Young Woman With Breast Cancer and Four Inherited Cancer-Risk Variants

What happened, in summary

A 31-year-old woman was referred for genetic evaluation after developing breast cancer at a young age. The year before, she had been diagnosed with bicentric invasive ductal carcinoma. Her tumor was ER 40%, PgR 60%, HER2 0, and Ki-67 25%. She underwent nipple-sparing mastectomy, and the sentinel lymph nodes were negative. She then received 4 cycles of epirubicin and cyclophosphamide and also received exemestane. Earlier BRCA1 and BRCA2 testing had been negative. Because of her young age and family history, genetic testing was expanded beyond BRCA. The broader panel identified pathogenic germline variants in four genes: ATM, PALB2, PMS2, and MUTYH. This combination was considered consistent with multilocus inherited neoplasia allele syndrome. The findings were important for genetic counseling and for understanding cancer risks within the family, although they did not change her treatment regimen. Her cancer later spread rapidly to the brain, establishing Stage IV disease. She died within a few months of the metastatic progression. Her family history included a maternal grandfather who died from gastric cancer at 69 and a paternal grandfather who died from colorectal cancer at 85, both of whom are kept as separate family cancer cases rather than having their histories merged into hers.