Cancer Risks After Endometrial Cancer in Mismatch Repair Mutation Carriers

Extract

Recent years have seen increasing attention to the management of endometrial cancer risk in families with hereditary nonpolyposis colorectal cancer or Lynch syndrome (HNPCC/LS). Nevertheless, because endometrial cancer is less common and carries a lower mortality ( 1 ) than colorectal cancer in mismatch repair gene (MMR) mutation carriers, it may be an afterthought for many providers and patients.

Endometrial cancer can often be the sentinel event for a patient and family with HNPCC/LS. Because the prognosis for young women with endometrial cancer is good, such patients will live long enough to be at risk for other cancers. It is understood that most diagnoses of HNPCC/LS are made after a diagnosis of new colorectal cancers ( 2–4 ). However, clinicians are diagnosing MMR mutations in women through the same stepwise process that is followed in cases of colorectal cancer: initial microsatellite instability testing (by polymerase chain reaction–based assay or immunohistochemistry against MMR proteins), either triggered by early onset or family history ( 5 ) or performed on the basis of a more universal testing strategy ( 6 , 7 ). When informative, microsatellite instability testing is followed by germline mutation testing. Caveats are many, including that failure to detect a MMR mutation does not exclude a diagnosis of HNPCC/LS, such that in many cases clinically affected women continue to need to be treated as if HNPCC/LS is present. So, we can expect an increasing number of patients to begin cancer screening after an endometrial cancer diagnosis or to continue ongoing screening after a herald diagnosis of endometrial cancer.