Prophylactic surgery among germline TP53 mutation carriers in Germany – a multicentric observational study

Objective:

Li-Fraumeni syndrome comprises a rare inherited cancer susceptibility disorder caused by germline TP53 variants. It is associated with an increased life-time risk of breast cancer (BC) in up to 79% of female carriers with a mean age of 35 at the time of onset. In healthy mutation carriers, intensified surveillance programs or prophylactic mastectomy (PM) are possible. If unilateral BC occurs, mastectomy, as a radiation-free alternative to lumpectomy, as well as contralateral PM due to an increased contralateral BC risk of up to 31% should be discussed. Data for carriers' perception are missing; this study addresses PM among female TP53 mutation carriers in Germany.

Methods:

A quadruplet questionnaire addressed socio-demographics, cancer history, PM, surgical technique and its satisfaction among TP53 mutation carriers from eleven German centres between December 2016 and January 2018.

Results:

36 out of all 40 female responders, aged 40.8 ± 12.3 had a personal cancer history: 52.5% had single BC while 27.5% had multiple primary tumours including BC and 10% suffered from another solitary cancer. 45% underwent prophylactic surgery of whom 77.7% had a personal BC history. Most (57%) had chosen breast implants. 72% were highly satisfied with PM while more than 55% would re-perform surgery or recommend it to family members.

Perspective:

TP53 mutation carriers may opt for prophylactic mastectomy after a non-directive consultation, which should always account for age, personal and familial cancer history, as well as the counselee's preferences. However, prospective studies evaluating a potential survival benefit are needed for individual risk assessment.