1 |. INTRODUCTION
Cancer-related cognitive impairment (CRCI) is common and associated with a myriad of adverse patient-centered outcomes.1 The presence of cognitive impairment may impact the oncology provider’s decision to offer and patients’ ability to tolerate chemotherapy.2,3
A substantial barrier to routine cognitive screening in oncology is the absence of a reliable, cancer-specific test. The Blessed Orientation Memory Concentration (BOMC) Test4 has been incorporated in cancer-specific geriatric assessments (GA),5 but has no established score for CRCI. BOMC scores ≥5 are suggestive of cognitive impairment in non-cancer populations,6 and more recently were found to predict chemotherapy toxicity.2 To further investigate the BOMC ≥5 score in oncology, the current study aimed to identify cognitive impairment in chemotherapy naïve patients with early breast cancer and examine its relationship with functional, psychosocial, and medical variables from the cancer-specific GA.
2 |. METHODS
2.1 |. Study participants
Women with Stage I-III breast cancer, chemotherapy naïve, were recruited between 2009 and 2018 to three studies. The first study is an institutional cancer registry of adults age 65 and older (NCT01137825). The other two studies are intervention trials in women diagnosed with breast cancer who are under age 65 (NCT02167932) or 65 and older (NCT02328313) and scheduled for chemotherapy. The trials required participants to be English-speaking and capable of light walking. All participants provided written informed consent. The studies were approved by the Institutional Review Boards of the University of North Carolina and other participating sites.
2.2 |. Measures
The BOMC is a six-item cognitive screening test that evaluates orientation, concentration, and memory.4 Scores range from 0 to 28 (higher values indicate worse cognition).
All domains of the GA were included for potential association with the BOMC. Table 1 presents GA measures, along with demographic and cancer treatment variables. The GA measures have been described previously in detail.5,7 Except for the Time Up and Go test (TUG), all functional (Karnofsky Performance Status, Older American Resources and Services Instrumental Activities of Daily Living, Medical Outcomes Survey [MOS] Physical Function), psychosocial, and medical comorbidity variables are patient-reported.
TABLE 1.
Demographics, geriatric assessment measures, and associations with cognitive impairment (N = 331)
| N (%) | RR [95% CI] | |
|---|---|---|
| Demographics | ||
| Age, mean (SD) | 65.2 (14.2) | 1.03 [1.02,1.04] |
| Age ≥ 65 | 227 (69) | 1.58 [1.02,2.46] |
| White | 264 (80) | 0.77 [0.52,1.15] |
| Married | 185 (56) | 0.81 [0.57,1.16] |
| High school or less | 141 (43) | 2.33 [1.60,3.40] |
| Employed full-time | 68 (21) | 0.18 [0.07,0.48] |
| Previous surgery | ||
| None | 75 (41) | – |
| Mastectomy | 53 (29) | 0.43 [0.20,0.93] |
| Lumpectomy | 55 (30) | 0.47 [0.23,0.98] |
| Previous hormonal therapy | ||
| No | 137 (94) | – |
| Yes | 8(6) | 1.37 [0.39,4.79] |
| Cognition | ||
| BOMC ≥5 (range 0–28, higher is worse)a | 89 (27) | – |
| BOMC by age group, mean (SD), range | – | |
| <50 | 2.4 (2.7), 0–10 | |
| 50–64 | 3.1 (3.1), 0–10 | |
| 65–74 | 3.1 (3.0), 0–16 | |
| ≥ 75 | 5.8 (5.2), 0–21 | |
| Function | ||
| TUG >14 seconds (higher is worse)a | 63 (19) | 1.95 [1.37,2.78]** |
| Patient-reported KPS < 80 (range 10–100, higher is better) | 44 (14) | 2.06 [1.42,3.00] |
| OARS IADL <14 (range 0–14, higher is better) | 76 (24) | 1.74 [1.20,2.52] |
| Falls in the last 6 months | 56 (18) | 1.06 [0.91,1.23] |
| MOS Physical Function, mean (SD) (range 0–20, higher is better) | 15.1 (5.4) | 0.93 [0.91,0.95]*** |
| Psychosocial | ||
| MHI—Depression >12 (range 0–43, >12 signifies depression) | 77 (26) | 1.68 [1.15,2.46] |
| MHI—Anxiety >6 (range 0–20, >6 signifies anxiety) | 128 (42) | 0.83 [0.56,1.23] |
| Social activity limitations >50 (range 0–100, higher is worse) | 78 (25) | 1.72 [1.19,2.50] |
| Perceived social support (range 0–100, higher is better) | ||
| Emotional, mean (SD) | 88.6 (18.2) | 0.99 [0.98,1.00] |
| Tangible, mean (SD) | 86.4 (19.6) | 1.00 [0.99,1.01] |
| Medical | ||
| Arthritis or rheumatism | 143 (45) | 1.38 [0.95,2.00] |
| Glaucoma | 15 (5) | 1.61 [0.84,3.09] |
| Emphysema or chronic bronchitis | 14(4) | 1.40 [0.68,2.90] |
| High blood pressure | 136 (42) | 1.30 [0.90,1.87] |
| Heart disease | 27 (8) | 1.14 [0.62,2.11] |
| Peripheral vascular disease | 43 (14) | 1.89 [1.21,2.82]* |
| Diabetes | 42 (13) | 1.23 [0.75,2.02] |
| Stomach or intestinal disorders | 44 (14) | 1.36 [0.86,2.15] |
| Osteoporosis | 42 (13) | 0.71 [0.37,1.36] |
| Chronic liver or kidney disease | 7(2) | 1.09 [0.33,3.58] |
| Stroke | 13 (4) | 1.19 [0.51,2.74] |
Abbreviations: BOMC, blessed orientation memory concentration test; IADL, instrumental activities of daily living; KPS, Karnofsky performance status; MHI, mental health index; MOS, medical outcomes survey; OARS, Older American resources and services; TUG, time up and go test.
Indicates clinician administered. All other functional, psychosocial, and medical items are patient-reported.
P < .05,
P < .01,
P < .001 after adjustment for age, employment, and educational level.
2.3 |. Statistical analysis
Descriptive statistics were used to characterize participants. Unadjusted associations between cognitive impairment (defined as BOMC ≥5) with demographic and GA variables were assessed using log binomial regression analysis. Relative risks and corresponding 95% confidence intervals are reported. Multivariable models, adjusting for significant demographic characteristics, were fit for each variable significant at the P < .05 level. All analyses were conducted using SAS v9.4 statistical software (Cary, NC).
3 |. RESULTS
In this study of 331 patients, cognitive impairment was observed in 27% and in an unadjusted analysis was associated with older age, fewer years of education, and less than full-time employment (Table 1). In adjusted analyses, the risk of cognitive impairment was 66% higher for patients who completed the TUG in ≥14 seconds (P = .002) and 53% higher in patients with peripheral vascular disease (P = .02). After adjustment, every one-point increase in the MOS Physical Function score was associated with a 5% decrease in risk of cognitive impairment (P = .0004). Associations with mental health, social limitations, and previous breast cancer surgery were significant in unadjusted but not in multivariable analyses.
4 |. DISCUSSION
Pre-chemotherapy cognitive impairment in our study was less prevalent than in other studies. Specifically, in slightly older patients, cognitive impairment was identified in 36% using the same BOMC threshold.2 In another breast cancer cohort, cognitive impairment was identified in 35% before adjuvant chemotherapy.8 The higher prevalence in that sample may be due to the use of a comprehensive neuropsychological battery for evaluation. It may also be a consequence of exposure to surgery, though cognitive impairment was not more common in those who had received mastectomy or lumpectomy in our study.
We have previously identified several associations between cognitive and physical function.9 In the current study, we found that objective and self-reported physical function were also associated with cognitive impairment, emphasizing the strength of this relationship. We additionally observed an association with patient-reported peripheral vascular disease. To our knowledge the relationship between peripheral vascular disease and CRCI has not previously been reported.
Our study has some limitations. Relative to the overall newly diagnosed breast cancer population, our cohort was more educated and likely in better physical condition. Our sample size may not have been adequate to identify small associations with cognitive impairment (eg, depression and social activity limitations) that do exist. As a cross-sectional study, we were unable to clarify causal relationships between physical and cognitive impairment.
Given the profound impact of cognitive impairment on patients with cancer, it is critical to identify deficits as early as possible. The BOMC takes fewer than 5 minutes to administer, does not require extensive training, and has been used in oncology settings.5 By comparison, the more frequently used Mini Mental Status Exam takes longer to complete and has been shown to be inadequately sensitive for CRCI.10 The BOMC threshold of ≥5 has promise based on studies in non-cancer populations and its ability to predict chemotherapy toxicity. We have now shown its association with physical function impairment in women with early breast cancer. In future studies, we plan to investigate the sensitivity of the BOMC to detect cognitive decline resulting from cancer treatment.
Key Points.
This study investigated a Blessed Orientation Memory Concentration test (BOMC) score of ≥5 for cancer-related cognitive impairment (CRCI) screening.
Cognitive impairment was identified in 27% of chemotherapy naïve patients with early breast cancer.
Cognitive impairment was associated with both patient-reported and clinician-assessed functional impairment.
Cognitive impairment was also associated with patient-reported peripheral vascular disease.
A BOMC score of ≥5 may be promising for CRCI screening.
ACKNOWLEDGEMENTS
This study was supported by the Breast Cancer Research Foundation (New York, NY), the Kay Yow Cancer Fund (Raleigh, NC), the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill/University Cancer Research Fund (Chapel Hill, NC), and the National Institutes of Health [grant number 5K12HD001441; scholar: Nakamura].
Funding information
Breast Cancer Research Foundation; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Grant/Award Number: 5K12HD001441; Kay Yow Cancer Fund; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Footnotes
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
CONFLICT OF INTEREST
The authors declare no potential conflict of interest.
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