Germline TP53 Testing in Breast Cancers: Why, When and How?

Area of Science:

• Oncology
• Genetics
• Cancer Research

Background:

• Germline TP53 variants are a primary genetic driver of early-onset breast cancer, particularly before age 31.
• Increased use of multi-gene panels has led to more TP53 variant testing in breast cancer patients.
• Interpreting TP53 variants is challenging due to their predominantly missense nature and the need to rule out clonal hematopoiesis and circulating tumor DNA.

Purpose of the Study:

• To define criteria for systematic germline TP53 genetic testing in breast cancer patients.
• To guide clinical management and genetic counseling for individuals with germline TP53 variants.

Main Methods:

• Review of clinical criteria for TP53 variant interpretation.
• Development of guidelines for germline TP53 testing based on age of diagnosis, tumor characteristics, and family history.
• Consideration of management strategies for carriers, including radiotherapy avoidance and enhanced surveillance.

Main Results:

• Specific age and personal/familial history criteria are proposed for systematic germline TP53 testing in breast cancer.
• Testing is recommended for patients diagnosed before age 31, or before 36 with specific tumor types, or with a personal/family history of TP53-related cancers.
• Women diagnosed after 46 without suggestive history should not be routinely tested.

Conclusions:

• Germline TP53 testing in breast cancer patients should be judiciously applied based on defined risk factors.
• Management of carriers should involve avoiding radiotherapy when possible and implementing annual whole-body MRI surveillance.
• These guidelines aim to optimize genetic testing and patient care for hereditary breast cancer.