Older Breast Cancer Survivors Research Articles

Abstract PO2-19-04: Trial in Progress: The REJOIN Trial to Use Exercise and Education to Relieve Joint Pain in Older Breast Cancer Survivors Taking Aromatase Inhibitors

Abstract Background: Physical activity (PA) is a recommended part of breast cancer survivorship. PA promotes survival and mitigates symptoms in older breast cancer survivors (BCS), especially in reducing joint pain associated with Aromatase Inhibitors (AIs). The purpose of the study is to test if a self-management intervention (including education and exercise instruction) improve joint pain management better than standard care. Trial Design: This two-armed randomized controlled pilot trial (NCT03955627) includes insufficiently active BCS, 60 years and older, diagnosed with stage I-III hormone-sensitive breast cancer, who have completed primary cancer treatment and are within 6 months of initiating AIs. We adapted an evidence-based PA program for older adults (Fit and Strong!) that includes bi-weekly, supervised exercise sessions plus education (90 minutes total). The 16-week, evidence-based intervention program includes: 8-weeks of supervised sessions delivered remotely plus 8-weeks of self-guided home sessions with periodic phone coaching. We are conducting select geriatric assessments (e.g., cognitive assessment, polypharmacy) plus measurements of exercise (both self-reported and objectively measured by accelerometer), joint pain (brief pain inventory), and AI adherence (confirmed by self-report and prescription records) assessed four times (baseline, 4, 6 and 12 months). Eligibility Inclusion criteria: • Female, aged ≥ 60 years at enrollment  • Planning to initiate (or are < 24 weeks from initiating) AIs  • Diagnosed stages I-III breast cancer  • ER+ tumor (at least 5% of cells)  • Completed surgery, radiation and/or chemotherapy  • Independent ambulator (verified by treating clinician/staff)  • Physician approval to start an exercise program • Insufficiently active (less than 150 minutes per week of moderate intensity activity or less than two sessions per week of strength training)  • Able to complete surveys and forms/understand English  • Agree to random assignment to treatment or control group  • Can commit to 8 weeks, bi-weekly classes offered by Zoom video and 8 Weeks of at-home exercise.  • Must have internet access or data plan to support video conferencing software  • Minimum cognitive impairment (verified by cognitive screening questions administered by phone) Specific Aims: The primary aim is to test the efficacy of a self-management intervention (exercise plus education) on AI-associated arthralgia. Hypothesis: Participants in the treatment group will report less pain than the control group. –A secondary aim is to test the effect of the pilot intervention on adherence to AIs. Hypothesis: Participants in the treatment group will report better AI Adherence than controls. Statistical Methods: We will use the Wilcoxon-Mann-Whitney t-test to assess the effect size from the start to the end of the trial, assuming a power calculation of 80%, a two-sided alpha of 10%, and a pooled standard deviation of one between the outcomes of the two groups (usual care and treatment) being compared. Present Accrual and Target Accrual REJOIN enrolled 12 participants in 2022, but two withdrew after randomization. We now have data on 10 participants with a target accrual of 24 overall. The original 12 were accrued at Penn State College of Medicine. We subsequently opened a second site at Wake Forest University and are recruiting the remaining participants. Contact information: For more information about REJOIN, please contact the study director, Dr. Shirley Bluethmann at sblueth@wakehealth.edu or the REJOIN project manager, Angela Grubb, at agrubb@wakehealth.edu Citation Format: Shirley Bluethmann, Peri Newman, Cristina Truica, Nancy Olsen, Heidi Klepin. Trial in Progress: The REJOIN Trial to Use Exercise and Education to Relieve Joint Pain in Older Breast Cancer Survivors Taking Aromatase Inhibitors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-19-04.

Functional decline in older breast cancer survivors treated with and without chemotherapy and non-cancer controls: results from the Hurria Older PatiEnts (HOPE) prospective study.

This study aimed to assess whether physical functional decline in older women with early-stage breast cancer is driven by cancer, chemotherapy, or a combination of both. We prospectively sampled three groups of women aged ≥ 65: 444 with early-stage breast cancer receiving chemotherapy (BC Chemo), 98 with early-stage breast cancer not receiving chemotherapy (BC Control), and 100 non-cancer controls (NC Control). Physical function was assessed at two timepoints (T1 [baseline] and T2 [3, 4, or 6months]) using the Physical Functioning Subscale (PF-10) of the RAND 36-item Short Form. The primary endpoint was the change in PF-10 scores from T1 to T2, analyzed continuously and dichotomously (Yes/No, with "yes" indicating a PF-10 decline > 10 points, i.e., a substantial and clinically meaningful difference). Baseline PF-10 scores were similar across all groups. The BC Chemo group experienced a significant decline at T2, with a median change in PF-10 of -5 (interquartile range [IQR], -20, 0), while BC Control and NC Control groups showed a median change of 0 (IQR, -5, 5; p < 0.001). Over 30% of BC Chemo participants had a substantial decline in PF-10 vs. 8% in the BC Control and 5% in the NC Control groups (p < 0.001). In this cohort of older adults with early-stage breast cancer, the combination of breast cancer and chemotherapy contributes to accelerated functional decline. Our findings reinforce the need to develop interventions aimed at preserving physical function, particularly during and after chemotherapy. The high prevalence of accelerated functional decline in older women undergoing breast cancer chemotherapy underscores the urgency to develop interventions aimed at preserving physical function and improving health outcomes. NCT01472094, Hurria Older PatiEnts (HOPE) with Breast Cancer Study.

Prediction of cognitive decline in older breast cancer survivors: the Thinking and Living with Cancer study.

Cancer survivors commonly report cognitive declines after cancer therapy. Due to the complex etiology of cancer-related cognitive decline (CRCD), predicting who will be at risk of CRCD remains a clinical challenge. We developed a model to predict breast cancer survivors who would experience CRCD after systematic treatment. We used the Thinking and Living with Cancer study, a large ongoing multisite prospective study of older breast cancer survivors with complete assessments pre-systemic therapy, 12 months and 24 months after initiation of systemic therapy. Cognition was measured using neuropsychological testing of attention, processing speed, and executive function (APE). CRCD was defined as a 0.25 SD (of observed changes from baseline to 12 months in matched controls) decline or greater in APE score from baseline to 12 months (transient) or persistent as a decline 0.25 SD or greater sustained to 24 months. We used machine learning approaches to predict CRCD using baseline demographics, tumor characteristics and treatment, genotypes, comorbidity, and self-reported physical, psychosocial, and cognitive function. Thirty-two percent of survivors had transient cognitive decline, and 41% of these women experienced persistent decline. Prediction of CRCD was good: yielding an area under the curve of 0.75 and 0.79 for transient and persistent decline, respectively. Variables most informative in predicting CRCD included apolipoprotein E4 positivity, tumor HER2 positivity, obesity, cardiovascular comorbidities, more prescription medications, and higher baseline APE score. Our proof-of-concept tool demonstrates our prediction models are potentially useful to predict risk of CRCD. Future research is needed to validate this approach for predicting CRCD in routine practice settings.

Abstract 7454: Cognitive function in older breast cancer survivors after chemotherapy

Abstract Background: In the United States, over 60% of breast cancer survivors are 65 years and older; however, little is known about patient-reported symptoms and the effect that cancer treatments could have on survivors years after their primary treatment and diagnosis. This study evaluated perceived cognitive function in older breast cancer survivors and whether prior chemotherapy was associated with cognitive outcomes. Methods: Breast cancer patients aged 65 years and older, diagnosed 2012-2013, with local and regional stage disease, were identified through the linked Texas Cancer Registry-Medicare dataset (TCR). Survivors were mailed a survey to assess their cognitive function through the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog V3) instrument (section G of the survey). The survey also collected demographic and clinical data and was collected between April 2018 and October 2019. Utilizing the data from the self-administered questionnaires, TCR, and Medicare claims, the cognitive function and quality of life among elderly patients were evaluated to assess whether prior chemotherapy and/or endocrine therapy impacts long-term health. A linear regression model was used to examine the significance of receiving chemotherapy to FACT-Cog V3 primary score while controlling for respondent sociodemographic and clinical variables. Results: Of 4,448 eligible patients, 1,954 (43.9% response rate) responded to section G. Of these, 1,065 respondents completed all 4 sections, 37 questions. Eighty of those 1065 respondents self-reported disease recurrence which excluded them from the analyses in order to avoid biases, leaving a total of 985 cases for this study. Median time from diagnosis to survey completion was 68 months (IQR 62-73). Receipt of chemotherapy was associated with a slightly lower FACT-Cog score. In total, those with chemotherapy scored, on average, 105.6 (SD 21.2) while those without scored 107.1 (SD 22.3). The largest difference in mean scores is attributed to the Perceived Cognitive Impairment subsection (scored from 0-72) where those with chemotherapy scored, on average, 57.2 (SD 13.8) and those without scored 58.7 (SD 14.0). Responsible Conduct Of Research: We need to ensure that the privacy of our patients will be protected when using their information from the surveys. Conclusion: Adjuvant chemotherapy was associated with more self-reported cognitive impairment in older breast cancer survivors, even 5-6 years after diagnosis. However, the difference between patients who received chemotherapy versus those who did not was modest, suggesting limited clinical significance. Further research is needed to determine the long-term impact of cancer treatments, particularly in older cancer survivors. Citation Format: Rachel Kim, Kai-Ping Liao, Susan Peterson, Daria Zorzi, Liang Li, Mariana Chavez MacGregor, Sharon Giordano. Cognitive function in older breast cancer survivors after chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7454.

Abstract 3411: Health-related quality of life trajectories in older breast cancer survivors and noncancerous controls over ten years: SEER-MHOS analysis

Abstract Background: The adverse effects of cancer treatment on health-related quality of life (HRQOL) are the primary concern of older women diagnosed with breast cancer. The interplay of transient and progressive functional impairments caused by cancer therapies alongside the accelerated physical declines associated with the normal aging process are all negatively correlated to HRQL, yet it remains unclear whether this is an effect of cancer or solely aging; therefore, this study examined HRQL trajectory over ten years after diagnosis between cancer cases and controls. Methods: The cancer group included 1467 women (age ≥ 65) diagnosed with primary breast cancer in 1998 - 2012, registered in the Surveillance, Epidemiology, End Results (SEER) cancer registry, and completed Medical Health Outcomes (MHO) surveys before and after cancer diagnosis. Propensity score-matched controls were randomly selected with a 1:1 ratio. Participants reported their HRQOL using SF-36/VR-12. It was summarized into two summary scores (Physical Component Summary [PCS] and mental component summary [MCS]) and eight domain scores (physical functioning [PF], role limitation due to physical health [RP], bodily pain [BP], general health [GH], vitality [VT], social functioning [SF], mental health [MH], and role limitation due to emotional problem [RE]). Hierarchical linear modeling was utilized to assess the main effects of time and group and the interaction effect between time and group on HRQOL trajectory. Results: At diagnosis, cases fared worse than controls for all HRQOL domains and summary scores. Over the ten years, PCS, PF, GH, RP, SF, and VT worsened over time (all P for time &amp;lt; 0.05), while MCS, MH, and RE remained relatively constant over time (all P for time ≥ 0.05). Older women with breast cancer had lower HRQL over time than controls in PCS, GH, and RP domains, while they showed higher HRQOL than controls post 4 - 7 years in PF, SF, RE, and VT domains (all P for group &amp;lt; 0.05). However, only RE showed a statistically significant interaction effect (P =0.035), improving over time in cases but worsening in controls. Conclusions: This research shows both older women with breast cancer and propensity-matched controls experiencing deterioration of HRQOL, particularly physical health domains, over ten years after baseline, with cases’ HRQOL kept lower than controls over time. Needs assessment and more efficient interventions to improve physical health HRQOL among older women are warranted. Citation Format: Eunkyung Lee, Maria Azevedo Daruge, Katia Ferdowsi, Jianbin Zhu. Health-related quality of life trajectories in older breast cancer survivors and noncancerous controls over ten years: SEER-MHOS analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3411.

Brain white matter microstructural changes in chemotherapy-treated older long-term breast cancer survivors.

To assess white matter microstructural changes in older long-term breast cancer survivors 5-15 years post-chemotherapy treatment. Breast cancer survivors aged 65 years or older who underwent chemotherapy (C+) and who did not undergo chemotherapy (C-) and age- and sex-matched healthy controls (HC) were enrolled at time point 1 (TP1) and followed for 2 years for time point 2 (TP2). All participants underwent brain MRI with diffusion tensor images and neuropsychological (NP) testing with the NIH Toolbox Cognition Battery. Tract-based spatial statistics (TBSS) analysis was performed on the diffusion tensor images to assess white matter microstructural changes with the fractional anisotropy (FA) parameter. There were significant longitudinal alterations in FA within the C+ group over time. The C+ group showed diminished FA in the body and genu of corpus callosum, anterior corona radiate, and external capsule on both the whole brain and region of interest (ROI) based analyses after p < 0.05 family-wise error (FWE) correction. However, there were no significant group differences between the groups at TP1. Additionally, at TP1, a positive correlation (R = 0.58, p = 0.04) was observed between the FA value of the anterior corona radiata and the crystallized composite score in the C+ group. Brain white matter microstructural alterations may be the underlying neural correlates of cognitive changes in older breast cancer survivors who had chemotherapy treatment years ago.

GAIT PARAMETERS IN OLDER BREAST CANCER SURVIVORS WITH PERSISTENT CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY

Abstract Chemotherapy-induced peripheral neuropathy (CIPN) results from chemotherapy for breast cancer treatment. CIPN symptoms persist causing significant loss of functional abilities and increased risk of falls. This study aimed to assess the spatiotemporal gait parameters in breast cancer survivors with CIPIN using an IMU system. We hypothesized that spatiotemporal gait parameters will differ between patients with persistent CIPN as compared to normative values. Thirty-two women who completed taxane-based chemotherapy for breast cancer and who have symptomatic neuropathy &amp;gt;6 months following completion of chemotherapy. Gait was assessed using seven Inertial Measurement Unit (IMU) sensors positioned at the sacrum, upper and lower leg, and foot. Participants completed a 2-minute walk at a comfortable walking pace. The outcome variables assessed included gait speed, single limb support, stride length, gait cycle time, stance percent, swing percent, double support percent, and cadence. Mean age 65(10) years, gait speed was 0.95(0.2) meters/second, single limb support 37.9(2.2) % of gait cycle, stride length 1.1(0.2) meters, gait cycle time 1.2(0.1) seconds, stance percent 62.1(2.2)% GC, swing percent 37.9(2.2)% GC, double support percent 23.9(4.3)% GC, and cadence 104.6(12.3) steps/min. Gait parameters assessed in this study showed an excellent test-retest reliability (r &amp;gt;0.86; ICC &amp;gt; 0.90). This is the first study to assess gait parameters in older breast cancer survivors with CIPN. Breast cancer survivors with CIPN showed reductions in all gait parameters. Reduced gait speed and stride length are critical indicators of fall risk for women with CIPN. Our study confirmed differences in spatiotemporal parameters between patients with persistent CIPN.

Depressive symptom trajectories in older breast cancer survivors: the Thinking and Living with Cancer Study.

To identify trajectories of depressive symptoms in older breast cancer survivors and demographic, psychosocial, physical health, and cancer-related predictors of these trajectories. Recently diagnosed nonmetastatic breast cancer survivors (n= 272), ages 60-98 years, were evaluated for depressive symptoms (Center for Epidemiological Studies Depression Scale, CES-D; scores ≥16 suggestive of clinically significant depressive symptoms). CES-D scores were analyzed in growth-mixture models to determine depression trajectories from baseline (post-surgery, pre-systemic therapy) through 3-year annual follow-up. Multivariable, multinomial logistic regression was used to identify baseline predictors of depression trajectories. Survivors had three distinct trajectories: stable (84.6%), emerging depressive symptoms (10.3%), and recovery from high depressive symptoms at baseline that improved slowly over time (5.1%). Compared to stable survivors, those in the emerging (OR = 1.16; 95% CI = 1.08-1.23) or recovery (OR = 1.26; 95% CI = 1.15-1.38) groups reported greater baseline anxiety. Greater baseline deficit accumulation (frailty composite measure) was associated with emerging depressive symptoms (OR = 3.71; 95% CI = 1.90-7.26). Less social support at baseline (OR = 0.38; 95% CI = 0.15-0.99), but greater improvement in emotional (F= 4.13; p= 0.0006) and tangible (F= 2.86; p= 0.01) social support over time, was associated with recovery from depressive symptoms. Fifteen percent of older breast cancer survivors experienced emerging or recovery depressive symptom trajectories. Baseline anxiety, deficit accumulation, and lower social support were associated with worse outcomes. Our results emphasize the importance of depression screening throughout the course of cancer care to facilitate early intervention. Factors associated with depressive symptoms, including lower levels of social support proximal to diagnosis, could serve as intervention levers.

Incident Cardiovascular Disease Risk among Older Asian, Native Hawaiian and Pacific Islander Breast Cancer Survivors.

Cardiotoxicity among breast cancer survivors is associated with chemotherapy and radiation therapy. The risk of cardiovascular disease (CVD) among Asian, Native Hawaiian and Pacific Islander (ANHPI) breast cancer survivors in the United States is unknown. We used the SEER-Medicare linked database to estimate the risk of CVD among older breast cancer survivors. International Classification of Disease diagnosis codes were used to identify incident CVD outcomes. Cox proportional hazards models were used to estimate HRs and 95% confidence intervals (CI) comparing ANHPI with Non-Hispanic White (NHW) patients with breast cancer for CVD, and among ANHPI race and ethnicity groups. A total of 7,122 ANHPI breast cancer survivors and 21,365 NHW breast cancer survivors were identified. The risks of incident heart failure and ischemic heart disease were lower among ANHPI compared with NHW breast cancer survivors (HRheart failure, 0.72; 95% CI, 0.61-0.84; HRheart disease, 0.74; 95% CI, 0.63-0.88). Compared with Japanese patients with breast cancer, Filipino, Asian Indian and Pakistani, and Native Hawaiian breast cancer survivors had higher risks of heart failure. ischemic heart disease and death. Among ANHPI breast cancer survivors, risk factors for heart failure included older age, higher comorbidity score, distant cancer stage and chemotherapy. Our results support heterogeneity in CVD outcomes among breast cancer survivors among ANHPI race and ethnicity groups. Further research is needed to elucidate the disparities experienced among ANHPI breast cancer survivors. Filipino, Asian Indian and Pakistani, and Native Hawaiian patients with breast cancer had higher risks of heart failure, ischemic heart disease and death among ANHPI patients with breast cancer.

Associations between race/ethnicity and SEER-CAHPS patient care experiences among female Medicare beneficiaries with breast cancer

IntroductionWe aimed to determine if racial/ethnic disparities exist in survivorship care patient experiences among older breast cancer survivors. Materials and MethodsNineteen thousand seventeen female breast cancer survivors aged ≥65 at post-diagnosis survey contributed data via the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) and Centers for Medicare and Medicaid Services Consumer Assessment of Healthcare Providers & Systems (CAHPS) data linkage (2000–2019). Multivariable linear regression models were used to estimate adjusted beta (β) coefficients and standard error (SE) estimates for associations between race/ethnicity and survivorship care patient experiences. ResultsMost women were non-Hispanic (NH)-White (78.1%; NH-Black [8.1%], NH-Asian [6.5%], Hispanic [6.2%]). On average, women reported 76.3 years (standard deviation [SD] = 7.14) at CAHPS survey and 6.10 years since primary diagnosis (SD = 3.51). Compared with NH-White survivors, NH-Black survivors reported lower mean scores for Getting Care Quickly (β = −5.17, SE = 0.69, p ≤0.001), Getting Needed Care (β = −1.72, SE = 0.63, p = 0.006), and Overall Care Ratings (β = −2.72, SE = 0.48, p ≤0.001), mirroring the results for NH-Asian survivors (Getting Care Quickly [β = −7.06, SE = 0.77, p ≤0.001], Getting Needed Care [β = −4.43, SE = 0.70, p ≤0.001], Physician Communication [β = −1.15, SE = 0.54, p = 0.03], Overall Care Rating [β = −2.32, SE = 0.53, p ≤0.001]). Findings among Hispanic survivors varied, where mean scores were lower for Getting Care Quickly (β = −2.83, SE = 0.79, p ≤0.001), Getting Needed Care (β = −2.43, SE = 0.70, p = 0.001), and Getting Needed Prescription Drug(s) (β = −1.47, SE = 0.64, p = 0.02), but were higher for Health Plan Rating (β = 2.66, SE = 0.55, p ≤0.001). Education, Medicare plan, and multimorbidity significantly modified various associations among NH-Black survivors, and education was a significant modifier among NH-Asian and Hispanic survivors. DiscussionWe observed racial/ethnic disparities in the associations with survivorship care patient experience among NH-Black, Hispanic, and NH-Asian breast cancer survivors. Future research should examine the impact of education, Medicare plans, and multimorbidity on these associations.

Advances in Treatment and Health-Related Quality of Life: A Cohort Study of Older Adult Survivors of Breast Cancer.

To determine whether there are differences in the health-related quality of life (HRQOL) of older adult survivors of breast cancer (BC) diagnosed in different time periods and to gain insight into whether advances in BC treatment have improved HRQOL. Three cohorts of older adult survivors of BC diagnosed before 1995, from 1996 to 2005, and from 2006 to 2015 were examined using the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey linked databases. HRQOL was measured using the Veterans RAND 12-Item Health Survey. Mean cohort HRQOL scores were compared using analysis of variance, then multivariate regression models were used to examine the effects of cohort membership and covariates on mental and physical HRQOL. Adjusted mean HRQOL scores trended significantly lower with each successive cohort. Higher comorbidity count and increased functional limitations were negatively associated with HRQOL, and income, education level, and better general health perceptions were positively associated with HRQOL. Regardless of time since diagnosis, older survivors of BC are at risk for poor HRQOL and should be regularly assessed. Maximizing HRQOL requires consideration of the survivor's resources, comorbidities, and functional limitations when planning care.

Patient-reported outcomes in older breast cancer survivors with and without prior chemotherapy treatment.

Little is known about long-term treatment-related symptoms in older breast cancer survivors. We characterized long-term patient-reported symptoms and examined factors associated with the presence and severity of symptoms, and symptom interference with daily activities. Texas Cancer Registry (TCR) Medicare linkage data was used to identify breast cancer patients age 65 and older with local/regional stage disease diagnosed between 2012-2013. Symptom burden was assessed using breast-specific items from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™). Demographic and clinical data also were collected. Logistic regression models were used to assess the association between symptom burden and respondent sociodemographic and clinical characteristics. Of 4448 eligible patients, 1594 (response-rate 35.8%) completed questionnaires. Of these, 1245 eligible respondents were included in the analysis based on self-reported data. Median time from diagnosis to survey completion was 68 months (IQR: 62-73). Most frequently reported symptoms were fatigue/lack of energy (76.8%), aching muscles (72.1%) and aching joints (72.5%). Receipt of chemotherapy was associated with higher symptom burden. Patients treated with adjuvant chemotherapy had higher risk of numbness/tingling (OR: 3.16; 95% CI: 2.36-4.24), hair loss (OR: 2.72; 95% CI: 2.05-3.60), and fatigue/lack of energy (OR: 1.80; 95% CI: 1.29-2.52). Similarly, patients who received chemotherapy were more likely to report the majority of symptoms as moderate to severe and as interfering with daily activities. Receipt of chemotherapy is associated with significant symptom burden more than 5 years after breast cancer treatment. Long-term chemotherapy impact should be discussed with patients in a shared-decision making process and approaches to symptom management during survivorship care are needed.

Cognitive Aging in Older Breast Cancer Survivors.

Cancer and cancer treatments may affect aging processes, altering the trajectory of cognitive aging, but the extant studies are limited in their intervals of assessment (two-five years). We studied the cognitive performance of a cohort of survivors and controls aged from 60 to 89 years utilizing cross-sectional cognitive performance data as an indicator of potential aging trajectories and contrasted these trends with longitudinal data collected over two years. Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5- to 15-year survivors (N = 328) and non-cancer controls (N = 158) were assessed at enrollment and at 8, 16, and 24 months with standard neuropsychological tests and comprehensive geriatric assessment. A cross-sectional baseline analysis found the expected inverse association of age with cognition in both groups, with survivors performing lower overall than controls in learning and memory (LM). Younger survivors, i.e., those under 75 years of age, exhibited lower performance in both LM and attention, and processing speed and executive function (APE), compared to controls, with no differences being observed between older survivors and controls, which tracked with deficit accumulation trends. Cognitive differences between the survivors and controls for the LM and APE domains were prominent in younger survivors, as was deficit accumulation, suggesting a mediating effect on cognition. Deficit accumulation may represent a modifiable risk factor in cancer survivorship that may be targeted for prevention and intervention.

Epigenetic aging in older breast cancer survivors and noncancer controls: preliminary findings from the Thinking and Living with Cancer Study.

Cancer and its treatments may accelerate aging in survivors; however, research has not examined epigenetic markers of aging in longer term breast cancer survivors. This study examined whether older breast cancer survivors showed greater epigenetic aging than noncancer controls and whether epigenetic aging related to functional outcomes. Nonmetastatic breast cancer survivors (n=89) enrolled prior to systemictherapy and frequency-matched controls (n=101) ages 62 to 84years provided two blood samples to derive epigenetic aging measures (Horvath, Extrinsic Epigenetic Age [EEA], PhenoAge, GrimAge, Dunedin Pace of Aging) and completed cognitive (Functional Assessment of Cancer Therapy-Cognitive Function) and physical (Medical Outcomes Study Short Form-12) function assessments at approximately 24 to 36 and 60 months after enrollment. Mixed-effects models tested survivor-control differences in epigenetic aging, adjusting for age and comorbidities; models for functional outcomes also adjusted for racial group, site, and cognitive reserve. Survivors were 1.04 to 2.22years biologically older than controls on Horvath, EEA, GrimAge, and DunedinPACE measures (p=.001-.04) at approximately 24 to 36months after enrollment. Survivors exposed to chemotherapy were 1.97 to 2.71years older (p=.001-.04), and among this group, an older EEA related to worse self-reported cognition (p=.047) relative to controls. An older epigenetic age related to worse physical function in all women (p<.001-.01). Survivors and controls showed similar epigenetic aging over time, but Black survivors showed accelerated aging over time relative to non-Hispanic White survivors. Older breast cancer survivors, particularly those exposed to chemotherapy, showed greater epigenetic aging than controls that may relate to worse outcomes. If replicated, measurement of biological aging could complement geriatric assessments to guide cancer care for older women.

Association of surgery and radiotherapy with risk of thoracic soft tissue sarcoma among older survivors of breast cancer.

e24063 Background: Although breast cancer survivors are living longer, they have an increased risk of treatment-related second cancers including rare but deadly thoracic soft tissue sarcomas (tSTS), such as angiosarcomas, compared with the general population. Limited studies have examined the relationship between surgery type and radiotherapy on tSTS risk, due to the rarity of this event. We undertook this large-scale study to analyze the joint effects of surgery type and radiotherapy with tSTS risk among older breast cancer patients followed in SEER-Medicare. Methods: The SEER-Medicare analytic cohort included 162,507 patients diagnosed with a primary breast cancer between 2000-2017, aged 66-84 years, who survived 1 year, and were followed until 2018. We calculated the cumulative incidence of tSTS and angiosarcoma accounting for competing risks. We then examined the joint effects of breast surgery and radiotherapy receipt (mastectomy + no/unknown radiotherapy, mastectomy + radiotherapy, BCS + no/unknown radiotherapy, and BCS + radiotherapy), with risk of developing any tSTS or angiosarcoma specifically. We also explored the influence of extent of mastectomy (removal of whole breast only, removal of whole breast and chest wall). We calculated hazard ratios (HRs) from multivariable Cox proportional hazard models, with attained age as the time scale, and adjusted for year of diagnosis (2000-2004, 2005-2009, 2010-2017), chemotherapy (yes, no/unknown), and stage (in situ, localized, regional/distant, unknown). Results: Mean age of breast cancer diagnosis was 73.68 (SD: 5.18) years. Patients were diagnosed with in situ (17.74%), localized (59.89%), and regional/distant (21.94%) stage. Median follow-up time was 6.75 years (IQR: 2.00-3.92), and 139 patients developed a tSTS (95 angiosarcomas). By 5 years after diagnosis, cumulative incidence of tSTS was 0.036% (95% CI: 0.027-0.48) and angiosarcomas was 0.019% (95% CI: 0.012-0.029). Compared with patients who received mastectomy + no/unknown radiotherapy, patients receiving mastectomy + radiotherapy were not at elevated risk (HR: 2.18, 95% CI: 0.71-6.70), whereas patients who received BCS without radiotherapy (HR: 3.04, 95% CI: 1.19-7.76) or with radiotherapy (HR: 7.01, 95% CI: 3.55-13.84) were at elevated risk of developing tSTS. Patients who underwent removal of whole breast and chest wall had a lower risk of developing tSTS (HR: 0.32, 95% CI: 0.11-0.94), compared to whole breast only. Nearly all angiosarcomas occurred among patients treated with BCS + radiotherapy. Conclusions: Clinically, these results, while rare, indicate the greatest risk of tSTS observed after BCS + radiotherapy and the need for closer monitoring and heightened awareness of tSTS. Additional studies are needed to investigate biological underpinnings of tSTS and the potential role of other cancer treatments and comorbidities on development of tSTS.

Plasma levels of interleukin-6 mediate neurocognitive performance in older breast cancer survivors: The Thinking and Living With Cancer study.

Immune activation/inflammation markers (immune markers) were tested to explain differences in neurocognition among older breast cancer survivors versus noncancer controls. Women >60years old with primary breast cancer (stages 0-III) (n=400) were assessed before systemic therapy with frequency-matched controls (n=329) and followed annually to 60 months; blood was collected during annual assessments from 2016 to 2020. Neurocognition was measured by tests of attention, processing speed, and executive function (APE). Plasma levels of interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor α (TNF-α), and interferon γ were determined using multiplex testing. Mixed linear models were used to compare results of immune marker levels by survivor/control group by time and by controlling for age, racial/ethnic group, cognitive reserve, and study site. Covariate-adjusted multilevel mediation analyses tested whether survivor/control group effects on cognition were explained by immune markers; secondary analyses examined the impact of additional covariates (e.g., comorbidity and obesity) on mediation effects. Participants were aged 60-90years (mean, 67.7years). Most survivors had stage I (60.9%) estrogen receptor-positive tumors (87.6%). Survivors had significantly higher IL-6 levels than controls before systemic therapy and at 12, 24, and 60 months (p≤.001-.014) but there were no differences for other markers. Survivors had lower adjusted APE scores than controls (p<.05). Levels of IL-6, IL-10, and TNF-α were related to APE, with IL-6 explaining part of the relationship between survivor/control group and APE (p=.01). The magnitude of this mediation effect decreased but remained significant (p=.047) after the consideration of additional covariates. Older breast cancer survivors had worse long-term neurocognitive performance than controls, and this relationship was explained in part by elevated IL-6.

Differences in survivorship care experiences among older breast cancer survivors by clinical cancer characteristics, race/ethnicity, and socioeconomic factors: A SEER-CAHPS study.

To determine if disparities exist in survivorship care experiences among older breast cancer survivors by breast cancer characteristics, race/ethnicity, and socioeconomic factors. A total of 19,017 female breast cancer survivors (≥ 65 at post-diagnosis survey) contributed data via SEER-CAHPS data linkage (2000-2019). Analyses included overall and stratified multivariable linear regression to estimate beta (β) coefficients and standard errors (SE) to identify relationships between clinical cancer characteristics and survivorship care experiences. Minority survivors were mostly non-Hispanic (NH)-Black (8.1%) or NH-Asian (6.5%). Survivors were 76.3years (SD = 7.14) at CAHPS survey and were 6.10years (SD = 3.51) post-diagnosis on average. Survivors with regional breast cancer vs. localized at diagnosis (β = 1.00, SE = 0.46, p = 0.03) or treated with chemotherapy vs. no chemotherapy/unknown (β = 1.05, SE = 0.48, p = 0.03) reported higher mean scores for Getting Needed Care. Results were similar for Overall Care Ratings (β = 0.87, SE = 0.38, p = 0.02) among women treated with chemotherapy. Conversely, women diagnosed with distant breast cancer vs. localized reported lower mean scores for Physician Communication (β = -1.94, SE = 0.92, p = 0.03). Race/ethnicity, education, and area-level poverty significantly modified several associations between stage, estrogen receptor status, treatments, and various CAHPS outcomes. These study findings can be used to inform survivorship care providers treating women diagnosed with more advanced stage and aggressive disease. The disparities we observed among minority groups and by socioeconomic status should be further evaluated in future research as these interactions could impact long-term outcomes, including survival.

Mental health outcomes in older breast cancer survivors: Five-year follow-up from the CLIMB study

BackgroundThere is a lack of information on mental health outcomes for the increasing older population. Therefore, the aim of the current study is to assess depressive symptoms, loneliness, and apathy in older patients with breast cancer within the first 5 years after diagnosis. MethodsWomen aged ≥70 years with early-stage breast cancer were included. Multivariate linear mixed models were used to assess longitudinal changes in symptoms of depression (according to the 15-item Geriatric Depression Scale), loneliness (according to the De Jong Gierveld Loneliness Scale) and apathy (according to the Starkstein Apathy Scale) over time at 3, 9, 15, 27 and 60 months follow-up. ResultsIn total, 299 patients were included (mean [standard deviation (SD)] age: 75.8 [5.2] years). At 3 months follow-up, shortly after the acute treatment, 10% of patients had significant depressive symptoms, while loneliness and apathy were present in 31% and 41% of all patients, respectively. Depression, loneliness and apathy scores showed no clinically relevant changes over time in the whole cohort. Patients who received adjuvant systemic therapies (i.e. endocrine therapy and/or chemotherapy and/or targeted therapy (trastuzumab)) had similar mental health outcomes as those who did not. However, frail patients had more symptoms (p < 0.001) and were more prone to develop depressive symptoms over time than non-frail patients (p = 0.002). DiscussionDepression, loneliness and apathy were frequently observed in older women with breast cancer and did not change over time. Patients who received adjuvant systemic therapies had similar mental health outcomes as those who did not. However, frail patients were at higher risk to experience these symptoms.

Phase angle is associated with muscle health and cardiorespiratory fitness in older breast cancer survivors

Phase angle (PhA) obtained from bioelectrical impedance analysis (BIA) is an indicator of cellular integrity and relates to several chronic conditions. The purpose of this secondary analysis was to evaluate the association of PhA with health-related physical fitness, namely, cardiorespiratory fitness, skeletal muscle volume, and myosteatosis (i.e. muscle health) in older breast cancer survivors. Twenty-two women ≥60 years with a body mass index (BMI) ≥25kg/m2 and who completed chemotherapy for early-stage breast cancer were included. BIA, cardiopulmonary exercise tests and magnetic resonance imaging scans were completed before and after eight weeks of time-restricted eating. At baseline, PhA was associated with cardiorespiratory fitness (R2=0.54, p<0.01) and skeletal muscle volume (R2=0.83, p<0.01) and myosteatosis (R2=0.25, p=0.02). Results were similar at follow-up. Findings from this pilot study suggest that higher values of PhA are associated with better health-related physical fitness among older breast cancer survivors.

Physical Function and Physical Activity in Older Breast Cancer Survivors: 5-Year Follow-Up from the Climb Every Mountain Study.

A decline in physical activity and the ability to perform activities of daily living (ADL) and instrumental activities of daily living (IADL) could interfere with independent living and quality of life in older patients, but may be prevented with tailored interventions. The aim of the current study was to assess changes in physical activity and ADL/IADL in the first 5 years after breast cancer diagnosis in a real-world cohort of older patients and to identify factors associated with physical decline. Patients aged ≥70 years with in situ or stages I-III breast cancer were included in the prospective Climb Every Mountain cohort study. Linear mixed models were used to assess physical activity (according to Metabolic Equivalent of Task (MET) hours per week) and ADL/IADL (according to the Groningen Activity Restriction Scale (GARS)) over time. Secondly, the association with geriatric characteristics, treatment, quality of life, depression, apathy, and loneliness was analyzed. A total of 239 patients were included. Physical activity and ADL/IADL changed in the first 5 years after diagnosis (mean change from baseline -11.6 and +4.2, respectively). Geriatric characteristics at baseline were strongly associated with longitudinal change in physical activity and ADL/IADL, whereas breast cancer treatment was not. A better quality of life was associated with better physical activity and preservation of ADL/IADL, while depression and loneliness were negatively associated with these outcomes. Geriatric characteristics, loneliness, and depressive symptoms were associated with physical decline in older patients with breast cancer, while breast cancer treatment was not.