As well, these studies have clarified cancer risk among women with and without known genetic mutations.

Inherited mutations in two genes—BRCA1 and BRCA2—have been found to greatly increase the lifetime risk of developing breast and ovarian cancer. Alterations in these genes can be passed down through either the mother’s or the father’s side of the family. Mutations in other genes have also been linked with breast cancer, including mutations in the CHEK2, TP53, and PTEN genes.

Genetic testing for BRCA1 and BRCA2 mutations is often offered to women at high risk for carrying a gene mutation, but the technology used in the currently available test does not detect all types of mutations. To evaluate the frequency with which standard genetic testing misses potentially important gene mutations, researchers conducted a study among 300 individuals with breast or ovarian cancer.[1]All study subjects had at least four family members with breast or ovarian cancer, but the subjects had tested negative for BRCA1 and BRCA2 mutations.

Through the use of multiple different testing procedures, 12% of the study subjects were found to have a BRCA1 or BRCA2 mutation, 5% were found to have a CHEK2 mutation, and 1% were found to have a TP53 mutation. The researchers conclude that “Effective methods for identifying these mutations should be made available to women at high risk.” In addition, because a majority of the high-risk women in this study did not have mutations in any of the five genes evaluated, the researchers note that it will be important to continue the search for other genes that play a role in breast or ovarian cancer.

A second study evaluated whether mammography increases the risk of breast cancer among women with a BRCA1 or BRCA2 mutation.[2] Mammograms expose the breast to a low dose of radiation. Exposure to this low dose is not believed to increase breast cancer risk among women in the general population, but some have speculated that it could potentially increase risk among women with BRCA1 or BRCA2 mutations. Reassuringly, the study found that among women with BRCA1 or BRCA2 mutations, history of screening mammography did not appear to influence breast cancer risk.

A third study assessed treatment outcomes among early breast cancer patients with and without a BRCA1 or BRCA2 mutation.[3] All women in the study were treated with breast-conserving surgery and radiation therapy. Some of the women with a BRCA1 or BRCA2 mutation also underwent surgical removal of the ovaries (oophorectomy). Among women with BRCA1 or BRCA2 mutations, those who underwent oophorectomy in addition to breast-conserving surgery and radiation therapy had a lower risk of breast cancer recurrence; risk of recurrence in these women was similar to the risk observed among women without a BRCA1 or BRCA2 mutation. Risk of contralateral breast cancer (cancer in the opposite breast), however, remained elevated in mutation carriers compared to women without a mutation.

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Finally, a study assessed the risk of contralateral breast cancer in patients with hereditary breast cancer that was not due to a BRCA1 or BRCA2 mutation.[4] After 20 years, the probability of developing contralateral breast cancer was 27% among the women with hereditary breast cancer, compared to 5% among women with breast cancer in the general population. The risk of contralateral breast cancer was highest among women with hereditary breast cancer that was diagnosed before the age of 50. More than 40% of these women were expected to develop contralateral breast cancer during the 20 years after their initial breast cancer diagnosis. The researchers note that “When genetic counseling is provided for this group of women, it is important to consider and provide information regarding the risk of [contralateral breast cancer].”


[1]Walsh T, Casadei S, Coats KH et al. Spectrum of Mutations in BRCA1, BRCA2, CHEK2, and TP53 in Families at High Risk of Breast Cancer. JAMA. 2006;295:1379-1388.

[2]Narod SA, Lubinski J, Ghadirian P et al. Screening Mammography and Risk of Breast Cancer in BRCA1 and BRCA2 Mutations Carriers: A Case-Control Study. Lancet Oncology. Early Online Publication March 22, 2006.

[3]Pierce L, Levin A, Rebbeck T, et al. Multi-Institutional 10-Year Results of Breast-Conserving Surgery and Radiotherapy in BRCA1/2-Associated Stage I/II Breast Cancer. Journal of Clinical Oncology. 2006; published online ahead of print Apr 24 2006. DOI: 10.1200/JCO.2005.02.7888.

[4]Shahedi K, Emanuelsson M, Wiklund F et al. High Risk of Contralateral Breast Carcinoma in Women with Hereditary/Familial Non-BRCA1/BRCA2 Breast Carcinoma. Cancer. 2006;106:1237-42.