Neuropsychological assessment of cognitive functioning following chemotherapy for breast cancer

Cancer patients' complaints of impaired cognition following chemotherapy are fairly common but poorly documented among adult patients. Neuropsychological testing was used to evaluate current cognitive functioning of 28 stage I and II breast cancer patients (ages 28–54) who had completed 3 to 18 months of adjuvant chemotherapy, from 0.5 to 12 months prior to testing. Effects of drug regimen, length of treatment and level of depression on cognitive functioning were examined. Despite estimated high-normal pre-morbid intelligence (mean FSIQ 113) patients scored significantly below age-, education-, and gender-corrected test norms in areas of verbal and visual memory, mental flexibility and speed of processing, attention and concentration, visuospatial ability and motor function. Of patients, 75% scored -2SDs (moderate impairment) on one or more test measures. Level of cognitive impairment was unrelated to depression, type of chemotherapy and time since treatment, but was positively related to length of chemotherapy treatment. These preliminary findings suggest that cognitive impairment may follow conventional adjuvant chemotherapy treatment and warrant replication with a controlled and more rigorous longitudinal design.     

Cognitive complaints and cognitive impairment following BEP chemotherapy in patients with testicular cancer

Introduction. There is growing concern that some cytotoxic regimens for cancer affect cognitive functioning. This study examined the prevalence of cognitive complaints and deficits in testicular cancer (TC) patients treated with the worldwide standard BEP (bleomycin, etoposide and cisplatin) chemotherapy. Materials and methods. Seventy TC patients treated with BEP chemotherapy after surgery (S+CT) were examined with interviews and neuropsychological tests. These patients were compared with 57 TC patients treated with radiotherapy after surgery (S+RT) and with 55 TC patients that received surgery only (S). Patients were examined a median of 3 years after completion of treatment. Results. Thirty two percent of the S+CT patients reported cognitive complaints compared with 32% of the S+RT patients and 27% of the S patients (p=0.85). No differences in mean cognitive test performance were observed between the groups. On individual impairment scores, more S+CT patients showed cognitive dysfunction compared with S patients, but not compared with S+RT patients (S+CT versus S [p=0.038, OR=4.6, CI=1.1-19.7], S+CT versus S+RT [p=0.70, OR=0.8, CI=0.3-2.4] and S+RT versus S [p=0.070, OR=3.7, CI=0.8-15.7). Cognitive complaints were not related to cognitive test performance, but to emotional distress and fatigue. Discussion. Cognitive complaints are common among TC patients, independent of treatment modality. These complaints are related to emotional distress and fatigue and not to formal cognitive deficits. The finding of a small group of TC patients treated with chemotherapy exhibiting cognitive deficits should be confirmed in a prospective study before we can decide on its cause and relevance.     

The cognitive effects of adjuvant chemotherapy in early stage breast cancer: a prospective study

PURPOSE: The primary purpose of this study was to evaluate the cognitive effects of adjuvant chemotherapy in post-menopausal breast cancer patients. PATIENTS AND METHODS: Breast cancer patients scheduled to receive adjuvant chemotherapy (n = 61) completed comprehensive cognitive testing before and after treatment. A control group of women receiving adjuvant hormonal therapy (n = 51) was tested at comparable intervals. RESULTS: Mean scores for both patient groups were within the normal range relative to published norms on all cognitive tests at both time points, and generally inclined or stayed the same from baseline to retest in both groups. However, in an analysis of individual change scores, the chemotherapy patients were 3.3 times more likely than the hormonal patients to show reliable cognitive decline (31 and 12%, respectively). Chemotherapy subjects showing decline were less educated and had higher baseline depression scores than their counterparts who did not decline. Working memory was the cognitive domain most vulnerable to the effects of chemotherapy. CONCLUSION: These data support previous findings of a subtle negative influence of chemotherapy on cognitive function in a subgroup of breast cancer patients. The results are discussed in terms of the importance of study design.     

Objective and self-reported cognitive dysfunction in breast cancer women treated with chemotherapy: a prospective study

The objective of this study is to investigate if changes in cognitive functions can be recognised in patients undergoing chemotherapy for breast cancer. Forty women with breast cancer and without depression underwent cognitive evaluation before and after 6 months of chemotherapy; emotional evaluation was performed before and after 1, 3 and 6 months of chemotherapy. Self-reported cognitive deficit evaluation was included. Global cognitive functioning before starting chemotherapy was good. After 6 months of treatment there was a significant decline in some cognitive functions, particularly involving the attention subdomain. Objective cognitive deficit resulted independent from the emotional status. On the contrary, self-perceived mental dysfunction was unrelated to the objective cognitive decline, but it was associated with depression and anxiety. Breast cancer chemotherapy can induce domain-specific cognitive dysfunction. Patients' self-perception of mental decline is unrelated to objective cognitive deficit. Breast cancer patients negatively judge their cognitive performances if they have a negative emotional functioning.     

Change in cognitive function after chemotherapy: a prospective longitudinal study in breast cancer patients

Some breast cancer survivors experience cognitive decline following chemotherapy. We prospectively examined changes in cognitive performance among high-risk breast cancer patients who had received high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTC group; n = 28) or standard-dose chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC group; n = 39); stage-I breast cancer patients who had received no systemic chemotherapy (no-CT group; n = 57); and healthy control subjects (n = 60). All patients underwent neuropsychologic testing before and 6 months after treatment (12-month interval); control subjects underwent repeated testing over a 6-month interval. No differences in cognitive functioning between the four groups were observed at the first assessment. More of the CTC group than the control subjects experienced a deterioration in cognitive performance over time (25% versus 6.7%; odds ratio [OR] = 5.3, 95% confidence interval [CI] = 1.3 to 21.2, P = .02). No such difference was observed for the FEC or the no-CT groups (FEC versus control: OR = 2.2, 95% CI = 0.5 to 9.1, P = .27; no-CT versus Control: OR = 2.2, 95% CI = 0.6 to 8.0; P = .21). Some cytotoxic treatment for breast cancer affects cognition in a subset of women.     

Leukemia following chemotherapy for breast cancer

Leukemia following chemotherapy for breast cancer was studied among patients diagnosed during 1973-1985 within the population-based tumor registries in the Surveillance, Epidemiology, and End Results Program. Among 13,734 women given initial chemotherapy, 24 developed acute nonlymphocytic leukemia (ANLL) compared to 2.1 expected based on general population rates (observed/expected = 11.5; 95% confidence interval = 7.4-17.1). Overall, 58 excess ANLL occurred per 100,000 women-years at risk for patients treated with chemotherapy. The cumulative incidence was 0.7% at 10 years. Risk remained high over all periods of observation up to 9 years after treatment. Among 7974 women treated only with surgery during 1973 and 1974, a period before the widespread use of adjuvant chemotherapy for breast cancer, ANLL was not significantly increased (observed = 7, expected = 5.1). A case-control study was then conducted in Connecticut to evaluate in more detail the risk associated with adjuvant chemotherapy in the general population. Among 20 cases (17 incident leukemias and 3 deaths due to preleukemia) and 60 matched controls, alkylating agents were linked to an 11.9-fold risk of ANLL and preleukemia (95% confidence interval = 2.6-55). Chemotherapy regimens including melphalan were related to a higher risk of leukemic conditions than those including cyclophosphamide. These data suggest that women in the general population treated with adjuvant chemotherapy for breast cancer are at an increased risk of leukemia, that the risk remains high among long-term survivors, and that risk differs by type of alkylating agent administered.     

Risk for endometrial cancer following breast cancer: a prospective study in Sweden

The risk for endometrial cancer among women with breast cancer might increase following use of tamoxifen, recently classified as a carcinogen of the human endometrium. However, the strength of the association remains uncertain and it is unknown whether use of this drug - widely prescribed in Sweden since the mid-1980s - has had any measurable effect at the population level. We analyzed all cases of breast cancer (n = 131,614) detected in the nationwide Swedish Cancer Registry in 1958-93. Incident cases of endometrial cancer during follow-up were identified also through the Cancer Registry. Standardized incidence ratios (SIR) and their 95 percent confidence intervals(CI) were computed by use of nationwide rates of endometrial cancer, adjusted for age and calendar year. During follow-up of up to 35 years of the breast cancer cohort, 803 incident endometrial cancers were identified, yielding an overall SIR of 1.58 (CI = 1.47-1.70). In univariate analyses, there was no increase in SIR in recent years. However, the excess risk increased linearly with increasing age at breast cancer diagnosis (P trend < 0.0001) and decreased markedly with longer follow-up (P trend < 0.0001). A multivariate regression analysis, with adjustment for age and year of follow-up, revealed no increased risk for subsequent endometrial cancer among breast cancer cases diagnosed more recently (P trend = 0.19); compared with the period 1958-63,the risk estimate in the last time period (1989-93) was 0.72 (CI =0.51-1.01). We conclude that the risk for endometrial cancer following breast cancer has not increased over time in Sweden. This revised version was published online in July 2006 with corrections to the Cover Date.     

The influence of erythropoietin on cognitive function in women following chemotherapy for breast cancer

Objective: Cognitive dysfunction is a potential side effect of chemotherapy, and erythropoietin might be protective. A previously reported study compared quality‐of‐life in women undergoing chemotherapy for breast cancer who were randomized to receive epoetin‐alfa or standard care. Here, we report a non‐randomized sub‐study in which cognitive function of participants was evaluated at 12–30 months after chemotherapy. Methods: The primary endpoint was the proportion of women with moderate–severe cognitive impairment, as measured by the High Sensitivity Cognitive Screen (HSCS). Subjects also completed the Revised Hopkins Verbal Learning Test (HVLT‐R), the Functional Assessment of Cancer Therapy—Fatigue (FACT‐F) and FACT‐G self‐report questionnaires for fatigue and quality‐of‐life, and the Hospital Anxiety and Depression Scale. Results: Of 278 patients receiving adjuvant treatment in the primary study, 87 participated in the sub‐study: 45 had received epoetin‐alfa and 42 standard care. Groups were well matched for age and type of chemotherapy. Eight patients (9%) had moderate–severe cognitive dysfunction by the HSCS: six of them in the epoietin‐alfa group (not significant). There were no significant differences in the HVLT‐R, or in fatigue, but patients who had received epoetin‐alfa reported better quality‐of‐life. Conclusion: This study failed to demonstrate a protective effect of epoetin‐alfa against the development of delayed cognitive dysfunction after chemotherapy. Copyright © 2008 John Wiley & Sons, Ltd.     

A prospective evaluation of antibiotic prophylaxis efficacy for breast cancer surgery following previous chemotherapy

Use of antibiotic prophylaxis (AP) in clean breast cancer surgery is still controversial. We assessed the efficacy of preoperative AP in a prospective study of 171 clean breast cancer procedures following previous anticancer chemotherapy. From June 1998 to July 2001, we analyzed 171 procedures. In 133 cases. AB with cefuroxime was performed. Wound infection rate was 3 out of 171 procedures (WI rate of 2/131 with AP compared with 1/37 without AP, p = 1.0). This study suggests that AP is not systematically required in breast cancer surgery following previous anticancer chemotherapy.     

A prospective investigation of pain and fatigue following pelvic exenteration

AimTo describe the long-term course of pain and fatigue in patients undergoing pelvic exenteration and to evaluate potential prognostic factors for these outcomes.DesignProspective cohort study.SettingsRoyal Prince Alfred Hospital, Sydney, Australia.PatientsConsecutive patients undergoing pelvic exenteration surgery between July 2008 and December 2017.Main outcome measuresPain and fatigue scores collected via SF-36v2 Health surveys pre-operatively and at eight time-points post-operatively for a period of 5-years. The course of pain and fatigue were described according to the following prognostic factors; bone resection (yes/no), cancer type (primary/recurrent), margin status (R0/R1-2) and extent of exenteration (complete/partial).Results345 of 459 eligible patients (75 %) consented to the study. The course of pain and fatigue over the 5 year follow-up was favourable. Patients undergoing pelvic exenteration with an R0 resection margin or without bone resection presented lower pain levels throughout the follow-up period. Bone resection, positive surgical margin (R1/R2) and type of cancer did not influence fatigue trajectories. Patients undergoing complete pelvic exenteration were more likely to report a higher level of pain and fatigue in the initial follow-up period, however this difference was not observed in the longer-term.ConclusionsPatients undergoing PE (Austin and Solomon, 2015) [1] can expect improvement but an incomplete recovery in the levels of pain and fatigue postoperatively over the 5-year follow-up period. Bone resection as part of exenteration demonstrated higher levels of pain and fatigue.     

No indications of cognitive side-effects in a prospective study of breast cancer patients receiving adjuvant chemotherapy

Objective: A number of cross‐sectional studies have reported reduced cognitive function in cancer patients receiving chemotherapy compared with other cancer patients and healthy controls, suggesting that chemotherapy could be associated with cognitive side‐effects. Recently published prospective studies question this hypothesis, but it is still unclear whether cancer patients should regard cognitive problems as a potential risk when receiving chemotherapy. Methods: In the present study we examine whether cancer patients (n=34) receiving chemotherapy differed in cognitive changes during treatment compared with cardiac patients (n=12) and healthy controls (n=12) tested at 3–4 months interval. Results: Our results showed no differences with respect to changes in cognitive performance over time between cancer patients in chemotherapy, cardiac patients, and healthy controls. In addition, the number of individuals showing reliable decline or improvement on cognitive tests did not differ between groups. Conclusion: Taken together, our results do not support a hypothesis of cognitive side‐effects of standard‐dose chemotherapy in breast cancer patients. Copyright © 2008 John Wiley & Sons, Ltd.     

A prospective study of cognitive complaints in patients with testicular cancer

Introduction

Cognitive complaints are frequent among patients with cancer. Oncologists and patients have become concerned that systemic chemotherapy may have cognitive side effects. After this concern became public there was a risk of expectation bias in studies of cognitive complaints. We prospectively explored cognitive complaints in patients with testicular cancer treated with chemotherapy or radiotherapy during the 1990s, before today's increased awareness of this possible side effect.

Patients and Methods

The European Organisation for Research and Treatment of Cancer (EORTC) quality of life (QoL) questionnaire (QLQ-C30) and a testicular cancer module (TC module) were completed before treatment (baseline), at 3 months, and at 12 months by 276 chemotherapy and 71 radiotherapy patients enrolled in 3 EORTC studies. Cognitive complaints were based on the cognitive function (CF) items (concentration and memory) of the QLQ-C30. Other QLQ-C30 functions and symptoms represented adjustment variables.

Results

The chemotherapy group (CHEMO) showed a significant increase in prevalence of cognitive complaints from baseline to 3 months. At 12 months these rates were back at baseline levels. The radiotherapy group (RAD) showed no significant change in the prevalence of cognitive complaints over time. Significant differences between the 2 treatment groups were observed only at the 3-month follow-up. In multivariate analyses, treatment modality did not show significant association with cognitive complaints at any time point, whereas current fatigue showed significant associations at all time points.

Conclusion

In patients with testicular cancer with no information or expectation bias, an increased rate of cognitive complaints was observed shortly after chemotherapy, with return to baseline levels at 12 months. Treatment modality (chemotherapy vs. radiotherapy) was not associated with cognitive complaints at any time point after adjustment for relevant QoL variables.     

Objective and subjective cognitive impairment following chemotherapy for cancer: A systematic review

Evidence suggests that some cancer survivors experience cognitive difficulties following chemotherapy. However, perceived or subjective cognitive impairment is more frequently reported than prevalence revealed by objective assessments. The aim of this review was to examine the relationship between subjective and objective measures of cognitive impairment following treatment for cancer and to determine the number of studies that found a significant relationship between these measures of cognition. A comprehensive search for articles, published between 1980 and 2012, comparing subjective and objective cognition in cancer patients treated with chemotherapy was conducted. Of 818 potentially relevant articles, 23 studies met the inclusion criteria for the current review and one article was sourced from reference lists of included studies. Only eight of 24 included studies found a significant relationship between objective and subjective measures of cognitive performance. These studies were more likely to involve breast cancer patients and to assess the relationship between memory and perceived cognitive impairment. The failure to consistently find an association between subjective and objective measures of cognition could be explained by variations in assessment methods or the definition of impairment. Alternatively, objective and perceived cognitive impairment may be unrelated because perceived impairment may be an indicator of psychological distress rather than cognitive impairment. Despite these discrepancies, patients' perceptions of impairment are important due to its significant impact on quality of life. Further research is required to explore whether objective measures of everyday functioning better predict the impact of chemotherapy related cognitive impairment on daily functioning.     

Gray matter reduction associated with systemic chemotherapy for breast cancer: a prospective MRI study

Brain gray matter alterations have been reported in cross-sectional magnetic resonance imaging (MRI) studies of breast cancer patients after cancer treatment. Here we report the first prospective MRI study of women undergoing treatment for breast cancer, with or without chemotherapy, as well as healthy controls. We hypothesized that chemotherapy-associated changes in gray matter density would be detectable 1 month after treatment, with partial recovery 1 year later. Participants included breast cancer patients treated with (CTx+, N = 17) or without (CTx−, N = 12) chemotherapy and matched healthy controls (N = 18). MRI scans were acquired at baseline (after surgery but before radiation, chemotherapy, and/or anti-estrogen treatment), 1 month after completion of chemotherapy (M1), and 1 year later (Y1). Voxel-based morphometry (VBM) was used to evaluate gray matter density differences between groups and over time. There were no between-group gray matter differences at baseline. Group-by-time interactions showed declines from baseline to M1 in both cancer groups relative to controls. Within-group analyses indicated that at M1 relative to baseline the CTx+ group had decreased gray matter density in bilateral frontal, temporal, and cerebellar regions and right thalamus. Recovery was seen at Y1 in some regions, although persistent decreases were also apparent. No significant within-group changes were found in the CTx− or control groups. Findings were not attributable to recency of cancer surgery, disease stage, psychiatric symptoms, psychotropic medication use, or hormonal treatment status. This study is the first to use a prospective, longitudinal approach to document decreased brain gray matter density shortly after breast cancer chemotherapy and its course of recovery over time. These gray matter alterations appear primarily related to the effects of chemotherapy, rather than solely reflecting host factors, the cancer disease process, or effects of other cancer treatments.