EGFR-mutant lung adenocarcinoma in Li-Fraumeni syndrome: relapse-free after lobectomy and chemotherapy

What happened, in summary

This 47-year-old nonsmoking woman had Li-Fraumeni syndrome, confirmed by a hereditary TP53 variant, and a long history of cancer. Her earlier illnesses included HER2-positive bilateral breast cancer at age 28, a liver perivascular epithelioid cell tumor treated with partial hepatectomy at age 38, a grade 3 pleomorphic spindle cell sarcoma in the right thigh, and another right breast infiltrating ductal carcinoma. She had received multiple prior treatments, including mastectomies, chemotherapy, trastuzumab-based treatment for the later breast cancer, tamoxifen, sarcoma surgery, and radiotherapy. During surveillance imaging for her sarcoma, a 1.4 cm nodule was found in the lingula of the lung when she was 46. She had no lung symptoms and no abnormal findings on physical examination. Biopsy confirmed lung adenocarcinoma. Genetic testing of the tumor detected an EGFR exon 19 deletion, while testing of peripheral lymphocytes did not find EGFR mutation, supporting a tumor-specific EGFR alteration rather than inherited EGFR disease. She was treated with left inferior lobectomy, followed by pemetrexed and cisplatin. The lung lesion was found through cancer surveillance rather than symptoms, which is important because people with Li-Fraumeni syndrome can develop multiple primary tumors over time. Genetic testing also showed that the EGFR exon 19 deletion was not present in peripheral lymphocytes, separating the lung tumor driver from her inherited TP53 syndrome. No EGFR-targeted therapy was given for this lung cancer. As of July 2024, she was free of relapse 2 years after lung cancer treatment. Her story is notable because the lung adenocarcinoma occurred in the setting of Li-Fraumeni syndrome and multiple prior cancers, but without a family history of lung cancer.