Abstract P6-08-18: Breast cancer in Li-Fraumeni syndrome and risk-reduction mastectomy in TP53 p.R337H carriers
Authors: Alves Mariana Cartaxo , Sandoval Renata Lazari , Pisani Janina Pontes , Quirino Carla Vanessa , Santos Elizabeth Santana , Achatz Maria Isabel 
Published: March 2020

Abstract
Li-Fraumeni syndrome (LFS) is a hereditary genetic condition that predisposes to a wide variety of tumors. Early-onset breast cancer is the most prevalent tumor in female carriers, with a 49% risk by age 60. The risk of developing a second primary breast cancer in LFS remains unknown but it is estimated to be 33%. The Toronto protocol was proposed by Villani et al. (2011) and defined effective strategies for cancer screening in carriers. Risk-reduction mastectomy (RRM) may reduce over 90% breast cancer risk. Due to a founder mutation, TP53 p.R337H, LFS has been observed in a higher-than-expected prevalence in Brazil. This mutation occurs in the oligomerization domain and seems to have a milder lifetime penetrance than regular DNA binding domain mutations. Due to its estimated high frequency in the Brazillian population, this is a public health problem and implementation of effective strategies in breast cancer risk-reduction are needed. In this study, we have evaluated risk-reduction mastectomy in women who carried the founder TP53 p.R337H mutation. A total of 106 women from the Brazilian LFS TP53 p.R337H cohort were included in this study. Imaging surveillance was offered and RRM was discussed. All participants received genetic counseling and signed informed consent. The study was approved by the local ethics committee (HSL-02433418.5.0000.5461).
A total of 65.1% (69/106) did not develop breast cancer at the time of this study. Among those, four women opted to perform bilateral prophylactic mastectomy (5.8% - 4/69). Overall, 34.9% (37/106) developed breast cancer prior to enrollment and 12 women were lost to follow-up. A total of 25 women opted to continue surveillance. Eleven (44%) opted to undergo RRM and 14 (66%) chose to continue annual breast magnetic resonance imaging (MRI), according to the Toronto protocol. A total of 32% (8/25) had been diagnosed with a second primary breast cancer prior to the study enrollment. The most common breast cancer histopathological subtype was invasive ductal carcinoma, present in 64% (16/25) in our study population. Only one woman was diagnosed with invasive lobular carcinoma (4%). Twelve percent (3/25) were in situ carcinomas. Estrogen and progesterone receptors stained positive in 76% (19/25). HER-2 was negative in 52% (13/25) of all cases. Our findings show that BPM was not a common procedure in carriers (5.8%). Nevertheless, RRM was performed in 44% of all women who have been previously diagnosed with breast cancer. Ductal invasive carcinoma is the most common cancer in TP53 p.R337H women and most of them have hormone receptor status positive. Unlike other previously published studies on LFS breast can cancer, HER-2 gene was non-amplified in most cases (52%). This is the first study to evaluate the frequency of RRM in a cohort of women with breast cancer carrying the same germline pathogenic variant, TP53 p.R337H.
Citation Format: Mariana Cartaxo Alves, Renata Lazari Sandoval, Janina Pontes Pisani, Carla Vanessa Quirino, Elizabeth Santana Santos, Maria Isabel Achatz. Breast cancer in Li-Fraumeni syndrome and risk-reduction mastectomy in TP53 p.R337H carriers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-18.