Breast cancer survival and incidence of second primary cancers after 30 years in a randomized study of two versus five years of adjuvant tamoxifen therapy.

Background: Tamoxifen is an established treatment for breast cancer, but its long-term effects on survival and on secondary cancers are not fully evaluated.

Material And Methods: We studied 30 years outcome of 4124 postmenopausal patients who were randomized to receive (totally) two or five years of adjuvant tamoxifen.

Results: After 5 years of follow-up, when tamoxifen treatment was finished in both groups, until 15 years of follow-up, overall mortality (HR 0.

Content analysis of Journal of Genetic Counseling research articles: A multi-year perspective.

Content analyses of published papers in journals inform readers, editors, and members of the profession about historical publication patterns and how the journal has represented the field. This study is a content analysis of original research papers published in the Journal of Genetic Counseling from January 2011 through December 2017. This is the first study of its kind for the flagship journal of the National Society of Genetic Counseling.

Financial hardship after traumatic brain injury: a brief scale for family caregivers.

Objective: Financial hardship is frequently posited as a significant factor influencing family health and adjustment after brain injury, though traditional methods of measurement have shown limited usefulness. The purpose of this study was to adapt and test the utility of a brief scale of financial hardship (BSFH-BI) for use with family caregivers after TBI.

Methods: The researchers constructed the BSFH-BI using financial well-being items adapted from three survey instruments.

Intratumorally injected pro-inflammatory allogeneic dendritic cells as immune enhancers: a first-in-human study in unfavourable risk patients with metastatic renal cell carcinoma.

Background: Accumulating pre-clinical data indicate that the efficient induction of antigen-specific cytotoxic CD8+ T cells characterizing viral infections is caused by cross-priming where initially infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected bystander DCs. Our DC-based immunotherapy concept is guided by such bystander view and accordingly, we have developed a cellular adjuvant consisting of pre-activated allogeneic DCs producing high levels of DC-recruiting and DC-activating factors. This concept doesn't require MHC-compatibility between injected cells and the patient and therefore introduces the possibility of using pre-produced and freeze-stored DCs from healthy blood donors as an off- the-shelf immune enhancer.

Long-term effects on the incidence of second primary cancers in a randomized trial of two and five years of adjuvant tamoxifen.

Background: Tamoxifen is a well established treatment for breast cancer, but its long-term effects on the incidence of secondary cancers are not fully evaluated.

Material And Methods: We have studied 4128 postmenopausal patients with early stage breast cancer who were alive and free of breast cancer recurrence after two years of tamoxifen, and who were randomized to receive totally two or five years of therapy.

Results: Compared to patients randomized to two years of tamoxifen the incidence of contralateral breast cancer [hazard ratio (HR) 0.

Allogeneic lymphocyte-licensed DCs expand T cells with improved antitumor activity and resistance to oxidative stress and immunosuppressive factors.

Adoptive T-cell therapy of cancer is a treatment strategy where T cells are isolated, activated, in some cases engineered, and expanded ex vivo before being reinfused to the patient. The most commonly used T-cell expansion methods are either anti-CD3/CD28 antibody beads or the "rapid expansion protocol" (REP), which utilizes OKT-3, interleukin (IL)-2, and irradiated allogeneic feeder cells. However, REP-expanded or bead-expanded T cells are sensitive to the harsh tumor microenvironment and often short-lived after reinfusion.

Effects of adjuvant tamoxifen therapy on cardiac disease: results from a randomized trial with long-term follow-up.

Tamoxifen is associated with a reduced risk of coronary heart disease (CHD). However, there are few reports on long-term effects. Using data from a large Swedish randomized trial of 5 and 2 years of adjuvant tamoxifen in women with early breast cancer, we here present results on morbidity and mortality from cardiac diseases during treatment and long-term after treatment.

The peptide AF-16 decreases high interstitial fluid pressure in solid tumors.

Background: The high interstitial fluid pressure (IFP) in solid tumors restricts the access to nutrients, oxygen and drugs.

Material And Methods: We investigated the ability of the peptide AF-16, involved in water and ion transfer through cell membranes, to lower the IFP in two different solid rat mammary tumors, one chemically induced, slowly growing, and the other transplantable, and rapidly progressing having high cellularity. AF-16 was administered either in the tumor capsule, intranasally or intravenously.

Time dependent effects of adjuvant tamoxifen therapy on cerebrovascular disease: results from a randomised trial.

Background: Tamoxifen has been associated with an increased risk of stroke. There is, however, little information on the effect in the post-treatment period. Using data from the Swedish Breast Cancer Group adjuvant trial of 5 vs 2 years of tamoxifen treatment, we now report both short-term and long-term effects on morbidity as well as mortality because of cerebrovascular disease.

BRCA1 gene mutations may explain more than 80% of excess number of ovarian cancer cases after breast cancer - a population based study from the Western Sweden Health Care region.

Aim: In a previous cohort study, we showed that there was a significant variation in the frequency of ovarian cancer after having breast cancer in Sweden, with the highest risk occuring in the Western region. The present study aimed to evaluate whether the high prevalence of the founder mutation BRCA1 3171ins5 may explain the excess number of ovarian cancer.

Method: Among more than 26 000 women with breast cancer in the Western Swedish Health Care Region, 159 cases were subsequently diagnosed with ovarian cancer, whereas the expected number was 96.

The role of the number of uninvolved lymph nodes in predicting locoregional recurrence in breast cancer.

Purpose: To identify groups of early breast cancer patients with substantial risk (10-year risk > 20%) for locoregional failure (LRF) who might benefit from postmastectomy radiotherapy (RT).

Patients And Methods: Prognostic factors for LRF were evaluated among 6,660 patients (2,588 node-negative patients, 4,072 node-positive patients) in International Breast Cancer Study Group Trials I to IX treated with chemotherapy and/or endocrine therapy, and observed for a median of 14 years. In total, 1,251 LRFs were detected.

Genome-wide linkage scan for breast cancer susceptibility loci in Swedish hereditary non-BRCA1/2 families: suggestive linkage to 10q23.32-q25.3.

The two breast cancer genes BRCA1 and BRCA2 were identified more than 10 years ago and, depending on population, mutations in these genes are responsible for a varying percentage of familial breast cancer. In more than half the families, the increased risk of breast cancer cannot be explained by mutations in these genes, and the goal of this study was to locate novel susceptibility genes. One of the main difficulties in identifying the cause of hereditary non-BRCA1/BRCA2 breast cancer is genetic heterogeneity, possibly due to multiple, incompletely penetrant susceptibility genes, along with ethnic and geographic differences.

Histopathological risk factors for ipsilateral breast events after breast conserving treatment for ductal carcinoma in situ of the breast--results from the Swedish randomised trial.

Aim: The primary aims were to study risk factors for an ipsilateral breast event (IBE) after sector resection for ductal carcinoma in situ of the breast (DCIS) in a trial comparing adjuvant radiotherapy to no therapy and to assess predictive factors for response to radiotherapy. Secondary aims were to analyse reproducibility of the histopathological evaluation and to estimate correctness of diagnosis in the trial.

Setting: A randomised trial in Sweden (the SweDCIS trial), including 1046 women with a median of 5.

Occurrence of both breast and ovarian cancer in a woman is a marker for the BRCA gene mutations: a population-based study from western Sweden.

Aim: This study aimed to analyze whether the occurrence of both breast and ovarian cancer in a woman serves as a marker for BRCA gene mutations.

Material And Methods: This population-based study included 256 women in western Sweden who developed both invasive breast and ovarian tumors between 1958 and 1999. Archival paraffin tissue blocks of their tumors were retrieved for DNA-extraction to analyze the founder mutation, BRCA1 c.

SweDCIS: Radiotherapy after sector resection for ductal carcinoma in situ of the breast. Results of a randomised trial in a population offered mammography screening.

We studied the effect of postoperative radiotherapy (RT) after breast sector resection for ductal carcinoma in situ (DCIS). The study protocol stipulated radical surgery but microscopically clear margins were not mandatory. We randomised 1,046 operated women to postoperative RT or control between 1987 and 1999.

Novel findings in Swedish patients with MYH-associated polyposis: mutation detection and clinical characterization.

Background & Aims: Biallelic mutations in the base-excision repair gene MYH have recently been associated with recessive inheritance of multiple colorectal adenomas. An investigation and characterization of MYH mutations in Swedish patients were therefore carried out.

Methods: A set of 15 unrelated adenomatous polyposis coli (APC)-mutation negative patients from the Swedish Polyposis Registry was screened for germline mutations in the MYH gene.

The direct pathway of human T-Cell allorecognition is not tolerized by stimulation with allogeneic peripheral blood mononuclear cells irradiated with high-dose ultraviolet B.

Transfusions of high-dose (> or =10,000 Joule/m(2)) ultraviolet-B (UVB)-irradiated allogeneic leukocytes in rodent models have been shown to induce immunologic tolerance that is mediated by allospecific regulatory CD4(+) T cells. Whether these regulatory T cells recognize alloantigens through the direct or indirect pathway of allorecognition is controversial. Here, we demonstrate that the proliferative response obtained in standard primary mixed leukocyte reactions (MLRs) with human peripheral blood mononuclear cells (PBMCs) reflected a CD4(+) T-cell-dependent direct pathway of allorecognition and that high-dose UVB irradiation of PBMCs totally inhibited their capacity to induce a proliferative alloresponse.

Coronary heart disease mortality after 5 years of adjuvant tamoxifen therapy: results from a randomized trial.

From January 1, 1983, through December 31, 1992, a total of 4610 patients entered a randomized trial that compared mortality among patients receiving 2 years of adjuvant tamoxifen therapy with that in patients receiving 5 years of adjuvant tamoxifen therapy, 4175 of whom were recurrence free after 2 years of tamoxifen therapy. Among the 2046 patients randomly assigned to the 5-year group all-cause mortality, breast cancer-specific mortality, and the incidence of contralateral breast cancer were reduced, compared with those among 2129 patients randomized in the 2-year group, but the incidence of endometrial cancer was increased. In addition, mortality from coronary heart disease was statistically significantly reduced in the 5-year group, compared with that in the 2-year group (hazard ratio = 0.

Direct allorecognition promotes activation of bystander dendritic cells and licenses them for Th1 priming: a functional link between direct and indirect allosensitization.

T-cell sensitization to indirectly presented alloantigens (indirect pathway of allorecognition) plays a critical role in chronic rejection. The usual very efficient priming of such self-restricted, T helper type 1 (Th1)-deviated CD4+ T cells obviously conflicts with the fact that allogeneic MHC molecules are poorly immunogenic per se. The aim of the present study is to elucidate whether direct allosensitization induces production of inflammatory mediators that may affect recruitment and activation of immature bystander (host) dendritic cells (DC).

Fatigue, psychological distress, coping and quality of life in patients with uterine cancer.

Background: Cancer-related fatigue (CRF) is a subjectively experienced symptom that is multidimensional and multifactorial. Patients with cancer have identified fatigue as one of the major troubling symptoms and the primary cause of distress in their lives.

Aims: The major aim of the study was to examine how patients diagnosed with uterine cancer describe their experience of fatigue, psychological distress, coping resources and quality of life.

A systematic overview of radiation therapy effects in rectal cancer.

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for rectal cancer is based on data from 42 randomized trials and 3 meta-analyses.

Breast conservation surgery, with and without radiotherapy, in women with lymph node-negative breast cancer: a randomised clinical trial in a population with access to public mammography screening.

The effect of postoperative radiotherapy after sector resection for stage I-II lymph node-negative breast cancer was evaluated in a patient population with access to public mammographical screening. 1187 women were randomised to no further treatment or postoperative radiotherapy following a standardised sector resection and axillary dissection. Radiation was administered to a dose of 48-54 Gy.

Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII.

Purpose: To explore prognostic factors for locoregional failures (LRF) among women treated for invasive breast cancer within clinical trials of adjuvant therapies.

Patients And Methods: The study population consisted of 5,352 women who were treated with a modified radical mastectomy and enrolled in one of seven International Breast Cancer Study Group randomized trials. A total of 1,275 women with node-negative disease received either no adjuvant therapy or a single cycle of perioperative chemotherapy, and 4,077 women with node-positive disease received adjuvant chemotherapy of at least 3 months' duration and/or tamoxifen.