genes in malignant breast tumors

Background:Cognitive problems have been reported in breast cancer patients after chemotherapy. A small group of older breast cancer survivors carrying the APOE4 gene, receiving chemotherapy, was at increased risk of long-term impairment of brain function. We have analyzed the expression of APOE and the next 23-ranked Alzheimer’s disease (AD) susceptibility genes in malignant breast tumors. We wished to determine if these 24 genes might be related to breast cancer.Methods:To identify the most important AD susceptibility genes, we consulted the ALZGENE database (www.alzgene.org/) which displays this information and regularly updates it. To analyze the effect of AD susceptibility genes on breast cancer, we used The Cancer Genome Atlas (TCGA). We analyzed TCGA data with cBioPortal for Cancer Genomics. cBioPortal provides visualization, analysis, and download of large-scale cancer genomic data sets. cBioPortal can analyze APOE in breast tumors but cannot distinguish its three alleles: E2, E3, and E4.Results:About 1.6% of the tumors had APOE amplification (copy number alteration). Two percent of the tumors had CD33 alterations. None of the tumors had APOE mutations. Two tumors had CD33 missense mutations of unknown significance. Expression heatmap shows that over- or underexpression of APOE and CD33 was correlated in most of the tumors. APOE alteration significantly co-occurred with CD33 and CD2AP.Conclusion:Alterations of certain cancer genes tend to co-occur, indicating that they may work in tandem to drive tumor formation and development. This may be the case with the co-occurring alterations of APOE, CD33, and CD2AP. It would be important to know which APOE allele(s) were co-occurrent with CD33 and CD2AP and whether co-occurrence in the tumor predicted increased risk of AD. This information could help in identification of specific risk factors for breast cancer-related cognitive decline in older women, which has important implications for oncology care.

Correspondence Between Objective and Self-reported Endocrine Therapy Adherence Among Women With Breast Cancer.

Among the approximately 70% of women with hormone receptor-positive breast cancer, endocrine therapies lower the likelihood of recurrence. Nonadherence to endocrine therapy predicts lower survival. We examined concordance between self-reported and objective indicators of adherence and predictors of over-reporting endocrine therapy adherence among survivors of breast cancer. Women with breast cancer (N = 112) receiving their initial endocrine therapy prescription completed three assessments at prescription initiation (Time 1), 1 month (Time 2), and 4 months later (Time 3). At Time 1, participants were provided a medication event monitoring system (MEMS) cap to assess adherence; it was collected at Time 3. Women completed items regarding self-reported adherence, depressive symptoms, cancer-related coping processes, and the patient-physician relationship. MEMS was significantly negatively correlated with the self-reported nonadherence measurements of occasionally forgetting (Time 2, ρ = -.29, p < .01; Time 3, ρ = -.24, p < .01), nonadherence in the past week (Time 2, ρ = -.53, p < .01; Time 3, ρ = -.45, p < .01), and nonadherence in an average week in the past month (Time 2, ρ = -.38, p < .01; Time 3, ρ = -.39, p < .01). Concordance in objective and self-reported adherence measures was evident in 83% of women at Time 2 and 73% at Time 3. Older age was significantly associated (p < .01) with discordance. Findings reveal moderate correspondence between objective and self-report measures, with self-report overestimating objective adherence. Clinicians should be aware when treating older breast cancer survivors that they are more likely to over self-report their endocrine therapy adherence.

Factors associated with self-reported falls, balance or walking difficulty in older survivors of breast, colorectal, lung, or prostate cancer: Results from Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey linkage.

BackgroundCancer and its treatment affect body systems that are important in preventing falls and controlling balance/walking. This study examined factors associated with self-reported falls and balance/walking difficulty in the past 12 months in older survivors of four major cancers.MethodsThis was a cross-sectional study analyzing population-based data from Surveillance, Epidemiology, and End Results–Medicare Health Outcomes Survey (SEER-MHOS). Data from cohorts 9 to 14 (January 2006 to December 2013) were extracted. Inclusion criteria were: age ≥65 years at cancer diagnosis, first MHOS completed during years 1–5 post-cancer diagnosis, first primary breast (n = 2725), colorectal (n = 1646), lung (n = 752), and prostate (n = 4245) cancer, and availability of cancer staging information. Primary outcomes were self-reported falls and balance/walking difficulty in the past 12 months. Multivariable logistic regression was constructed for each cancer type to examine independent factors associated with falls and balance/walking difficulty.ResultsIn all cancer types, advancing age at cancer diagnosis and dependence in activities of daily living were significant independent factors associated with increased odds of reporting falls and balance/walking difficulty in the past 12 months. Additionally, depression was independently associated with falls and sensory impairment in feet was independently linked to balance/walking difficulty in all cancer types. Other independent factors of falls and balance/walking difficulty varied across cancer types. In breast cancer only, localized or regional cancer stage was significantly associated with increased odds of reporting falls and balance/walking difficulty, whereas treatment with radiation decreased the odds of falling. No association between falls and balance/walking difficulty with time since cancer diagnosis, cancer stage, or cancer treatment was found in colorectal, lung, and prostate cancer.ConclusionThere exists some heterogeneity in factors associated with self-reported falls and balance/walking difficulty between different cancer types. Future research is necessary to ascertain factors predictive of falls and balance/walking difficulty in older cancer survivors, particularly factors related to cancer diagnosis and treatment.

Survivorship issues in older breast cancer survivors.

Almost half of breast cancer survivors are aged ≥ 65 years and the proportion is likely to increase due to the aging of the population. The objectives of this article were to review studies of health outcomes among older breast cancer survivors ≥ 65 years to identify gaps in the published literature and offer suggestions for future research. The present review is based upon bibliographic searches in PubMed and CINAHL and relevant search terms. Articles published in English from January 1, 1970 through October 1, 2018 were identified using the following MeSH search terms and Boolean algebra commands. This review has revealed that older breast cancer survivors cope with health issues related to cancer treatment and the aging process, including comorbidities, osteoporosis, symptoms, physical functioning, cognitive functioning, nutrition, and physical activity. Additional research is needed to examine therapeutic interventions to address the health conditions older breast cancer survivors are coping with. Particular focus of further research should be on the nutritional status and physical activity levels of older breast cancer survivors. Individualized nutrition plans and tailored physical activity programs for older survivors are needed that meet people where they are and that form habits.

Pretreatment Psychoneurological Symptoms and Their Association With Longitudinal Cognitive Function and Quality of Life in Older Breast Cancer Survivors

ContextSymptoms affect quality of life (QOL), functional status, and cognitive function in cancer survivors, but older survivors are understudied. ObjectivesThe objectives of this study were to identify prototypical presystemic therapy psychoneurological symptom clusters among older breast cancer survivors and determine whether these symptom clusters predicted cognition and QOL over time. MethodsWomen with newly diagnosed nonmetastatic breast cancer (n = 319) and matched noncancer controls (n = 347) aged 60+ years completed questionnaires and neuropsychological tests before systemic therapy and 12 and 24 months later. Latent class analysis identified clusters of survivors based on their pretherapy depression, anxiety, fatigue, sleep disturbance, and pain. Linear mixed-effects models examined changes in objective cognition, perceived cognition, and functional status (Instrumental Activities of Daily Living disability, functional well-being, and breast cancer–specific QOL) by group, controlling for covariates. ResultsNearly one-fifth of older survivors were classified as having high pretherapy symptoms (n = 51; 16%); the remainder had low symptoms (n = 268; 84%); both groups improved over time on all outcomes. However, compared to the low symptom group and controls, survivors with high symptoms had lower baseline objective cognition and lower perceived cognition at baseline and 24 months, lower functional well-being at baseline and 12 months, greater Instrumental Activities of Daily Living disability at baseline, and lower breast cancer–specific QOL at all time points (all P < 0.05). ConclusionNearly one-fifth of older breast cancer survivors had high psychoneurological symptoms at diagnosis, which predicted clinically meaningful decrements in perceived cognition and function in the first 24 months after diagnosis. Pretreatment psychoneurological symptom clusters could identify survivors for monitoring or intervention.

Evaluation of osteopenia and osteoporosis in younger breast cancer survivors compared with cancer-free women: a prospective cohort study

BackgroundOsteoporosis, an indicator of significant bone loss, has been consistently reported among older breast cancer survivors. Data are limited on the incidence of osteopenia, an earlier indicator of bone loss, and osteoporosis in younger breast cancer survivors compared with cancer-free women.MethodsWe prospectively examined bone loss in 211 breast cancer survivors (mean age at breast cancer diagnosis = 47 years) compared with 567 cancer-free women in the same cohort with familial risk for breast cancer. Multivariable-adjusted Cox proportional hazards models were used to estimate HRs and 95% CIs of osteopenia and/or osteoporosis incidence based on physician diagnosis.ResultsDuring a mean follow-up of 5.8 years, 66% of breast cancer survivors and 53% of cancer-free women reported having a bone density examination, and 112 incident cases of osteopenia and/or osteoporosis were identified. Breast cancer survivors had a 68% higher risk of osteopenia and osteoporosis compared to cancer-free women (HR = 1.68, 95% CI = 1.12–2.50). The association was stronger among recent survivors after only 2 years of follow-up (HR = 2.74, 95% CI = 1.37–5.47). A higher risk of osteopenia and osteoporosis was also observed among survivors aged ≤ 50 years, estrogen receptor-positive tumors, and those treated with aromatase inhibitors alone or chemotherapy plus any hormone therapy relative to cancer-free women.ConclusionsYounger breast cancer survivors are at higher risk for osteopenia and osteoporosis compared to cancer-free women. Studies are needed to determine effective approaches to minimize bone loss in this population.

Patient-reported and objectively measured physical function in older breast cancer survivors and cancer-free controls.

Older breast cancer survivors (BCS) consistently report more functional limitations than women without cancer, but whether or not these differences remain when using objective measures of physical functioning and the correlates of these measures is unknown. Cross-sectional study comparing older (≥60 years old) BCS (n = 84) to similarly aged women without cancer (n = 40). Patient-reported physical function was assessed by the SF-36 physical function (SF-36PF) subscale and the Late Life Function & Disability Instrument (LLFDI). Objective measures included the short Physical Performance Battery (sPPB), usual walk speed (m/s), chair stand time (sec) and, grip strength (kg). Potential predictors included age, comorbidities, symptom severity, fatigue and skeletal muscle index (SMI; kg/m2). Patient-reported physical function was significantly lower in BCS than controls using SF-36PF (47.3 ± 0.1 vs. 52.9 ± 4.0, p < 0.001) and LLFDI (68.2 ± 10.5 vs. 75.0 ± 8.9, p = 0.001). BCS had significantly lower sPPB scores (10.7 ± 0.1 vs. 11.7 ± 0.5, p < 0.001), longer chair stand times (12.6 ± 3.7 vs. 10.1 ± 1.4 s, p < 0.001), and lower handgrip strength (22.3 ± 5.0 vs. 24.3 ± 4.4 kg, p = 0.03) than controls, but similar walk speed (1.1+0.2 vs. 1.1+0.1 m/s, p = 0.75). Within BCS, age, comorbidities, SMI, symptom severity and fatigue explained 17.3%-33.1% of the variance across physical function measures. Fatigue was the variable most consistently associated with patient-reported physical functioning and age and comorbidities were the variables most consistently associated with objectively measured physical functioning. Older BCS should be screened for functional limitations using simple standardized objective tests and interventions that focus on improving strength and reducing fatigue should be tested.

Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study.

To determine treatment and aging-related effects on longitudinal cognitive function in older breast cancer survivors. Newly diagnosed nonmetastatic breast cancer survivors (n = 344) and matched controls without cancer (n = 347) 60 years of age and older without dementia or neurologic disease were recruited between August 2010 and December 2015. Data collection occurred during presystemic treatment/control enrollment and at 12 and 24 months through biospecimens; surveys; self-reported Functional Assessment of Cancer Therapy-Cognitive Function; and neuropsychological tests that measured attention, processing speed, and executive function (APE) and learning and memory (LM). Linear mixed-effects models tested two-way interactions of treatment group (control, chemotherapy with or without hormonal therapy, and hormonal therapy) and time and explored three-way interactions of ApoE (ε4+ v not) by group by time; covariates included baseline age, frailty, race, and cognitive reserve. Survivors and controls were 60 to 98 years of age, were well educated, and had similar baseline cognitive scores. Treatment was related to longitudinal cognition scores, with survivors who received chemotherapy having increasingly worse APE scores ( P = .05) and those initiating hormonal therapy having lower LM scores at 12 months ( P = .03) than other groups. These group-by-time differences varied by ApoE genotype, where only ε4+ survivors receiving hormone therapy had short-term decreases in adjusted LM scores (three-way interaction P = .03). For APE, the three-way interaction was not significant ( P = .14), but scores were significantly lower for ε4+ survivors exposed to chemotherapy (-0.40; 95% CI, -0.79 to -0.01) at 24 months than ε4+ controls (0.01; 95% CI, 0.16 to 0.18; P < .05). Increasing age was associated with lower baseline scores on all cognitive measures ( P < .001); frailty was associated with baseline APE and self-reported decline ( P < .001). Breast cancer systemic treatment and aging-related phenotypes and genotypes are associated with longitudinal decreases in cognitive function scores in older survivors. These data could inform treatment decision making and survivorship care planning.

Symptom cluster of emotional distress, fatigue and cognitive difficulties among young and older breast cancer survivors: The mediating role of subjective stress

To examine the nature of the symptom cluster of emotional distress, fatigue, and cognitive difficulties in young and older breast cancer survivors (BCS); To assess the mediating role of subjective stress and coping strategies (emotional control and meaning-focused coping) in the association between age and symptom cluster. Participants were 170 BCS, stages I-III, 1-12 months post-chemotherapy, filled-out the Fatigue, Emotional Control, Meaning-focused Coping, Emotional Distress and the Cognitive Difficulties Questionnaires. Statistical analyses included tests for difference between-groups Pearson correlations and Structural Equation Modeling for the assessment of the study model. Older BCS (aged 60-82) reported lower levels of emotional distress (M = 0.87, SD = 0.87), fatigue (M = 3.85, SD = 2.38), and cognitive difficulties (M = 1.17, SD = 1.07) compared to the younger BCS (aged 24-59) (emotional distress M = 1.17, SD = 0.85, fatigue M = 5.02, SD = 2.32, and cognitive difficulties M = 1.66, SD = 1.23, p < .01-,05). The older survivors reported lower levels of subjective stress and used more emotional control strategies compared to the younger BCS. The empirical model had good fit indices (χ2 = 27.60, p = 0.20, χ2/df = 1.26; CFI = 0.98; TLI = 0.98; NFI = 0.95; RMSEA = 0.04 (90% CI = 0.00, 10) and showed that subjective stress, but not coping strategies, mediated the effect of age on symptom cluster severity. Lower levels of subjective stress, but not coping strategies, mediated the association of age with the symptom cluster of emotional distress, fatigue and cognitive difficulties. Further research is needed to explore differences in subjective stress by age.

Effects of resistance plus aerobic training on body composition and metabolic markers in older breast cancer survivors undergoing aromatase inhibitor therapy.

To evaluate the effects of combined aerobic + resistance training on body composition and metabolic markers in older breast cancer survivors undergoing aromatase inhibitor therapy. Older breast cancer survivors were randomized to an exercise [resistance + aerobic training]: n = 18, or placebo control group: n = 18. Body composition (measured by DXA) and blood markers of lipid and glucose were measured at baseline, and at 12, 24, and 36 weeks. The exercise group performed 40 min of resistance exercises on machines followed by 30 min of aerobic training on a treadmill, three times per week. Separate 2 (group) × 4 (time) repeated-measure ANOVAs were used to compare groups over time. Significant group × time interactions were found for total and trunk fat mass (p < 0.001 and p = 0.001) and % body fat (p < 0.001), where women in the exercise group lost fat compared to slight gains among women in the stretching control group. There were no significant differences between groups for lean mass, hip or spine BMD, metabolic markers, or CRP. Our aerobic + resistance exercise program prevented fat gain, but may not have been sufficient to improve metabolic or bone health markers in older breast cancer survivors undergoing aromatase inhibitor therapy.

Divergence from osteoporosis screening guidelines in older breast cancer patients treated with anti-estrogen therapy: A population-based cohort study.

Older Breast Cancer (BC) survivors are an increased risk of osteoporosis due to natural aging and long-term cancer treatment-related toxicity. It is well known that anti-estrogen therapy (AET), especially aromatase inhibitors (AI), is associated with rapid bone loss and thus increases the risk of osteoporosis. This study characterizes patterns and predictors of receiving guideline-recommended bone densitometry (BD) screening at AET initiation. A retrospective cohort study (1998-2012) of all women ≥65 years of age initiating AET was designed using claims data from Quebec's universal health care. Associations with BD screening were estimated using a generalized estimating equations regression model, adjusting for clustering of patients within physicians. Among 16,480 women initiating AET, 36.1% received a baseline BD. Among AI users, the rate was 58.4%. In the multivariate analysis, age, lower socioeconomic status, tamoxifen use, lack of periodic health exam and having a general practitioner as the AET prescriber were associated with lower odds of BD screening. In terms of quality of care-related variables, lack of guideline-appropriate radiotherapy (OR: 0.69 (95% CI, 0.57-0.83), or chemotherapy consideration (0.82 (95% CI, 0.71-0.94)) and non-adherence to AET (0.76 (95% CI, 0.68-0.84)) were associated with lower odds of receiving BD screening. Women diagnosed with BC after 2003 had significantly better odds of being screened. Despite an increase in rates since 2003, BD screening remains suboptimal, especially for women at higher risk of osteoporosis. Coordination of health care and service-delivery monitoring can potentially optimize long-term management of treatment-related toxicity in older BC survivors.

Fear of recurrence among older breast, ovarian, endometrial, and colorectal cancer survivors: Findings from the WHI LILAC study.

To examine the prevalence of and factors associated with fear of recurrence (FCR) following treatment for breast, ovarian, endometrial, and colorectal cancer among older women. Participants were enrolled in the Women's Health Initiative Life and Longevity After Cancer study. Descriptive statistics and multivariate logistic regression models were used to assess the association of demographic, clinical, and quality of life variables with survivors' FCR, dichotomized as <14 (low) or ≥14 (high) using the Cancer Worry Scale. Out of the 4259 participants, 3124 (73.3%) were diagnosed with breast cancer, 559 (13.1%) with colorectal cancer, 493 (11.6%) with endometrial cancer, and 83 (2%) with ovarian cancer. There were no significant differences in FCR by cancer type (P=.75), with a mean scale score of 10.8±2.87 for all participants combined. Approximately 16% (n=679) were in the high FCR group. Multivariable analyses indicated that being younger at diagnosis, reporting a symptom score of ≥8, receipt of chemotherapy, and lower self-rated health were significantly associated with high FCR. Women who were widowed or never married were less likely to report high FCR. Fear of recurrence was experienced by a small but important proportion of older, long-term cancer survivors and is associated with multiple demographic and clinical variables. These results will better inform researchers and clinicians regarding the individuals who are at risk of FCR.

Predictors of falls in older survivors of breast and prostate cancer: A retrospective cohort study of surveillance, epidemiology and end results-Medicare health outcomes survey linkage.

To identify predictors of falls in older breast and prostate cancer survivors. This retrospective cohort study analyzed population-based Surveillance, Epidemiology and End Results-Medicare Health Outcomes Survey (SEER-MHOS) linkage. Inclusion criteria were age >65 years at cancer diagnosis, first primary female breast or prostate cancer, cancer staging information available, completion of baseline MHOS during years 2-3 and follow-up MHOS during years 4-5 post-diagnosis, and falls information available. Data from 437 breast and 660 prostate cancer survivors were analyzed. Multivariable logistic regression was constructed to evaluate variables from baseline MHOS with relation to falls from follow-up MHOS. Model accuracy was assessed using area under receiver-operating-characteristic curve (AUC). At follow-up MHOS, 26% of breast and 22% of prostate cancer survivors reported falls in the past 12 months. In breast cancer, a history of falls (odds ratio (OR) = 4.95, 95% confidence interval (CI) = 2.44-10.04) and sensory impairment in feet (OR = 3.33, 95%CI = 1.51-7.32) were significant predictors of falls. In prostate cancer, a history of falls (OR = 3.04, 95%CI = 1.79-5.15), unmarried (OR = 1.82, 95%CI = 1.12-2.95), lower physical summary score of quality-of-life(OR = 0.96, 95%CI = 0.94-0.98), urinary incontinence (OR = 1.69, 95%CI = 1.08-2.65), older age at diagnosis (OR = 1.05, 95%CI = 1.01-1.09), and shorter time post-diagnosis (OR = 0.96, 95%CI = 0.93-0.99) were significant predictors of falls. AUC was 0.67 and 0.77 for breast and prostate cancer, respectively, indicating moderate accuracy of models in detecting fallers. Asking older breast and prostate cancer survivors about falls in the past 12 months is imperative in fall prevention. Further examination of deficits specific to each cancer is necessary to assess fall risks.

Physical Functioning in Older Breast Cancer Survivors

The largest age group of breast cancer survivors (BCS) in the U.S. is comprised of women ages 65+, who are susceptible to age-related decrements in physical function accelerated by cancer treatment toxicities. Though exercise is known to reverse age-related functional limitations, older BCS may be heterogeneous in baseline functioning which may affect the efficacy of exercise to reverse functional declines. PURPOSE: Determine the efficacy of each aerobic and resistance training to improve physical function in older BCS, considering baseline physical functioning. METHODS: Older, early-stage, BCS (mean age=72), who underwent chemo- or radio-therapy in the previous 2 years were randomized to 12 months of supervised, group aerobic (AER) or resistance (RES) training or control (CON) flexibility exercise, followed by 6 months of home-based training. Physical function was assessed by the Physical Performance Battery (PPB), 5x chair stand time (sec), maximum bench and leg press (kg), and 4-meter usual walk speed (m/sec) tests and self-reported lower-body function with the Late-Life Function and Disability Instrument (LLFDI). A linear mixed effects model was used to assess function after 12 and 18 months on the full sample and only in BCS with PPB scores ≥9. RESULTS: 114 BCS were enrolled and randomized to AER (n=37), RES (n=39), or CON (n=38). Within the full sample there was a significant improvement in bench press strength at 12 months (p=0.03) and PPB at 18 months in RES vs CON. After removing participants with low baseline physical functioning (n=79), the following additional significant differences were found between: 1) RES (αmean=2.72±1.7) and CON (αmean=-3.06±2.0) for self-report physical function at both 12 (p=0.04) and 18 months (p=0.005), 2) AER (αmean=0.4±0.0) and CON (αmean=-0.03±0.0) at 12-months for average walk speed and, 3) AER (αmean=0.32±0.3) and RES (αmean=0.50±0.2) at 18 months, for chair time (p=0.05). CONCLUSIONS: Although AE and RT are efficacious in improving physical function in older BCS across a range of baseline physical functioning, broader improvements may only be possible among women with better functioning and thus capable of achieving a greater dose of exercise. Older BCS may need to be stratified into groups based on their initial functioning, then matched to appropriate training.

Health-Related Quality of Life in a Predictive Model for Mortality in Older Breast Cancer Survivors.

To develop a predictive model and risk score for 10-year mortality using health-related quality of life (HRQOL) in a cohort of older women with early-stage breast cancer. Prospective cohort. Community. U.S. women aged 65 and older diagnosed with Stage I to IIIA primary breast cancer (N=660). We used medical variables (age, comorbidity), HRQOL measures (10-item Physical Function Index and 5-item Mental Health Index from the Medical Outcomes Study (MOS) 36-item Short-Form Survey; 8-item Modified MOS Social Support Survey), and breast cancer variables (stage, surgery, chemotherapy, endocrine therapy) to develop a 10-year mortality risk score using penalized logistic regression models. We assessed model discriminative performance using the area under the receiver operating characteristic curve (AUC), calibration performance using the Hosmer-Lemeshow test, and overall model performance using Nagelkerke R2 (NR). Compared to a model including only age, comorbidity, and cancer stage and treatment variables, adding HRQOL variables improved discrimination (AUC 0.742 from 0.715) and overall performance (NR 0.221 from 0.190) with good calibration (p=0.96 from HL test). In a cohort of older women with early-stage breast cancer, HRQOL measures predict 10-year mortality independently of traditional breast cancer prognostic variables. These findings suggest that interventions aimed at improving physical function, mental health, and social support might improve both HRQOL and survival.

Resistance training reduces inflammation and fatigue and improves physical function in older breast cancer survivors.

Resistance training (RT) reduces fatigue and improves physical function and quality of life (QOL) in breast cancer survivors (BCS). This may be related to reductions in systemic and tissue-specific inflammation. This pilot study examines the hypothesis that RT induces changes in systemic and tissue-specific inflammation that contribute to improvements in physical and behavioral function in postmenopausal BCS. Eleven BCS (60 ± 2 years old, body mass index 30 ± 1 kg/m, mean ± SEM) underwent assessments of fatigue (Piper Fatigue Scale), physical function, QOL (SF-36), glucose and lipid metabolism, and systemic, skeletal muscle, and adipose tissue inflammation (n = 9) before and after 16 weeks of moderate-intensity whole-body RT. Muscle strength improved by 25% to 30% (P < 0.01), QOL by 10% (P = 0.04), chair stand time by 15% (P = 0.01), 6-minute walk distance by 4% (P = 0.03), and fatigue decreased by 58% (P < 0.01), fasting insulin by 18% (P = 0.04), and diastolic and systolic blood pressure by approximately 5% (P = 0.04) after RT. BCS with the worst fatigue and QOL demonstrated the greatest improvements (absolute change vs baseline: fatigue: r = -0.95, P < 0.01; QOL: r = -0.82, P < 0.01). RT was associated with an approximately 25% to 35% relative reduction in plasma and adipose tissue protein levels of proinflammatory interleukin (IL)-6sR, serum amyloid A, and tumor necrosis factor-α, and 75% relative increase in muscle pro-proliferative, angiogenic IL-8 protein content by 75% (all P < 0.05). BCS with the highest baseline proinflammatory cytokine levels had the greatest absolute reductions, and the change in muscle IL-8 correlated directly with improvements in leg press strength (r = 0.53, P = 0.04). These preliminary results suggest that a progressive RT program effectively lowers plasma and tissue-specific inflammation, and that these changes are associated with reductions in fatigue and improved physical and behavioral function in postmenopausal BCS.

Perspective of older African-American and Non-Hispanic white breast cancer survivors from diverse socioeconomic backgrounds toward physical activity: A qualitative study.

We sought to explore the perspective of older breast cancer survivors (BCS) from diverse racial and socioeconomic backgrounds toward physical activity (PA) to inform the design of a PA program that fosters acceptability. Participants included sixty women, ≥65years, within two years of treatment completion for stage I-III breast cancer. We purposely sampled ≥ten patients in each race [African-American (AA) and Non-Hispanic White (NHW)] and socioeconomic status (SES) [SES disadvantaged and SES non-disadvantaged] group. Participants completed in-person interviews (n=60) and follow-up focus groups (n=45). Thematic analyses were employed. The median age was 71.0years (range: 65-87years). Five themes emerged: 1) importance of PA; 2) current PA participants engaged in; 3) influence of race and culture on PA attitudes and beliefs; 4) barriers to PA and facilitators to PA; and 5) PA preferences. Barriers included health issues (43%), particularly cancer treatment side effects such as fatigue. Facilitators included religious faith (38%) and family (50%). Preferences included group exercise (97%) and strength training (80%) due to concerns participants had with diminished upper body strength after cancer treatment. Although AA (59%) and SES non-disadvantaged (78%) participants reported that race and culture influenced their attitudes toward PA, it did not translate to racial and SES differences in preferences. Among older BCS, physical activity preferences were shaped by cancer experience, rather than by race and SES. Physical activity programs for older BCS should focus on addressing cancer treatment-related concerns and should include strength training to ensure PA programs are more acceptable to older BCS.

Long-term Patient-Reported Outcomes in Older Breast Cancer Survivors: A Population-Based Survey Study

For older women with breast cancer, local therapy options may include lumpectomy plus whole-breast irradiation (Lump+WBI), lumpectomy plus brachytherapy (Lump+Brachy), lumpectomy alone (Lump alone), mastectomy without radiation therapy (Mast alone), and mastectomy plus radiation therapy (Mast+RT). We surveyed a population-based cohort of older breast cancer survivors to assess the association of local therapy with long-term quality-of-life outcomes. We used nationally comprehensive Medicare claims to identify women aged ≥67years in whom nonmetastatic breast cancer was diagnosed in 2009, who were treated with 1 of the 5 aforementioned treatment options, and who were still alive in 2015. From this cohort, 1650 patients (330 patients per treatment) were randomly selected. A survey that included the CanSORT (Cancer Surveillance and Outcomes Research Team) Satisfaction with Breast Cosmetic Outcome, BREAST-Q, Decisional Regret Scale, and EQ-5D-3L was mailed to potential participants.We used multivariable linear regression to assess associations between local therapy and outcomes after adjusting for patient, disease, and treatment covariates. Among the 489 women who returned the surveys (30% response rate), the median age at diagnosis was 72years (range, 67-87years). The interval from diagnosis to survey completion was approximately 6years for all patients. Compared with Lump+WBI (adjusted score, 3.40), the CanSORT cosmetic satisfaction scores were higher for Lump+Brachy (score, 3.77; P = .007) and Lump alone (score, 3.80; P = .04) and lower for Mast+RT (score, 3.01; P = .006). Similar trends were seen for BREAST-Q cosmetic satisfaction. BREAST-Q psychosocial, sexual, and physical well-being and EQ-5D-3L global health status tended to be better in patients treated with less irradiation and less surgery.BREAST-Q adverse radiation effects were worse for Lump+WBI compared with Lump+Brachy. Decisional regret regarding surgery and radiation therapy did not differ across groups. Compared with patients treated with Lump+WBI, patients treated with Lump+Brachy and Lump alone reported slightly higher rates of in-breast recurrence (excess risk of 5.8% and 6.4%, respectively; P = .01). In this nationally diverse cohort, less irradiation and less surgery were associated with better long-term quality-of-life outcomes. However, patient regret regarding surgery and radiation therapy was similar across all groups.

Risk of myeloid neoplasms after radiotherapy among older women with localized breast cancer: A population-based study.

BackgroundThere are inconsistent and limited data regarding the risk of myeloid neoplasms (MN) among breast cancer survivors who received radiotherapy (RT) in the absence of chemotherapy. Concern about subsequent MN might influence the decision to use adjuvant RT for women with localized disease. As patients with therapy-related MN have generally poor outcomes, the presumption of subsequent MN being therapy-related could affect treatment recommendations.MethodsWe used the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database to study older women with in-situ or stage 1–3 breast cancer diagnosed 2001–2009 who received surgery. Chemotherapy and RT were ascertained using Medicare claims, and new MN diagnoses were captured using both SEER registry and Medicare claims. We excluded women who received chemotherapy for initial treatment, and censored at receipt of subsequent chemotherapy. Competing-risk survival analysis was used to assess the association between RT and risk of subsequent MN adjusting for relevant characteristics.ResultsMedian follow-up for 60,426 eligible patients was 68 months (interquartile range, 46 to 92 months), with 47.6% receiving RT. In total, 316 patients (0.52%) were diagnosed with MN; the cumulative incidence per 10,000 person-years was 10.6 vs 9.0 among RT-treated vs non-RT-treated women, respectively (p = .004); the increased risk of subsequent MN persisted in the adjusted analysis (hazard ratio = 1.36, 95% confidence interval: 1.03–1.80). The results were consistent in multiple sensitivity analyses.ConclusionsOur data suggest that RT is associated with a significant risk of subsequent MN among older breast cancer survivors, though the absolute risk increase is very small. These findings suggest the benefits of RT outweigh the risks of development of subsequent MN.

Obesity, physical activity, and breast cancer survival among older breast cancer survivors in the Cancer Prevention Study-II Nutrition Cohort.

Nearly half of the 3.5 million female breast cancer survivors in the US are aged 65years or older at diagnosis, yet little is known about associations of obesity and physical activity with breast cancer-specific mortality (BCSM) among older survivors. Between 1992 and 2013, 5254 women in the Cancer Prevention Study-II Nutrition Cohort were diagnosed with local or regional breast cancer among whom 1771 deaths (505 breast cancer deaths) occurred. Multivariable Cox proportional hazards regression models were used to examine associations of pre- and post-diagnosis body mass index (BMI) and moderate-vigorous physical activity (MET-hours/week) with mortality outcomes stratified by age at diagnosis (<65, ≥65years). Among women ≥65years of age at diagnosis (n=4226), pre- and post-diagnosis BMI (per 5kg/m2) were associated with a higher risk of BCSM (pre-diagnosis, HR 1.27, 95% CI 1.14-1.41; post-diagnosis, HR 1.19, 95% CI 1.04, 1.36); neither pre- nor post-diagnosis physical activity was associated with BCSM. Among women <65years of age at diagnosis (n=1028), BMI at both time points were not significantly associated with BCSM; however, there was a significant inverse trend of post-diagnosis physical activity with BCSM (P-trend=0.01). Among both age groups, BMI and physical activity, regardless of when assessed, were significantly associated with all-cause mortality. Higher BMI, pre- or post-diagnosis, was associated with a higher risk of BCSM in older patients, independent of comorbidities and stage at diagnosis. Weight management should be discussed even with women aged 65years or older to lower rates of BCSM.