Search

The proband was a 55-year-old white female who sought pretest counseling when she learned that her father was a BRCA1 mutation carrier. Her father is 85 years old, in good health, and is a brother of a woman who died as a result of ovarian cancer at the age of 35. He learned his mutation status as a participant in a National Cancer Institute research study of familial breast and ovarian cancer. He encouraged all of his children to enroll onto the study and to consider testing. The proband and her siblings (two sisters ages 40 and 48, and a brother age 38, all unaffected) decided to obtain pretest counseling and consider genetic testing. During pretest counseling, the proband revealed her preference that information related to a positive mutation test, in either herself or her siblings, be withheld from her parents. Her rationale was to protect her father from the guilt of having passed a mutation on to an offspring. She stated that her test results “were her own,” and that she would not disclose results to her relatives, whether she tested negative or positive. She also indicated that she would attempt to influence how her siblings communicated their personal test results within the family, by encouraging them to withhold their results, should they learn that they were mutation carriers. All four siblings chose to be tested and their results were disclosed in individual sessions on the same day. The proband, one sister, and her brother had the same mutation that had been identified in their father; the other sister tested negative. The proband was assured that the research team would preserve the confidentiality of her information. She stated that she clearly understood the implications of her test results for her children, that she would “take care of them,” promising that they would be informed of the test results when it “was appropriate.” The proband’s siblings shared their mutation results with family members in the waiting room following their disclosure session. However, in the presence of several members of the research team, the proband lied to her family members about her test results, informing her family that she had tested negative for the BRCA1 mutation.

1526Background: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome primarily caused by germline TP53 mutations. LFS is associated with very high lifetime cancer risk and early onset of a wide range of cancers. Cancer surveillance is challenging given the tumor spectrum, although an MRI-based regimen has shown promise. An important aim of NCI’s LFS cohort study (NCT01443468) is to establish an effective cancer-screening regimen. Methods: Individuals with a germline TP53 mutation were eligible for screening with annual rapid sequence whole-body (WB) MRI, brain MRI, and breast MRI if applicable, colonoscopy every 3 years, and blood tests every 4 months; children < 17 years also have abdominal ultrasound every 4 months. Here we report the findings at baseline screening of the first 100 participants. Results: Twenty of the 100 WB MRIs had abnormalities requiring additional imaging. Subsequent biopsies in 3 individuals led to the diagnosis of 1 stage Ib lung cancer and 1 oste...