Two sisters with invasive lobular breast cancer and a shared CDH1 mutation

What happened, in summary

This family story involves 2 sisters, ages 62 and 70, who were diagnosed with invasive lobular breast carcinoma and found to carry the same pathogenic CDH1 mutation. The younger sister, age 62, had a suspicious right breast focal asymmetry with a 4.1 cm mass-like appearance on routine mammography. Biopsy showed ER-positive, HER2/neu-negative invasive lobular carcinoma, staged T2N0M0, grade 2, Stage IIA. She was treated with lumpectomy, radiation, and tamoxifen. Genetic testing found a pathogenic heterozygous CDH1 p.G239R mutation. Because CDH1 mutations are associated with hereditary diffuse gastric cancer, she began gastric surveillance. Initial EGD showed benign antral mucosa with superficial hyperplastic changes, and follow-up EGD with EUS and Cambridge-protocol biopsies showed reactive gastropathy without malignancy. She declined prophylactic total gastrectomy and chose annual EGD plus mammographic surveillance. The older sister, age 70, first had a 2.7 cm left breast invasive lobular carcinoma, T2N0M0, grade 2, Stage IA, ER/PR-positive and HER2/neu-negative. She underwent lumpectomy and radiotherapy and did not require chemotherapy or hormonal therapy at that time. Three years later, she developed right breast invasive lobular carcinoma, also T2N0M0, grade 2, Stage IA, ER/PR-positive and HER2/neu-negative. She underwent bilateral mastectomy and started anastrozole. Genetic testing showed the same CDH1 p.G239R mutation plus a PTCH1 p.A1141V variant of uncertain significance. She also chose annual EGD surveillance instead of prophylactic total gastrectomy. As of January 2025, neither sister had signs of hereditary diffuse gastric cancer or metastatic breast cancer, and annual surveillance was continuing.