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Cognitive function following breast cancer treatment and associations with concurrent symptoms

Cognitive function following breast cancer treatment and associations with concurrent symptoms www.nature.com/npjbcancer BRIEF COMMUNICATION OPEN Cognitive function following breast cancer treatment and associations with concurrent symptoms 1,2 2,3 2,4 2 2,5,6 Kathleen Van Dyk , Julienne E. Bower , Catherine M. Crespi , Laura Petersen and Patricia A. Ganz Cognitive changes after breast cancer treatment are often attributed to chemotherapy, without considering other important factors such as other treatments (e.g., surgery, radiation, endocrine therapy (ET)). We compared neuropsychological functioning in the domains of learning, memory, attention, visuospatial, executive function, and processing speed according to primary breast cancer treatment exposures in early survivorship, before the initiation of ET (n = 189). We were also interested in the association of neuropsychological functioning with select clinical, psychological, and behavioral factors. Compared to those who only underwent surgery (n = 28), all neuropsychological domain scores were comparable in a sample of breast cancer survivors with different treatment exposures, i.e., radiation therapy (n = 64), chemotherapy (n = 20), or both (n = 77), p’s < 0.05, adjusted for age, IQ, depression, and time since treatment completion. Physical fatigue, pain, and sleep correlated with several cognitive domains regardless of treatment exposure. There are minimal treatment-related neuropsychological differences on neuropsychological measures in early breast cancer survivorship, but the influence of other co-occurring symptoms warrants attention. npj Breast Cancer (2018) 4:25 ; doi:10.1038/s41523-018-0076-4 INTRODUCTION Depression Inventory, 2nd edition (BDI-II) did not correlate with any domain, and was included as an additional control. In Cognitive dysfunction following breast cancer treatment is an additional exploratory analyses (data not presented) we examined important survivorship concern. Studies predominantly focus on linear regression models of domains that included treatment chemotherapy treatment as the primary risk, although other group and interactions between treatment group and each treatments such as endocrine therapy (ET) and co-occurring clinical/psychosocial factor, none of which emerged as signifi- factors likely also play a role. The mind body study (MBS) was a cantly related to cognitive domains. prospective, longitudinal, cohort study of early-stage breast cancer survivors (BCS) designed to assess the impact of ET on neurocognitive function; baseline analyses of this sample allows us to examine the effects of primary cancer treatments without DISCUSSION the confound of concomitant ET. In prior baseline analyses, we Neuropsychological performance did not significantly vary based found that higher subjective cognitive complaints were linked to on primary breast cancer treatment exposure in this early combined chemotherapy and radiation therapy exposure. The survivorship period. Strengths of our study are assessment prior current baseline study extends those findings by comparing to ET exposure and the surgery-only comparison group. The neuropsychological functioning across treatment exposures; we current null findings are in contrast with our prior report of further explored relationships with modifiable clinical, psycholo- subjective cognition. Such inconsistency is not uncommon in gical, and behavioral factors. survivorship studies, which compellingly portray the cognitive effects of cancer and its treatment by self-report, raising the RESULTS possibility that neuropsychological methods may not be the most sensitive to these subtle effects. Table 1 displays sample characteristics and cognitive outcomes by Neurocognitive function did correlate with physical fatigue, treatment exposure. We found comparable rates of impairment sleep quality, and pain, regardless of treatment. Fatigue is a known across treatment groups, and also failed to find any differences on correlate of self-reported cognition in BCS, but pain and sleep neuropsychological domain scores between No Adjuvant and any disturbance are surprisingly understudied risks despite their adjuvant treatment group; effect sizes were small to negligible prevalence in survivorship and known risk in other popula- (see Supplementary Information for model details). Select clinical 5–7 tions. Coefficients are small but portray a consistent pattern. and psychosocial factors were correlated with several domains, Cognitive function is complex and multi-determined; it is notably the Pittsburgh Sleep Quality Index (PSQI), the Multi- important to exhaust all risks and opportunities for improvement, dimensional Fatigue Symptom Inventory–Short Form (MFSI) reflected in existing recommendations for multi-modal Physical, and the Breast Cancer Prevention Trial Symptom Checklist (BCPT) Musculoskeletal Pain, see Table 2. Beck approaches to intervention. 1 2 3 UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA; Departments of Psychology and Psychiatry/Biobehavioral Sciences, University of California-Los Angeles, Los Angeles, CA, USA; Department of Biostatistics, UCLA Fielding School of Public Health, 5 6 Los Angeles, CA, USA; UCLA David Geffen School of Medicine, Los Angeles, CA, USA and UCLA Fielding School of Public Health, Los Angeles, CA, USA Correspondence: Patricia A. Ganz (pganz@mednet.ucla.edu) Received: 1 May 2018 Revised: 11 July 2018 Accepted: 13 July 2018 Published in partnership with the Breast Cancer Research Foundation Cognitive function following breast cancer treatment and K Van Dyk et al. Table 1. Sample characteristics and cognitive performance by treatment group Treatment groups Whole sample (A) No Adjuvant (B) Rad Only (C) Chemo Only (D) Chemo + Rad (n= 77) p across groups (n = 189) (n = 28) (n = 64) (n = 20) Age mean (SD) 51.35 (8.34) 51.57 (6.08) 53.88 (7.95) 46.95 (8.06) 50.31 (8.88) 0.001 Education, n (%) Less than college 34 (18%) 2 (7%) 14 (22%) 3 (15%) 15 (19%) 0.55 College degree 56 (30%) 8 (29%) 16 (25%) 8 (40%) 24 (31%) More than college 99 (52%) 18 (64%) 34 (53%) 9 (45%) 38 (49%) Marital status, n (%) married 124 (66%) 11 (39%) 24 (38%) 6 (30%) 24 (31%) 0.78 Race, n (%) White 151 (80%) 23 (82%) 53 (83%) 16 (80%) 59 (77%) 0.82 Annual income, n (%; n= 186) >$100,000 112 (60%) 18 (64%) 40 (65%) 11 (55%) 43 (57%) 0.72 <$100,000 74 (40%) 10 (36%) 22 (35%) 9 (45%) 33 (43%) Employment status, n (%) employed FT or PT 122 (66%) 20 (71%) 44 (69%) 10 (50%) 48 (63%) 0.38 Post-menopausal, n (%) 100 (53%) 15 (54%) 40 (62%) 5 (25%) 40 (52%) 0.03 Surgery Lumpectomy 125 4 63 0 58 < 0.01 Mastectomy 64 24 1 20 19 Months since treatment completion, mean (SD) 1.197 (1.038) 2.48 (0.731) 0.960 (0.951) 1.282 (0.92) 0.908 (0.879) <0.01 Anthracycline treatment, n (%) 24 (25%) NA NA 3 (15%) 21 (27%) 0.385 Stage at diagnosis, n (% of group) 0 25 (13%) 14 (50%) 11 (17%) 0 (0%) 0 (0%) <0.01 1 87 (46%) 13 (46%) 44 (69%) 7 (35%) 23 (30%) 2 59 (31%) 1 (4%) 9 (14%) 12 (60%) 37 (48%) 3 18 (10%) 0 (0%) 0 (0%) 1 (5%) 17 (22%) Endocrine therapy planned, n (%; n = 181) 129 (71%) 13 (48%) 50 (81%) 15 (75%) 51 (71%) 0.03 PSQI, mean (SD) (n= 186) 8.28 (3.46) 7.61 (3.79) 6.59 (3.36) 8.35 (4.03) 8.26 (3.31) 0.034 BDI-II, mean (SD) 8.85 (6.87) 7.36 (6.92) 6.86 (6.76) 12.75 (8.48) 10.04 (5.85) <0.01 State anxiety inventory, mean (SD) 35.51 (8.75) 35.14 (8.24) 35.11 (9.38) 37.42 (9.95) 35.48 (8.16) 0.77 IQ WTAR, mean (SD) (n = 188) 114.28 (9.09) 116.61 (8.18) 114.37 (8.77) 111.10 (9.33) 114.18 (9.50) 0.23 MFSI total, mean (SD) 11.46 (19.34) 6.43 (19.02) 6.71 (19.12) 18.20 (20.16) 15.48 (18.32) <0.01 MFSI mental, mean (SD) 5.51 (4.66) 3.61 (3.45) 4.11 (4.10) 7.30 (5.09) 6.91 (4.81) <0.01 MFSI physical, mean (SD) 4.15 (4.29) 4.43 (4.83) 2.75 (3.54) 6.35 (3.50) 4.64 (4.52) <0.01 BCPT scale, musculoskeletal pain mean (SD) 1.26 (0.95) 1.25 (0.88) 0.96 (0.75) 1.32 (0.75) 1.50 (1.10) <0.01 # of impaired neuropsychological measures (z < −1.5) 1.40 (1.73) 1.46 (1.71) 1.17 (1.60) 1.15 (1.59) 1.64 (1.86) 0.39 # of impaired neuropsychological measures (z < −2) 0.075 (1.31) 0.64 (1.10) 0.66 (1.18) 0.65 (1.04) 0.88 (1.55) 0.71 Impaired by ICCTF guidelines n (% group) 89 (47%) 13 (46%) 27 (42%) 9 (45%) 40 (52%) 0.71 Neuropsychological domains Standardized coefficients (95% CI) for A vs. B, A vs. C, and A vs. D Learning, mean (SD) 0.39 (0.70) 0.47 (0.80) 0.43 (0.75) 0.38 (0.64) 0.32 (0.65) 0.03, 0.04, −0.02 Memory, mean (SD) 0.21 (0.62) 0.19 (0.68) 0.29 (0.63) 0.16 (0.65) 0.17 (0.58) 0.07, 0.06, 0.14 Attention, mean (SD) 0.46 (0.65) 0.66 (0.61) 0.49 (0.62) 0.31 (0.42) 0.40 (0.73) −0.03, −0.08, −0.10 Visuospatial, mean (SD) −0.35 (0.74) −0.24 (0.69) −0.28 (0.77) −0.54 (0.79) −0.40 (0.72) −0.06, −0.08, −0.11 Executive function, mean (SD) 0.23 (0.76) 0.42 (0.86) 0.28 (0.73) 0.06 (0.64) 0.16 (0.76) −.07, −0.09, −0.15 Processing speed, mean (SD) −0.06 (0.67) 0.08 (0.55) −0.01 (0.71) −0.12 (0.65) −0.15 (0.68) 0.11, −0.05, 0.02 BDI-II Beck Depression Inventory, 2nd edition, MFSI Multidimensional Fatigue Symptom Inventory, BCPT Breast Cancer Prevention Trial Symptom Checklist, PSQI Pittsburgh Sleep Quality Index, ICCTF International Cognition and Cancer Task Force Coefficients in linear models adjusted for age, IQ, BDI-II, and time since treatment completion; all p’s > 0.1 Unadjusted scores Study limitations include the predominantly white and highly health in BCS. Our future work will extend this baseline report to educated sample aged 65 or younger. Additional work should characterize the cognitive effects of ET and other risks over time. examine the roles of socioeconomic factors, education, age, and comorbidity. The smaller sizes of the Chemo Only and No METHODS Adjuvant groups likely reduced power and we did not control for As previously described, three recruitment took place from multiple comparisons, but effect sizes were nonetheless mostly 2007–2011 through clinical oncology practices and rapid case negligible. Importantly, we did not have pre-treatment assess- ascertainment using the Los Angeles County Surveillance, ments, which would permit more precise inferences about Epidemiology, and End Results Program registry with collaborat- treatment-related differences. To conclude, we failed to find differences on neuropsycholo- ing physicians and hospitals. This is a report of baseline data only; gical test performance based on primary breast cancer treatment. participants were age 21–65 years, had a recent early-stage breast The commonly reported symptoms of physical fatigue, pain, and cancer diagnosis, had completed primary treatment within the last sleep disturbance are promising targets for supporting cognitive 3 months but did not yet start ET. We excluded women with active npj Breast Cancer (2018) 25 Published in partnership with the Breast Cancer Research Foundation 1234567890():,; Cognitive function following breast cancer treatment and K Van Dyk et al. Table 2. Correlations between cognitive domains and other symptoms MFSI total MFSI physical MFSI mental PSQI global BCPT musculoskeletal pain Learning Correlation 0.02 −0.08 −0.07 −0.18 −0.15 p 0.84 0.28 0.36 0.02 0.04 df 180 180 180 177 180 Memory Correlation −0.01 −0.14 −0.04 −0.22 −0.16 p 0.92 0.06 0.59 <0.01 0.04 df 179 179 179 177 179 Attention Correlation −0.13 −0.25 −0.09 −0.29 −0.13 p 0.09 <0.01 0.24 <0.01 0.08 df 179 179 179 177 179 Visuospatial Correlation 0.09 −0.08 0.04 −0.15 −0.12 p 0.24 0.30 0.64 0.05 0.11 df 179 179 179 177 179 Executive function Correlation −0.15 −0.25 −0.12 −0.17 −0.21 p 0.04 <0.01 0.10 0.02 <0.01 df 181 181 181 178 181 Processing speed Correlation −0.10 −0.20 −0.08 −0.14 −0.08 p 0.16 <0.01 0.30 0.06 0.29 df 181 181 181 178 181 Controls: Age, IQ, Time since TX, BDI-II BDI-II Beck Depression Inventory, 2nd edition, MFSI Multidimensional Fatigue Symptom Inventory, BCPT Breast Cancer Prevention Trial Symptom Checklist, PSQI Pittsburgh Sleep Quality Index. Bold values indicate p< .05 psychotic or major depressive disorders, or any history of Data availability treatments or conditions with known effects on cognition or On reasonable request, the data analyzed in this study are inflammation. The UCLA institutional review board approved the available from the corresponding author in accordance with study and all participants provided written informed consent. institutional policies. We obtained demographic and clinical information from medical records and self-report questionnaires. The following 9 10 11 12 ACKNOWLEDGEMENTS measures were used: BCPT, PSQI, MFSI, and BDI-II. We We would also like to thank Steven Castellon, PhD, for his role in developing and administered a neuropsychological battery composed of standar- collecting neuropsychological assessments. This research was supported by funding dized clinical neuropsychological tests (see Supplementary from the National Cancer Institute R01CA109650, P30 CA16042, the Breast Cancer Information); z-scores based on published normative data were Research Foundation (to PAG), and the AmericanCancer Society (to KVD). averaged into domain scores. All participants received surgery; those with no adjuvant treatment (No Adjuvant) were considered the no-treatment AUTHOR CONTRIBUTIONS comparison group, and the rest were grouped by specific adjuvant K.V.D. conducted the data analysis, interpretation, and drafted the manuscript. J.B. contributed to the overall study design, data collection, interpretation and therapy—those who received only chemotherapy (Chemo Only), manuscript text. C.C. guided the statistical approach, interpretation of findings, and only radiation therapy (Rad Only), or both chemotherapy and manuscript text. L.P. contributed to the data management and processing, radiation (Chemo + Rad). We compared demographic, clinical, and interpretation of findings and manuscript text. P.G. is the PI and guarantor—she impairment variables using two-sided analysis of variance contributed to the overall design of the study, the data collection, statistical (ANOVA) and chi-square tests. Multivariable linear regression approach, interpretation of findings, and manuscript text. This research was models of neuropsychological domain scores controlled for age, supported by funding from the National Cancer Institute R01 CA109650, P30 CA16042, the Breast Cancer Research Foundation (to P.A.G.), and the American intelligence quotient (IQ), time since treatment completion, and Cancer Society (to K.V.D.). BDI-II, with treatment group dummy coded making No Adjuvant the reference group. We obtained partial correlations between cognitive domain scores and clinical and behavioral measures ADDITIONAL INFORMATION controlling for age, IQ, time since treatment completion and BDI-II. Supplementary information accompanies the paper on the npj Breast Cancer We used SPSS software (IBM SPSS Statistics for Windows, V.24.0. website (https://doi.org/10.1038/s41523-018-0076-4). Armonk, NY: IBM Corp) and set statistical significance at p < 0.05. Published in partnership with the Breast Cancer Research Foundation npj Breast Cancer (2018) 25 Cognitive function following breast cancer treatment and K Van Dyk et al. Competing interests: Dr. Ganz discloses that she is a member of the Scientific 9. Stanton, A. L., Bernaards, C. A. & Ganz, P. A. The BCPT Symptom Scales: A measure Advisory Board of the Breast Cancer Research Foundation. The other authors declare of physical symptoms for women diagnosed with or at risk for breast cancer. JNCI no competing interests. J. Natl Cancer Inst. 97, 448–456 (2005). 10. Buysse, D. J., Reynolds, C. F., Monk, T. H., Berman, S. R. & Kupfer, D. J. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims research. Psychiatry Res. 28, 193–213 (1989). in published maps and institutional affiliations. 11. Stein, K. D., Martin, S. C., Hann, D. M. & Jacobsen, P. B. A multidimensional measure of fatigue for use with cancer patients. Cancer Pr. 6, 143–152 (1998). 12. Beck, A. T., Steer, R. A. & Brown, G. K. Beck Depression Inventory-II. (Psychological REFERENCES Corporation: San Antonio, 1996). 1. Buchanan, N. D. et al. Post-treatment neurocognition and psychosocial care 13. Wefel, J. S., Vardy, J., Ahles, T. & Schagen, S. B. International Cognition and Cancer among breast cancer survivors. Am. J. Prev. Med. 49, S498–S508 (2015). Task Force recommendations to harmonise studies of cognitive function in 2. Wefel, J. S., Kesler, S. R., Noll, K. R. & Schagen, S. B. Clinical characteristics, patients with cancer. Lancet Oncol. 12, 703–708 (2011). pathophysiology, and management of noncentral nervous system cancer-related cognitive impairment in adults. Ca. Cancer J. Clin. 65, 123–138 (2015). 3. Ganz, P. A. et al. Cognitive complaints after breast cancer treatments: examining Open Access This article is licensed under a Creative Commons the relationship with neuropsychological test performance. J. Natl Cancer Inst. Attribution 4.0 International License, which permits use, sharing, 105, djt073 (2013). adaptation, distribution and reproduction in any medium or format, as long as you give 4. Janelsins, M. C. et al. Longitudinal assessment of cancer-related cognitive appropriate credit to the original author(s) and the source, provide a link to the Creative impairment (CRCI) up to six-months post-chemotherapy with multiple cognitive Commons license, and indicate if changes were made. The images or other third party testing methods in 943 breast cancer (BC) patients and controls. J. Clin. Oncol. 35, material in this article are included in the article’s Creative Commons license, unless 10014 (2017). indicated otherwise in a credit line to the material. If material is not included in the 5. Moriarty, O., Mcguire, B. E. & Finn, D. P. The effect of pain on cognitive function: A article’s Creative Commons license and your intended use is not permitted by statutory review of clinical and preclinical research. Prog. Neurobiol. 93, 385–404 (2011). regulation or exceeds the permitted use, you will need to obtain permission directly 6. Yaffe, K. et al. Sleep-disordered breathing, hypoxia, and risk of mild cognitive from the copyright holder. To view a copy of this license, visit http://creativecommons. impairment and dementia in older women. JAMA 306, 613–619 (2011). org/licenses/by/4.0/. 7. Shilling, V. & Jenkins, V. Self-reported cognitive problems in women receiving adjuvant therapy for breast cancer. Eur. J. Oncol. Nurs. 11,6–15 (2007). 8. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guide- © The Author(s) 2018 lines in Oncology—Survivorship. (2018). Available at: https://www.nccn.org/ professionals/physician_gls/pdf/survivorship.pdf. npj Breast Cancer (2018) 25 Published in partnership with the Breast Cancer Research Foundation http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png npj Breast Cancer Springer Journals

Cognitive function following breast cancer treatment and associations with concurrent symptoms

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Springer Journals
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Biomedicine; Biomedicine, general; Cancer Research; Oncology; Human Genetics; Cell Biology
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Abstract

www.nature.com/npjbcancer BRIEF COMMUNICATION OPEN Cognitive function following breast cancer treatment and associations with concurrent symptoms 1,2 2,3 2,4 2 2,5,6 Kathleen Van Dyk , Julienne E. Bower , Catherine M. Crespi , Laura Petersen and Patricia A. Ganz Cognitive changes after breast cancer treatment are often attributed to chemotherapy, without considering other important factors such as other treatments (e.g., surgery, radiation, endocrine therapy (ET)). We compared neuropsychological functioning in the domains of learning, memory, attention, visuospatial, executive function, and processing speed according to primary breast cancer treatment exposures in early survivorship, before the initiation of ET (n = 189). We were also interested in the association of neuropsychological functioning with select clinical, psychological, and behavioral factors. Compared to those who only underwent surgery (n = 28), all neuropsychological domain scores were comparable in a sample of breast cancer survivors with different treatment exposures, i.e., radiation therapy (n = 64), chemotherapy (n = 20), or both (n = 77), p’s < 0.05, adjusted for age, IQ, depression, and time since treatment completion. Physical fatigue, pain, and sleep correlated with several cognitive domains regardless of treatment exposure. There are minimal treatment-related neuropsychological differences on neuropsychological measures in early breast cancer survivorship, but the influence of other co-occurring symptoms warrants attention. npj Breast Cancer (2018) 4:25 ; doi:10.1038/s41523-018-0076-4 INTRODUCTION Depression Inventory, 2nd edition (BDI-II) did not correlate with any domain, and was included as an additional control. In Cognitive dysfunction following breast cancer treatment is an additional exploratory analyses (data not presented) we examined important survivorship concern. Studies predominantly focus on linear regression models of domains that included treatment chemotherapy treatment as the primary risk, although other group and interactions between treatment group and each treatments such as endocrine therapy (ET) and co-occurring clinical/psychosocial factor, none of which emerged as signifi- factors likely also play a role. The mind body study (MBS) was a cantly related to cognitive domains. prospective, longitudinal, cohort study of early-stage breast cancer survivors (BCS) designed to assess the impact of ET on neurocognitive function; baseline analyses of this sample allows us to examine the effects of primary cancer treatments without DISCUSSION the confound of concomitant ET. In prior baseline analyses, we Neuropsychological performance did not significantly vary based found that higher subjective cognitive complaints were linked to on primary breast cancer treatment exposure in this early combined chemotherapy and radiation therapy exposure. The survivorship period. Strengths of our study are assessment prior current baseline study extends those findings by comparing to ET exposure and the surgery-only comparison group. The neuropsychological functioning across treatment exposures; we current null findings are in contrast with our prior report of further explored relationships with modifiable clinical, psycholo- subjective cognition. Such inconsistency is not uncommon in gical, and behavioral factors. survivorship studies, which compellingly portray the cognitive effects of cancer and its treatment by self-report, raising the RESULTS possibility that neuropsychological methods may not be the most sensitive to these subtle effects. Table 1 displays sample characteristics and cognitive outcomes by Neurocognitive function did correlate with physical fatigue, treatment exposure. We found comparable rates of impairment sleep quality, and pain, regardless of treatment. Fatigue is a known across treatment groups, and also failed to find any differences on correlate of self-reported cognition in BCS, but pain and sleep neuropsychological domain scores between No Adjuvant and any disturbance are surprisingly understudied risks despite their adjuvant treatment group; effect sizes were small to negligible prevalence in survivorship and known risk in other popula- (see Supplementary Information for model details). Select clinical 5–7 tions. Coefficients are small but portray a consistent pattern. and psychosocial factors were correlated with several domains, Cognitive function is complex and multi-determined; it is notably the Pittsburgh Sleep Quality Index (PSQI), the Multi- important to exhaust all risks and opportunities for improvement, dimensional Fatigue Symptom Inventory–Short Form (MFSI) reflected in existing recommendations for multi-modal Physical, and the Breast Cancer Prevention Trial Symptom Checklist (BCPT) Musculoskeletal Pain, see Table 2. Beck approaches to intervention. 1 2 3 UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA; Departments of Psychology and Psychiatry/Biobehavioral Sciences, University of California-Los Angeles, Los Angeles, CA, USA; Department of Biostatistics, UCLA Fielding School of Public Health, 5 6 Los Angeles, CA, USA; UCLA David Geffen School of Medicine, Los Angeles, CA, USA and UCLA Fielding School of Public Health, Los Angeles, CA, USA Correspondence: Patricia A. Ganz (pganz@mednet.ucla.edu) Received: 1 May 2018 Revised: 11 July 2018 Accepted: 13 July 2018 Published in partnership with the Breast Cancer Research Foundation Cognitive function following breast cancer treatment and K Van Dyk et al. Table 1. Sample characteristics and cognitive performance by treatment group Treatment groups Whole sample (A) No Adjuvant (B) Rad Only (C) Chemo Only (D) Chemo + Rad (n= 77) p across groups (n = 189) (n = 28) (n = 64) (n = 20) Age mean (SD) 51.35 (8.34) 51.57 (6.08) 53.88 (7.95) 46.95 (8.06) 50.31 (8.88) 0.001 Education, n (%) Less than college 34 (18%) 2 (7%) 14 (22%) 3 (15%) 15 (19%) 0.55 College degree 56 (30%) 8 (29%) 16 (25%) 8 (40%) 24 (31%) More than college 99 (52%) 18 (64%) 34 (53%) 9 (45%) 38 (49%) Marital status, n (%) married 124 (66%) 11 (39%) 24 (38%) 6 (30%) 24 (31%) 0.78 Race, n (%) White 151 (80%) 23 (82%) 53 (83%) 16 (80%) 59 (77%) 0.82 Annual income, n (%; n= 186) >$100,000 112 (60%) 18 (64%) 40 (65%) 11 (55%) 43 (57%) 0.72 <$100,000 74 (40%) 10 (36%) 22 (35%) 9 (45%) 33 (43%) Employment status, n (%) employed FT or PT 122 (66%) 20 (71%) 44 (69%) 10 (50%) 48 (63%) 0.38 Post-menopausal, n (%) 100 (53%) 15 (54%) 40 (62%) 5 (25%) 40 (52%) 0.03 Surgery Lumpectomy 125 4 63 0 58 < 0.01 Mastectomy 64 24 1 20 19 Months since treatment completion, mean (SD) 1.197 (1.038) 2.48 (0.731) 0.960 (0.951) 1.282 (0.92) 0.908 (0.879) <0.01 Anthracycline treatment, n (%) 24 (25%) NA NA 3 (15%) 21 (27%) 0.385 Stage at diagnosis, n (% of group) 0 25 (13%) 14 (50%) 11 (17%) 0 (0%) 0 (0%) <0.01 1 87 (46%) 13 (46%) 44 (69%) 7 (35%) 23 (30%) 2 59 (31%) 1 (4%) 9 (14%) 12 (60%) 37 (48%) 3 18 (10%) 0 (0%) 0 (0%) 1 (5%) 17 (22%) Endocrine therapy planned, n (%; n = 181) 129 (71%) 13 (48%) 50 (81%) 15 (75%) 51 (71%) 0.03 PSQI, mean (SD) (n= 186) 8.28 (3.46) 7.61 (3.79) 6.59 (3.36) 8.35 (4.03) 8.26 (3.31) 0.034 BDI-II, mean (SD) 8.85 (6.87) 7.36 (6.92) 6.86 (6.76) 12.75 (8.48) 10.04 (5.85) <0.01 State anxiety inventory, mean (SD) 35.51 (8.75) 35.14 (8.24) 35.11 (9.38) 37.42 (9.95) 35.48 (8.16) 0.77 IQ WTAR, mean (SD) (n = 188) 114.28 (9.09) 116.61 (8.18) 114.37 (8.77) 111.10 (9.33) 114.18 (9.50) 0.23 MFSI total, mean (SD) 11.46 (19.34) 6.43 (19.02) 6.71 (19.12) 18.20 (20.16) 15.48 (18.32) <0.01 MFSI mental, mean (SD) 5.51 (4.66) 3.61 (3.45) 4.11 (4.10) 7.30 (5.09) 6.91 (4.81) <0.01 MFSI physical, mean (SD) 4.15 (4.29) 4.43 (4.83) 2.75 (3.54) 6.35 (3.50) 4.64 (4.52) <0.01 BCPT scale, musculoskeletal pain mean (SD) 1.26 (0.95) 1.25 (0.88) 0.96 (0.75) 1.32 (0.75) 1.50 (1.10) <0.01 # of impaired neuropsychological measures (z < −1.5) 1.40 (1.73) 1.46 (1.71) 1.17 (1.60) 1.15 (1.59) 1.64 (1.86) 0.39 # of impaired neuropsychological measures (z < −2) 0.075 (1.31) 0.64 (1.10) 0.66 (1.18) 0.65 (1.04) 0.88 (1.55) 0.71 Impaired by ICCTF guidelines n (% group) 89 (47%) 13 (46%) 27 (42%) 9 (45%) 40 (52%) 0.71 Neuropsychological domains Standardized coefficients (95% CI) for A vs. B, A vs. C, and A vs. D Learning, mean (SD) 0.39 (0.70) 0.47 (0.80) 0.43 (0.75) 0.38 (0.64) 0.32 (0.65) 0.03, 0.04, −0.02 Memory, mean (SD) 0.21 (0.62) 0.19 (0.68) 0.29 (0.63) 0.16 (0.65) 0.17 (0.58) 0.07, 0.06, 0.14 Attention, mean (SD) 0.46 (0.65) 0.66 (0.61) 0.49 (0.62) 0.31 (0.42) 0.40 (0.73) −0.03, −0.08, −0.10 Visuospatial, mean (SD) −0.35 (0.74) −0.24 (0.69) −0.28 (0.77) −0.54 (0.79) −0.40 (0.72) −0.06, −0.08, −0.11 Executive function, mean (SD) 0.23 (0.76) 0.42 (0.86) 0.28 (0.73) 0.06 (0.64) 0.16 (0.76) −.07, −0.09, −0.15 Processing speed, mean (SD) −0.06 (0.67) 0.08 (0.55) −0.01 (0.71) −0.12 (0.65) −0.15 (0.68) 0.11, −0.05, 0.02 BDI-II Beck Depression Inventory, 2nd edition, MFSI Multidimensional Fatigue Symptom Inventory, BCPT Breast Cancer Prevention Trial Symptom Checklist, PSQI Pittsburgh Sleep Quality Index, ICCTF International Cognition and Cancer Task Force Coefficients in linear models adjusted for age, IQ, BDI-II, and time since treatment completion; all p’s > 0.1 Unadjusted scores Study limitations include the predominantly white and highly health in BCS. Our future work will extend this baseline report to educated sample aged 65 or younger. Additional work should characterize the cognitive effects of ET and other risks over time. examine the roles of socioeconomic factors, education, age, and comorbidity. The smaller sizes of the Chemo Only and No METHODS Adjuvant groups likely reduced power and we did not control for As previously described, three recruitment took place from multiple comparisons, but effect sizes were nonetheless mostly 2007–2011 through clinical oncology practices and rapid case negligible. Importantly, we did not have pre-treatment assess- ascertainment using the Los Angeles County Surveillance, ments, which would permit more precise inferences about Epidemiology, and End Results Program registry with collaborat- treatment-related differences. To conclude, we failed to find differences on neuropsycholo- ing physicians and hospitals. This is a report of baseline data only; gical test performance based on primary breast cancer treatment. participants were age 21–65 years, had a recent early-stage breast The commonly reported symptoms of physical fatigue, pain, and cancer diagnosis, had completed primary treatment within the last sleep disturbance are promising targets for supporting cognitive 3 months but did not yet start ET. We excluded women with active npj Breast Cancer (2018) 25 Published in partnership with the Breast Cancer Research Foundation 1234567890():,; Cognitive function following breast cancer treatment and K Van Dyk et al. Table 2. Correlations between cognitive domains and other symptoms MFSI total MFSI physical MFSI mental PSQI global BCPT musculoskeletal pain Learning Correlation 0.02 −0.08 −0.07 −0.18 −0.15 p 0.84 0.28 0.36 0.02 0.04 df 180 180 180 177 180 Memory Correlation −0.01 −0.14 −0.04 −0.22 −0.16 p 0.92 0.06 0.59 <0.01 0.04 df 179 179 179 177 179 Attention Correlation −0.13 −0.25 −0.09 −0.29 −0.13 p 0.09 <0.01 0.24 <0.01 0.08 df 179 179 179 177 179 Visuospatial Correlation 0.09 −0.08 0.04 −0.15 −0.12 p 0.24 0.30 0.64 0.05 0.11 df 179 179 179 177 179 Executive function Correlation −0.15 −0.25 −0.12 −0.17 −0.21 p 0.04 <0.01 0.10 0.02 <0.01 df 181 181 181 178 181 Processing speed Correlation −0.10 −0.20 −0.08 −0.14 −0.08 p 0.16 <0.01 0.30 0.06 0.29 df 181 181 181 178 181 Controls: Age, IQ, Time since TX, BDI-II BDI-II Beck Depression Inventory, 2nd edition, MFSI Multidimensional Fatigue Symptom Inventory, BCPT Breast Cancer Prevention Trial Symptom Checklist, PSQI Pittsburgh Sleep Quality Index. Bold values indicate p< .05 psychotic or major depressive disorders, or any history of Data availability treatments or conditions with known effects on cognition or On reasonable request, the data analyzed in this study are inflammation. The UCLA institutional review board approved the available from the corresponding author in accordance with study and all participants provided written informed consent. institutional policies. We obtained demographic and clinical information from medical records and self-report questionnaires. The following 9 10 11 12 ACKNOWLEDGEMENTS measures were used: BCPT, PSQI, MFSI, and BDI-II. We We would also like to thank Steven Castellon, PhD, for his role in developing and administered a neuropsychological battery composed of standar- collecting neuropsychological assessments. This research was supported by funding dized clinical neuropsychological tests (see Supplementary from the National Cancer Institute R01CA109650, P30 CA16042, the Breast Cancer Information); z-scores based on published normative data were Research Foundation (to PAG), and the AmericanCancer Society (to KVD). averaged into domain scores. All participants received surgery; those with no adjuvant treatment (No Adjuvant) were considered the no-treatment AUTHOR CONTRIBUTIONS comparison group, and the rest were grouped by specific adjuvant K.V.D. conducted the data analysis, interpretation, and drafted the manuscript. J.B. contributed to the overall study design, data collection, interpretation and therapy—those who received only chemotherapy (Chemo Only), manuscript text. C.C. guided the statistical approach, interpretation of findings, and only radiation therapy (Rad Only), or both chemotherapy and manuscript text. L.P. contributed to the data management and processing, radiation (Chemo + Rad). We compared demographic, clinical, and interpretation of findings and manuscript text. P.G. is the PI and guarantor—she impairment variables using two-sided analysis of variance contributed to the overall design of the study, the data collection, statistical (ANOVA) and chi-square tests. Multivariable linear regression approach, interpretation of findings, and manuscript text. This research was models of neuropsychological domain scores controlled for age, supported by funding from the National Cancer Institute R01 CA109650, P30 CA16042, the Breast Cancer Research Foundation (to P.A.G.), and the American intelligence quotient (IQ), time since treatment completion, and Cancer Society (to K.V.D.). BDI-II, with treatment group dummy coded making No Adjuvant the reference group. 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