Treatment-related myelodysplastic syndrome in a breast cancer survivor with TP53 mosaicism: the genetic dilemma

Background: Breast cancer patients commonly undergo germ line genetic testing to screen for pathogenic variants in cancer susceptibility genes. When detected, pathogenic variants justify augmented tumor surveillance and family counseling. We present a case of somatic TP53 mosaicism in a patient with breast cancer who developed treatment-related Myelodysplastic Syndrome (MDS).                
Case Report: An 84-year-old woman with an extensive family history of cancer was diagnosed with breast cancer. On germ line genetic testing, she was found to have a mosaic TP53 mutation. A healthy skin biopsy was negative for TP53 pathologic variants. The patient declined bone marrow biopsy to exclude clonal hematopoiesis progressing to MDS, agreeing only to periodic surveillance. Three years later, she was diagnosed with treatment-related MDS, which was refractory to standard therapies. She died less than one month after diagnosis.
Conclusion: Our case demonstrates the challenges associated with identifying the clinical significance of mosaic TP53 mutation and highlights the importance of proper cancer surveillance in this patient population.