General Information

The Yale Breast Pathology service provides a comprehensive range of diagnostic services, including cytopathology, histopathology, immunohistochemistry, in situ hybridization, flow cytometry, and electron microscopy.

HIGHLIGHTS

• Comprehensive evaluation of biopsies and resections for prognosis and assessment of therapeutic options

• Ancillary studies, including immunohistochemical evaluation of hormone receptors, flow cytometry for ploidy and S-phase fraction, and evaluation of HER2/neu status by immunohistochemistry and fluorescence in situ hybridization (FISH)

• Coordination of clinical care with Yale diagnostic and therapeutic radiologists, surgeons, and oncologists within the Yale Comprehensive Breast Program and the Yale Comprehensive Cancer Center

• Development of new programs and research activities in collaboration with basic and clinical scientists

 

Special Procedures:

In addition to determining if cancer is present in breast biopsy tissue, the pathologist evaluates a number of factors that will be used to guide therapy. These factors include size and characteristics of the tumor, extension into surrounding breast tissue, and spread into the lymph nodes.

Ancillary studies that are important in predicting which therapies will be most successful for treating each individual tumor are also performed for invasive cancers.

Expression of receptors for estrogen and progesterone are studied by immunohistochemistry to predict the tumor’s likely response to antihormonal therapies.

HER2/neu status is also assessed. The HER2/neu gene is amplified (i.e., more gene copies than normal) in 15-30% of breast cancers. The status of HER2/neu can be assessed either by fluorescence in situ hybridization or by immunohistochemistry.

HER2/neu amplified cancers are more likely to respond to high-dose anthracycline chemotherapy and to the monoclonal antibody Trastuzumab.

Breast Cancer Research

Every year, one hundred and seventy-five thousand American women develop breast cancer. Although many die from this disease, more than 130,000 women survive; the key to their survival is early detection, prompt localization and appropriate treatment. Regular self examination, a regular examination by your doctor, and regular mammograms can go a long way toward the early recognition of breast cancer, offering the best chance of cure.

The Yale Pathology Department has been active locally and nationally in perfecting the team effort needed to maximize early detection, staging, and conservative treatment. Yale Pathology researchers are also investigating basic mechanisms by which cancer forms in the breast. Yale pathologists have participated in local and national studies and published data concerning interpretation of needle biopsies obtained at the time of mammography; the identification of prognostic factors which predict the efficacy of safe conservative therapy by local excision and radiotherapy; the examination of sentinel lymph node biopsies; and the determination of prognostic and therapeutic factors that predict the likelihood of a response to systemic hormonal agents, chemotherapy, radiotherapy, and immunotherapy. Investigators in the department have been at the forefront of the investigation of the role of the HER-2/neu gene in the development of breast cancer.

The receptor HER-2/neu is overexpressed in a subset of breast cancers where it foreshadows poorer prognosis. HER-2 is the target for the new antibody drug Herceptin, the first FDA-approved drug to target an oncogene product. Pathology Professor David F. Stern, Ph.D., is a pioneer in the investigation of HER-2/neu. Dr. Stern has developed a new strategy for the analysis of breast tumors based on detection of the activation state of HER-2/neu or other growth receptors. This strategy identifies a set of high-risk patients with active HER-2, who are likely to benefit most from HER-2-directed therapies.

Pathologists play a critical role in determining clinical treatment decisions based on tissue removed by either needle or surgical biopsy. Should malignancy be present, the pathologist documents the characteristics of the cancer and its extent, and determines the feasibility of local excision and the efficacy of radiotherapy. Examination of the sentinel lymph nodes determines the stage of breast cancer. Immunohistochemical determination of estrogen and progesterone receptors and HER-2/neu status is also performed by the pathologist. The growth rate of the tumor is determined by flow cytometry.

 

Frequently Asked Questions

What is the difference between immunohistochemical evaluation of HER2 and FISH?

Evaluation of HER2/neu by immunohistochemistry uses an antibody that recognizes the HER2 protein on the surface of the cancer cells. A normal light microscope is used to observe the results, which are scored on a scale of 0, 1+, 2+, or 3+, depending upon the degree of positive signal observed. Fluorescence in situ hybridization (FISH) for HER2/neu involves marking the gene rather than the protein. Since a fluorescent tag is used, this test requires more specialized equipment than immunohistochemistry does and is, therefore, not as widely available.

How is FISH for HER2/neu scored?

FISH for HER2/neu is scored by comparing the number of red/orange signals (HER2/neu) to the number of green signals (number of copies of chromosome 17) in each tumor cell. After counting signals in at least 30 cells, the ratio of HER2/neu to chromosome 17 signals is calculated. Non-amplified tumors show ratios from 0.1 to 1.99. Tumors considered to be amplified show ratios of 2.0 or more.

Does FISH require fresh tissue or other special tissue processing?

No. FISH for HER2/neu can be performed on routinely processed formalin-fixed, paraffin-embedded tissues. Tumor tissues can usually be used for FISH even after storage for many years.