Minimal impact of adjuvant exemestane or tamoxifen treatment on mammographic breast density in postmenopausal breast cancer patients: a Dutch TEAM trial analysis.

Background: Mammographic breast density is one of the strongest independent risk factors for developing breast cancer. We examined the effect of exemestane and tamoxifen on breast density in Dutch postmenopausal early breast cancer patients participating in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.

Material And Methods: Analogue mammograms of selected TEAM participants before start, and after one and two (and if available after three) years of adjuvant endocrine therapy were collected centrally and reviewed.

Effects of tamoxifen and exemestane on cognitive functioning of postmenopausal patients with breast cancer: results from the neuropsychological side study of the tamoxifen and exemestane adjuvant multinational trial.

Purpose: To evaluate the influence of adjuvant tamoxifen and exemestane on cognitive functioning in postmenopausal patients with breast cancer (BC).

Patients And Methods: Neuropsychological assessments were performed before the start (T1) and after 1 year of adjuvant endocrine treatment (T2) in Dutch postmenopausal patients with BC, who did not receive chemotherapy. Patients participated in the international Tamoxifen and Exemestane Adjuvant Multinational trial, a prospective randomized study investigating tamoxifen versus exemestane as adjuvant therapy for hormone-sensitive BC.

The impact of different definitions and reference groups on the prevalence of cognitive impairment: a study in postmenopausal breast cancer patients before the start of adjuvant systemic therapy.

Objective: Several prospective studies into the effects of adjuvant systemic therapy on cognitive functioning suggest that a proportion of breast cancer patients show cognitive deficits already before the start of systemic therapy. Owing to, among others, methodological inconsistency, studies report different rates of this pre-treatment cognitive impairment. We examined the impact of four different criteria of cognitive impairment and two types of reference groups (a study-specific healthy reference group versus published normative data) on the prevalence of cognitive impairment.

Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group.

Purpose: This phase III randomized open-label clinical trial was designed to evaluate the efficacy and safety of the steroidal aromatase inactivator exemestane versus the antiestrogen tamoxifen as first-line treatment for metastatic breast cancer (MBC) in postmenopausal women.

Patients And Methods: The study was conducted at 81 centers and enrolled postmenopausal patients with measurable hormone-sensitive metastatic or locally advanced breast cancer. Prior adjuvant chemotherapy and/or tamoxifen were allowed.

Neuropsychological functioning in postmenopausal breast cancer patients treated with tamoxifen or exemestane after AC-chemotherapy: cross-sectional findings from the neuropsychological TEAM-side study.

Background: Previous studies have indicated that a subset of cancer patients treated with chemotherapy show cognitive deficits and/or experience cognitive complaints, whereas literature about the influence of hormonal therapies on cognition is sparse. Because of the accumulating knowledge about the importance of estrogen for cognitive functioning, there is growing concern about adjuvant hormonal therapy for breast cancer (BC) affecting cognition. We examined the cognitive functioning of postmenopausal BC patients who were, following doxorubicin/cyclophosphamide (AC) chemotherapy, randomized to tamoxifen or exemestane, and compared their performance with that of non-cancer controls.

Stage IV epithelial ovarian carcinoma in an 18 year old patient presenting with a Sister Mary Joseph's nodule and metastasis in both breasts: a case report and review of the literature.

Background: The most frequent ovarian malignancy in mature women is of epithelial origin. In children and adolescents, it is very rare, and in such cases it mostly concerns tumors of low malignant potential or low stage I tumors.

Case: We describe an 18-year-old girl presenting with umbilical metastasis as a first sign of an extremely aggressive stage IV ovarian serous papillary adenocarcinoma without an objective response to chemotherapy and endocrine therapy.

The prognostic value of proliferation in lymph-node-negative breast cancer patients is age dependent.

In lymph-node-negative invasive breast cancer patients<55 years, the proliferation marker mitotic activity index (MAI) has previously been shown to be the strongest prognosticator. In studies without age definition, MAI was not strongly prognostic. We investigated the age dependency of the prognostic value of proliferation for distant metastasis-free (MFS) and overall cancer-related survival (OS) in 1004 histologically diagnosed T1-3N0M0 invasive breast cancers (n=516, <55 years; n=322, 55-70 years; n=166, >70 years) without systemic adjuvant therapy and long follow-up (median: 108 months).

Risk factors for non-sentinel lymph node metastases in patients with breast cancer. The outcome of a multi-institutional study.

Background: In this multi-institutional prospective study, we evaluated whether we could identify risk factors predictive for non-sentinel lymph node (non-SN) metastases in breast cancer patients with a positive sentinel lymph node (SN).

Methods: In this multi-institutional study, 541 eligible breast cancer patients were included prospectively.

Results: The occurrence of non-SN metastases was related to the size of the SN metastasis (P = .

Multicenter validation of a gene expression-based prognostic signature in lymph node-negative primary breast cancer.

Purpose: We previously identified in a single-center study a 76-gene prognostic signature for lymph node-negative (LNN) breast cancer patients. The aim of this study was to validate this gene signature in an independent more diverse population of LNN patients from multiple institutions.

Patients And Methods: Using custom-designed DNA chips we analyzed the expression of the 76 genes in RNA of frozen tumor samples from 180 LNN patients who did not receive adjuvant systemic treatment.

Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy: a longitudinal study.

Purpose: Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients.

Patients And Methods: Eight hundred eighty-five patients were randomly assigned between two chemotherapy regimens both followed by radiotherapy and tamoxifen. Fatigue was assessed using vitality scale (score < or = 46 defined as fatigue), poor mental health using mental health scale (score < or = 56 defined as poor mental health) both of Short-Form 36, muscle and joint pain with Rotterdam Symptom Checklist, and Hb levels were assessed before and 1, 2, and 3 years after chemotherapy.

Prospective multicenter validation of the independent prognostic value of the mitotic activity index in lymph node-negative breast cancer patients younger than 55 years.

Purpose: To validate the independent strong prognostic value of mitotic activity index (MAI) in lymph node (LN) -negative invasive breast cancer patients younger than 55 years in a nationwide multicenter prospective study.

Patients And Methods: Analysis of routinely assessed MAI and other prognosticators in 516 patients (median follow-up, 118 months; range, 8 to 185 months), without systemic adjuvant therapy or previous malignancies.

Results: Distant metastases occurred in 127 patients (24.

Survivin is an independent prognostic marker for risk stratification of breast cancer patients.

Background: Results in previous qualitative studies of the association of the apoptosis inhibitor survivin with prognosis of breast cancer patients have been contradictory.

Methods: Survivin mRNA was measured by quantitative TaqMan reverse transcription-PCR in 275 breast cancer tissues from patients with operable tumors and was correlated with established clinicopathologic factors, relapse-free survival [(RFS); 102 events], and overall survival [(OS); 81 events].

Results: High survivin mRNA concentrations were found mainly in tissues from younger patients and in high-grade cancer tissues.

Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition.

Background: The value of regular surveillance for breast cancer in women with a genetic or familial predisposition to breast cancer is currently unproven. We compared the efficacy of magnetic resonance imaging (MRI) with that of mammography for screening in this group of high-risk women.

Methods: Women who had a cumulative lifetime risk of breast cancer of 15 percent or more were screened every six months with a clinical breast examination and once a year by mammography and MRI, with independent readings.

Complex of urokinase-type plasminogen activator with its type 1 inhibitor predicts poor outcome in 576 patients with lymph node-negative breast carcinoma.

Background: The ability of a solid tumor to grow and metastasize has a significant dependence on protease systems, such as the plasminogen activation system. The plasminogen activation system includes the urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1), among other molecules. Both uPA and PAI-1 are established prognostic factors for patients with breast carcinoma.

Predicting early failure after adjuvant chemotherapy in high-risk breast cancer patients with extensive lymph node involvement.

Purpose: There is limited knowledge of risk factors for breast cancer recurrence within 2 years. This study aimed to predict early failure and identify high-risk patients for prognostic and therapeutic purposes.

Experimental Design: We studied 739 patients from a randomized trial who were <56 years of age and had >/=4 or more positive lymph nodes, no distant metastases, and no previous other malignancies.

Tissue inhibitors of metalloproteinase expression in human breast cancer: TIMP-3 is associated with adjuvant endocrine therapy success.

Tissue inhibitors of matrix metalloproteinase (TIMPs) may be involved in tumour growth, apoptosis, angiogenesis, invasion, and the development of metastases. This study has evaluated the association of the expression levels of the TIMP forms 1, 2, 3, and 4, measured by quantitative real-time RT-PCR, with classical clinicopathological characteristics, ie age, menopausal status, tumour size, histological grade, number of involved lymph nodes, and steroid hormone receptor status, and with disease progression and treatment sensitivity in 273 breast cancer patients. The mRNA levels of TIMP-1 and TIMP-2 were not associated with any known clinicopathological tumour feature.

The complex between urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-I) independently predicts response to first-line endocrine therapy in advanced breast cancer.

It has been shown that urokinase-type plasminogen activator (uPA) and its main inhibitor (PAI-I) have predictive value for therapy success in advanced breast cancer. Levels of the complex between uPA and PAI-I, formed when both molecules are in their active form, might have superior predictive power. Here, we investigate the association between levels of uPA:PAI-I complex and rate of response to first-line systemic therapy for advanced breast cancer.

Mammaglobin is associated with low-grade, steroid receptor-positive breast tumors from postmenopausal patients, and has independent prognostic value for relapse-free survival time.

Purpose: The tumor mRNA expression levels of mammaglobin, a novel breast-specific and breast cancer-associated marker, were correlated with disease outcome in 280 patients with primary breast cancer.

Patients And Methods: Mammaglobin expression levels were assessed by quantitative reverse transcriptase polymerase chain reaction in frozen tumor tissue from breast cancer patients with a median age of 60 years (range, 30 to 88 years) and a median follow-up of 85 months (range, 2 to 169 months).

Results: High expression levels were associated with low-grade tumors (P =.

Predictive impact of urokinase-type plasminogen activator: plasminogen activator inhibitor type-1 complex on the efficacy of adjuvant systemic therapy in primary breast cancer.

One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system. This system comprises of, among others, the urokinase-type plasminogen activator (uPA) and its main inhibitor (PAI-1). In this study we investigated whether the uPA:PAI-1 complex is associated with the responsiveness of patients with primary breast cancer to adjuvant systemic therapy.

Vascular endothelial growth factor independently predicts the efficacy of postoperative radiotherapy in node-negative breast cancer patients.

Purpose: Vascular endothelial growth factor (VEGF) is a mediator of angiogenesis and is up-regulated under hypoxic conditions. Hypoxic tumors are known to exhibit resistance to radiotherapy. We investigated the association between VEGF levels in tumor tissue and the effect of radiotherapy for relapse-free survival (RFS) and overall survival (OS) in node-negative breast cancer.

Vascular endothelial growth factor is associated with the efficacy of endocrine therapy in patients with advanced breast carcinoma.

Background: Vascular endothelial growth factor (VEGF) is a mediator of angiogenesis and is associated with a poor prognosis in patients with primary breast carcinoma. In the current study, the authors investigated whether there was an association between VEGF levels in tumor tissues and response rates to first-line, systemic therapy in patients with advanced breast carcinoma.

Methods: In 172 tumors from patients with primary breast carcinoma who developed distant metastases during follow-up, cytosolic levels of VEGF were measured using a quantitative enzyme-linked immunosorbent assay.

Cyclin-E is a strong predictor of endocrine therapy failure in human breast cancer.

Recently, cyclin-E was reported to be the most prominent prognostic factor for breast cancer outcome described so far, even surpassing axillary nodal involvement. Earlier studies on the prognostic value of cyclin-E in breast cancer, however, yielded heterogeneous results. Therefore, we set out to confirm and extend these results by quantitative Taqman RT-PCR of cyclin-E levels in 277 resectable breast cancers.

High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer.

Background: The use of high-dose adjuvant chemotherapy for high-risk primary breast cancer is controversial. We studied its efficacy in patients with 4 to 9 or 10 or more tumor-positive axillary lymph nodes.

Methods: Patients younger than 56 years of age who had undergone surgery for breast cancer and who had no distant metastases were eligible if they had at least four tumor-positive axillary lymph nodes.

Molecular beacon reverse transcription-PCR of human chorionic gonadotropin-beta-3, -5, and -8 mRNAs has prognostic value in breast cancer.

Background: The beta-subunit of human chorionic gonadotropin (hCG) is encoded by four genes, of which expression of the hCGbeta-3, -5, and -8 genes could have prognostic value in breast cancer.

Methods: Applying a new, modified Molecular Beacon reverse transcription-PCR assay, we investigated the prognostic value of the hCGbeta-3, -5, and -8 gene transcripts in 129 sporadic unilateral breast cancer samples from patients with a median follow-up of 62.3 months.