Germline BRCA2 Mutation and Lynch Syndrome in a Patient With Multiple Primary Malignancies.

Deficiency in genes leads to impediment in DNA repair and is associated with an increased lifetime risk of breast, ovarian, prostate, and pancreatic cancer and melanoma. Lynch syndrome is caused by inherited mutations in genes responsible for DNA mismatch repair, with resultant increase in lifetime risk of colorectal, endometrial, ovarian, stomach, urinary, pancreatic, and CNS malignancies. Here, we present a patient with a rare coexistence of both and mutation in the setting of metastatic pancreatic and prostate cancer. The patient was initially diagnosed with metastatic prostate adenocarcinoma at the age of 57, when a screening PSA of 22.9 warranted biopsy and staging scans revealed involvement of the aortocaval lymph node. Treatment with androgen deprivation therapy with the addition of abiraterone and prednisone was initiated. Additionally, a PET scan showed a hypermetabolic isolated lung nodule, which upon wedge resection showed Stage I lung cancer. Three years later, a pancreatic mass and multiple liver lesions were found on a surveillance scan. Biopsy confirmed the diagnosis of pancreatic cancer, and germline testing revealed the coexistence of and mutations. The patient completed four cycles of cisplatin and gemcitabine, followed by the initiation of olaparib as per the POLE study. About 12 months after the diagnosis of metastatic pancreatic cancer and 4 years after the diagnosis of metastatic prostate cancer, the patient has excellent control of the disease with performance status ECOG 0 and minimal side effects from maintenance therapy. This case presents a unique combination of two coexistent inherited syndromes with the approximate combined incidence of 1:357,000. The presence of two advanced malignancies in our patient underlines the cumulative effects of combined deficiency in the DNA repair pathway and possibly an even higher lifetime risk of cancer. This may explain the presence of lung cancer with a minimal smoking history of less than 10 pack years. PARP inhibitors may be effective in controlling metastatic pancreatic cancer, and thus, genetic counseling is important for this patient and his family members, who will need appropriate cancer screening. The probability of carrying two pathogenic variants may be expected to increase as a result of next-generation sequencing and germline testing.