A recent study from France included over 400 patients with Li-Fraumeni Syndrome (all of whom had an inherited TP53 gene mutation). Cancer types among children and adults differed, with the main cancer types among children being osteosarcomas, adrenocortical carcinomas, central nervous system (CNS) tumors and soft tissue sarcomas; whereas among adults, the main cancer types were breast cancer and soft tissue sarcomas.
The study also evaluated whether the type of mutation was associated with a specific presentation of cancer. What they found was that average age at which cancer presented was substantially lower among those who had a ‘dominant negative’ missense mutation (21.3 years) compared to those with all types of loss-of-function mutations (28.5 years) or genomic rearrangements (35.8 years). With the exception of children with adrenocortical carcinoma, most affected children had dominant-negative missense mutations.
Among women ages 30 or younger with breast cancer, TP53 mutations were detected in 6%. Breast cancer pathology reports were evaluated in a group of TP53 carriers, and showed that 55% were HER2 receptor positive and 37% were triple positive (i.e., ER, PR and HER2 receptor positive). Among women with breast cancer and a TP53 mutation, the development of contralateral breast cancer (cancer in the opposite breast) was very high at 31% compared to an estimated 10% contralateral breast cancer risk among women in the general population.
There was a high rate (43%) of multiple primary cancers among TP53 mutation carriers, the majority of which were cancers that developed following an initial cancer diagnosis. Treatment records were available on a subset of patients who received radiation treatment for their first tumor which showed that 30% developed secondary tumors in the radiation field, within 2-26 years (mean, 10.7 years) following their initial cancer treatment.
With the increasing use of multi-gene tests, mutations in TP53 are unexpectedly being identified in individuals without a family history characteristic of Li-Fraumeni Syndrome.2
Consequently, clinicians and researchers are pursuing efforts to better understand the expanding cancer risks and how cancer presents among some of these individuals who are unexpectedly found to have a TP53 mutation, which is needed to further tailor their medical care.
1Bougeard G et al. J Clin Oncol. 2015 Jul 20;33(21):2345-52. PMID: 26014290
2Kamihara J,et al. Hum Mutat. 2014 Jun;35(6):654-62. PMID: 24706533