Examination of the time interval between diagnoses in women with metachronous primary endometrial and colorectal cancers supporting universal Lynch testing

Purpose: The time interval between diagnoses of endometrial and colorectal cancers is not well established in women with metachronous primary tumors of both sites. The authors sought to examine the time interval between diagnoses, identify associations with clinicopathologic factors, and compare current genetic screening practices. Materials and Methods: The authors identified 53 patients who developed both cancers between 1966-2014. These patients were divided into two groups based on having colorectal (group 1) or endometrial (group 2) cancer first. Risks of MLH1, MSH2, MSH 6, or BRCA1/2 mutations, as well as the chance of developing a subsequent ovarian or breast cancer were estimated. Results: There were 18 and 35 patients in groups 1 and 2, respectively. The mean time interval was longer in group 2, 70 vs. 43 months. Median PFS and OS for endometrial cancer tended to be longer in group 2 (PFS: 66 vs. 58 and OS: 77 vs. 58 months). Median PFS and OS for colorectal cancer were significantly longer in group 1 (PFS: 22 vs.74 and OS: 22 vs. 86 months). The estimated risk of any MMR mutations was at least 25% in the majority of the patents, with 21 of those patients > 50%, and 13 > 75%. Conclusions: The mean estimated prevalence of MMR mutation in patients with metachronous endometrial and colorectal cancers is 100-fold greater than the general population. The time interval between the diagnosis of endometrial and colorectal carcinomas is 5.8 years if endometrial cancer develops first and 3.5 years if colorectal develops first. These results are useful in counseling women at risk.

Endometrial cancer; Colorectal cancer; Lynch syndrome.

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