Type of test

 Microscopic examination

Normal findings

DNA ploidy Aneuploid is unfavorable.

 Diploid is favorable.

S-phase fraction

> 5.5% is unfavorable.

< 5.5% is favorable.

HER-2 protein

IHC method: 0 to 1 +

FISH method: < 2 copies/cell

Oncotype DX method: < 10.7 units

Cathepsin D

> 10% is unfavorable.

 < 10% is favorable.

p53 protein

> 10% is unfavorable.

< 10% is favorable.

Ki67 protein

> 20% is unfavorable.

10% to 20% is borderline.

 < 20% is favorable.

Test explanation and related physiology

The most important predictor of recurrent breast cancer is stage of disease, including lymph node status. Patients with positive lymph node metastasis are more likely to develop recurrence. However, nearly 30% of the patients whose tumors have been completely removed and who have no evidence of lymph node metastasis will also develop recurrence. Conventional predictors such as tumor size, grade, histologic type, and hormone receptors  are able to identify some of the patients who are at increased risk for recurrence. However, it is important to accurately predict the patients who are destined for recurrence so that they can be selected for systemic therapy; patients who will not have a recurrence can be spared the morbidity of a treatment that is not needed.

DNA ploidy status and S-phase fraction

These are measurements of the rapidity with which the cells in a breast cancer grow.

Cathepsin D

This protein catabolic enzyme was found to be absent in resting breast tissue but significantly elevated in malignant tissue. This protein exists on tumor cell membrane and is correlated with worse clinical outcomes. The exact cutoff point between a favorable prognosis and unfavorable prognosis has yet to be standardized.

HER-2 (c erbB2, neu) protein

HER-2/neu, which stands for human epidermal growth factor receptor 2, is a protein associated with worse clinical outcomes. The HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor with extensive similarity to other epidermal growth factor receptors. It is normally involved in the pathways leading to cell growth and survival. Approximately 15% to 20% of breast cancers have an amplification of the HER-2/neu gene or overexpression of its protein product.

The HER-2 gene can act as a target for an antineoplastic monoclonal antibody drug such as trastuzumab (Herceptin).

p53 protein

The p53 gene is a tumor suppressor gene that is overexpressed in more aggressive breast cancer cells. Mutation of the gene causes overexpression and a buildup of mutant proteins on the surface of the cancer cells.

 Ki67 protein

 The Ki67 gene encodes the synthesis for the Ki67 protein that is associated with worse clinical outcomes.

Interfering factors

 • Delay in tissue fixation may cause deterioration of marker proteins and may produce lower values.

* Preoperative use of some chemotherapy agents may cause decreased levels of some marker proteins.

Procedure and patient care

 Before

* Inform the patient that an examination for these tumor predictor markers may be performed on their breast cancer tissue.

* Provide psychological and emotional support to the breast cancer patient.

During

• The surgeon obtains tumor tissue.

• This tissue should be placed on ice or in formalin.

• Part of the tissue is used for routine histology. A portion of the paraffin block is sent to a reference laboratory.

 After

* Explain to the patient that results are usually available in 1 week.

 Abnormal findings

Unfavorable test results indicating a risk of cancer reoccurrence