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Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance).

ABSTRACT: PURPOSE:To investigate the effects of cognitive function on discontinuation of hormonal therapy in breast cancer survivors ages 65+ ("older"). METHODS:Older breast cancer survivors with invasive, non-metastatic disease, and no reported cognitive difficulties were recruited from 78 Alliance sites between 2004 and 2011. Eligible survivors (n = 1280) completed baseline interviews; follow-up was conducted annually for up to 7 years. Survivors with estrogen-receptor-positive (ER+) cancers who initiated hormonal therapy (n = 990) were included. Self-reported cognitive function was measured using the EORTC-QLQ30 scale; a difference of eight points on the 0-100 scale was considered clinically significant. Based on varying rates of discontinuation over time, discontinuation was evaluated separately for three time periods: early (<1 year); midpoint (1-3 years); and late discontinuation (>3-5 years). Cox models for each time period were used to evaluate the effects of cognition immediately preceding discontinuation, controlling for age, chemotherapy, and other covariates. RESULTS:Survivors were 65-91 years old (mean 72.6 years), and 79% had stages 1 or 2A disease. Overall, 43% discontinued hormonal therapy before 5 years. Survivors who reported lower cognitive function in the period before discontinuation had greater hazards of discontinuing therapy at the treatment midpoint (HR 1.22 per 8-point difference, CI 1.09-1.40, p < 0.001), considering covariates, but cognition was not related to discontinuation in the other periods. CONCLUSIONS:Self-reported cognitive problems were a significant risk factor for discontinuation of hormonal therapy 1-3 years post-initiation. Additional research is needed on the temporality of cognitive effects and hormonal therapy to support survivorship care needs of older survivors.

SUBMITTER: Bluethmann SM

PROVIDER: S-EPMC5709158 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance).

Bluethmann Shirley M SM Alfano Catherine M CM Clapp Jonathan D JD Luta George G Small Brent J BJ Hurria Arti A Cohen Harvey J HJ Sugarman Steven S B Muss Hyman H Isaacs Claudine C Mandelblatt Jeanne S JS

Breast cancer research and treatment 20170626 3

<h4>Purpose</h4>To investigate the effects of cognitive function on discontinuation of hormonal therapy in breast cancer survivors ages 65+ ("older").<h4>Methods</h4>Older breast cancer survivors with invasive, non-metastatic disease, and no reported cognitive difficulties were recruited from 78 Alliance sites between 2004 and 2011. Eligible survivors (n = 1280) completed baseline interviews; follow-up was conducted annually for up to 7 years. Survivors with estrogen-receptor-positive (ER+) canc ...[more]

PMID: 28653250

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Project description:BackgroundThe number of survivors of breast cancer aged ?65 years ("older") is growing, but to the authors' knowledge, little is known regarding the cognitive outcomes of these individuals.MethodsA cohort of cognitively intact older survivors with nonmetastatic, invasive breast cancer was recruited from 78 sites from 2004 through 2011; approximately 83.7% of the survivors (1280 survivors) completed baseline assessments. Follow-up data were collected at 6 months and annually for up to 7 years (median, 4.1 years). Cognitive function was self-reported using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30); scores ranged from 0 to 100, with a higher score indicating better function. Group-based trajectory modeling determined trajectories; women were assigned to a trajectory group based on the highest predicted probability of membership. Multinomial logistic regression evaluated the association between receipt of chemotherapy (with or without hormonal treatment) and trajectory group.ResultsSurvivors were aged 65 to 91 years; approximately 41% received chemotherapy. There were 3 cognitive trajectories: "maintained high" (42.3% of survivors); "phase shift" (50.1% of survivors), with scores slightly below but parallel to maintained high; and "accelerated decline" (7.6% of survivors), with the lowest baseline scores and greatest decline (from 71.7 [standard deviation, 19.8] to 58.3 [standard deviation, 21.9]). The adjusted odds of being in the accelerated decline group (vs the maintained high group) were 2.1 times higher (95% confidence interval, 1.3-3.5) for survivors who received chemotherapy (with or without hormonal therapy) versus those treated with hormonal therapy alone. Greater comorbidity and frailty also were found to be associated with accelerated decline.ConclusionsTrajectory group analysis demonstrated that the majority of older survivors maintained good long-term self-reported cognitive function, and that only a small subset who were exposed to chemotherapy manifested accelerated cognitive decline. Future research is needed to determine factors that place some older survivors at risk of experiencing cognitive decline. Cancer 2016;122:3555-3563. © 2016 American Cancer Society.

Project description:Simple Summary The impact of cancer and cancer treatment on longer-term cognitive aging trajectories is currently unknown. Cancer and cancer treatment accelerate biological aging and may accelerate cognitive decline in older individuals. We compared younger and older breast cancer survivors with younger and older non-cancer controls using standard cognitive measures to estimate age- and cancer-related differences over time. We found the expected inverse association of age with cognition in both groups, lower learning and memory performance for survivors as a whole, and more prominent differences in learning and memory as well as attention, processing speed, and executive function in younger survivors, i.e., those under 75 years of age. These differences were similar to trends across the age span in deficit accumulation, with larger differences in younger survivors that may indicate a mechanism of cognitive aging more generally, and in younger survivors specifically. Abstract Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Project description:Adjuvant hormonal therapy significantly improves long-term survival of breast cancer patients with hormone receptor-positive disease. Despite the proven clinical efficacy of tamoxifen and aromatase inhibitors, many breast cancer survivors either fail to take the correct dosage at the prescribed frequency (adherence) or discontinue therapy (persistence). This systematic review aims to: (1) determine the prevalence of adherence and persistence to adjuvant hormonal therapy among breast cancer survivors in clinical practice, and (2) identify correlates of adherence and persistence. We searched Medline, PubMed, PsycINFO, and CINAHL for studies that measured rates and/or correlates of adherence and/or persistence to adjuvant hormonal therapy. Studies were reviewed in a multi-step process: (1) the lead author screened titles and abstracts of all potentially eligible studies; (2) each coauthor reviewed a random 5 % sample of abstracts; and (3) two sets of coauthors each reviewed half of all "maybe" abstracts. Any disagreements were discussed until consensus was reached. Twenty-nine studies met inclusion criteria. Prevalence of adherence ranged from 41 to 72 % and discontinuation (i.e., nonpersistence) ranged from 31 to 73 %, measured at the end of 5 years of treatment. Extremes of age (older or younger), increasing out-of-pocket costs, follow-up care with a general practitioner (vs. oncologist), higher CYP2D6 activity, switching from one form of therapy to another, and treatment side effects were negatively associated with adherence and/or persistence. Taking more medications at baseline, referral to an oncologist, and earlier year at diagnosis were positively associated with adherence and/or persistence. Adherence and persistence to adjuvant hormonal therapy among breast cancer survivors is suboptimal. Many of the correlates of adherence and persistence studied to date are not modifiable. Our review reveals a critical need for further research on modifiable factors associated with adherence to adjuvant hormonal therapy, and the development of behavioral interventions to improve adherence in this population.

Dataset Information

Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance).

Publications

Cognitive function and discontinuation of adjuvant hormonal therapy in older breast cancer survivors: CALGB 369901 (Alliance).

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