Historical Biobanks in Breast Cancer Metabolomics- Challenges and Opportunities.

Metabolomic characterization of tumours can potentially improve prediction of cancer prognosis and treatment response. Here, we describe efforts to validate previous metabolomic findings using a historical cohort of breast cancer patients and discuss challenges with using older biobanks collected with non-standardized sampling procedures. In total, 100 primary breast cancer samples were analysed by high-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS) and subsequently examined by histology.

DNA methylation signature (SAM40) identifies subgroups of the Luminal A breast cancer samples with distinct survival.

Breast cancer patients with Luminal A disease generally have a good prognosis, but among this patient group are patients with good prognosis that are currently overtreated with adjuvant chemotherapy, and also patients that have a bad prognosis and should be given more aggressive treatment. There is no available method for subclassification of this patient group. Here we present a DNA methylation signature (SAM40) that segregates Luminal A patients based on prognosis, and identify one good prognosis group and one bad prognosis group.

Systematic analysis of challenge-driven improvements in molecular prognostic models for breast cancer.

Although molecular prognostics in breast cancer are among the most successful examples of translating genomic analysis to clinical applications, optimal approaches to breast cancer clinical risk prediction remain controversial. The Sage Bionetworks-DREAM Breast Cancer Prognosis Challenge (BCC) is a crowdsourced research study for breast cancer prognostic modeling using genome-scale data. The BCC provided a community of data analysts with a common platform for data access and blinded evaluation of model accuracy in predicting breast cancer survival on the basis of gene expression data, copy number data, and clinical covariates.

Gefitinib in Combination with Weekly Docetaxel in Patients with Metastatic Breast Cancer Caused Unexpected Toxicity: Results from a Randomized Phase II Clinical Trial.

In patients with metastatic breast cancer, taxane treatment demonstrates activity but is not curative. Targeted treatment modalities are therefore necessary in order to improve outcomes in this group. A randomized placebo-controlled phase II trial was initiated to evaluate effect and toxicity of gefitinib (250 mg QD) and docetaxel 35 mg/m(2) (six of seven weeks) (NCT 00319618).

Radiation-induced effects on gene expression: an in vivo study on breast cancer.

Background And Purpose: Breast cancer is diagnosed worldwide in approximately one million women annually and radiation therapy is an integral part of treatment. The purpose of this study was to investigate the molecular basis underlying response to radiotherapy in breast cancer tissue.

Material And Methods: Tumour biopsies were sampled before radiation and after 10 treatments (of 2 Gray (Gy) each) from 19 patients with breast cancer receiving radiation therapy.

Reduction in bone relapse and improved survival with oral clodronate for adjuvant treatment of operable breast cancer [ISRCTN83688026].

Introduction: Experimental and clinical data show that the oral bisphosphonate clodronate (Bonefos) can inhibit tumor-induced osteoclastic bone resorption. This randomized, double-blind, placebo-controlled, multicenter trial was designed to determine if the addition of oral clodronate to standard treatment for primary operable breast cancer could reduce the subsequent occurrence of bone metastases and thereby improve overall survival.

Methods: 1,069 patients with primary operable stage I-III breast cancer were randomized to receive oral clodronate (1,600 mg/day) or placebo for 2 years, in conjunction with standard treatment for primary breast cancer including surgery, radiotherapy, adjuvant chemotherapy, and/or tamoxifen.

Effects of tamoxifen and octreotide LAR on the IGF-system compared with tamoxifen monotherapy.

The insulin-like growth factor (IGF)-system was evaluated in 150 breast cancer patients participating in a randomised phase III trial comparing octreotide pamoate and tamoxifen with tamoxifen+placebo. Alterations in the IGF-system in the two treatment arms and individual changes with respect to outcome were compared. Serum IGF-I and -II, free IGF-I, and insulin-like growth factor binding protein 1-3 (IGFBP1-3) were measured by radioimmmunoassay (RIA)/immunoradiometric assay (IRMA) and IGFBPs by Western ligand blots (WLB) before and during treatment.

[Breast cancer patients' assessment of waiting time before radiotherapy].

Background And Methods: Radiotherapy capacity in Norway is limited because of higher cancer incidence and more complex treatment modalities. Breast cancer patients referred for post-operative radiotherapy were asked to respond to a questionnaire on waiting time and their attitude to treatment outside the Norwegian Radium Hospital. From 130 referred patients we received 109 questionnaires.

Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer.

Purpose: The development of bone metastases depends on tumor-induced osteoclastic resorption of bone, which may be inhibited by the antiosteolytic bisphosphonate clodronate. Given to patients with primary breast cancer, clodronate might reduce the subsequent incidence of bone metastases.

Patients And Methods: This double-blind, multicenter trial accrued 1,069 assessable patients with operable breast cancer between 1989 and 1995.

Expression of EGFR family and steroid hormone receptors in ductal carcinoma in situ of the breast.

The expression of EGFR family and steroid hormone receptors was examined in a series of 40 cases of pure ductal carcinoma in situ (DCIS) of the breast by immunohistochemical staining of paraffin-embedded sections. Hematoxylin and eosin-stained sections were used to classify the tumors according to the published criteria by Holland et al. (Holland R, Peterse JL, Millis RR, et al.

Influence of neoadjuvant anastrozole (Arimidex) on intratumoral estrogen levels and proliferation markers in patients with locally advanced breast cancer.

Anastrozole (Arimidex) is a novel, selective, and potent aromatase inhibitor used for the treatment of postmenopausal breast cancer. The drug has been shown to inhibit in vivo aromatization by 96--97% and to suppress plasma estrogen levels by 84--94%. However, the effects of anastrozole on intratumoral estrogen levels have not been studied.

Loss of heterozygosity at 11q23.1 in breast carcinomas: indication for involvement of a gene distal and close to ATM.

Previous reports have suggested that heterozygotes for ataxia-telangiectasia (A-T) have an increased risk of cancer, in particular breast cancer. The ATM gene, responsible for A-T, was recently cloned. Loss of heterozygosity (LOH) in the chromosome band 11q23, where the ATM gene is located, has been reported in several types of tumours including breast carcinomas.

Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal women with breast cancer.

The effect of anastrozole ('Arimidex', ZD1033), a new, selective, non-steroidal aromatase inhibitor on in vivo aromatisation and plasma oestrogen levels was evaluated in post-menopausal women with breast cancer. Twelve patients progressing after treatment with tamoxifen were randomised to receive anastrozole 1 mg or 10 mg once daily for a 28 day period in a double-blinded crossover design. In vivo aromatisation and plasma oestrogen levels were determined before commencing treatment and at the end of each 4-week period.

[Chemotherapy-induced hemolytic uremic syndrome. A complication to mitomycin treatment of breast carcinoma].

Mitomycin is a cytotoxic antibiotic that was first introduced into clinical use in 1958. Not until twenty years later was it recognised that haemolytic uremic syndrome could develop after treatment with mitomycin. It can be asked whether this condition was undiagnosed in previous years, since its frequency is now reported to be 4-15%.

Prognostic significance of TP53 alterations in breast carcinoma.

Constant denaturant gel electrophoresis (CDGE) was used to screen 179 breast carcinomas for mutations in the conserved regions of the TP53 gene (exons 5 through 8). Mutations were found in 35 of 163 primary tumours (21%) and in 5 of 16 metastases (31%) and resided predominantly in exon 7. The majority of the mutations were G:C-->A:T transitions.

Flow cytometric DNA analysis as prognostic factor in human breast carcinoma.

Fresh tumour tissue from 198 primary invasive breast carcinomas was analysed by DNA flow cytometry. 108 tumours were non-diploid. A significantly higher proportion of non-diploid tumours was found among node-positive patients, patients with oestrogen receptor negative tumours and among patients with ductal carcinomas.

Amplification of c-erbB-2, int-2 and c-myc genes in node-negative breast carcinomas. Relationship to prognosis.

Primary tumours from 100 Norwegian node-negative breast carcinoma patients were examined for c-erbB-2, int-2, and c-myc proto-oncogene amplification. c-erbB-2, int-2, and c-myc amplification was found in 12.1% (12 of 99), 8.

Screening for germ line TP53 mutations in breast cancer patients.

The constant denaturant gel electrophoresis technique was used to screen for TP53 germ line mutations in 237 women with breast carcinoma (167 unselected patients, 30 patients with at least one first-degree relative with breast cancer, and 40 women diagnosed with breast cancer before age 35). A germ line mutation at codon 181 was noted in one of the unselected patients and a codon 245 mutation in one of the early-onset patients. Both had a family history of breast cancer and other malignancies suggestive of Li-Fraumeni syndrome.

Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q in human breast carcinomas.

Fifty-nine primary breast carcinomas and 11 metastases were examined to identify genetic alterations in the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q. Loss of heterozygosity (LOH) was frequently observed on chromosome arms 17p (p144D6 lost in 75%, pYNZ22.1 in 55%, and TP53 in 48% of the primary tumours), 13q (RBI lost in 40% of the primary tumours), and 17q (pRMU3 lost in 35%, pTHH59 in 29%, and NM23HI in 26% of the primary tumours).

The c-erbB-2 protein in primary and metastatic breast carcinomas.

Material from 41 patients with primary breast carcinoma and lymph node metastases at the time of primary surgical intervention was immunostained for c-erbB-2 protein, neuron-specific enolase (NSE), and estrogen receptors. Thirty of the primary breast carcinomas were of ductal type. Six were classified as infiltrating lobular carcinomas, 2 were apocrine, 1 was mucinous, and 1 was a tubular carcinoma.

C-erbB-2 protein and neuroendocrine expression in breast carcinomas.

90 primary breast carcinomas and 18 metastases were immunostained for c-erbB-2 protein and neuron specific enolase. 30 tumours were c-erbB-2 negative and NSE positive, 23 tumours were NSE negative and c-erbB-2 positive. 1 tumour expressed focal immunoreactivity for both markers.

Amplification and protein over-expression of the neu/HER-2/c-erbB-2 protooncogene in human breast carcinomas: relationship to loss of gene sequences on chromosome 17, family history and prognosis.

c-erbB-2 gene amplification and protein over-expression were investigated in 89 primary tumours and 24 metastases from Norwegian breast cancer patients. Amplification occurred in 22.5% of the primary tumours and 50% of the metastases.

The effect of pre-morbid height and weight on the survival of breast cancer patients.

A total of 8,427 women with breast cancer with height and weight measured prior to the diagnosis were followed up for on average 4.3 years. 2,383 women died from breast cancer and 430 from other causes.