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Figure.
Longitudinal Adjusted Means of Raw Neuropsychological Test Scores by Treatment Group

All means were adjusted for age, intelligence quotient, and history of treatment with endocrine therapy. Error bars show the standard error of the adjusted means. CVLT-II indicates California Verbal Learning Test, 2nd Edition; T1, within 3 months following primary treatments (n = 190); T2, at 6 months (n = 173); T3, at 1 year (n = 173); and TF, at a mean (SD) 4.8 (0.7) (range, 3.5-6.9) years after treatment (n = 102).

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Longitudinal Adjusted Means of Raw Neuropsychological Test Scores by Treatment Group
Table.
Sample Characteristics by Treatment Group
References
1.
Kesler  SR, Blayney  DW.  Neurotoxic effects of anthracycline- vs nonanthracycline-based chemotherapy on cognition in breast cancer survivors.  JAMA Oncol. 2016;2(2):185-192.PubMedGoogle ScholarCrossref
2.
Ganz  PA, Kwan  L, Castellon  SA,  et al.  Cognitive complaints after breast cancer treatments: examining the relationship with neuropsychological test performance.  J Natl Cancer Inst. 2013;105(11):791-801.PubMedGoogle ScholarCrossref
3.
Ganz  PA, Petersen  L, Castellon  SA,  et al.  Cognitive function after the initiation of adjuvant endocrine therapy in early-stage breast cancer: an observational cohort study.  J Clin Oncol. 2014;32(31):3559-3567.PubMedGoogle ScholarCrossref
4.
Ganz  PA, Petersen  L, Bower  JE, Crespi  CM.  Impact of adjuvant endocrine therapy on quality of life and symptoms: observational data over 12 months from the Mind-Body Study.  J Clin Oncol. 2016;34(8):816-824.PubMedGoogle ScholarCrossref
Research Letter
July 2016

Comparison of Neurocognitive Function After Anthracycline-Based Chemotherapy vs Nonanthracycline-Based Chemotherapy

Author Affiliations
  • 1University of California Los Angeles Semel Institute for Neuroscience and Human Behavior
  • 2Division of Cancer Prevention and Control Research, University of California Los Angeles Jonsson Comprehensive Cancer Center
JAMA Oncol. 2016;2(7):964-965. doi:10.1001/jamaoncol.2016.0350

As a whole, the possible adverse effects of breast cancer and its treatment on cognitive function are now widely acknowledged, but the risks of specific chemotherapies are still undetermined. A recent retrospective cross-sectional study found lower memory scores on average 2 years after treatment among breast cancer survivors who underwent anthracycline treatment vs those who underwent other chemotherapies or no chemotherapy, accompanied by lower functional connectivity in default mode network regions.1 However, in an earlier report examining a large sample of patients with breast cancer immediately after primary treatment and adjuvant chemotherapy (the Mind Body Study [MBS]),2 we found no association between anthracycline exposure and cognitive complaints. To determine risk of lasting cognitive decline with anthracycline treatment, we performed a secondary analysis of cognitive function across multiple domains from the MBS prospective longitudinal study of breast cancer survivors, with evaluations at up to 4 time points.

Methods

We analyzed data from the MBS,2-4 in which breast cancer survivors underwent baseline neuropsychological evaluations within 3 months following primary treatments (n = 190), at 6 months (n = 173), at 1 year (n = 173), and at a mean (SD) 4.8 (0.7) (range, 3.5-6.9) years after treatment (n = 102). To examine the effects of anthracycline treatment, we categorized women by receipt of chemotherapy: no chemotherapy, chemotherapy but not anthracycline, or chemotherapy with anthracycline. The neuropsychological tests selected for these analyses measure memory, processing speed, and executive functions. The full study design and the neuropsychological battery have been detailed elsewhere.2 Raw neuropsychological test scores were compared among treatment groups across all 4 assessment points using mixed models controlling for age, intelligence quotient, and history of treatment with endocrine therapy. The MBS was approved by the University of California Los Angeles institutional review board, and all participants provided written informed consent.

Results

See the Table for group demographic and clinical characteristics at baseline (within 3 months following primary treatment). Of the 7 neuropsychological tests examined in mixed models, there were no significant group effects. There were also no significant group × time interactions in any of the 7 mixed models (P > .05). In addition to the 4 neuropsychological test results presented in the Figure, no group effects or interactions were found on tests of executive functioning/verbal fluency (FAS) or visual memory (Brief Visual Memory Test–Revised, total and delayed recall scores).

Discussion

We examined the association of treatment type (chemotherapy with and without anthracycline, and no chemotherapy) with neuropsychological performance among breast cancer survivors immediately after primary treatment through at least 3 years after treatment. We found no differences among groups across time points and no group × time interaction on any measure. Our findings indicate that cognitive functioning following cancer treatment in the areas of memory, processing speed, and executive functioning was comparable among those who received chemotherapy with or without anthracycline and those who did not receive chemotherapy. Furthermore, cognitive functioning over time (ie, during and after recovery) was also comparable between groups up to 7 years after treatment. We did not find an association between anthracycline exposure and neuropsychological performance on any measure examined.

Our findings based on data from a longitudinal prospective study are in contrast to the cross-sectional study of Kesler and Blayney.1 We found no differential effect of anthracycline treatment on neuropsychological performance. Furthermore, our neuropsychological battery included more challenging memory measures than those in the study of Kesler and Blayney, so the discrepancy is not due to differential sensitivity. In conclusion, in this study we could not find evidence to support the claim that anthracycline treatment confers greater risk of cognitive decline for breast cancer survivors.

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Article Information

Corresponding Author: Patricia A. Ganz, MD, UCLA Jonsson Comprehensive Cancer Center, Division of Cancer Prevention and Control Research, 650 Charles Young Dr S, A2-125 CHS, PO Box 956900, Los Angeles, CA 90095-6900 (pganz@mednet.ucla.edu).

Published Online: April 21, 2016. doi:10.1001/jamaoncol.2016.0350.

Author Contributions: Dr Ganz had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Ganz.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Van Dyk.

Critical revision of the manuscript for important intellectual content: Petersen, Ganz.

Statistical analysis: Petersen.

Obtained funding: Ganz.

Administrative, technical, or material support: Ganz.

Study supervision: Ganz.

Conflict of Interest Disclosures: Dr Ganz is a member of the Scientific Advisory Board of the Breast Cancer Research Foundation. No other disclosures are reported.

Funding/Support: This research was supported by funding from the National Cancer Institute (R01 CA 109650) and the Breast Cancer Research Foundation.

Role of the Funder/Sponsor: Neither of the funding organizations played any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
References
1.
Kesler  SR, Blayney  DW.  Neurotoxic effects of anthracycline- vs nonanthracycline-based chemotherapy on cognition in breast cancer survivors.  JAMA Oncol. 2016;2(2):185-192.PubMedGoogle ScholarCrossref
2.
Ganz  PA, Kwan  L, Castellon  SA,  et al.  Cognitive complaints after breast cancer treatments: examining the relationship with neuropsychological test performance.  J Natl Cancer Inst. 2013;105(11):791-801.PubMedGoogle ScholarCrossref
3.
Ganz  PA, Petersen  L, Castellon  SA,  et al.  Cognitive function after the initiation of adjuvant endocrine therapy in early-stage breast cancer: an observational cohort study.  J Clin Oncol. 2014;32(31):3559-3567.PubMedGoogle ScholarCrossref
4.
Ganz  PA, Petersen  L, Bower  JE, Crespi  CM.  Impact of adjuvant endocrine therapy on quality of life and symptoms: observational data over 12 months from the Mind-Body Study.  J Clin Oncol. 2016;34(8):816-824.PubMedGoogle ScholarCrossref
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