Baseline psychosocial predictors of survival in localised breast cancer

Despite the large number of studies on the impact of psychosocial factors on breast cancer progression, there is no certainty about the contributing factors or processes involved. We investigated the relative impacts of socioeconomic, psychological, and psychosocial factors on survival in breast cancer. A consecutive sample of 102 patients (participation 82%) under 72 years of age with locoregional breast cancer completed validated questionnaires on coping with cancer, emotional expression (anger), perceived available support, noncancer life stresses, and quality of life 3-4 months after diagnosis. Survival times were measured from the date of diagnosis to the date of relapse and further to the date of death or date of last follow-up. Cumulative Cox regression analyses were carried out. After controlling for biological prognostic factors, age, and baseline treatment, longer survival was predicted by a long education and a minimising-related coping, while shorter survival was predicted by emotional defensiveness (antiemotionality), behavioural-escape coping, and a high level of perceived support. A shorter event-free time was also predicted by unemployment and depressive symptoms. Cancer survival is affected by a complex combination of psychosocial factors, among which minimising predicts a favourable prognosis and anger nonexpression and escape behaviour an unfavourable prognosis. Higher socioeconomic status is associated with longer survival. High scores in well-being scales may reflect emotional nonexpression.     

Vinorelbine plus trastuzumab combination as first-line therapy for HER 2-positive metastatic breast cancer patients: an international phase II trial

The aim of this international phase II trial was to determine the efficacy and safety profile of weekly vinorelbine plus trastuzumab as first-line chemotherapy for women with HER 2-overexpressing metastatic breast cancer. Sixty-nine patients with tumours overexpressing HER 2 received vinorelbine: 30 mg m-2 week-1 and trastuzumab: 4 mg kg-1 on day 1 as a loading dose followed by 2 mg kg-1 week-1 starting on day 8. Sixty-two patients were evaluable for response and 69 patients were evaluable for toxicity. The overall response rate was 62.9%. The median time to response was 8.4 weeks, the median duration of response was 17.5 months, the median progression-free survival was 9.9 months (95% CI, 5.6-12.1) and the one-year progression-free survival was 39.1%. The median survival for all patients was 23.7 months (95% CI, 18.4-32.6). This regimen was safe: grade 3-4 neutropenia were observed over 17.7% of courses in 83.8% of patients, with only two episodes of febrile neutropenia (0.1%) in two patients (2.9%). Only one patient discontinued treatment due to grade 3 symptomatic cardiac dysfunction that resolved with therapy. Vinorelbine plus trastuzumab is one of the most active treatment regimens for patients with HER 2-positive metastatic breast cancer and demonstrates a very favourable safety profile allowing prolonged treatment with long-term survival. This study has been presented in part at the following conferences: The San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 2003; The American Society of Clinical Oncology, Orlando, FL, USA, 2005.     

Decision making in terminal care: a survey of finnish doctors' treatment decisions in end-of-life scenarios involving a terminal cancer and a terminal dementia patient

GOALS: The physicians' decision-making process in terminal care is complex: medical, ethical, legal and psychological aspects are all involved, particularly in critical situations. Here, a study was made of the association of personal background factors with end-of-life decisions. METHODS: A questionnaire was sent to 300 surgeons, 300 internists, 500 health centre practitioners (GPs) and all 82 Finnish oncologists. The response rate was 62%. Two scenarios were presented: one involving a terminal cancer patient, the other a dementia patient. Sociodemographic factors, general life values and attitudes related to end-of-life care were asked. MAIN RESULTS: In the cancer case (Scenario 1) 17%, and in the dementia case (Scenario 2) 43% of all the respondents chose active treatment. In a logistic regression analysis of treatment decisions in Scenario 1, physician's age, specialty, marital status and attitudes to assisted suicide and withdrawal of life-sustaining treatment (LST) entered the model. In Scenario 2, the variables were physician's age, physician's own experience of severe disease in the family, attitude to withdrawal of LST and opinion of advanced directives. CONCLUSIONS: Doctors' end-of-life decisions vary widely according to personal background factors. The findings underline the importance of advance communication, making these decisions in accordance with the patient's wishes.     

Correlation of embryonic development and adult neoplastic changes of human prostate

We have studied embryonic and fetal differentiation of the human prostate in relation to androgen-producing Leydig cell differentiation. We have studied the differentiation of human prostatic glands and the synthesis of acid phosphatase in vivo and in vitro. These studies have shown that the mesenchyme at the level of the openings of the para- and mesonephric ducts to the urethra was the local initiator of prostatic differentiation. All prostatic acini developed by epithelial outgrowths from the urethral epithelium. None of them grew from para- or mesonephric ducts. However, the epithelium on the colliculus seminalis differed from the rest of the urethral epithelium morphologically and in acid phosphatase content. Androgens accelerated differentiation in vitro and acid phosphatase activity was shown to be present in prostatic urethral epithelium and prostatic acini both in vivo and in vitro. According to these studies embryonic differentiation gives no direct answer to the localisation of adult neoplastic changes in different parts of the prostate, although in the posterior part there might be a mixture of cells from ductal and urethral epithelium. Secretion of acid phosphatase seems to be a constitutional phenomenon of this part of epithelium and is partly regulated by androgens. Epitheliomesenchymal interaction is important in differentiation and the role of this interaction in adult diseases might be valuable to be studied.     

Cancer-specific social support received by newly diagnosed cancer patients: validating the new Structural-Functional Social Support Scale (SFSS) measurement tool

GOALS OF WORK: To investigate potentially health-enhancing domains of cancer patients' social relationships we evaluated various dimensions of social support as experienced in early cancer. PATIENTS AND METHODS: In consecutive samples of 72 melanoma and 103 breast cancer patients diagnosed 3-4 months earlier, we evaluated the cancer-specific social network and received social support by the Structural-Functional Social Support Scale (SFSS) validated within the study. In addition, social support was measured by the MOS Social Support Survey as perceived support, and by Seeking Social Support items from the Ways of Coping Questionnaire as coping activity. SFSS measures the number of people who have been aware of the patient's cancer and the amount of social support the patients have received from them. MAIN RESULTS: A large number of people from various potential support-providing sources had been aware of the patients' cancer, and the patients had received support through these interactions. A greater number of support providers did not mean an increase in the support received. Social support was distinguished into subgroups according to its source, but the division into functional support types was weak. Support assessed as perceived support or as a coping activity did not cover the received disease-specific support of several sources. CONCLUSIONS: With the SFSS, it was possible to obtain detailed information on the disease-specific social network and social support. It may be beneficial to distinguish support according to the sources and to also measure support beyond the closest relationships. We hope that our measure and the results obtained will assist in identifying the targets for psychosocial interventions.     

Attitudes to terminal patients’ unorthodox therapy: Finnish doctors’ responses to a case scenario

We carried out a postal survey of a sample of Finnish doctors (n=1182) concerning their attitudes and ethical decisions in end-of-life care. A scenario was presented in which a patient with terminal cancer wished to obtain unorthodox treatment. Factors possibly influencing decision making such as general attitudes, life values and demographics were investigated. The response rate was 62%. The patients plan to use unorthodox treatment was accepted by 54% of doctors. Gender or speciality did not influence the decision, but doctors age was a significant factor (P=0.0005). Doctors aged 35–49 years were more accepting; younger and older ones less accepting. Doctors who had clinical experience in terminal care were more compliant to the patients plan (P=0.034). A stepwise logistic regression analysis was used to create a model for explaining not accepting versus accepting the treatment with the background variables. Altogether eight independent significant variables were included in the final model of explaining a doctors choice in the presented scenario. According to the model the patients wish was more frequently accepted if the doctor was middle-aged, had clinical experience in terminal care, valued a high standard of living, considered terminal care satisfying, was less critical of health economics, considered advance directives helpful, had a high fear-of-death index score, and valued professional status less.     

Hormonal treatment of advanced breast cancer. A randomized trial of tamoxifen versus nandrolone decanoate

The response to tamoxifen (TAM) (10 mg to 20 mg twice orally) was compared with the response to nandrolone decanoate (NAN) (50 mg every second week or 100 mg every third week intramuscularly) in this randomized study in previously untreated women with advanced breast cancer. Patients were postmenopausal or postmenopause was induced with irradiation therapy. The two treatment groups were highly similar in different patient characteristics. Of 67 evaluable patients treated with TAM, ten (15%) had a complete or partial remission, 28 (42%) had stabilized disease and 29 (43%) had progressive disease. In the 60 patients treated with NAN, the figures were ten (17%), 22 (37%) and 28 (47%) respectively. The response rates did not differ significantly. Tam was as good as NAN in osseous metastases. Four of 34 patients responded to TAM and three of 38 patients responded to NAN. NAN had a tendency for better response in the treatment of visceral metastases. Six (43%) of 14 patients responded to NAN while only three (14%) of 21 responded to TAM (P = 0.11). The median duration of remission was 24 months in the TAM arm and 17 months in NAN (insignificant). As second line treatment, NAN after TAM gave one complete remission and three partial remissions, but none responded to TAM after NAN. The side-effects of both drugs were rare and mild. These data indicate that TAM and NAN are comparable in the treatment of advanced breast cancer.     

Regulated expression of the inhibitory receptor LAIR-1 on human peripheral T cells during T cell activation and differentiation

The leukocyte-associated Ig-like receptor-1 (LAIR-1) is capable of inhibiting immune cell function through interaction with collagens. LAIR is expressed on the majority of peripheral blood mononuclear cells. The abundant expression of both receptor and ligand calls for regulatory mechanisms to relieve the continuous interaction between collagens and LAIR-1. This regulation may occur at the expression level of the receptor. Here, we report that LAIR-1 is indeed differentially expressed during human T cell differentiation. Naive CD4(+) and CD8(+) T cells as well as CD8(+) T cells of the effector phenotype express higher levels of LAIR-1 compared to memory T cells. In vitro stimulation revealed a decrease in LAIR-1 expression upon activation, and the lower LAIR-1 expression on CD127(-) T cells suggests that activation-induced down-modulation of LAIR-1 may also occur in vivo. Furthermore, crosslinking of LAIR-1 on primary T cells results in an inhibition of T cell function. Our data suggest that regulated expression of LAIR-1 and the subsequent change in the threshold for activation may be a mechanism to modulate inhibition of the immune system.