Functional polymorphisms in UDP-glucuronosyl transferases and recurrence in tamoxifen-treated breast cancer survivors.

Background: Tamoxifen is oxidized by cytochrome-P450 enzymes (e.g., CYP2D6) to two active metabolites, which are eliminated via glucuronidation by UDP-glucuronosyl transferases (UGT).

Use of tamoxifen with postsurgical irradiation may improve survival in estrogen and progesterone receptor-positive male breast cancer.

Background: The purpose of this study is to assess the impact of adjuvant therapy on survival in males with non-metastatic breast cancer.

Materials And Methods: A retrospective analysis of male breast cancers treated between 1990 and 2003 was performed. Age, estrogen and progesterone receptor (ER/PgR) status, tumor histology and stage, and details of surgical and adjuvant therapy were recorded.

Expression of microRNA and their gene targets are dysregulated in preinvasive breast cancer.

Introduction: microRNA (miRNA) are short, noncoding RNA that negatively regulate gene expression and may play a causal role in invasive breast cancer. Since many genetic aberrations of invasive disease are detectable in early stages, we hypothesized that miRNA expression dysregulation and the predicted changes in gene expression might also be found in early breast neoplasias.

Methods: Expression profiling of 365 miRNA by real-time quantitative polymerase chain reaction assay was combined with laser capture microdissection to obtain an epithelium-specific miRNA expression signature of normal breast epithelium from reduction mammoplasty (RM) (n = 9) and of paired samples of histologically normal epithelium (HN) and ductal carcinoma in situ (DCIS) (n = 16).

CYP2D6 inhibition and breast cancer recurrence in a population-based study in Denmark.

Background: Cytochrome P450 2D6 (CYP2D6) inhibition reduces the concentration of 4-hydroxylated tamoxifen metabolites, but the clinical relevance remains uncertain.

Methods: We conducted a large case-control study nested in the population of 11 251 women aged 35-69 years at diagnosis of stage I-III breast cancer between 1985 and 2001 on Denmark's Jutland Peninsula and registered with the Danish Breast Cancer Cooperative Group. We identified 541 recurrent or contralateral breast cancers among women with estrogen receptor-positive (ER+) disease treated with tamoxifen for at least 1 year and 300 cancers in women with ER-negative (ER-) disease never treated with tamoxifen.

Concordance of metabolic enzyme genotypes assayed from paraffin-embedded, formalin-fixed breast tumors and normal lymphatic tissue.

Objectives: Translational epidemiology studies often use archived tumor specimens to evaluate genetic hypotheses involving cancer outcomes. When the exposure of interest is a germline polymorphism, a key concern is whether the genotype assayed from tumor-derived DNA is representative of the germline. We evaluated the concordance between breast tumor-derived and normal lymph node-derived genotypes for three polymorphic tamoxifen-metabolizing enzymes.

Gene expression profiles of estrogen receptor-positive and estrogen receptor-negative breast cancers are detectable in histologically normal breast epithelium.

Purpose: Previously, we found that gene expression in histologically normal breast epithelium (NlEpi) from women at high breast cancer risk can resemble gene expression in NlEpi from cancer-containing breasts. Therefore, we hypothesized that gene expression characteristic of a cancer subtype might be seen in NlEpi of breasts containing that subtype.

Experimental Design: We examined gene expression in 46 cases of microdissected NlEpi from untreated women undergoing breast cancer surgery.

Breast cancer recurrence risk related to concurrent use of SSRI antidepressants and tamoxifen.

Background: Up to one-quarter of breast cancer patients suffer clinically significant depression in the year after diagnosis, which may respond to intervention. About half may be prescribed a psychotropic medication, such as a selective serotonin reuptake inhibitor (SSRI), while completing breast cancer therapy. Cytochrome P-450 2D6 (CYP2D6) metabolizes SSRIs and also metabolizes tamoxifen to more active forms.

Early dysregulation of cell adhesion and extracellular matrix pathways in breast cancer progression.

Proliferative breast lesions, such as simple ductal hyperplasia (SH) and atypical ductal hyperplasia (ADH), are candidate precursors to ductal carcinoma in situ (DCIS) and invasive cancer. To better understand the relationship of breast lesions to more advanced disease, we used microdissection and DNA microarrays to profile the gene expression of patient-matched histologically normal (HN), ADH, and DCIS from 12 patients with estrogen receptor positive sporadic breast cancer. SH were profiled from a subset of cases.

Triple-negative breast cancers are increased in black women regardless of age or body mass index.

Introduction: We investigated clinical and pathologic features of breast cancers (BC) in an unselected series of patients diagnosed in a tertiary care hospital serving a diverse population. We focused on triple-negative (Tneg) tumours (oestrogen receptor (ER), progesterone receptor (PR) and HER2 negative), which are associated with poor prognosis.

Methods: We identified female patients with invasive BC diagnosed between 1998 and 2006, with data available on tumor grade, stage, ER, PR and HER2 status, and patient age, body mass index (BMI) and self-identified racial/ethnic group.

CDKN1C/p57kip2 is a candidate tumor suppressor gene in human breast cancer.

Background: CDKN1C (also known as p57KIP2) is a cyclin-dependent kinase inhibitor previously implicated in several types of human cancer. Its family members (CDKN1A/p21CIP1 and B/p27KIP1) have been implicated in breast cancer, but information about CDKN1C's role is limited. We hypothesized that decreased CDKN1C may be involved in human breast carcinogenesis in vivo.

Gene expression abnormalities in histologically normal breast epithelium of breast cancer patients.

Normal-appearing epithelium of cancer patients can harbor occult genetic abnormalities. Data comprehensively comparing gene expression between histologically normal breast epithelium of breast cancer patients and cancer-free controls are limited. The present study compares global gene expression between these groups.

A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study.

Background: Breast and prostate cancer are two commonly diagnosed cancers in the United States. Prior work suggests that cancer causing genes and cancer susceptibility genes can be identified.

Methods: We conducted a genome-wide association study (Affymetrix 100K SNP GeneChip) of cancer in the community-based Framingham Heart Study.

Safe administration of iron sucrose in a patient with a previous hypersensitivity reaction to ferric gluconate.

A 67-year-old woman with iron deficiency anemia required parenteral iron therapy and was treated with intravenous ferric gluconate. She tolerated the first dose, but after the second dose, she developed a tingling feeling all over her body, along with swelling in her hands and feet, and a rash with hives over most of her body. It was thought that she had likely experienced a hypersensitivity reaction to ferric gluconate.

In utero exposure to diethylstilbestrol (DES) does not increase genomic instability in normal or neoplastic breast epithelium.

Background: In 1992, the National Cancer Institute (NCI) established the Continuation of Follow-Up of DES-Exposed Cohorts to study the long-term health effects of exposure to diethylstilbestrol (DES). Genetic effects on human breast tissue have not been examined. The authors investigated whether breast tissue of women exposed in utero to DES might exhibit the genetic abnormalities that characterize other DES-associated tumors.

Allele imbalance, or loss of heterozygosity, in normal breast epithelium of sporadic breast cancer cases and BRCA1 gene mutation carriers is increased compared with reduction mammoplasty tissues.

Purpose: Normal-appearing breast epithelium can contain genetic abnormalities, including allele imbalance (AI), also referred to as loss of heterozygosity. Whether abnormalities are associated with cancer or cancer risk is unknown.

Patients And Methods: We performed a miniallelotype, using 20 microsatellites, on each of 460 histologically normal, microdissected breast terminal ducto-lobular units (TDLUs) from three groups of women: sporadic breast cancer patients (SP; n = 18), BRCA1 gene mutation carriers (BRCA1; n = 16), and controls undergoing reduction mammoplasty (RM; n = 18).

Reliability and reproducibility of gene expression measurements using amplified RNA from laser-microdissected primary breast tissue with oligonucleotide arrays.

Combined use of microdissection and high-density oligonucleotide arrays is a powerful technique to study in vivo gene expression. Because microdissection generally yields ng quantities of RNA, RNA amplification is necessary but affects array results. We tested the reliability and reproducibility of oligonucleotide array data obtained from small sample amplified RNA isolated from primary tissues via laser capture microdissection, to determine whether gene expression measurements obtained under these now customary conditions are reliable and reproducible enough to detect authentic expression differences between clinical samples.

Loss of heterozygosity in serial plasma DNA samples during follow-up of women with breast cancer.

We evaluated the potential utility of occult circulating tumor DNA as a molecular marker of disease in subjects previously diagnosed with breast cancer. Using 24 microsatellite markers located at sites of frequent loss of heterozygosity (LOH) or allele imbalance in breast cancer, we analyzed DNA from 16 primary tumors (Stage IIA or more advanced) and 30 longitudinally collected plasma specimens. Clinical data at the time of plasma collection were obtained.

Risk of breast cancer in women exposed to diethylstilbestrol in utero: prelimiinary results (United States).

Background: A synthetic estrogen, diethylstilbestrol (DES), was widely prescribed to pregnant women during the 1950s and 1960s but was later discovered to be associated with an increased risk of clear-cell carcinoma of the vagina and cervix in female offspring. DES has not been linked to other cancers in female offspring, but studies of other prenatal factors such as twin gestation and pre-eclampsia have indicated that in-utero estrogen levels may influence breast cancer risk. We evaluated the relation of in-utero DES exposure to the risk of adult breast cancer.

Loss of heterozygosity or allele imbalance in histologically normal breast epithelium is distinct from loss of heterozygosity or allele imbalance in co-existing carcinomas.

To better understand early steps in human breast carcinogenesis, we examined allele imbalance or loss of heterozygosity (LOH), in co-existing normal-appearing breast epithelium and cancers. We microdissected a total of 173 histologically normal ducts or terminal ductolobular units (TDLUs) and malignant epithelial samples from 18 breast cancer cases, and examined their DNA for LOH at 21 microsatellite markers on 10 chromosome arms. Fourteen of 109 (13%) normal ducts/TDLUs, from 8 of 18 (44%) cases, contained LOH.