The Importance of Distinguishing Sporadic Cancers from Those Related to Cancer Predisposing Germline Mutations

AbstractChoosing the optimal therapy for a patient's cancer has long been based on whether the cancer demonstrates a predictive marker of efficacy. The U.S. Food and Drug Administration (FDA) has now approved use of a targeted therapy based solely on tumor molecular markers (pembrolizumab for tumors with deficient mismatch repair [MMR] and high microsatellite instability [MSI]) and approved another therapy based solely on a germline mutation as the predictive marker of benefit (olaparib for BRCA carriers with ovarian or breast cancer) [New Engl J Med 2017;377:1409–1412, N Engl J Med 2012;366:1382–1392, N Eng J Med 2017;377:523–533].Here, a patient is presented with a molecular diagnosis of Lynch syndrome and with breast cancer. Yet the breast cancer showed proficient expression of the same MMR gene found to be mutated in her germline testing. The case underscores the importance of tumor testing for MMR and MSI and of not assuming that the tumor is related to the Lynch syndrome rather than being sporadic. This is particularly true in patients with cancers (e.g., breast cancer) whose association with Lynch syndrome is not well established.The case presented also underscores the importance of considering next‐generation sequencing of the tumor when the therapies approved are based on a germline mutation being the predictive marker. For example, the FDA‐approved use of the PARP inhibitor olaparib is for ovarian or breast cancers in patients harboring a BRCA germline mut...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Precision Medicine, Breast Cancer Precision Medicine Clinic: Molecular Tumor Board Source Type: research