TRENDS IN RESEARCH AND TRIAL UPDATES FOR BREAST CANCER DETECTION AND TREATMENT IMPLICATIONS FOR SURGEONS

Microarrays in Breast Cancer: Distinctive Gene
Expression and Therapeutic Implications

Breast cancer is a heterogeneous disease, with varying etiology, clinical course, and response to therapies. “Each tumor has a unique pattern of expressed genes, and it is our hope that expression profiling will predict subsequent clinical course and response to different therapies,” said Stefanie S. Jeffrey, MD, Associate Professor of Surgery, and Chief, Breast Surgery, Stanford University Medical Center, Stanford, California. Indeed, according to Dr. Jeffrey, the use of newly developed complementary DNA (cDNA) microarray technology allows for the identification of tumor subtypes, and potentially an increased understanding of the biology and treatment of breast cancer.

cDNA Microarray: How It Works
cDNA microarray technology allows the measurement of relative expression levels of thousands of genes, and the assessment of the molecular profile of a tumor cell on a genome-wide scale. “Essentially, cDNA microarray helps researchers to view cell types and determine which genes are being expressed by the cancer cells,” Dr. Jeffrey explained. cDNA microarrays involve the use of a glass slide, treated with an adhesive and spotted with different genes. Human tumor tissue samples are collected and snap-frozen; RNA is isolated from these samples, reverse transcribed into cDNA, and labeled with red fluorescent dye. A universal RNA reference sample is also reverse transcribed and is labeled with a green fluorescent dye. These two samples are then hybridized on the glass slide. After scanning the microarray at different wave lengths, the ratios of red and green dye are calculated, with genes expressed more in tumor showing red and genes expressed less in tumor being green. Genes expressed equally in tumor and reference samples are shown as yellow. “We currently are able to create expression profiles for approximately 42,000 genes. The cDNA microarray gene expression profiles provide a snapshot of the structure and functioning of the tumor,” Dr. Jeffrey said.

Identifying Breast Cancer Subtypes
Using the cDNA microarray technique and database to assess breast cancer cells, Jeffrey and colleagues have been able to separate tumor epithelial cells, lymphocyte clusters, and stromal clusters. Ultimately, these researchers identified five subtypes of breast cancer, including luminal and basal-like tumor subtypes, that may be associated with differing biology, clinical course, and response to therapies. “Importantly, we are beginning to be able to further categorize estrogen receptor-positive patients into two subgroups within the luminal subtype, whose differences in gene expression profiles may be associated with differences in therapeutic response and long-term survival,” Dr. Jeffrey explained. In addition, Dr. Jeffrey’s group and others are beginning to identify other genes associated with favorable and unfavorable response to treatment and survival in persons with breast cancer.

In conclusion, Dr. Jeffrey noted, “It is hoped that further molecular profiling of breast cancer cells will result in a greater understanding of disease biology and progression, an ability to target treatments to specific tumor subtypes, and ultimately improved outcomes for persons with breast cancer.”