Table I.
Extracted data from 8 studies including a total number of 1,253 participants, of whom 800 were patients with breast cancer.
| Study [Author, year (Ref.)] | Country | Study design | No. of patients | Sample characteristics | Measures of stress | Measures of cognitive parameters | Time of measurements | Main findings |
|---|---|---|---|---|---|---|---|---|
| Cognitive impairment in a subset of patients with breast cancer following systemic therapy - results from a longitudinal study, Menning et al, 2016 (26) | The Netherlands | Longitudinal case-control | 88 | Case BC+SYST group: n=31, ≥70 years old, 39% post-menopausal. BC group: n=24, 54% post-menopausal Control NC group: nn=33, ≥70 years old, 55% post-menopausal | PSS IES (at T2) | COWA test, BADS-Zoo Map test, TMT parts A&B, EFT, VRT test, DS of the WAIS-III, VRT of the WMS-R, HVL-R test, DSC test of the WAIS-III, FT | T1: Before the initiation of the treatment T2: 6 months after the completion of the treatment | At secondary analysis, cognitively impaired patients exhibited statistically significant higher levels of distress (P=0.019) in comparison with the non-impaired patients |
| Effects of breast cancer treatment on the hormonal and cognitive consequences of acute stress, Andreano et al, 2012 (27) | USA (California) | Case-control and field experiment study | 40 | Case n=20, 27–49 years old, female breast cancer survivors treated with Lupron (6 additionally treated with aromatase inhibitors, 4 with tamoxifen and 1 with chemotherapy). At the initiation total sample premenopausal. Control n=20, 26–48 years old, healthy and naturally cycled women | CPT Salivary cortisol | Subtests from the WMS-III (working memory, verbal paired associate memory and narrative recall) | Salivary cortisol: At baseline, 10, 20 and 30 min and 1 week after CPS test. WMS-III: At baseline, after 1 week | Logical recall: Significant decrease in total recall in week 2 but independently of stress condition [F(1,36)=4.465, P<0.05, η2=0.019]. Significant interaction between the drug and stress condition when testing stories separately [F(3,36)=2.792, P<0.05, η2=0.018). Significant positive correlation between recall of story A and 20 min′ salivary cortisol post-stressor (r=0.544, P<0.05, df=9). The cortisol/memory association for story A differed significantly between control and breast cancer groups by Fisher's z test (z=2.18, P<0.05) |
| Measures of cognitive function and work in occupationally active breast cancer survivors, Calvio et al, 2010 (28) | USA (Washington DC) | Case-control | 235 | Case n=122, 18–65 years old, female breast cancer survivors (non metastatic), working ≥1 year prior to the study, between 1 and 10 years of breast cancer treatment completion (surgery, chemotherapy, HT, BT). Control n=113, 18–65 years old, female non-cancer participants, without a prior diagnosis of any type of cancer | Behavioral risk factor surveillance survey (1 item used to assess job stress in this study) | Perceived cognitive function: CSC-modified performance-based cognitive function: CNSVS | A single measurement following a screening to determine the eligibility of the participants | Case: Job stress had a significant impact on the cognitive limitations at work either according to performance (β=0.29, P<0.01), or according to the patients' reports (β=0.29, P<0.01). Control: β indicator did not show a statistically significant correlation (β=−0.06 and β=0,06, respectively) |
| Cognitive function and quality of life after surgery for early breast cancer in North Jutland, Denmark, Debess et al, 2009 (29) | Denmark (North Jutland) | Case-control | 348 | Case n=124, <60 years old female, right after primary breast cancer surgery, no metastasis. Control n=224, female, age matched, not prior history of any type of cancer | POMS | Four questions about memory, concentration/attention, mental fatigue and vitality from the ISPOCD 2 and 4 tests: VL test, CS test, SCWI test, LDC test. DART | All tests were administered in a mean 34.5 days after surgery (19–75 days) for the cases and at the date of inclusion for the controls | Case: Psychological stress was significantly correlated with subjective cognitive function (Spearman's rho: −0.3 to −0.4, P<0.05). Control: Fewer correlations between POMs' subscales and subjective cognitive function were found (Spearman's rho: −0.2 to −0.3, P<0.05) |
| Symptom cluster of emotional distress, fatigue and cognitive difficulties among young and older breast cancer survivors: The mediating role of subjective stress, Levkovich et al, 2018, (30) | Israel | Cross-sectional | 170 | Case N=120 BCS aged 20–59 and N=50 BCS aged 60–82, stages I–III, 1–12 months post-chemotherapy, patients receiving HT and BT included, with no current evidence of disease | Subjective stress scale BSI 18 | Cognitive difficulties scale (four-item subscale taken from the EORTC QLQ) | All tests were administered within 1–12 months post-chemotherapy | The older-aged survivors reported lower levels of subjective stress (M=4.59, SD=2.38) and cognitive difficulties (M=1.17, SD=1.07), compared to the younger-aged survivors (M=5.38, SD=2.84 and M=1.66, SD=1.23, P<0.01–0.05). The association between age and cognitive difficulties was linear and negative, and statistically significant, meaning that the higher the age, the lower the symptoms. Subjective stress mediated the effect of age on cognitive difficulties |
| Modifiable correlates of perceived cognitive function in breast cancer survivors up to 10 years after chemotherapy completion, Henneghan et al, 2018, (31) | USA (Texas) | Cross-sectional | 90 | Case Ν=90 BCS 6 months to 10 years post-chemotherapy (average 3 years), patients receiving HT included. Age 20–65 years, stages I–III. | PSS | FACT-Cog | All tests were administered within 6 months to 10 years post-chemotherapy | Mediation analyses revealed that stress both directly and indirectly impacts perceived cognitive function (P<0.02) according to the SEM model (P<0.01–0.05) |
| Effects of childhood trauma exposure and cortisol levels on cognitive functioning among breast cancer survivors, Kamena et al, 2017 (32) | USA | Cross-sectional | 56 | Case n=56 BCS, aged ≥21 years, mean age, 53.6 years, SD=9.8 ≥2 weeks post treatment (except HT), stages I–IV | TES Salivary cortisol levels | FACT-Cog | T1: Upon waking T2: 30 min after waking; T3: at 9:00 p.m. for 2 days | Childhood trauma exposure is associated with self-reported cognitive functioning among breast cancer survivors and is mediated by cortisol dysregulation, as shown by steeper cortisol slope in the exposed patients (P=0.02) |
| Chemotherapy and post-traumatic stress in the causation of cognitive dysfunction in breast cancer patients, Hermelink et al, 2017 (33) | Germany | Longitudinal, case-control | 226 | Case n=166 BC patients, aged 18 and 65 years, female sex, diagnosed with yet untreated stage 0 to IIIc BC, scheduled to receive appropriate treatment Control n=60, female, age matched, negative BC imaging or not prior history of any type of cancer | Structured clinical interview according to DSM-IV criteria for PTSD | Alternate forms of the VLMT cognitive difficulties scale (four-item subscale taken from the EORTC QLQ) FEDA | T1: Prior to primary surgery or neoadjuvant chemotherapy for breast cancer patients and a minimum of one week after negative breast imaging for control subjects; T2: ≥1 week after completion of chemotherapy or at matched intervals after T1 T3: 1 year after T1. | Case: Patients demonstrated overall cognitive decline (group*time effect on composite z-score: −0.13, P ¼ .04) and scored consistently worse on Go/Nogo errors. The latter effect was mediated by PTSD symptoms (mediation effect: B ¼ 0.15, 95% confidence interval ¼ 0.02 to 0.38). Only patients receiving chemotherapy exhibited a declined reaction time on a computerized alertness test at 1 year. Overall, cognitive performance correlated with self-reported cognitive problems at one year (T3) (T ¼ −0.11, P ¼ .02). Control: Controls performed consistently better than patients on a computerized measure of behavioral control and Go/No go errors |
BC, breast cancer; BCS, breast cancer survivor; BC+SYST group, breast cancer patients receiving systemic treatment; BC group: breast cancer patients not receiving systemic treatment; NC group: non-cancer control group; PSS, perceived stress scale; IES, impact of events scale; COWA test, controlled oral word association test; BADS-Zoo Map test, behavioral assessment of the dysexecutive syndrome - Zoo Map Test; TMT parts A&B, trail making test parts A&B; EFT: Eriksen fanker task; VRT test, visual reaction time test; DS of the WAIS-III, digit span of the Wechsler adult intelligence scale III; VRT of the WMS-R, visual reproduction test of the Wechsler memory scales revised; HVL-R test, Hopkins verbal learning test revised; DSC test of the WAIS-III, digit symbol-coding test of the WAIS-III; FT, finger tapping; CPT, cold pressor test; WMS-III, Weschler memory scale III; CSC-Modified, cognitive symptoms checklist-modified; CNSVS, central nervous system vital signs; POMS, profile of mood states; ISPOCD 2, international study of post-operative cognitive dysfunction; VL test, visual learning test; CS test, concept shifting test; SCWI test, Stroop color word interference test; LDC test, letter-digit coding test; DART, Danish adult reading test; HT, hormonal treatment; BT, biological treatment; EORTC, the European organization for research and treatment of cancer; QLQ, quality of life questionnaire; SEM, structural equation model; FACT-Cog, cancer therapy-cognitive function instrument version 3; TES, traumatic events survey; DSM-IV, diagnostic and statistical manual of mental disorders version 4; PTSD, post-traumatic stress disorder; VLMT, verbal learning and memory test; FEDA, questionnaire of experienced deficits of attention.