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Genetic Testing and Cancer Risk Assessment
Jeffrey N. Weitzel
We have the evidence, and we have the tools. Professor Jeffrey Weitzel opened his talk with the uncomfortable part: 74 percent of the people carrying an actionable cancer gene would never ha...
We have the evidence, and we have the tools. Professor Jeffrey Weitzel opened his talk with the uncomfortable part: 74 percent of the people carrying an actionable cancer gene would never have qualified for testing under our own guidelines.
Professor Weitzel traces genetic risk assessment from the first observations of hereditary cancer to whole-genome sequencing and polygenic risk scores, and he argues that the field's central failure is now reach, not science. He shows why family history still matters, why population-based testing finds carriers that criteria miss, and why identifying these patients is one of the most compelling interventions in medicine, because for BRCA carriers, risk-reducing surgery lowers all-cause mortality.
Key points for clinicians:
Pathogenic variants appear in at least 10 percent of breast cancer patients, 25 percent of ovarian cancer patients, and roughly 10 percent of prostate cancer patients.
Guidelines can be simplified toward testing essentially all breast cancer patients, but carriers should not be managed identically, since a 35-year-old and a 60-year-old with the same variant face very different lifetime risk.
Removing the tubes and ovaries carries the highest level of evidence, an all-cause mortality reduction, and there is effectively no upper age limit for considering it.
In a Sloan Kettering series, 16 percent of patients had an actionable variant, and 74 percent of them would not have met testing criteria.
Polygenic risk scores are now ancestry-anchored and entering clinical use, as in the 28,000-woman WISDOM trial, yet US germline testing for ovarian cancer still sits under 50 percent, which is why training, mainstreaming, and cascade testing matter.