Aberrant methylation of imprinted genes is associated with negative hormone receptor status in invasive breast cancer.

Epigenetic regulation of imprinted genes enables monoallelic expression according to parental origin, and its disruption is implicated in many cancers and developmental disorders. The expression of hormone receptors is significant in breast cancer because they are indicators of cancer cell growth rate and determine response to endocrine therapies. We investigated the frequency of aberrant events and variation in DNA methylation at nine imprinted sites in invasive breast cancer and examined the association with estrogen and progesterone receptor status.

Sequence-based detection of mutations in cadherin 1 to determine the prevalence of germline mutations in patients with invasive lobular carcinoma of the breast.

Background: Loss of cadherin 1 (CDH1) expression, which is normally involved in cell adhesion and maintenance of tissue architecture, is a hallmark of invasive lobular carcinoma (ILCA). Because hereditary cancers may require different risk reduction, counseling and treatment options than sporadic cancer, it is critical to determine the prevalence of germline CDH1 mutations in patients with ILCA.

Methods: All patients with ILCA (n = 100) previously enrolled in the Clinical Breast Care Project were identified.

Molecular response of the axillary lymph node microenvironment to metastatic colonization.

Breast stroma plays an active role in tumorigenesis, undergoing both phenotypic and molecular changes that facilitate and promote tumor development and growth. The metastatic microenvironment also plays a role in successful colonization; however, genetic changes in these secondary microenvironments are not well described. To improve understanding of molecular changes associated with metastatic colonization, gene expression patterns from lymph node tissues from women with at least one positive, as well as one negative node, were compared.

Leukocyte DNA as surrogate for the evaluation of imprinted Loci methylation in mammary tissue DNA.

There is growing interest in identifying surrogate tissues to identify epimutations in cancer patients since primary target tissues are often difficult to obtain. Methylation patterns at imprinted loci are established during gametogenesis and post fertilization and their alterations have been associated with elevated risk of cancer. Methylation at several imprinted differentially methylated regions (GRB10 ICR, H19 ICR, KvDMR, SNRPN/SNURF ICR, IGF2 DMR0, and IGF2 DMR2) were analyzed in DNA from leukocytes and mammary tissue (normal, benign diseases, or malignant tumors) from 87 women with and without breast cancer (average age of cancer patients: 53; range: 31-77).

Genomic (in)stability of the breast tumor microenvironment.

The breast tumor microenvironment plays an active role in tumorigenesis. Molecular alterations have been identified in tumor-associated stroma; however, there is considerable debate as to whether the stroma is characterized by genomic instability or whether detection of chromosomal alterations reflects technological artifact rather than the true genomic content of the tumor microenvironment. Thus, breast stroma specimens from 112 women undergoing reductive mammoplasty (n = 7), prophylactic mastectomy (n = 6), or mastectomy for a breast disease (n = 99) were frozen in optimal cutting temperature medium.

Impact of lifestyle factors on prognosis among breast cancer survivors in the USA.

Advances in diagnostic screening and adjuvant therapy have dramatically increased the number of breast cancer survivors in the USA, who may face changes in physical and mental health, social support, quality of life and economics. Women living with breast cancer are increasingly interested in lifestyle modification to decrease the risk of recurrence and mortality while increasing physical and emotional wellbeing. Although organizations such as the American Cancer Society support a healthy diet, frequent physical activity and stress reduction for decreasing breast cancer risk, studies examining the effects of lifestyle on clinical outcomes including survival and prognosis have been inconclusive.

Effect of ASCO/CAP guidelines for determining ER status on molecular subtype.

Background: Determination of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status is standard for predicting prognosis and determining treatment options for patients with breast cancer. In 2010, the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) issued guidelines that tumors with ≥1% positively staining cells should be considered ER positive. Here, we determined how this cutoff relates to molecular subtype.