Dados do Trabalho

Título

BREAST CANCER PENETRANCE IN TP53 RELATED CANCER SYNDROME - DATA FROM A SIGLE TERTIARY INSTITUTION

Introdução

TP53 related cancer syndrome predisposes to a myriad of cancer types, including adrenocortical carcinoma, early onset breast cancer, soft tissue and osteossarcomas. Case series reports claim evidence that germline R337H TP53 variant predisposes to a less penetrant phenotype, compared to DNA binding domain (DBD) TP53 germline pathogenic variants. However, no direct analytic study has been performed nor specific cancer sites were assessed. Since female breast cancer is the most common neoplasia reported in this scenario, we envisioned that our single institution casuistic would be appropriate to estimate age related penetrance among those different classes of mutation.

Objetivo

To compare breast cancer risk between TP53 R337H germline carriers and DBD TP53 mutation carriers in a single tertiary institution in Brazil.

Método

Female carriers of TP53 germline pathogenic variants (R337H or DBD) were retrospectively identified in the institution Oncogenetics Department Registry. Date of birth were considered for the starting point of observation. Follow up was censored at diagnosis of the first invasive breast cancer, date of death (for other causes) or date last information was obtained from medical charts. Breast cancer risk according to age was estimated using Kaplan-Meier test, for both R337H and DBD mutation carriers. Log-rank test was performed for comparison between groups. This project approved by IRB (CAAE: 17950319.2.0000.5437).

Resultado

Among 318 TP53 mutation female carriers, 278 (87.4%) had R337H, 28 (8,8%) had DBD mutation and 12 (3.8%) had other mutations. Regarding breast cancer occurrence, 27.3% of R337H and 53.6% of DBD mutation female carriers had at least one primary breast cancer. Kaplan-Meier risk estimate showed that breast cancer penetrance for R337H carriers was 2.6%, 16.7%, 36.8% and 53.2% at ages 30, 40, 50 and 60, respectively; and, for DBD mutation carriers, 31.2%, 52.9%, 70.6% and 76.5% at ages 30, 40, 50 and 60, respectively. The difference between the risk curves was statistically significant (p=0.00).

Conclusão

In a group of female TP53 R337H carriers, compared to TP53 DBD mutation carriers, followed up in an oncogenetics unit at a tertiary institution, age related breast cancer penetrance was, indeed, lower.

Palavras-chave

TP53 related cancer syndrome, R337H, early onset breast cancer