Chemotherapy Was Not Associated With Cognitive Decline in Older Adults With Breast and Colorectal Cancer
*Department of Health Sciences, School of Health Professions †Department of Psychological Sciences, College of Arts and Science, University of Missouri, Columbia, MO ‡Department of Internal Medicine, University of Michigan Medical School §Veterans Affairs Health Services Research and Development Center of Excellence ∥Institute for Social Research, University of Michigan, Ann Arbor, MI. Medical care
(Impact Factor: 3.23).
06/2012; 50(10):849-55. DOI: 10.1097/MLR.0b013e31825a8bb0
: This study tested 2 hypotheses: (1) chemotherapy increases the rate of cognitive decline in breast and colorectal cancer patients beyond what is typical of normal aging and (2) chemotherapy results in systematic cognitive declines when compared with breast and colorectal cancer patients who did not receive chemotherapy.
: Data came from personal interviews with a prospective cohort of patients with breast (n=141) or colorectal cancer (n=224) with incident disease drawn from the nationally representative Health and Retirement Study (1998-2006) with linked Medicare claims.
: The 27-point modified Telephone Interview for Cognitive Status was used to assess cognitive functioning, focusing on memory and attention. We defined the smallest clinically significant change as 0.4 points per year.
: We used Bayesian hierarchical linear models to test the hypotheses, adjusting for multiple possible confounders. Eighty-eight patients were treated with chemotherapy; 277 were not. The mean age at diagnosis was 75.5. Patients were followed for a median of 3.1 years after diagnosis, with a range of 0 to 8.3 years. We found no differences in the rates of cognitive decline before and after diagnosis for patients who received chemotherapy in adjusted models (P=0.86, one-sided 95% posterior intervals lower bound: 0.09 worse after chemotherapy), where patients served as their own controls. Moreover, the rate of cognitive decline after diagnosis did not differ between patients who had chemotherapy and those who did not (P=0.84, one-sided 95% posterior intervals lower bound: 0.11 worse for chemotherapy group in adjusted model).
: There was no evidence of cognitive decline associated with chemotherapy in this sample of older adults with breast and colorectal cancer.
Available from: PubMed Central
- "Colorectal cancer has an incidence of approximately 150,000 per year in the United States and is the third leading cause of cancer-related deaths in both men and women
. Although surgery, chemotherapy and radiotherapy have been the mainstay of colorectal cancer treatment, traditional Chinese medicine (TCM) has the advantage of reducing cancer therapy-induced toxicity and is a popular form of complementary and alternative medicine (CAM) in China
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A Chinese herbal formula, Yi-Qi-Fu-Sheng (YQFS), has long been employed clinically to treat cancer patients. We aimed to determine its effectiveness as a treatment method for colorectal cancer. We investigated the therapeutic effects of YQFS on colorectal cancer, as well as the underlying mechanisms, which have not previously been explored.
First, YQFS was extracted and chemically characterized. We then tested the effects of YQFS on proliferation and migration by MTT and transwell migration assays in vitro. Mouse xenograft models of colorectal cancer were established by inoculation with HCT-116 cells, and mice received one of three oral doses (200, 400 and 800 mg/kg/day) to evaluate the effects of YQFS extract. Metalloproteinase-2/9 (MMP-2/9) expression in mice was evaluated by gelatin zymography assay. Apoptosis was evaluated by flow cytometry (FCM) analysis in vitro and by TUNEL assay in vivo. ERK and p-ERK expression were evaluated by western blot analysis at the protein level in vitro, and by quantitative RT-PCR at mRNA level in vivo.
Our results show that YQFS significantly inhibits colorectal cancer cell proliferation and induces apoptosis and cell cycle arrest at the G1− and S-phase in HCT-116 cells. Furthermore, YQFS effectively retards tumor cell migration and invasion by inhibiting metalloproteinase-2/9 (MMP-2/9) expression, both in vitro and in vivo. Moreover, YQFS had an inhibitory effect on tumor growth in vivo, and induced apoptosis through the inhibition of the ERK1/2 pathway both in vitro and in vivo.
These findings demonstrate that YQFS extract has an anti-tumor effect in colorectal cancer, which could be attributed to ERK1/2-dependent inhibition of MMP-2/9 expression.
BMC Complementary and Alternative Medicine 03/2013; 13(1):65. DOI:10.1186/1472-6882-13-65 · 2.02 Impact Factor
Available from: Gretchen Kimmick
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ABSTRACT: Cognitive changes in older women receiving chemotherapy are poorly understood. We examined self-reported cognitive function for older women who received adjuvant chemotherapy on Cancer and Leukemia Group B (CALGB) 49907. CALGB 49907 randomized 633 women aged ≥65 with stage I–III breast cancer to standard adjuvant chemotherapy (cyclophosphamide–methotrexate–5-fluorouracil or doxorubicin–cyclophosphamide) versus capecitabine. We examined self-reported cognitive function in 297 women (CALGB 361002) who enrolled on the quality of life substudy and had no gross impairment on cognitive screening. Women were evaluated using an 18-item instrument at six time points (baseline through 24 months). At each time point for each patient, we calculated a cognitive function score (CFS) defined as the mean response of items 1–18 and defined impairment as a score >1.5 standard deviations above the overall average baseline score. Differences in scores by patient characteristics were evaluated using a Kruskal–Wallis test. A linear mixed-effects model was used to assess CFSs by treatment over time. Among 297 women, the median age was 71.5 (range 65–85) and 73 % had performance status of 0. Baseline depression and fatigue were reported in 6 and 14 % of patients, respectively. The average CFS at baseline was 2.08 (corresponding to “normal ability”), and baseline cognitive function did not differ by treatment regimen (p = 0.350). Over 24 months, women reported minimal changes at each time point and insignificant differences by treatment arm were observed. In a healthy group of older women, chemotherapy was not associated with longitudinal changes in self-reported cognitive function.
Breast Cancer Research and Treatment 12/2012; 139(2). DOI:10.1007/s10549-013-2562-6 · 3.94 Impact Factor
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ABSTRACT: Studies assessing cognitive functioning in women treated for breast cancer have used primarily standardized neuropsychological tests and examined accuracy and/or reaction time as outcome measures: they have been inconsistent in identifying the cognitive domains affected and the severity of deficits. In other contexts of neural development and disorders, measures of Intra-individual variability (IIV) have proven useful in identifying subtleties in performance deficits that are not captured by measures of central tendency. This article presents proof of concept that assessing IIV may also increase understanding of the cognitive effects of cancer treatment. We analyzed mean accuracy and reaction time, as well as IIV from 65 women with breast cancer and 28 age and education matched controls who performed the Conner's Continuous Performance Test, a "Go-NoGo" task. Although there were no significant differences between groups using measures of central tendency, there was a group × inter-stimulus interval (ISI) interaction for IIV Dispersion (p < .001). Patient Dispersion was more variable at shorter ISI than controls and less variable at long ISI, suggesting greater sensitivity to presentation speed. Interpretation of IIV differences requires further investigation. Our results suggest that future studies would benefit from designs that allow analysis of IIV measures in studies assessing cognition in cancer survivors. (JINS, 2014, 20, 1-11).
Journal of the International Neuropsychological Society 03/2014; 20(04):1-11. DOI:10.1017/S1355617714000125 · 2.96 Impact Factor
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