Genetic Testing

BRCA 1 = breast cancer 1

BRCA 2 = breast cancer 2

Approximately 5% - 10% of women diagnosed with breast cancer have a hereditary form of the disease. Alterations or mutations in certain genes make some women more susceptible to developing breat cancer and other types of cancer. BRCA 1 and BRCA 2 are involved in many cases of hereditary breast and ovarian cancer. Researchers are searching for other genes that also may increase a woman's cancer risk.

A woman's lifetime risk of developing breast cancer is 13.2% (132 out of 1000). Women with an altered BRCA 1 or BRCA 2 have a lifetime risk of 36% - 85% (360 - 850 out of 1000; 3 - 7 times more likely) of developing breast cancer. Keep in mind these figures are estimates and may change as more research data are added.

A positive BRCA1 or BRCA 2 test means that other family members should be tested to see if they have the same specific alteration. However, a positive result only provides information about a persons risk of developing cancer. It can't predict whether cancer will actually develop or when. Not all woman who inherit an altered gene will develop breast of ovarian cancer.

A positive test result means it's possible to pass the alteration on to sons and daughters. However, not all children of people who have the altered gene will inherit it.

A negative test result means it's highly unlikely to have an inherited susceptibility to cancer. This does not mean a person won't get cancer; it means ones risk of cancer is the same as the general population.

A positive test result can bring relief from uncertainty and allow people to make informed decisions about their future, including taking steps to reduce cancer risk. In addition, many people are able to participate in medical research that may, in the long run, decrease the risk of death from breast cancer.1

Genetics Testing on Tumors Predict Prognosis

Patients with ER+/lymph node negative breast cancer have an unacceptably high rate of recurrence: 24% when treated with Tamoxifen (Nolvadex®) and down to 13% when treated with both tamoxifen and chemotherapy at the 12 year follow-up2.

Breast cancer gene expression ratio is a prognostic marker used to identify patients who may benefit from more aggressive therapy. Scientists found and association between tumor recurrence and the expression of two genes: the homeobox gene (HOXB13) and the interleukin-17B receptor gene (IL17BR)3.

The ratio of these two genes (a.k.a. H:I) predicted recurrence seperate of standard markers in node-negative breast cancer but not node positive. Therefore, the test is useful in predicting risk of breast cancer recurrence in women with ER+/lymph node-negative, early stage breast cancer.4 The five year risk of recurrence increases with an increasing H:I.

CellSearch® is a blood test that measures circulating tumor cells (CTC's). CTC's are rarely present in healthy individuals and patients with nonmalignant diseases but can be detected in patients with metastatic cancer. Clinical studies have found that the number of CTC's predicts progression-free survival and overall survival before treatment, and at first follow-up after initiation of new therapy for patients with metastatic breast cancer5.

DNA Cell Cycle Analysis & Ki-67:
Rapidly growing breast cancer cells are factors for prognosis. Cells actively producing DNA S-phase fraction and Ki-67 can be analyzed for predicting outcome. Ki-67 is a nuclear non-histone protein, present at low levels with inactive cells but higher levels with rapidly growing cells. Basically, the less Ki-67 in cancer cells, the better, and the higher, the worse. Studies show the prognostic value of Ki-67 is more useful in node-negative than in node-positive. However, if the tumor had <10% fast growing cells the lower recurrence, and longer survival, regardless of node status6

p53 Gene Mutation:
The tumor suppressor gene p53 plays a key role in cell cycle control and programmed cell death. Mutation in tumor p53 was associated with higher mortality rate, regardless of tumor size, node status, and hormone receptor status. Overexpression of p53 protein detected by IHC is a surrogate marker of p53 mutation and is associated with poor prognosis7.

1National Cancer Institute
2Fisher B, Jeong J-H, Bryant J, et al. Lancet. 2004; 364:858-868.
3Ma X-J, Hilsenbeck SG, Wang W, et al. Cancer Cell. 2004; 5:607-616.
4Ma X-J, Hilsenbeck SG, Wang W, et al. J Clin Oncol. 2006; 24:4611-4619.
`5Cristofanilli M, Budd T, Ellis M, et al. N Engl J Med. 2004; 351:781-791; Cristonfanilli M. Semin Oncol. 2006; 33:S9-S14.
6Wenger CR, Clark GM. Breast Cancer Res Treat. 1998; 51:255-265.
7Quest Diagnosis: Breast Cancer, Laboratory Support of Diagnosis and Management.

Karen Moody ...© All rights reserved