Chemotherapy and Post-traumatic Stress in the Causation of Cognitive Dysfunction in Breast Cancer Patients.

Background: Cancer-related cognitive dysfunction has mostly been attributed to chemotherapy; this explanation, however, fails to account for cognitive dysfunction observed in chemotherapy-naïve patients. In a controlled, longitudinal, multisite study, we tested the hypothesis that cognitive function in breast cancer patients is affected by cancer-related post-traumatic stress. Methods: Newly diagnosed breast cancer patients and healthy control subjects, age 65 or younger, underwent three assessments within one year, including paper-and-pencil and computerized neuropsychological tests, clinical diagnostics of post-traumatic stress disorder (PTSD), and self-reported cognitive function. Analysis of variance was used to compare three groups of participants-patients who did or did not receive chemotherapy and healthy control subjects-on age- and education-corrected cognitive performance and cognitive change. Differences that were statistically significant after correction for false discovery rate were investigated with linear mixed-effects models and mediation models. All statistical tests were two-sided. Results: Of 226 participants (166 patients and 60 control subjects), 206 completed all assessment sessions (attrition: 8.8%). Patients demonstrated overall cognitive decline (group*time effect on composite z -score: -0.13, P = .04) and scored consistently worse on Go/Nogo errors. The latter effect was mediated by PTSD symptoms (mediation effect: B = 0.15, 95% confidence interval = 0.02 to 0.38). Only chemotherapy patients showed declined reaction time on a computerized alertness test. Overall cognitive performance correlated with self-reported cognitive problems at one year ( T = -0.11, P = .02). Conclusions: Largely irrespective of chemotherapy, breast cancer patients may encounter very subtle cognitive dysfunction, part of which is mediated by cancer-related post-traumatic stress. Further factors other than treatment side effects remain to be investigated.

Oxytocin course over pregnancy and postpartum period and the association with postpartum depressive symptoms.

During the postpartum period, women are at higher risk of developing a mental disorder such as postpartum depression (PPD), a disorder that associates with mother-infant bonding and child development. Oxytocin is considered to play a key role in mother-infant bonding and social interactions and altered oxytocin plasma concentrations were found to be associated with PPD. In the present study, we evaluated oxytocin plasma levels and depressive symptoms during pregnancy and the postpartum period in healthy women. We evaluated 100 women twice during pregnancy (weeks 35 and 38) and three times in the postpartum period (within 2 days and 7 weeks and 6 months after delivery) by measuring oxytocin plasma levels with enzyme-linked immunosorbent assay (ELISA) and assessing depressive symptoms with the Montgomery-Asberg Depression Rating Scale. Oxytocin plasma levels significantly increased from the 35th week of gestation to 6 months postpartum in all women. However, levels decreased from the 38th week of gestation to 2 days after delivery in participants with postpartum depressive symptoms, whereas they continuously increased in the group without postpartum depressive symptoms; the difference between the course of oxytocin levels in the two groups was significant (Δt2-t3: t = 2.14; p = 0.036*). Previous depressive episodes and breastfeeding problems predicted postpartum depressive symptoms. Our results indicate that alterations in the oxytocin system during pregnancy might be specific for women who develop postpartum depressive symptoms. Future studies should investigate whether oxytocin plasma levels might have predictive value in women at high risk for PPD.

Short term quality of life with epirubicin-fluorouracil-cyclophosphamid (FEC) and sequential epirubicin/cyclophosphamid-docetaxel (EC-DOC) chemotherapy in patients with primary breast cancer - Results from the prospective multi-center randomized ADEBAR trial.

BACKGROUND: The recommendation for adjuvant dose-dense chemotherapy in high risk primary breast cancer is heterogeneous among guidelines. Understanding the impact on QoL is thereby a crucial factor, especially if the benefit is potentially low. This study aims to assess QoL as a secondary outcome in the prospective randomized multi-center ADEBAR trial. METHODS: QoL was assessed at baseline (t1), before cycle 4 FEC and cycle 5 EC-DOC (t2), 4 weeks after chemotherapy (t3) and 6 weeks after radiation (t4) using the European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) and the Breast Cancer-Specific Module (QLQ-BR23). RESULTS: 1306 patients were enrolled into the ADEBAR trial. 675 were assigned to the FEC and 688 to the EC-DOC arm. After the beginning of treatment, global QoL dropped in both arm by 3-4 points. In the EC-DOC arm, QoL dropped further at t3 by 7 points and stayed stable in the FEC arm. 6 weeks after radiation, QoL exceeded baseline in both arms by 6-8 points. The differences between treatment arms were strongest at t3 (53.0 vs. 49.5) but did not reach clinical relevance at any point in time. Physical functioning, nausea and vomiting, fatigue and systemic therapy side effects followed with some minor exceptions similar patterns but showed higher amplitudes. CONCLUSION: In conclusion, we could not detect a clinically relevant difference between the two treatment arms in global QoL, although the results consistently show that patients on EC-DOC report worse scores during the treatment.

Elucidating pretreatment cognitive impairment in breast cancer patients: the impact of cancer-related post-traumatic stress.

BACKGROUND: Pretreatment cognitive impairment in cancer patients is well established but unexplained. Similar cognitive compromise has been observed in post-traumatic stress disorder (PTSD) patients, and PTSD symptoms are a frequent concomitant of cancer diagnosis. We tested the hypothesis that pretreatment cognitive impairment is attributable to cancer-related post-traumatic stress. METHODS: Women aged 65 years or younger who were diagnosed with breast cancer (case patients) or had undergone negative routine breast imaging (control patients) at one of six participating breast centers underwent traditional and computerized neuropsychological testing, clinician-administered diagnostic assessment of stress disorders, and self-report assessments of cognitive function and depression. To minimize confounding, case patients were evaluated prior to any local or systemic treatment. Cognitive indices of case patients, control patients, and normative samples were compared. The patients' risk of overall cognitive impairment was determined. Linear regression and a mediation model were used to test the study hypothesis. All statistical tests were two-sided. RESULTS: The 166 case patients and 60 well-matched control patients showed near-identical deviations from population norms. Case patients scored worse than control patients on two of 20 cognitive indices (Go/Nogo commission errors, Go/Nogo omission errors). Self-reported cognitive problems were associated with Go/Nogo omission errors and more pronounced in case patients. Only PTSD symptoms (Beta = 0.27, P = .004) and age (Beta = 0.22, P = .04) statistically significantly predicted Go/Nogo errors. The effect of having cancer on Go/Nogo errors was mediated by PTSD symptoms. Case patients did not have an increased risk of overall cognitive impairment. CONCLUSION: Prior to any treatment, breast cancer patients may show limited cognitive impairment that is apparently largely caused by cancer-related post-traumatic stress.

Brief Distress Screening in Clinical Practice: Does it Help to Effectively Allocate Psycho-Oncological Support to Female Cancer Inpatients?

BACKGROUND: The usefulness of distress screening in cancer inpatient settings has rarely been investigated. This study evaluated a brief distress screening of inpatients in a breast cancer centre and a gynaecological cancer centre. PATIENTS AND METHODS: Hospitalised patients with breast or gynaecological cancers were screened with the Distress Thermometer. Patients who scored above the cut-off, were referred by the medical staff, or self-referred were offered bedside psycho-oncological counselling. RESULTS: Of 125 patients, 68 (54.4%) received an offer of counselling, and 62 patients (49.6%) accepted. Most of the counselling was induced by distress screening. Only 4 (3.2%) patients self-referred to the counselling service. Of the counselled patients, 65.8% stated that they had substantially benefited from psycho-oncological support; only 5.6% of the non-counselled patients indicated that they might have benefited from psycho-oncological support. CONCLUSION: Almost all patients who will accept and benefit from psycho-oncological counselling can be identified if distress screening is used in conjunction with referrals by physicians and nurses. Distress screening is a worthwhile component in a framework of psycho-oncological support in a cancer inpatient setting. It paves the way to counselling for cancer inpatients who need it and are willing to accept it but hesitate to self-refer to psycho-oncological services.

Prenatal immunologic predictors of postpartum depressive symptoms: a prospective study for potential diagnostic markers.

In postpartum depression (PPD), immunologic changes have been proposed to be involved in the disease pathology. The study evaluates the regulation of the innate and adaptive immune response over the course of late pregnancy and postpartum period and their association with the development of postpartum depressive symptoms. Furthermore, prenatal immunologic markers for a PPD were investigated. Hundred pregnant women were included. At 34th and 38th week of pregnancy as well as 2 days, 7 weeks and 6 months postpartum, immune parameters (neopterin, regulatory T cells, CXCR1, CCR2, MNP1 and CD11a) were measured by flow cytometry/ELISA, and the psychopathology was evaluated. We found that regulatory T cells were significantly increased prenatal (p=0.011) and postnatal (p=0.01) in mothers with postnatal depressive symptoms. The decrease in CXCR 1 after delivery was significantly higher in mother with postnatal depressive symptoms (p=0.032). Mothers with postnatal depressive symptoms showed already prenatal significantly elevated neopterin levels (p=0.049). Finally, regulatory T cells in pregnancy strongly predict postnatal depressive symptoms (p=0.004). The present study revealed that prenatal and postnatal immunologic parameters are associated with postpartum depressive symptoms in mothers. In addition, we found immune markers that could eventually be the base for a biomarker set that predicts postnatal depressive symptoms already during pregnancy.

The effect of including a 'psychooncological statement' in the discharge summary on patient-physician communication: a randomized controlled trial.

OBJECTIVE: The objective of this study is to determine whether the inclusion of a 'psychooncological statement' (PO-statement) in the discharge summary enhances patient-physician communication about psychosocial issues across the inpatient and outpatient sector. METHODS: A total of 1416 cancer patients were randomly assigned to the intervention (with PO-statement in the discharge summary) or control group (discharge summary without PO-statement). Shortly before discharge from the hospital (T1), patients from the intervention group were screened for psychosocial distress. Based on the electronic clinical documentation system, screening results were subsequently integrated into the discharge summary, which automatically generated a PO-statement. To determine the effect of the PO-statement, patients as well as their primary care physicians (n = 596) were asked during follow-up care (T2) whether psychosocial distress was discussed during the last consultation. RESULTS: Including a PO-statement in the discharge summary did not result in more frequent discussions about psychosocial issues compared with the control group from the patients' and physicians' perspectives. Instead, discussions about psychosocial well-being were significantly associated with women of the patient (p = <0.001) and the physician (p = 0.011), medical discipline (gynecologists; p = 0.002), cancer diagnosis (gynecological cancer; p = 0.002), metastases (p = <0.001), professional training of patients (none, p = 0.026), and psychosocial qualification of physicians (p = 0.018). CONCLUSION: Written information on psychosocial distress in the discharge summary alone does not affect communication.

Quality of life, anxiety, and oncological factors: a follow-up study of breast cancer patients.

BACKGROUND: The number of long-term survivors of breast cancer has increased over recent decades because of many treatment advances. Thus, long-term quality of life (QoL) and factors affecting it are of growing research interest. OBJECTIVE: The authors investigated longitudinal changes in QoL and anxiety in breast cancer patients and differences in QoL and anxiety in various oncological subgroups. METHOD: A group of 236 women with a primary diagnosis of breast cancer or carcinoma in-situ completed questionnaires after surgical treatment, 6 months, and 12 months post-surgery. RESULTS: QoL scores of breast cancer patients improved over time, but impairments in terms of anxiety, body image, and sexual functioning were still observed. Younger patients were more likely to be distressed by cancer diagnosis and treatment. DISCUSSION: Surgical modality and tumor prognostic factors, however, seemed to play a minor role in patients' subjective QoL, which is discussed in terms of the "well-being paradox."

Personality traits and psychosocial stress: quality of life over 2 years following breast cancer diagnosis and psychological impact factors.

OBJECTIVE: The aim of this study was to investigate changes in the quality of life (QoL) and body image among breast cancer patients over 2 years and to examine different predictive factors for QoL 2 years after the primary operation. METHODS: A total of 203 women with a primary diagnosis of breast cancer completed the questionnaires 2 weeks and 6, 12, 18, and 24 months after surgery. Quality of Life Questionnaire (QLQ-C30), Breast Cancer Specific Quality of Life Questionnaire Module (QLQ-BR23), Questionnaire on Stress in Cancer Patients (QSC-R23), Freiburg Personality Inventory (FPI-R), Life Orientation Test (LOT) were used as standardized measures. RESULTS: The overall QoL and most functional and symptom scales improved during the 2-year period. However, cognitive functioning, body image, and the three symptom scales of insomnia, constipation, and diarrhea did not change. Age was only capable of predicting physical functioning, whereas tumor size, axillary surgery, and adjuvant chemotherapy were not predictive of the long-term QoL functional scores. Initial distress was the most potent predictive factor for long-term QoL. Baseline functioning predicted functional QoL scores 2 years later. And higher scores for neuroticism were associated with a poorer QoL. However, optimism was not capable of predicting the QoL 2 years later. CONCLUSION: Screening measures should be implemented at the time when breast cancer is diagnosed, in order to identify psychologically vulnerable patients and offer them professional psycho-oncological help.