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Research Highlights

  • The NCI study team participated in the 5th International LFS association Symposium that was held virtually in October 2020. Various team members were invited to give talks at the conference.
  • Congratulations to NCI LFS Study team members Dr. Wegman-Ostrosky and Mr. de Andrade who, along with Dr. Pedro Saint-Maurice, received the 2018 National Cancer Institute Director’s Intramural Innovation Award. Their application entitled, “Life-course physical activity associations with mitochondrial DNA copy number and cancer outcomes in Li-Fraumeni Syndrome” was accepted and fully funded in December 2017. This study will commence soon.

In August 2017, we published a report on the NCI LFS cohort’s prevalence of cancer at baseline screening in JAMA Oncology. The study team observed a higher than expected prevalence of cancer at baseline screening in individuals with LFS. Of the 116 study participants screened, 8 cancers were diagnosed and all but 1 were treated by resection only. Additional studies were required to further investigate 40 other abnormalities, 32 of which were not malignant, detected at time of screening, inferring a ~ 30% false-positive rate. This research shows the feasibility of a comprehensive cancer screening protocol for this high-risk population.

A meta-analysis, published in the same issue of JAMA Oncology, involved 578 participants with LFS in 13 cohorts at multiple research centers around the world. Similarly, utilizing rapid whole-body MRI, the investigators observed an overall detection rate of 7 percent for new primary cancers at baseline screening, confirming the results of the study conducted at NCI.

The published studies can be found on PubMed:

  • Prevalence of Cancer at Baseline Screening in the National Cancer Institute Li-Fraumeni Syndrome Cohort
  • Baseline Surveillance in Li-Fraumeni Syndrome Using Whole-Body Magnetic Resonance Imaging: A Meta-analysis

Reproductive factors associated with breast cancer risk in Li-Fraumeni syndrome

In the first study to evaluate reproductive factors and breast cancer risk in women with Li-Fraumeni Syndrome (LFS), NCI investigators report lifetime breastfeeding of at least seven months to be associated with a 43 percent reduction in breast cancer risk. NCI investigators analyzed questionnaire data from 152 women with confirmed germline TP53 variants enrolled in the NCI LFS study; 85 of whom had at least one breast cancer diagnosis. These results are an important contribution to the conversation between clinicians, genetic counselors, and patients about the medical benefits of breastfeeding in the context of cancer screening and prophylactic mastectomy for cancer prevention in women with LFS.

LFS Cancer Incidence

In August 2016, our LFS team reported on cancer incidence from our NCI cohort in the journal Cancer. Read the paper online: “Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort.”

In this publication, we presented our findings from 286 individuals with TP53 mutations who enrolled in our study since it opened in 2011. We examined the cancer risk by gender as well as by specific cancer site. We observed that by age 31, 50% of females had developed cancer; for males it was by age 36. By age 70, nearly 100% of both males and females had developed some type of cancer.

Approximately 49% of those with one cancer developed at least one other cancer after 10 years. Our findings confirm the cancer risk in TP53 mutation carriers is very high, but varies by age, sex, and cancer type. Further research is needed to better inform personalized risk management for these individuals.

Psychosocial Aspects of LFS

In November 2015, our LFS team published an article in the Journal of Genetic Counseling (JoGC). Read the epub version of the article: “Easing the Burden: Describing the Role of Social, Emotional and Spiritual Support in Research Families with Li-Fraumeni SyndromeExternal Web Site Policy.”

This paper presents the findings from assessments of the social support and emotional status of the first 66 participants who attended the LFS clinic at the NIH Clinical Center. We saw patients with or without cancer, along with relatives and spouses. Most people did not indicate distress on a standardized measure. We found that reported friendships varied widely and were an important source of informational, tangible, emotional, and spiritual support. In some families, organized religion was a major source of coping. Confidantes tended to be best friends and/or spouses. Our results shed preliminary light on how some people in LFS families handle tremendous medical, social, and emotional challenges.

LFS Family Interview Study

In 2012, CGB launched the Family Interview study as an extension of the psychosocial research conducted in the LFS study. The purpose of the family interviews is to explore and understand the ways in which members of families with LFS or LFL communicate with and support each other. A trained couples and family therapist conducts in-depth interviews with two or more family members during their visits to the Clinical Center. During the interviews, we explore the specific challenges that arise in navigating a wide range of individual and family issues that might be impacted by the presence of LFS or LFL.