Predicting Recurrence of Breast Cancer
  . . . and it's response to treatment

When cancer develops in more than one member of a family, it often prompts such comments as “Cancer must run in that family.” But because cancer is common, it can develop in several members of a family purely by chance rather than through an inherited abnormal gene (a genetic mutation). In fact, only about 5 percent to 10 percent of cancers are strongly linked to inherited genetic mutations.


Oncologists consider several factors when predicting the likelihood that breast cancer will recur (come back) after treatment. These factors include the grade and size of the tumor, the presence of cancer cells in lymph nodes in the armpit, the presence or absence of hormone receptors (estrogen and progesterone), the amount of HER2/neu produced by the cancer cells, and the age and menopausal status of the woman. These clinical characteristics also play a role in what kind of treatments will be most effective.

Oncologists now have additional tools to help them make accurate predictions about the course of disease and the response to treatment. These tools are helping to usher in the era of personalized cancer medicine, or treatment targeted to the unique characteristics of an individual’s tumor.

Predicting Recurrence

Two tests for early-stage breast cancer take advantage of a technology known as gene-expression profiling, which allows for several genes in a tumor specimen to be studied simultaneously. The analysis (which is different from genetic testing for BRCA1 and 2 genes) provides information about the expression (activity) of genes that either activate or suppress the development of cancer cells. Researchers have found that the genetic profile of a tumor is related to its behavior; that is, the activity of specific genes can indicate whether the tumor will recur or metastasize.

One test, MammaPrint® (Agendia, Amsterdam, Netherlands, is an assay of 70 genes that research has found to be related to distant recurrence of breast cancer. It is performed on fresh or freshly frozen biopsy material. With this test, a tissue specimen from the breast cancer is analyzed for the activity of these 70 genes, and the results indicate either a high or low risk of the cancer recurring within 10 years after diagnosis. Several studies have demonstrated that MammaPrint is a reliable predictor of disease-free survival, and in 2007, the U.S. Food and Drug Administration has cleared the test for use in the United States (not a requirement for use).

Similar to MammaPrint is Oncotype DX® (Genomic Health, Redwood, Calif., which also provides a profile of the activity of genes in a breast-cancer tumor. Oncotype DX evaluates the activity of 21 genes (16 cancer genes and five control genes) in a tissue specimen, and the activity is calculated as a Recurrence Score® of 0 to 100 points. A low score indicates low risk and a high score indicates high risk of recurrence within 10 years after diagnosis.  This test can be done on stored tissue (paraffin blocks).

Oncotype DX assay has been recommended by two expert cancer organizations. Both the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) (which publishes treatment guidelines for all types of cancer) recommend using the test to predict the risk of recurrence for women with newly diagnosed estrogen-receptor-positive, node-negative breast cancer. The ASCO statement also notes that the test can be used to identify patients who may be successfully treated with hormonal therapy and may therefore not require adjuvant chemotherapy.

The benefit of both MammaPrint and Oncotype DX is that treatment can be tailored — or customized — to the specific risk and needs of each individual woman. In determining the optimum treatment plan, an oncologist will consider the likelihood of recurrence, which can be ascertained by either test in addition to traditional factors, such as the size or grade of the tumor. In general, women with a low risk of recurrence can avoid the side effects of chemotherapy and be treated safely with hormone therapy alone. Women with a high risk can be treated with adjuvant chemotherapy to help reduce the risk of recurrence and can be monitored closely to help ensure early intervention if cancer does recur.

Aduvant! Online is a Web site that offers tools cancer specialists can use to help them determine the risks and benefits of providing patients with adjuvant therapy (chemotherapy, hormone therapy or both) after surgery. Specialists can enter data about a patient’s cancer, such as tumor size and stage and any nodal involvement, and information about the patient, such as the patient’s age. The site’s software provides information back that helps doctors and other health-care professionals estimate the risk of a negative outcome without giving adjuvant therapy, such as a relapse of the cancer, or, alternately, the risks of side effects if adjuvant therapy is provided.

Metastatic Breast Cancer

For individuals whose cancer has already spread onto another organ in their body, another test helps predict how metastatic breast cancer responds to treatment. The test, CellSearch® (Veridex, a Johnson & Johnson company, Raritan, N.J.), measures the number of circulating tumor cells (CTCs) in the bloodstream. CTCs are intact cells that are thought to detach from metastatic tumors and enter the bloodstream. The number of CTCs decreases as a tumor shrinks in response to treatment. Thus, knowing the number of CTCs (the CTC count) can help physicians better determine how effective treatment is and then change therapy if necessary.

The primary benefit of using CTC counts to monitor response to treatment is that monitoring can begin earlier than with imaging studies (such as computed tomography or ultrasound). This earlier assessment means that disease response can be evaluated sooner, which improves decision-making and increases the chance for a better outcome. However, many researchers believe that further studies are necessary to confirm the value of the test, and so there are no recommendations for the use of CTC counts to guide treatment planning.

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