Genetic Testing for Breast and Ovarian Cancer Susceptibility: A Family Experience

Marcia Van Riper, RN, PhD

Disclosures

J Midwifery Womens Health. 2004;49(3) 

In This Article

Factors to Consider Before Offering Genetic Testing

The main factors that midwives and other health care providers need to consider before offering genetic testing for breast and ovarian cancer susceptibility are 1) the client's estimated risk of developing hereditary breast and ovarian cancer, 2) benefits, risk, and limitations of genetic testing for breast and ovarian cancer susceptibility, and 3) current recommendations concerning when to offer genetic testing for breast and ovarian cancer susceptibility.

The American Cancer Society estimates that in 2003 there will be 211,300 new cases of invasive breast cancer diagnosed among women in the United States.[34] In addition, there will be 55,700 new cases of in situ breast cancer and 25,400 new cases of ovarian cancer. An estimated 40,000 women will die of breast cancer in 2003 and 14,300 women will die of ovarian cancer. According to a report by the National Cancer Institute,[35] a female infant born today in the United States has a 1 in 8 chance (approximately 13.3%) of being diagnosed with breast cancer sometime during her lifetime. However, if she inherits a BRCA1 or BRCA2 mutation from one of her parents, her chance of being diagnosed with breast cancer or ovarian cancer is significantly increased.

Although it is clear that inherited mutations in the BRCA1 and BRCA2 genes confer high risks of breast and ovarian cancer, the exact magnitude of these risks remains uncertain ( Table 1 ). In a metanalysis[36] that included data from 22 studies, the average cumulative risks in BRCA1-mutation carriers by age 70 years were 65% for breast cancer and 39% for ovarian cancer. Corresponding estimates for BRCA2-mutation carriers were 45% for breast cancer and 11% for ovarian cancer. Recently reported findings from the New York Breast Cancer Study[37] suggest higher risks of breast cancer in BRCA mutation carriers: 69% for BRCA1-mutation carriers by age 70 years and 71% for BRCA2-mutation carriers. Risks of developing a second contralateral breast cancer have been reported to be 64% by the age of 70 years[38] or 20% within 5 years of the initial diagnosis in persons who are BRCA1-mutation carriers[39] and 50% by the age of 70 years[40] or 12% within 5 years of the initial diagnosis in persons who are BRCA2-mutation carriers.[41]

Men found to carry a BRCA2 mutation have a 6% lifetime risk of developing male breast cancer.[40] In addition, even though only a small percentage of the men who carry a BRCA mutation develop breast cancer, all men who carry a BRCA mutation have a 50% chance of passing the mutation on to their offspring. BRCA mutations also confer an increased risk of prostate cancer.[22] The increased risk for prostate cancer is threefold for BRCA1-mutation carriers[22] and three- to sevenfold for BRCA2-mutation carriers.[40] Carriers of BRCA1 mutations are also at increased risk for colon cancer,[23] and carriers of BRCA2 mutations are at increased risk for pancreatic cancer, gallbladder and bile duct cancer, stomach cancer, and malignant melanoma.[42,43]

Currently, two models, the Gail model[44,45] and the Claus model,[46] are widely used in research studies and clinical counseling to predict a woman's lifetime risk of developing breast cancer ( Table 2 ). Calculation of a 5-year and lifetime breast cancer risk according to the Gail model[44,45] can be performed by accessing the National Cancer Institute's Web site (https://www.nci.nih.gov) and searching for information on breast cancer risk.[17] The Claus model[46] projects the probability of developing breast cancer for women with a family history of breast cancer. As noted in Table 2 , both models have limitations, but they are the best methods currently available for predicting a woman's lifetime risk of developing breast cancer.

In addition to the models that have been developed to predict lifetime risk of breast cancer, there have also been at least two models developed to estimate the likelihood of finding a BRCA mutation ( Table 3 ). Using the first of these, the Myriad model, health care providers can estimate the likelihood of their client being a carrier of a BRCA mutation by using a table of mutation prevalence data available on the Myriad Web site (https://www.myriad.com/gtmp.html). Health care providers can estimate the likelihood of their client carrying a BRCA1 or BRCA2 mutation by using this computer program, which is based on data from published studies of prevalence, penetrance, and mutation frequency. Further information about this model can be found at https://www.astor.som.jhmi.edu/brcapro/. The second model, a computer program called BRCAPRO,[47,48,49] allows the health care provider to estimate the probability of their client carrying a BRCA1 or BRCA2 mutation using data from published studies of prevalence, penetrance, and mutation frequency. Information about this model can be found at https://www.astor.som.jhmi.edu/brcapro/.

Although the models described above can be helpful in estimating a client's risk of developing breast and ovarian cancer, they should not be the only approach used by health care providers. The models need to be used in conjunction with data from a family pedigree that spans at least three generations. The family pedigree should include information such as who in the family had cancer, what type of cancer family members had, how old family members were when they were diagnosed with cancer, surveillance and treatment choices made by family members, and how old family members who died of cancer were when they died. It is important that the pedigree includes both paternal and maternal lineage because fathers are just as likely as mothers to transmit BRCA mutations to their children. Features revealed in the family pedigree will help health care providers identify individuals and families who should be offered genetic testing because of their increased risk for hereditary breast and ovarian cancer. Features suggestive of hereditary breast and ovarian cancer are listed in Table 4 . If the total number of female family members is small, it may be difficult to estimate the client's risk for hereditary breast and ovarian cancer. In addition, if the family is extremely large, with many female family members, the client's risk of developing a hereditary breast and ovarian cancer may be overestimated.

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