Background Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome characterized by very high lifetime cancer risk and early age at diagnosis of a wide cancer spectrum. Precise estimates for first and subsequent cancers risk are lacking. Methods The NCI’s LFS Study includes families meeting diagnostic criteria for LFS or Li-Fraumeni-like syndrome, and individuals with a germline TP53 mutation, choroid plexus carcinoma, adrenocortical carcinoma, or ≥3 cancers. We estimated cumulative risk and annual hazards for first and second cancer among TP53 mutation carriers (TP53+) using MATLAB. Results We evaluated 286 TP53+ individuals from 107 families. Cumulative cancer incidence was 50% by age 31 among TP53+ females and 46 among males, and nearly 100% by age 70 for both. Cancer risk was highest after age 20 for females, mostly due to breast cancer, while among males risk was higher in childhood and later adulthood. Among females, the cumulative incidence by age 70 for breast cancer, soft tissue sarcoma (STS), brain cancer, and osteosarcoma were 54%, 15%, 6%, and 5%, respectively. Among males, the incidence was 22%, 19%, and 11% for STS, brain cancer, and osteosarcoma. 49% of those with one cancer developed at least another cancer after a median of 10 years. Average age-specific risk of developing a second cancer was comparable to that of developing a first cancer. Conclusions Cumulative cancer risk in TP53+ individuals was high and varied by gender, age, and cancer type. Additional work, including prospective risk estimates, is needed to better inform personalized risk management.

Key Points Question What are efficient approaches for triage of human papillomavirus–positive women in cervical cancer screening? Findings This cohort study of 3225 women found that p16/Ki-67 dual stain, alone or in combination with human papillomavirus 16/18 genotyping, provides better risk stratification than comparable cytologic-based strategies. Meaning Triage of human papillomavirus–positive women with dual stain may lead to lower referral to undergo colposcopy with similar detection of precancerous lesions compared with cytologic screening, making cervical cancer screening more efficient.

Abstract:This study was designed to develop and test a system to monitor adherence with nonhormonal oral chemotherapeutic agents using an automated voice response (AVR) system plus nursing intervention. Participants received the Symptom Management This pilot study demonstrated the ability to accrue patients for a longitudinal trial and informed intervention design, while providing guidance for future interventions and research studies.