Genetic and Protein Profiling in Normal and Cancerous Breast Tissue

Background: Defining the molecular profile (gene and protein expression) of normal breast
tissue is essential to identifying markers for cellular subtypes in the normal human breast.
These markers could serve as biomarkers for prevention trials or represent new therapeutic
targets if they are also expressed in early breast cancers. The gene and protein expression
in normal breast tissue may be dependent on the stage of the menstrual cycle, whether the
woman is pre- or post-menopausal, prior pregnancy and breast feeding history, and age. The
molecular profile of metastatic breast tumors may differ from that of the primary tumor and
differ in metastases from different anatomic sites. Identification of genes/proteins unique
to these lesions may help identify the processes responsible for metastatic spread at a
molecular level and lead to the development of new molecularly targeted drugs. Similarly,
isolation and characterization of breast cancer stem cells could provide new approaches for
the treatment and prevention of breast cancer.

Objectives: To define the molecular profile of normal breast tissue from pre- and
post-menopausal women of varying age and parity (nulliparous to multiparous) and in
different phases of the menstrual cycle; to study the molecular profile of primary and
metastatic breast cancer lesions; and to identify and characterize breast cancer stem cells
and establish cell lines from the pleural fluid of women with breast cancer and malignant
pleural effusions.

Eligibility: Women who are undergoing cosmetic breast surgery that entails resection of a
portion of the breast (e.g., reduction mammoplasty) and who do not have a history of breast
cancer; women with known or suspected breast cancer who are having a primary tumor biopsied
or resected or having a metastatic lesion biopsied or resected; or women with breast cancer
who are undergoing pleurocentesis for a suspected or known malignant pleural effusion.

Design: Normal breast tissues from cosmetic breast procedures that are performed in women
without a history of breast cancer at Suburban Hospital will be snap frozen in liquid
nitrogen and sent to the NCI for storage and analysis. Demographic information will be
collected from the women undergoing the procedure. Similarly, a portion of biopsies obtained
from primary or metastatic lesions in women with suspected or known breast cancer at
Suburban Hospital or the NIH will be collected after materials are obtained for diagnostic
purposes, snap frozen in liquid nitrogen, and sent to the NCI with demographic information.
The unneeded fluid from pleurocenteses performed in women with breast cancer and malignant
pleural effusions will be transported (unfrozen) to an NCI lab for immediate processing (FAC
sorting to isolate breast cancer stem cells). RNA will be extracted from tissues and cDNA
microarrays will be used to study gene expression. Proteomic analysis of normal and
malignant breast tissue will be studied using reverse-phase tissue lysates.

- INCLUSION CRITERIA:

1. Subjects of any age who are undergoing cosmetic breast surgery that entails
resection of breast tissue (e.g., reduction mammoplasty) for any reason.

2. Women (18 years of age or older) with known or suspected breast cancer who are
undergoing a diagnostic biopsy or resection of a primary breast lesions or a
site of metastatic tumor.

3. Women (18 years of age or older) with breast cancer who are undergoing a
pleurocentesis for removal of fluid from a known or suspected malignant pleural
effusion.

4. All patients or their legal guardians (if the patient is less than 18 years of
age) must sign a document of informed consent indicating their understanding
that the specimens collected and demographic information provided is only for
research purposes. Written assent will be obtained from pediatric patients (less
than 18 years of age).

EXCLUSION CRITERIA:

1. Subjects who are undergoing cosmetic breast procedures such as reduction mammoplasty
(collection of normal breast tissue) are excluded if they have a prior history of breast
cancer.